Anticoagulation Hub

BOSTON – Black people with new-onset atrial fibrillation have a 60% increased risk for stroke compared with white people who have incident atrial fibrillation when not maintained on an appropriate anticlotting regimen, according to prospectively collected data from more than 56,000 subjects at a U.S. center.

But in the subgroup of new-onset atrial fibrillation (AF) patients who received appropriate treatment with aspirin or an anticoagulant, the stroke rates among white and blacks equalized. The analysis showed that 46% of the more than 3,000 people who developed AF during follow-up received aspirin if their CHA2DS2-VASc score was less than 2, or anticoagulation with warfarin or a new oral anticoagulant if their score was 2 or greater, Dr. Parin J. Patel said at the annual scientific sessions of the Heart Rhythm Society.

Mitchel L. Zoler/Frontline Medical News

The majority of the followed cohort with incident atrial fibrillation did not receive this treatment, and in the total group, the relative rate of stroke among blacks exceeded that of whites by a statistically significant 60% in an analysis that adjusted for several demographic and clinical features. The excess of strokes occurred at about the same rate in black women compared with white women, and in black men compared with white men, reported Dr. Patel, an electrophysiologist at the University of Pennsylvania in Philadelphia.

The implication is that because their stroke risk is greater, blacks with AF should especially receive appropriate stroke prophylaxis and AF therapy, he said. The overall findings also highlight the substantial stroke risk faced by all AF patients.

The data came from the University of Pennsylvania Atrial Fibrillation-Free study of 91,274 people who underwent an ECG examination in the University of Pennsylvania health system during 2004-2009 along with an index clinical encounter within 30 days. Excluding patients with a prevalent AF or other arrhythmia, prevalent stroke, or incomplete data left 56,835 AF- and stroke-free people to follow for incident AF, which occurred in 3,891 patients. At the time of AF diagnosis, the average age of patients was 63 years; more than a third had hypertension; a fifth had diabetes; and a fifth had heart failure. One-third of the incident-AF group was black, 58% were white, and the remainder were from other demographic groups.

Dr. Patel and his associates defined an AF-related stroke as any that occurred within 6 months before AF diagnosis or anytime after, which occurred in 645 (17%) of the incident-AF patients. The more than 50,000 AF-free people followed in the study had a total of 3,001 strokes not related to AF during follow-up, which meant that 18% of all strokes in the entire cohort were AF related.

Among the 645 AF-related strokes, roughly half occurred during the 6 months before AF diagnosis, and the other half following AF diagnosis. An analysis that focused exclusively on strokes that occurred after AF diagnosis showed that this subset of AF-associated strokes also occurred significantly more often in blacks than in whites.

Dr. Patel had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON – Black people with new-onset atrial fibrillation have a 60% increased risk for stroke compared with white people who have incident atrial fibrillation when not maintained on an appropriate anticlotting regimen, according to prospectively collected data from more than 56,000 subjects at a U.S. center.

But in the subgroup of new-onset atrial fibrillation (AF) patients who received appropriate treatment with aspirin or an anticoagulant, the stroke rates among white and blacks equalized. The analysis showed that 46% of the more than 3,000 people who developed AF during follow-up received aspirin if their CHA2DS2-VASc score was less than 2, or anticoagulation with warfarin or a new oral anticoagulant if their score was 2 or greater, Dr. Parin J. Patel said at the annual scientific sessions of the Heart Rhythm Society.

Mitchel L. Zoler/Frontline Medical News

The majority of the followed cohort with incident atrial fibrillation did not receive this treatment, and in the total group, the relative rate of stroke among blacks exceeded that of whites by a statistically significant 60% in an analysis that adjusted for several demographic and clinical features. The excess of strokes occurred at about the same rate in black women compared with white women, and in black men compared with white men, reported Dr. Patel, an electrophysiologist at the University of Pennsylvania in Philadelphia.

The implication is that because their stroke risk is greater, blacks with AF should especially receive appropriate stroke prophylaxis and AF therapy, he said. The overall findings also highlight the substantial stroke risk faced by all AF patients.

The data came from the University of Pennsylvania Atrial Fibrillation-Free study of 91,274 people who underwent an ECG examination in the University of Pennsylvania health system during 2004-2009 along with an index clinical encounter within 30 days. Excluding patients with a prevalent AF or other arrhythmia, prevalent stroke, or incomplete data left 56,835 AF- and stroke-free people to follow for incident AF, which occurred in 3,891 patients. At the time of AF diagnosis, the average age of patients was 63 years; more than a third had hypertension; a fifth had diabetes; and a fifth had heart failure. One-third of the incident-AF group was black, 58% were white, and the remainder were from other demographic groups.

Dr. Patel and his associates defined an AF-related stroke as any that occurred within 6 months before AF diagnosis or anytime after, which occurred in 645 (17%) of the incident-AF patients. The more than 50,000 AF-free people followed in the study had a total of 3,001 strokes not related to AF during follow-up, which meant that 18% of all strokes in the entire cohort were AF related.

Among the 645 AF-related strokes, roughly half occurred during the 6 months before AF diagnosis, and the other half following AF diagnosis. An analysis that focused exclusively on strokes that occurred after AF diagnosis showed that this subset of AF-associated strokes also occurred significantly more often in blacks than in whites.

Dr. Patel had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON – Black people with new-onset atrial fibrillation have a 60% increased risk for stroke compared with white people who have incident atrial fibrillation when not maintained on an appropriate anticlotting regimen, according to prospectively collected data from more than 56,000 subjects at a U.S. center.

But in the subgroup of new-onset atrial fibrillation (AF) patients who received appropriate treatment with aspirin or an anticoagulant, the stroke rates among white and blacks equalized. The analysis showed that 46% of the more than 3,000 people who developed AF during follow-up received aspirin if their CHA2DS2-VASc score was less than 2, or anticoagulation with warfarin or a new oral anticoagulant if their score was 2 or greater, Dr. Parin J. Patel said at the annual scientific sessions of the Heart Rhythm Society.

Mitchel L. Zoler/Frontline Medical News

The majority of the followed cohort with incident atrial fibrillation did not receive this treatment, and in the total group, the relative rate of stroke among blacks exceeded that of whites by a statistically significant 60% in an analysis that adjusted for several demographic and clinical features. The excess of strokes occurred at about the same rate in black women compared with white women, and in black men compared with white men, reported Dr. Patel, an electrophysiologist at the University of Pennsylvania in Philadelphia.

The implication is that because their stroke risk is greater, blacks with AF should especially receive appropriate stroke prophylaxis and AF therapy, he said. The overall findings also highlight the substantial stroke risk faced by all AF patients.

The data came from the University of Pennsylvania Atrial Fibrillation-Free study of 91,274 people who underwent an ECG examination in the University of Pennsylvania health system during 2004-2009 along with an index clinical encounter within 30 days. Excluding patients with a prevalent AF or other arrhythmia, prevalent stroke, or incomplete data left 56,835 AF- and stroke-free people to follow for incident AF, which occurred in 3,891 patients. At the time of AF diagnosis, the average age of patients was 63 years; more than a third had hypertension; a fifth had diabetes; and a fifth had heart failure. One-third of the incident-AF group was black, 58% were white, and the remainder were from other demographic groups.

Dr. Patel and his associates defined an AF-related stroke as any that occurred within 6 months before AF diagnosis or anytime after, which occurred in 645 (17%) of the incident-AF patients. The more than 50,000 AF-free people followed in the study had a total of 3,001 strokes not related to AF during follow-up, which meant that 18% of all strokes in the entire cohort were AF related.

Among the 645 AF-related strokes, roughly half occurred during the 6 months before AF diagnosis, and the other half following AF diagnosis. An analysis that focused exclusively on strokes that occurred after AF diagnosis showed that this subset of AF-associated strokes also occurred significantly more often in blacks than in whites.

Dr. Patel had no disclosures.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

VIENNA – Handheld ECG monitors offered a practical, noninvasive solution to detecting atrial fibrillation in patients who had been diagnosed with ischemic stroke or transient ischemic attack in a retrospective hospital-based study.

The results presented at the annual European Stroke Conference showed an overall detection rate of 7.6%, which is in the same range seen in previous studies of handheld ECG monitors but was higher than in most studies that used 24-hour Holter monitoring, said study investigator Dr. Ann-Sofie Olsson of Hallands Hospital Halmstead (Sweden).

The retrospective study included data on 356 patients who had been seen at the hospital for ischemic stroke or transient ischemic attack (TIA) and who had undergone intermittent handheld ECG testing to monitor for atrial fibrillation (AF). The mean age of patients was 66 years, 53% were male, and 46% were diagnosed with ischemic stroke and 56% with TIA. The mean baseline CHA₂DS₂-VASc score was 4.2, suggesting patients were at reasonably moderate risk of subsequent AF-related stroke.

The ECG monitor used consisted of a small, lightweight plastic box that patients held by two thumb sensors for 10, 20, or 30 seconds, with measurements taken twice a day (morning and evening) for 14 days. The sensors, which provided lead I of a standard ECG, provided information on atrial movement that was transmitted to a data server and was viewed via a web browser.

“We defined a positive investigation as either atrial fibrillation for a minimum of 10 seconds or a short, irregular supraventricular arrhythmia, Dr. Olsson explained.

Overall, 27 (7.6%) of the 356 patients evaluated had a positive result, with a 95% confidence interval ranging from 5.1% to 10.1%. While there was no statistically significant difference in AF detection rates between men (8.5%) and women (6.5%), detection rates were higher if patients had had an ischemic stroke rather than a TIA (11% vs. 5%, P = .032). There was also a trend (P = .051) for better detection rates in older (≥65 years) than younger (<65 years) patients, at 8.8% vs. 4.2%, respectively.

“It is natural to ask ourselves whether we can improve the detection rates by selecting higher-risk patients,” Dr. Olsson said, commenting on the lower detection rate seen in TIA patients despite there being more TIA cases in the study cohort.

“We saw high adherence to the monitoring; only six (1.5%) patients did not complete the investigation,” said Dr. Olsson, noting that older age did not seem to be an obstacle to performing the ECG with the handheld monitor as the oldest patient in the study was 90 years.

Dr. Olsson noted that the monitor used in the study had a sensitivity of 96% and a specificity of 92%.

Dr. Olsson reported having no relevant financial disclosures.

VIENNA – Handheld ECG monitors offered a practical, noninvasive solution to detecting atrial fibrillation in patients who had been diagnosed with ischemic stroke or transient ischemic attack in a retrospective hospital-based study.

The results presented at the annual European Stroke Conference showed an overall detection rate of 7.6%, which is in the same range seen in previous studies of handheld ECG monitors but was higher than in most studies that used 24-hour Holter monitoring, said study investigator Dr. Ann-Sofie Olsson of Hallands Hospital Halmstead (Sweden).

The retrospective study included data on 356 patients who had been seen at the hospital for ischemic stroke or transient ischemic attack (TIA) and who had undergone intermittent handheld ECG testing to monitor for atrial fibrillation (AF). The mean age of patients was 66 years, 53% were male, and 46% were diagnosed with ischemic stroke and 56% with TIA. The mean baseline CHA₂DS₂-VASc score was 4.2, suggesting patients were at reasonably moderate risk of subsequent AF-related stroke.

The ECG monitor used consisted of a small, lightweight plastic box that patients held by two thumb sensors for 10, 20, or 30 seconds, with measurements taken twice a day (morning and evening) for 14 days. The sensors, which provided lead I of a standard ECG, provided information on atrial movement that was transmitted to a data server and was viewed via a web browser.

“We defined a positive investigation as either atrial fibrillation for a minimum of 10 seconds or a short, irregular supraventricular arrhythmia, Dr. Olsson explained.

Overall, 27 (7.6%) of the 356 patients evaluated had a positive result, with a 95% confidence interval ranging from 5.1% to 10.1%. While there was no statistically significant difference in AF detection rates between men (8.5%) and women (6.5%), detection rates were higher if patients had had an ischemic stroke rather than a TIA (11% vs. 5%, P = .032). There was also a trend (P = .051) for better detection rates in older (≥65 years) than younger (<65 years) patients, at 8.8% vs. 4.2%, respectively.

“It is natural to ask ourselves whether we can improve the detection rates by selecting higher-risk patients,” Dr. Olsson said, commenting on the lower detection rate seen in TIA patients despite there being more TIA cases in the study cohort.

“We saw high adherence to the monitoring; only six (1.5%) patients did not complete the investigation,” said Dr. Olsson, noting that older age did not seem to be an obstacle to performing the ECG with the handheld monitor as the oldest patient in the study was 90 years.

Dr. Olsson noted that the monitor used in the study had a sensitivity of 96% and a specificity of 92%.

Dr. Olsson reported having no relevant financial disclosures.

VIENNA – Handheld ECG monitors offered a practical, noninvasive solution to detecting atrial fibrillation in patients who had been diagnosed with ischemic stroke or transient ischemic attack in a retrospective hospital-based study.

The results presented at the annual European Stroke Conference showed an overall detection rate of 7.6%, which is in the same range seen in previous studies of handheld ECG monitors but was higher than in most studies that used 24-hour Holter monitoring, said study investigator Dr. Ann-Sofie Olsson of Hallands Hospital Halmstead (Sweden).

The retrospective study included data on 356 patients who had been seen at the hospital for ischemic stroke or transient ischemic attack (TIA) and who had undergone intermittent handheld ECG testing to monitor for atrial fibrillation (AF). The mean age of patients was 66 years, 53% were male, and 46% were diagnosed with ischemic stroke and 56% with TIA. The mean baseline CHA₂DS₂-VASc score was 4.2, suggesting patients were at reasonably moderate risk of subsequent AF-related stroke.

The ECG monitor used consisted of a small, lightweight plastic box that patients held by two thumb sensors for 10, 20, or 30 seconds, with measurements taken twice a day (morning and evening) for 14 days. The sensors, which provided lead I of a standard ECG, provided information on atrial movement that was transmitted to a data server and was viewed via a web browser.

“We defined a positive investigation as either atrial fibrillation for a minimum of 10 seconds or a short, irregular supraventricular arrhythmia, Dr. Olsson explained.

Overall, 27 (7.6%) of the 356 patients evaluated had a positive result, with a 95% confidence interval ranging from 5.1% to 10.1%. While there was no statistically significant difference in AF detection rates between men (8.5%) and women (6.5%), detection rates were higher if patients had had an ischemic stroke rather than a TIA (11% vs. 5%, P = .032). There was also a trend (P = .051) for better detection rates in older (≥65 years) than younger (<65 years) patients, at 8.8% vs. 4.2%, respectively.

“It is natural to ask ourselves whether we can improve the detection rates by selecting higher-risk patients,” Dr. Olsson said, commenting on the lower detection rate seen in TIA patients despite there being more TIA cases in the study cohort.

“We saw high adherence to the monitoring; only six (1.5%) patients did not complete the investigation,” said Dr. Olsson, noting that older age did not seem to be an obstacle to performing the ECG with the handheld monitor as the oldest patient in the study was 90 years.

Dr. Olsson noted that the monitor used in the study had a sensitivity of 96% and a specificity of 92%.

Dr. Olsson reported having no relevant financial disclosures.

For patients with proximal large-vessel anterior stroke, neurovascular thrombectomy with a stent retriever plus medical therapy in the REVASCAT trial reduced the severity of poststroke disability and raised the rate of functional independence, compared with medical therapy alone, according to a report in the New England Journal of Medicine.

To assess the efficacy and safety of thrombectomy with a stent retriever, investigators performed a prospective, open-label, phase III clinical trial involving 206 adults up to 85 years of age treated at four designated comprehensive stroke centers in Catalonia, Spain.

All the participants in the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) had either not responded to intravenous alteplase administered within 4.5 hours of symptom onset or had contraindications to alteplase therapy. They were randomly assigned in equal numbers to undergo endovascular treatment with a stent retriever or medical therapy alone, said Dr. Tudor G. Jovin, director of the Stroke Institute, University of Pittsburgh Medical Center, and his associates.

The trial was halted early when the first interim analysis showed “lack of equipoise” between the two study groups, and because emerging results from three other studies demonstrated the superior efficacy of thrombectomy. The primary efficacy outcome measure – severity of disability at 90 days, as measured by expert assessors blinded to treatment assignment – significantly favored thrombectomy over medical therapy. The proportion of patients who achieved functional independence by day 90 on the modified Rankin scale also demonstrated the clear superiority of thrombectomy (43.7%) over medical therapy (28.2%).

Only 6.5 patients would need to be treated with thrombectomy to prevent 1 case of functional dependency or death. In addition, “thrombectomy was associated with a shift toward better outcomes across the entire spectrum of disability,” Dr. Jovin and his associates said (N. Engl. J. Med. 2015 [doi:10.1056/NEJMoa1503780]).

Regarding safety, the rate of death at 90 days did not differ significantly between patients who underwent thrombectomy (18.4%) and control subjects (15.5%). Rates of intracranial hemorrhage were the same, 1.9%, in both groups, and rates of other serious adverse events also were similar.

These findings are consistent with those of several other recently reported clinical trials and show that “in patients with acute stroke caused by a proximal large-vessel occlusion and an absence of a large infarct on baseline imaging, mechanical thrombectomy with [a] stent retriever was safe and led to improved clinical outcomes, as compared with medical therapy alone,” the investigators said.

REVASCAT was funded by an unrestricted grant from Covidien, maker of the stent retriever, and by grants from several Spanish research institutes. Dr. Jovin reported ties to Covidien, Silk Road Medical, Air Liquide, Medtronic, and Stryker Neurovascular.

For patients with proximal large-vessel anterior stroke, neurovascular thrombectomy with a stent retriever plus medical therapy in the REVASCAT trial reduced the severity of poststroke disability and raised the rate of functional independence, compared with medical therapy alone, according to a report in the New England Journal of Medicine.

To assess the efficacy and safety of thrombectomy with a stent retriever, investigators performed a prospective, open-label, phase III clinical trial involving 206 adults up to 85 years of age treated at four designated comprehensive stroke centers in Catalonia, Spain.

All the participants in the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) had either not responded to intravenous alteplase administered within 4.5 hours of symptom onset or had contraindications to alteplase therapy. They were randomly assigned in equal numbers to undergo endovascular treatment with a stent retriever or medical therapy alone, said Dr. Tudor G. Jovin, director of the Stroke Institute, University of Pittsburgh Medical Center, and his associates.

The trial was halted early when the first interim analysis showed “lack of equipoise” between the two study groups, and because emerging results from three other studies demonstrated the superior efficacy of thrombectomy. The primary efficacy outcome measure – severity of disability at 90 days, as measured by expert assessors blinded to treatment assignment – significantly favored thrombectomy over medical therapy. The proportion of patients who achieved functional independence by day 90 on the modified Rankin scale also demonstrated the clear superiority of thrombectomy (43.7%) over medical therapy (28.2%).

Only 6.5 patients would need to be treated with thrombectomy to prevent 1 case of functional dependency or death. In addition, “thrombectomy was associated with a shift toward better outcomes across the entire spectrum of disability,” Dr. Jovin and his associates said (N. Engl. J. Med. 2015 [doi:10.1056/NEJMoa1503780]).

Regarding safety, the rate of death at 90 days did not differ significantly between patients who underwent thrombectomy (18.4%) and control subjects (15.5%). Rates of intracranial hemorrhage were the same, 1.9%, in both groups, and rates of other serious adverse events also were similar.

These findings are consistent with those of several other recently reported clinical trials and show that “in patients with acute stroke caused by a proximal large-vessel occlusion and an absence of a large infarct on baseline imaging, mechanical thrombectomy with [a] stent retriever was safe and led to improved clinical outcomes, as compared with medical therapy alone,” the investigators said.

REVASCAT was funded by an unrestricted grant from Covidien, maker of the stent retriever, and by grants from several Spanish research institutes. Dr. Jovin reported ties to Covidien, Silk Road Medical, Air Liquide, Medtronic, and Stryker Neurovascular.

For patients with proximal large-vessel anterior stroke, neurovascular thrombectomy with a stent retriever plus medical therapy in the REVASCAT trial reduced the severity of poststroke disability and raised the rate of functional independence, compared with medical therapy alone, according to a report in the New England Journal of Medicine.

To assess the efficacy and safety of thrombectomy with a stent retriever, investigators performed a prospective, open-label, phase III clinical trial involving 206 adults up to 85 years of age treated at four designated comprehensive stroke centers in Catalonia, Spain.

All the participants in the Randomized Trial of Revascularization With Solitaire FR Device Versus Best Medical Therapy in the Treatment of Acute Stroke Due to Anterior Circulation Large Vessel Occlusion Presenting Within Eight Hours of Symptom Onset (REVASCAT) had either not responded to intravenous alteplase administered within 4.5 hours of symptom onset or had contraindications to alteplase therapy. They were randomly assigned in equal numbers to undergo endovascular treatment with a stent retriever or medical therapy alone, said Dr. Tudor G. Jovin, director of the Stroke Institute, University of Pittsburgh Medical Center, and his associates.

The trial was halted early when the first interim analysis showed “lack of equipoise” between the two study groups, and because emerging results from three other studies demonstrated the superior efficacy of thrombectomy. The primary efficacy outcome measure – severity of disability at 90 days, as measured by expert assessors blinded to treatment assignment – significantly favored thrombectomy over medical therapy. The proportion of patients who achieved functional independence by day 90 on the modified Rankin scale also demonstrated the clear superiority of thrombectomy (43.7%) over medical therapy (28.2%).

Only 6.5 patients would need to be treated with thrombectomy to prevent 1 case of functional dependency or death. In addition, “thrombectomy was associated with a shift toward better outcomes across the entire spectrum of disability,” Dr. Jovin and his associates said (N. Engl. J. Med. 2015 [doi:10.1056/NEJMoa1503780]).

Regarding safety, the rate of death at 90 days did not differ significantly between patients who underwent thrombectomy (18.4%) and control subjects (15.5%). Rates of intracranial hemorrhage were the same, 1.9%, in both groups, and rates of other serious adverse events also were similar.

These findings are consistent with those of several other recently reported clinical trials and show that “in patients with acute stroke caused by a proximal large-vessel occlusion and an absence of a large infarct on baseline imaging, mechanical thrombectomy with [a] stent retriever was safe and led to improved clinical outcomes, as compared with medical therapy alone,” the investigators said.

REVASCAT was funded by an unrestricted grant from Covidien, maker of the stent retriever, and by grants from several Spanish research institutes. Dr. Jovin reported ties to Covidien, Silk Road Medical, Air Liquide, Medtronic, and Stryker Neurovascular.

The novel oral anticoagulants dabigatran and rivaroxaban have had only “modest” uptake into real-world clinical practice as thromboembolism prevention in high-risk patients with atrial fibrillation, according to a report published online June 9 in Circulation: Cardiovascular Outcomes and Quality.

These drugs have proved to be at least as effective as warfarin at prophylaxis in this patient population, appear to be safer than warfarin regarding the risk of intracranial hemorrhage, and are more practical because they don’t require routine monitoring and have more predictable treatment effects. Yet little is known about their adoption into real-world practice, said Dr. Priyesh A. Patel of Duke Clinical Research Institute in Durham, N.C., and his associates.

©GuidoVrola/thinkstockphotos.com

The investigators examined the issue by analyzing hospital records in the database of the Get With The Guidelines–Stroke initiative, a project aimed at improving overall stroke care. They focused on 61,655 patients with AF who were hospitalized for ischemic stroke or transient ischemic attack (TIA) and discharged on dabigatran, rivaroxaban, or warfarin during a 2-year period after FDA approval of the new agents. Dabigatran was prescribed to 9.6% of these patients, rivaroxaban to 1.5%, and warfarin to 88.9%.

“Our study shows modest early adoption rates for novel oral anticoagulant therapy” of 16%-17%. Yet this rate falls in the upper range of estimated uptakes in studies that describe early utilization patterns of drugs – including the initially modest adoption of warfarin for this indication, Dr. Patel and his associates said (Circ. Cardiovasc. Qual. Outcomes 2015 June 9 [doi:10.1161/circoutcomes.114.000907]).

The relative expense of the newer agents likely played a role in hindering diffusion into clinical practice because patients who lacked health insurance or were covered by Medicare/Medicaid were more likely to receive warfarin. In addition, clinicians may hesitate to prescribe dabigatran or rivaroxaban because real-world patients differ markedly from those included in clinical trials of these drugs. In this study, for example, participants were older, more likely to be female, less likely to be ambulatory, and had higher scores on measures of risk such as CHADS₂ and CHA₂DS₂-VASc scores, compared with clinical study subjects, they said.

This study also uncovered one particularly worrying fact: 1.4% of patients discharged on dabigatran or rivaroxaban had prosthetic heart valves and 31% had known coronary artery disease, which can be contraindications to using these agents. “Further education on the risks and benefits of novel oral anticoagulation therapy may be needed to increase familiarity with these drugs and prevent risk-treatment mismatches or adverse events,” Dr. Patel and his associates added.

This study was funded by grants from the American Heart Association and the National Institutes of Health. Dr. Patel reported having no financial disclosures; his associates reported ties to numerous industry sources.

The novel oral anticoagulants dabigatran and rivaroxaban have had only “modest” uptake into real-world clinical practice as thromboembolism prevention in high-risk patients with atrial fibrillation, according to a report published online June 9 in Circulation: Cardiovascular Outcomes and Quality.

These drugs have proved to be at least as effective as warfarin at prophylaxis in this patient population, appear to be safer than warfarin regarding the risk of intracranial hemorrhage, and are more practical because they don’t require routine monitoring and have more predictable treatment effects. Yet little is known about their adoption into real-world practice, said Dr. Priyesh A. Patel of Duke Clinical Research Institute in Durham, N.C., and his associates.

©GuidoVrola/thinkstockphotos.com

The investigators examined the issue by analyzing hospital records in the database of the Get With The Guidelines–Stroke initiative, a project aimed at improving overall stroke care. They focused on 61,655 patients with AF who were hospitalized for ischemic stroke or transient ischemic attack (TIA) and discharged on dabigatran, rivaroxaban, or warfarin during a 2-year period after FDA approval of the new agents. Dabigatran was prescribed to 9.6% of these patients, rivaroxaban to 1.5%, and warfarin to 88.9%.

“Our study shows modest early adoption rates for novel oral anticoagulant therapy” of 16%-17%. Yet this rate falls in the upper range of estimated uptakes in studies that describe early utilization patterns of drugs – including the initially modest adoption of warfarin for this indication, Dr. Patel and his associates said (Circ. Cardiovasc. Qual. Outcomes 2015 June 9 [doi:10.1161/circoutcomes.114.000907]).

The relative expense of the newer agents likely played a role in hindering diffusion into clinical practice because patients who lacked health insurance or were covered by Medicare/Medicaid were more likely to receive warfarin. In addition, clinicians may hesitate to prescribe dabigatran or rivaroxaban because real-world patients differ markedly from those included in clinical trials of these drugs. In this study, for example, participants were older, more likely to be female, less likely to be ambulatory, and had higher scores on measures of risk such as CHADS₂ and CHA₂DS₂-VASc scores, compared with clinical study subjects, they said.

This study also uncovered one particularly worrying fact: 1.4% of patients discharged on dabigatran or rivaroxaban had prosthetic heart valves and 31% had known coronary artery disease, which can be contraindications to using these agents. “Further education on the risks and benefits of novel oral anticoagulation therapy may be needed to increase familiarity with these drugs and prevent risk-treatment mismatches or adverse events,” Dr. Patel and his associates added.

This study was funded by grants from the American Heart Association and the National Institutes of Health. Dr. Patel reported having no financial disclosures; his associates reported ties to numerous industry sources.

The novel oral anticoagulants dabigatran and rivaroxaban have had only “modest” uptake into real-world clinical practice as thromboembolism prevention in high-risk patients with atrial fibrillation, according to a report published online June 9 in Circulation: Cardiovascular Outcomes and Quality.

These drugs have proved to be at least as effective as warfarin at prophylaxis in this patient population, appear to be safer than warfarin regarding the risk of intracranial hemorrhage, and are more practical because they don’t require routine monitoring and have more predictable treatment effects. Yet little is known about their adoption into real-world practice, said Dr. Priyesh A. Patel of Duke Clinical Research Institute in Durham, N.C., and his associates.

©GuidoVrola/thinkstockphotos.com

The investigators examined the issue by analyzing hospital records in the database of the Get With The Guidelines–Stroke initiative, a project aimed at improving overall stroke care. They focused on 61,655 patients with AF who were hospitalized for ischemic stroke or transient ischemic attack (TIA) and discharged on dabigatran, rivaroxaban, or warfarin during a 2-year period after FDA approval of the new agents. Dabigatran was prescribed to 9.6% of these patients, rivaroxaban to 1.5%, and warfarin to 88.9%.

“Our study shows modest early adoption rates for novel oral anticoagulant therapy” of 16%-17%. Yet this rate falls in the upper range of estimated uptakes in studies that describe early utilization patterns of drugs – including the initially modest adoption of warfarin for this indication, Dr. Patel and his associates said (Circ. Cardiovasc. Qual. Outcomes 2015 June 9 [doi:10.1161/circoutcomes.114.000907]).

The relative expense of the newer agents likely played a role in hindering diffusion into clinical practice because patients who lacked health insurance or were covered by Medicare/Medicaid were more likely to receive warfarin. In addition, clinicians may hesitate to prescribe dabigatran or rivaroxaban because real-world patients differ markedly from those included in clinical trials of these drugs. In this study, for example, participants were older, more likely to be female, less likely to be ambulatory, and had higher scores on measures of risk such as CHADS₂ and CHA₂DS₂-VASc scores, compared with clinical study subjects, they said.

This study also uncovered one particularly worrying fact: 1.4% of patients discharged on dabigatran or rivaroxaban had prosthetic heart valves and 31% had known coronary artery disease, which can be contraindications to using these agents. “Further education on the risks and benefits of novel oral anticoagulation therapy may be needed to increase familiarity with these drugs and prevent risk-treatment mismatches or adverse events,” Dr. Patel and his associates added.

This study was funded by grants from the American Heart Association and the National Institutes of Health. Dr. Patel reported having no financial disclosures; his associates reported ties to numerous industry sources.

BOSTON – Patients with atrial fibrillation who also require hemodialysis receive no added antistroke benefit from warfarin treatment and may be more likely to have a major bleeding episode while on warfarin, based on a retrospective study of 302 patients at a single U.S. center.

“The safety and effectiveness of warfarin in patients with atrial fibrillation and chronic hemodialysis is questionable,” Dr. Lohit Garg said at the annual scientific sessions of the Heart Rhythm Society.

Dr. Garg noted that about 90% of patients in the review received aspirin, and they would also receive heparin three times a week as part of their hemodialysis protocol. ”It’s a good hypothesis” that aspirin plus heparin during hemodialysis might provide enough anticoagulation, but without warfarin the rate of stroke or transient ischemic attack was “pretty high,” 11%, “higher than [in] the general population, so aspirin and heparin may not be enough,” he said. The thromboembolic event rate with warfarin was 8%, not a statistically significant difference.

Bruce Jancin/Frontline Medical News

Dr. Garg and his associates reviewed patient charts at Beaumont Health System in Royal Oak, Mich., from 2009 to 2012 to find patients on chronic hemodialysis just diagnosed with new-onset atrial fibrillation (AF), and patients with chronic AF newly started on hemodialysis. They identified 724 such patients, and narrowed this down to 302 when they excluded those with valve disease or prosthesis, venous thromboembolic disease, coagulation or bleeding disorder, cancer, renal transplant, and a few other exclusions.

The study group included 119 patients (39%) who received warfarin and 183 (61%) who did not, at the discretion of their treating physicians. Patients averaged 77 years of age, and those who received warfarin and those who didn’t showed roughly similar rates of comorbidities, with no statistically significant differences between the two subgroups.

During an average follow-up of 2 years, the rates of thromboembolic events showed no statistically significant difference between the patients on warfarin and those not receiving the drug. Major bleeds occurred in 22% of the warfarin patients and 14% of those not on warfarin, a relative 53% increased risk with warfarin use that approached but did not reach statistical significance, reported Dr. Garg of the Heart Rhythm Center of Beaumont Hospital in Royal Oak, Mich.

Further, the major bleed subcategory of intracranial bleeds occurred in 10% of patients on warfarin and 4% of those off warfarin, a greater than doubled rate with warfarin, again a difference that approached but did achieve statistical significance. All the intracranial bleeds were fatal.

Dr. Garg also highlighted that these were high-risk patients, with 1.8-year average survival, and a median survival of about 2 years for both patients on warfarin and those off. During follow-up that extended as long as 5 years, 80% of patients died with similar mortality rates in the two treatment subgroups, 82% for those on warfarin and 79% for those who did not receive warfarin.

“We as cardiologists tend to prescribe warfarin” to patients like these, “but obviously we have to rethink this because it seems to harm patients without adding benefit,” commented Dr. Philipp Sommer, an electrophysiologist at the University of Leipzig (Germany).

Dr. Garg had no relevant financial disclosures.

mzoler@frontlinemedcom.com


On Twitter @mitchelzoler

BOSTON – Patients with atrial fibrillation who also require hemodialysis receive no added antistroke benefit from warfarin treatment and may be more likely to have a major bleeding episode while on warfarin, based on a retrospective study of 302 patients at a single U.S. center.

“The safety and effectiveness of warfarin in patients with atrial fibrillation and chronic hemodialysis is questionable,” Dr. Lohit Garg said at the annual scientific sessions of the Heart Rhythm Society.

Dr. Garg noted that about 90% of patients in the review received aspirin, and they would also receive heparin three times a week as part of their hemodialysis protocol. ”It’s a good hypothesis” that aspirin plus heparin during hemodialysis might provide enough anticoagulation, but without warfarin the rate of stroke or transient ischemic attack was “pretty high,” 11%, “higher than [in] the general population, so aspirin and heparin may not be enough,” he said. The thromboembolic event rate with warfarin was 8%, not a statistically significant difference.

Bruce Jancin/Frontline Medical News

Dr. Garg and his associates reviewed patient charts at Beaumont Health System in Royal Oak, Mich., from 2009 to 2012 to find patients on chronic hemodialysis just diagnosed with new-onset atrial fibrillation (AF), and patients with chronic AF newly started on hemodialysis. They identified 724 such patients, and narrowed this down to 302 when they excluded those with valve disease or prosthesis, venous thromboembolic disease, coagulation or bleeding disorder, cancer, renal transplant, and a few other exclusions.

The study group included 119 patients (39%) who received warfarin and 183 (61%) who did not, at the discretion of their treating physicians. Patients averaged 77 years of age, and those who received warfarin and those who didn’t showed roughly similar rates of comorbidities, with no statistically significant differences between the two subgroups.

During an average follow-up of 2 years, the rates of thromboembolic events showed no statistically significant difference between the patients on warfarin and those not receiving the drug. Major bleeds occurred in 22% of the warfarin patients and 14% of those not on warfarin, a relative 53% increased risk with warfarin use that approached but did not reach statistical significance, reported Dr. Garg of the Heart Rhythm Center of Beaumont Hospital in Royal Oak, Mich.

Further, the major bleed subcategory of intracranial bleeds occurred in 10% of patients on warfarin and 4% of those off warfarin, a greater than doubled rate with warfarin, again a difference that approached but did achieve statistical significance. All the intracranial bleeds were fatal.

Dr. Garg also highlighted that these were high-risk patients, with 1.8-year average survival, and a median survival of about 2 years for both patients on warfarin and those off. During follow-up that extended as long as 5 years, 80% of patients died with similar mortality rates in the two treatment subgroups, 82% for those on warfarin and 79% for those who did not receive warfarin.

“We as cardiologists tend to prescribe warfarin” to patients like these, “but obviously we have to rethink this because it seems to harm patients without adding benefit,” commented Dr. Philipp Sommer, an electrophysiologist at the University of Leipzig (Germany).

Dr. Garg had no relevant financial disclosures.

mzoler@frontlinemedcom.com


On Twitter @mitchelzoler

BOSTON – Patients with atrial fibrillation who also require hemodialysis receive no added antistroke benefit from warfarin treatment and may be more likely to have a major bleeding episode while on warfarin, based on a retrospective study of 302 patients at a single U.S. center.

“The safety and effectiveness of warfarin in patients with atrial fibrillation and chronic hemodialysis is questionable,” Dr. Lohit Garg said at the annual scientific sessions of the Heart Rhythm Society.

Dr. Garg noted that about 90% of patients in the review received aspirin, and they would also receive heparin three times a week as part of their hemodialysis protocol. ”It’s a good hypothesis” that aspirin plus heparin during hemodialysis might provide enough anticoagulation, but without warfarin the rate of stroke or transient ischemic attack was “pretty high,” 11%, “higher than [in] the general population, so aspirin and heparin may not be enough,” he said. The thromboembolic event rate with warfarin was 8%, not a statistically significant difference.

Bruce Jancin/Frontline Medical News

Dr. Garg and his associates reviewed patient charts at Beaumont Health System in Royal Oak, Mich., from 2009 to 2012 to find patients on chronic hemodialysis just diagnosed with new-onset atrial fibrillation (AF), and patients with chronic AF newly started on hemodialysis. They identified 724 such patients, and narrowed this down to 302 when they excluded those with valve disease or prosthesis, venous thromboembolic disease, coagulation or bleeding disorder, cancer, renal transplant, and a few other exclusions.

The study group included 119 patients (39%) who received warfarin and 183 (61%) who did not, at the discretion of their treating physicians. Patients averaged 77 years of age, and those who received warfarin and those who didn’t showed roughly similar rates of comorbidities, with no statistically significant differences between the two subgroups.

During an average follow-up of 2 years, the rates of thromboembolic events showed no statistically significant difference between the patients on warfarin and those not receiving the drug. Major bleeds occurred in 22% of the warfarin patients and 14% of those not on warfarin, a relative 53% increased risk with warfarin use that approached but did not reach statistical significance, reported Dr. Garg of the Heart Rhythm Center of Beaumont Hospital in Royal Oak, Mich.

Further, the major bleed subcategory of intracranial bleeds occurred in 10% of patients on warfarin and 4% of those off warfarin, a greater than doubled rate with warfarin, again a difference that approached but did achieve statistical significance. All the intracranial bleeds were fatal.

Dr. Garg also highlighted that these were high-risk patients, with 1.8-year average survival, and a median survival of about 2 years for both patients on warfarin and those off. During follow-up that extended as long as 5 years, 80% of patients died with similar mortality rates in the two treatment subgroups, 82% for those on warfarin and 79% for those who did not receive warfarin.

“We as cardiologists tend to prescribe warfarin” to patients like these, “but obviously we have to rethink this because it seems to harm patients without adding benefit,” commented Dr. Philipp Sommer, an electrophysiologist at the University of Leipzig (Germany).

Dr. Garg had no relevant financial disclosures.

mzoler@frontlinemedcom.com


On Twitter @mitchelzoler

Tight glycemic control modestly reduced the rate of major cardiovascular events but didn’t improve mortality in an extended follow-up of a clinical trial involving 1,791 veterans with type 2 diabetes, which was published online June 3 in the New England Journal of Medicine.

At the conclusion of the treatment phase of the Veteran Affairs Diabetes Trial in 2008, the primary outcome – the rate of a first major CV event – was nonsignificantly lower with intensive glycemic control than with standard glycemic control. Researchers now report the findings after an additional 7.5 years of follow-up of 92% of the participants in that multicenter unblended randomized controlled trial.

During the treatment phase of the study, median glycated hemoglobin level differed by 1.5 percentage points between patients who received intensive therapy (6.9%) and patients who received standard therapy (8.4%). During follow-up, this difference declined to only 0.2-0.3 percentage points. “Even with the support of a dedicated research team, only approximately half the participants [achieved] a glycated hemoglobin level of less than 7%,” said Dr. Rodney A. Hayward of the VA Center for Clinical Management Research, VA Ann Arbor (Mich.) Healthcare System, and his associates.

During extended follow-up, there were 253 major CV events in the group randomly assigned to intensive therapy and 288 in the group assigned to standard therapy. Tight glycemic control using a multidrug regimen was associated with a significant, though modest, 17% relative reduction in a the primary composite outcome of heart attack, stroke, new or worsening congestive heart failure, death from CV causes, or amputation due to ischemic gangrene. This represents 8.6 CV events prevented per 1,000 person-years.

However, there was no evidence of any reduction in either cardiovascular or all-cause mortality. In addition, treatment effects were no different between patients at high and those at low cardiovascular risk, the investigators said (N. Engl. J. Med. 2015 June 3 [doi:10.1056/NEJMoa1414266]).

“In the absence of a reduction in total mortality, a small to moderate reduction in the rate of CV events needs to be weighed against potential harm due to overly aggressive care and the burden, long-term safety profile, and side effects of treatment, including weight gain and hypoglycemia,” they added.

Tight glycemic control modestly reduced the rate of major cardiovascular events but didn’t improve mortality in an extended follow-up of a clinical trial involving 1,791 veterans with type 2 diabetes, which was published online June 3 in the New England Journal of Medicine.

At the conclusion of the treatment phase of the Veteran Affairs Diabetes Trial in 2008, the primary outcome – the rate of a first major CV event – was nonsignificantly lower with intensive glycemic control than with standard glycemic control. Researchers now report the findings after an additional 7.5 years of follow-up of 92% of the participants in that multicenter unblended randomized controlled trial.

During the treatment phase of the study, median glycated hemoglobin level differed by 1.5 percentage points between patients who received intensive therapy (6.9%) and patients who received standard therapy (8.4%). During follow-up, this difference declined to only 0.2-0.3 percentage points. “Even with the support of a dedicated research team, only approximately half the participants [achieved] a glycated hemoglobin level of less than 7%,” said Dr. Rodney A. Hayward of the VA Center for Clinical Management Research, VA Ann Arbor (Mich.) Healthcare System, and his associates.

During extended follow-up, there were 253 major CV events in the group randomly assigned to intensive therapy and 288 in the group assigned to standard therapy. Tight glycemic control using a multidrug regimen was associated with a significant, though modest, 17% relative reduction in a the primary composite outcome of heart attack, stroke, new or worsening congestive heart failure, death from CV causes, or amputation due to ischemic gangrene. This represents 8.6 CV events prevented per 1,000 person-years.

However, there was no evidence of any reduction in either cardiovascular or all-cause mortality. In addition, treatment effects were no different between patients at high and those at low cardiovascular risk, the investigators said (N. Engl. J. Med. 2015 June 3 [doi:10.1056/NEJMoa1414266]).

“In the absence of a reduction in total mortality, a small to moderate reduction in the rate of CV events needs to be weighed against potential harm due to overly aggressive care and the burden, long-term safety profile, and side effects of treatment, including weight gain and hypoglycemia,” they added.

Tight glycemic control modestly reduced the rate of major cardiovascular events but didn’t improve mortality in an extended follow-up of a clinical trial involving 1,791 veterans with type 2 diabetes, which was published online June 3 in the New England Journal of Medicine.

At the conclusion of the treatment phase of the Veteran Affairs Diabetes Trial in 2008, the primary outcome – the rate of a first major CV event – was nonsignificantly lower with intensive glycemic control than with standard glycemic control. Researchers now report the findings after an additional 7.5 years of follow-up of 92% of the participants in that multicenter unblended randomized controlled trial.

During the treatment phase of the study, median glycated hemoglobin level differed by 1.5 percentage points between patients who received intensive therapy (6.9%) and patients who received standard therapy (8.4%). During follow-up, this difference declined to only 0.2-0.3 percentage points. “Even with the support of a dedicated research team, only approximately half the participants [achieved] a glycated hemoglobin level of less than 7%,” said Dr. Rodney A. Hayward of the VA Center for Clinical Management Research, VA Ann Arbor (Mich.) Healthcare System, and his associates.

During extended follow-up, there were 253 major CV events in the group randomly assigned to intensive therapy and 288 in the group assigned to standard therapy. Tight glycemic control using a multidrug regimen was associated with a significant, though modest, 17% relative reduction in a the primary composite outcome of heart attack, stroke, new or worsening congestive heart failure, death from CV causes, or amputation due to ischemic gangrene. This represents 8.6 CV events prevented per 1,000 person-years.

However, there was no evidence of any reduction in either cardiovascular or all-cause mortality. In addition, treatment effects were no different between patients at high and those at low cardiovascular risk, the investigators said (N. Engl. J. Med. 2015 June 3 [doi:10.1056/NEJMoa1414266]).

“In the absence of a reduction in total mortality, a small to moderate reduction in the rate of CV events needs to be weighed against potential harm due to overly aggressive care and the burden, long-term safety profile, and side effects of treatment, including weight gain and hypoglycemia,” they added.

NEW ORLEANS – Evidence seems to be mounting that the link between testosterone replacement therapy and increased hematocrit doesn’t lead to more cardiac or thrombotic events in men.

The association between testosterone and secondary erythrocytosis has been known for some time, Dr. Wayne J. G. Hellstrom said at the annual meeting of the American Urological Association. An increase in hematocrit almost invariably follows testosterone supplementation. “The question is, is there a causal relation between testosterone replacement therapy–induced erythrocytosis and venous thromboembolism or major cardiac events?” said Dr. Hellstrom of Tulane Medical Center, New Orleans. “The available evidence doesn’t support this claim.”

Erythrocytosis is defined as a packed red blood cell volume exceeding 125% of the age-predicted mass. This may be primary – an intrinsic alteration of the hematopoietic stem cells – or secondary. “And it may actually be a physiologically appropriate response to something, as in anemia,” Dr. Hellstrom said. “In fact, some anemias are primarily treated with testosterone.”

In the presence of exogenous testosterone, the condition may be due to a couple of things, he noted, such as:

• An overall increase in the erythropoietin set point.

• Increased availability of iron in the liver.

• The conversion of testosterone to estradiol, which tends to stimulate the bone marrow.

Erythrocytosis, obviously then, increases blood viscosity – and this is the primary concern for cardiovascular events.

Intramuscular testosterone is the only form that significantly increases hematocrit above normal levels. However, it does so strongly, with up to a 6% change from baseline. The runner-up is testosterone gel, with an average increase of 2.5% over baseline levels.

But despite concerns – which in March prompted the FDA to require on labeling a warning about the risk of cardiovascular events – the relationship has never been thoroughly investigated, Dr. Hellstrom said.

“We only have retrospective data, primarily extrapolating from the nephrology literature. When we look at the renal literature, we see that 10%-20% of kidney transplant patients develop polycythemia – an increase of both red and white cells, with hematocrit values of more than 51% or 52%.”

This has led to a recommendation by the American Society of Nephrology for frequent complete blood cell counts in the year after transplant and annual measurements thereafter.

The highest-quality mortality data for kidney transplant patients come from a 2013 study of 365 patients; the investigators found that those with polycythemia were 2.7 times more likely to die over 4 years. “But this is a true primary polycythemia,” which is often accompanied by procoagulative changes. It is not the secondary condition induced by testosterone, Dr. Hellstrom said.

Older studies suggested a significant link between increased hematocrit and cardiovascular or thrombotic events, especially after surgery. But prospective data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies have found no increased risk of cardiovascular death by increasing tertiles of either hematocrit or hemoglobin, with respective cut points of 43% and 14.5 g/dL.

In fact, a recent transgenic mouse model with hematopoietic overexpression, reaching an 85% hematocrit, found no evidence of either lung or cardiovascular thromboses. “This seems to be related to a reduction in clot strength and increased osmotic fragility in the presence of increasing hematocrit. It seems to mechanically deter the interaction of platelets and fibrin in the extravascular space and endothelium.”

He referred to an in-press mouse study showing that a short course of high-dose testosterone did raise whole blood viscosity and hematocrit. “But over time, this returned to normal, even with supraphysiolgic testosterone levels, so it seems likely that there is an adaptive mechanism that occurs in these animals.”

Additionally, he said, men who live at high altitudes develop naturally high hematocrits as a response to decreased oxygen in the atmosphere. “We routinely see men from these locations with hematocrits of 57% and 59% who have no problems at all.”

Extrapolating all these data to the testosterone/thrombosis link is confusing. The most recent study, however, provided some measure of reassurance. The large meta-analysis comprised 75 randomized, placebo-controlled trials involving about 5,500 men; they all examined cardiovascular risk and testosterone therapy.

“Our analyses, performed on the largest number of studies collected so far, indicate that testosterone supplementation is not related to any increase in cardiovascular risk, even when composite or single adverse events were considered,” wrote Dr. Giovanni Corona of the Maggiore-Bellaria Hospital, Bologna, Italy. “In randomized trials performed in subjects with metabolic derangements, a protective effect … was observed. … Our results are in agreement with a large body of literature from the last 20 years supporting testosterone supplementation of hypogonadal men as a valuable strategy in improving a patient’s metabolic profile, reducing body fat, and increasing lean muscle mass, which would ultimately reduce the risk of heart disease

“There is a definite need for large multicenter, randomized trials to determine the true risk,” Dr. Hellstrom said. However, in light of the current evidence, he recommends what he called a “conservative” approach to testosterone prescribing:

• Before prescribing, get a baseline complete blood count.

• If the baseline hematocrit is more than 47%, consider alternative treatments, but proceed if testosterone replacement therapy seems to be the best clinical option. Repeat testing at 3 and 12 months after therapy initiation and then annually.

• If hematocrit increases above 54%, discontinue treatment until there is a further clinical assessment, as detailed by the Endocrine Society.

• Closely monitor any new diagnoses of hypertension.

• If hematocrit does rise precipitously, phlebotomy rapidly resolved the problem.

Dr Hellstrom made the following financial disclosures: consultant, advisor, or leadership position for Abbvie, Allergan, American Medical Systems, Antares, Astellas, Auxilim, Allergan, Coloplast, Endo, Lilly, New England Research Institutes Inc. Pfizer, Promescent, Reros Therapeutics, and Theralogix.

msullivan@frontlinemedcom.com

NEW ORLEANS – Evidence seems to be mounting that the link between testosterone replacement therapy and increased hematocrit doesn’t lead to more cardiac or thrombotic events in men.

The association between testosterone and secondary erythrocytosis has been known for some time, Dr. Wayne J. G. Hellstrom said at the annual meeting of the American Urological Association. An increase in hematocrit almost invariably follows testosterone supplementation. “The question is, is there a causal relation between testosterone replacement therapy–induced erythrocytosis and venous thromboembolism or major cardiac events?” said Dr. Hellstrom of Tulane Medical Center, New Orleans. “The available evidence doesn’t support this claim.”

Erythrocytosis is defined as a packed red blood cell volume exceeding 125% of the age-predicted mass. This may be primary – an intrinsic alteration of the hematopoietic stem cells – or secondary. “And it may actually be a physiologically appropriate response to something, as in anemia,” Dr. Hellstrom said. “In fact, some anemias are primarily treated with testosterone.”

In the presence of exogenous testosterone, the condition may be due to a couple of things, he noted, such as:

• An overall increase in the erythropoietin set point.

• Increased availability of iron in the liver.

• The conversion of testosterone to estradiol, which tends to stimulate the bone marrow.

Erythrocytosis, obviously then, increases blood viscosity – and this is the primary concern for cardiovascular events.

Intramuscular testosterone is the only form that significantly increases hematocrit above normal levels. However, it does so strongly, with up to a 6% change from baseline. The runner-up is testosterone gel, with an average increase of 2.5% over baseline levels.

But despite concerns – which in March prompted the FDA to require on labeling a warning about the risk of cardiovascular events – the relationship has never been thoroughly investigated, Dr. Hellstrom said.

“We only have retrospective data, primarily extrapolating from the nephrology literature. When we look at the renal literature, we see that 10%-20% of kidney transplant patients develop polycythemia – an increase of both red and white cells, with hematocrit values of more than 51% or 52%.”

This has led to a recommendation by the American Society of Nephrology for frequent complete blood cell counts in the year after transplant and annual measurements thereafter.

The highest-quality mortality data for kidney transplant patients come from a 2013 study of 365 patients; the investigators found that those with polycythemia were 2.7 times more likely to die over 4 years. “But this is a true primary polycythemia,” which is often accompanied by procoagulative changes. It is not the secondary condition induced by testosterone, Dr. Hellstrom said.

Older studies suggested a significant link between increased hematocrit and cardiovascular or thrombotic events, especially after surgery. But prospective data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies have found no increased risk of cardiovascular death by increasing tertiles of either hematocrit or hemoglobin, with respective cut points of 43% and 14.5 g/dL.

In fact, a recent transgenic mouse model with hematopoietic overexpression, reaching an 85% hematocrit, found no evidence of either lung or cardiovascular thromboses. “This seems to be related to a reduction in clot strength and increased osmotic fragility in the presence of increasing hematocrit. It seems to mechanically deter the interaction of platelets and fibrin in the extravascular space and endothelium.”

He referred to an in-press mouse study showing that a short course of high-dose testosterone did raise whole blood viscosity and hematocrit. “But over time, this returned to normal, even with supraphysiolgic testosterone levels, so it seems likely that there is an adaptive mechanism that occurs in these animals.”

Additionally, he said, men who live at high altitudes develop naturally high hematocrits as a response to decreased oxygen in the atmosphere. “We routinely see men from these locations with hematocrits of 57% and 59% who have no problems at all.”

Extrapolating all these data to the testosterone/thrombosis link is confusing. The most recent study, however, provided some measure of reassurance. The large meta-analysis comprised 75 randomized, placebo-controlled trials involving about 5,500 men; they all examined cardiovascular risk and testosterone therapy.

“Our analyses, performed on the largest number of studies collected so far, indicate that testosterone supplementation is not related to any increase in cardiovascular risk, even when composite or single adverse events were considered,” wrote Dr. Giovanni Corona of the Maggiore-Bellaria Hospital, Bologna, Italy. “In randomized trials performed in subjects with metabolic derangements, a protective effect … was observed. … Our results are in agreement with a large body of literature from the last 20 years supporting testosterone supplementation of hypogonadal men as a valuable strategy in improving a patient’s metabolic profile, reducing body fat, and increasing lean muscle mass, which would ultimately reduce the risk of heart disease

“There is a definite need for large multicenter, randomized trials to determine the true risk,” Dr. Hellstrom said. However, in light of the current evidence, he recommends what he called a “conservative” approach to testosterone prescribing:

• Before prescribing, get a baseline complete blood count.

• If the baseline hematocrit is more than 47%, consider alternative treatments, but proceed if testosterone replacement therapy seems to be the best clinical option. Repeat testing at 3 and 12 months after therapy initiation and then annually.

• If hematocrit increases above 54%, discontinue treatment until there is a further clinical assessment, as detailed by the Endocrine Society.

• Closely monitor any new diagnoses of hypertension.

• If hematocrit does rise precipitously, phlebotomy rapidly resolved the problem.

Dr Hellstrom made the following financial disclosures: consultant, advisor, or leadership position for Abbvie, Allergan, American Medical Systems, Antares, Astellas, Auxilim, Allergan, Coloplast, Endo, Lilly, New England Research Institutes Inc. Pfizer, Promescent, Reros Therapeutics, and Theralogix.

msullivan@frontlinemedcom.com

NEW ORLEANS – Evidence seems to be mounting that the link between testosterone replacement therapy and increased hematocrit doesn’t lead to more cardiac or thrombotic events in men.

The association between testosterone and secondary erythrocytosis has been known for some time, Dr. Wayne J. G. Hellstrom said at the annual meeting of the American Urological Association. An increase in hematocrit almost invariably follows testosterone supplementation. “The question is, is there a causal relation between testosterone replacement therapy–induced erythrocytosis and venous thromboembolism or major cardiac events?” said Dr. Hellstrom of Tulane Medical Center, New Orleans. “The available evidence doesn’t support this claim.”

Erythrocytosis is defined as a packed red blood cell volume exceeding 125% of the age-predicted mass. This may be primary – an intrinsic alteration of the hematopoietic stem cells – or secondary. “And it may actually be a physiologically appropriate response to something, as in anemia,” Dr. Hellstrom said. “In fact, some anemias are primarily treated with testosterone.”

In the presence of exogenous testosterone, the condition may be due to a couple of things, he noted, such as:

• An overall increase in the erythropoietin set point.

• Increased availability of iron in the liver.

• The conversion of testosterone to estradiol, which tends to stimulate the bone marrow.

Erythrocytosis, obviously then, increases blood viscosity – and this is the primary concern for cardiovascular events.

Intramuscular testosterone is the only form that significantly increases hematocrit above normal levels. However, it does so strongly, with up to a 6% change from baseline. The runner-up is testosterone gel, with an average increase of 2.5% over baseline levels.

But despite concerns – which in March prompted the FDA to require on labeling a warning about the risk of cardiovascular events – the relationship has never been thoroughly investigated, Dr. Hellstrom said.

“We only have retrospective data, primarily extrapolating from the nephrology literature. When we look at the renal literature, we see that 10%-20% of kidney transplant patients develop polycythemia – an increase of both red and white cells, with hematocrit values of more than 51% or 52%.”

This has led to a recommendation by the American Society of Nephrology for frequent complete blood cell counts in the year after transplant and annual measurements thereafter.

The highest-quality mortality data for kidney transplant patients come from a 2013 study of 365 patients; the investigators found that those with polycythemia were 2.7 times more likely to die over 4 years. “But this is a true primary polycythemia,” which is often accompanied by procoagulative changes. It is not the secondary condition induced by testosterone, Dr. Hellstrom said.

Older studies suggested a significant link between increased hematocrit and cardiovascular or thrombotic events, especially after surgery. But prospective data from the Atherosclerosis Risk in Communities and Cardiovascular Health Studies have found no increased risk of cardiovascular death by increasing tertiles of either hematocrit or hemoglobin, with respective cut points of 43% and 14.5 g/dL.

In fact, a recent transgenic mouse model with hematopoietic overexpression, reaching an 85% hematocrit, found no evidence of either lung or cardiovascular thromboses. “This seems to be related to a reduction in clot strength and increased osmotic fragility in the presence of increasing hematocrit. It seems to mechanically deter the interaction of platelets and fibrin in the extravascular space and endothelium.”

He referred to an in-press mouse study showing that a short course of high-dose testosterone did raise whole blood viscosity and hematocrit. “But over time, this returned to normal, even with supraphysiolgic testosterone levels, so it seems likely that there is an adaptive mechanism that occurs in these animals.”

Additionally, he said, men who live at high altitudes develop naturally high hematocrits as a response to decreased oxygen in the atmosphere. “We routinely see men from these locations with hematocrits of 57% and 59% who have no problems at all.”

Extrapolating all these data to the testosterone/thrombosis link is confusing. The most recent study, however, provided some measure of reassurance. The large meta-analysis comprised 75 randomized, placebo-controlled trials involving about 5,500 men; they all examined cardiovascular risk and testosterone therapy.

“Our analyses, performed on the largest number of studies collected so far, indicate that testosterone supplementation is not related to any increase in cardiovascular risk, even when composite or single adverse events were considered,” wrote Dr. Giovanni Corona of the Maggiore-Bellaria Hospital, Bologna, Italy. “In randomized trials performed in subjects with metabolic derangements, a protective effect … was observed. … Our results are in agreement with a large body of literature from the last 20 years supporting testosterone supplementation of hypogonadal men as a valuable strategy in improving a patient’s metabolic profile, reducing body fat, and increasing lean muscle mass, which would ultimately reduce the risk of heart disease

“There is a definite need for large multicenter, randomized trials to determine the true risk,” Dr. Hellstrom said. However, in light of the current evidence, he recommends what he called a “conservative” approach to testosterone prescribing:

• Before prescribing, get a baseline complete blood count.

• If the baseline hematocrit is more than 47%, consider alternative treatments, but proceed if testosterone replacement therapy seems to be the best clinical option. Repeat testing at 3 and 12 months after therapy initiation and then annually.

• If hematocrit increases above 54%, discontinue treatment until there is a further clinical assessment, as detailed by the Endocrine Society.

• Closely monitor any new diagnoses of hypertension.

• If hematocrit does rise precipitously, phlebotomy rapidly resolved the problem.

Dr Hellstrom made the following financial disclosures: consultant, advisor, or leadership position for Abbvie, Allergan, American Medical Systems, Antares, Astellas, Auxilim, Allergan, Coloplast, Endo, Lilly, New England Research Institutes Inc. Pfizer, Promescent, Reros Therapeutics, and Theralogix.

msullivan@frontlinemedcom.com

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza, Spain.

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

Patrice Wendling/Frontline Medical News

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

pwendling@frontlinemedcom.com

On Twitter @pwendl

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza, Spain.

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

Patrice Wendling/Frontline Medical News

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

pwendling@frontlinemedcom.com

On Twitter @pwendl

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza, Spain.

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

Patrice Wendling/Frontline Medical News

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

pwendling@frontlinemedcom.com

On Twitter @pwendl

The risk of developing venous thromboembolism is generally greater for women using oral contraceptives with newer types of progestogen hormones than for those taking older, second-generation birth control pills, study results showed.

“Women exposed to drospirenone, gestodene, cyproterone, and desogestrel within the last 28 days had around a four times increased risk of venous thromboembolism,” the investigators found. Women exposed to levonorgestrel, norethisterone, and norgestimate had about a 2.5 times greater risk of venous thromboembolism than did women not exposed in the past year, said Yana Vinogradova and her colleagues at the University of Nottingham (England) (BMJ. 2015 May 26 [doi:10.1136/bmj.h2135]).

The researchers conducted two nested case-control studies using data from 618 primary care practices in the Clinical Practice Research Datalink (CPRD) and 722 practices in the QResearch primary care database. A total of 5,062 cases from CPRD and 5,500 cases from QResearch were matched one to five with 19,638 and 22,396 controls, respectively.

areeya_ann/Thinkstock.com

Approximately 29% of CPRD patients and 26% of QResearch patients used oral contraceptives, most commonly levonorgestrel. Overall, any use of combined oral contraceptives resulted in a three times increased risk for venous thromboembolism, compared with no use in the past year.

After accounting for smoking, obesity, a wide range of other health conditions, alcohol consumption, polycystic ovary syndrome and recent infections, surgeries, leg/hip fractures, and hospital admission, the researchers calculated an increased odds ratio for each hormone: desogestrel (4.28), cyproterone (4.27), drospirenone (4.12), gestodene (3.64), levonorgestrel (2.38), norgestimate (2.53), and norethisterone (2.56). The increased VTE risk in patients on these hormones was compared with no exposure to oral contraceptives in the previous year.

In terms of numbers needed to harm, the researchers estimated that use of levonorgestrel and norgestimate resulted in 6 extra cases of VTE each year per 10,000 treated women aged 15-49, and 7 extra cases for women aged 25-49.

Desogestrel and cyproterone each contributed 14 additional cases of VTE each year per 10,000 treated women aged 15-49, and drospirenone, desogestrel, and cyproterone each contributed to an extra 17 cases of VTE each year per 10,000 women aged 25-49.

“We believe this study has the statistical power and sufficient adjustment for relevant confounders to be regarded as an important clarifying study, which has produced the most reliable possible risk estimates using currently available U.K. prescription data,” the researchers wrote.

There was no external funding for the study. Julia Hippisley-Cox is the unpaid director of QResearch, a not-for-profit organization that is a joint partnership between the University of Nottingham and EMIS, a commercial IT supplier. She is also a paid director of ClinRisk, which produces clinical risk algorithm-related software.

The risk of developing venous thromboembolism is generally greater for women using oral contraceptives with newer types of progestogen hormones than for those taking older, second-generation birth control pills, study results showed.

“Women exposed to drospirenone, gestodene, cyproterone, and desogestrel within the last 28 days had around a four times increased risk of venous thromboembolism,” the investigators found. Women exposed to levonorgestrel, norethisterone, and norgestimate had about a 2.5 times greater risk of venous thromboembolism than did women not exposed in the past year, said Yana Vinogradova and her colleagues at the University of Nottingham (England) (BMJ. 2015 May 26 [doi:10.1136/bmj.h2135]).

The researchers conducted two nested case-control studies using data from 618 primary care practices in the Clinical Practice Research Datalink (CPRD) and 722 practices in the QResearch primary care database. A total of 5,062 cases from CPRD and 5,500 cases from QResearch were matched one to five with 19,638 and 22,396 controls, respectively.

areeya_ann/Thinkstock.com

Approximately 29% of CPRD patients and 26% of QResearch patients used oral contraceptives, most commonly levonorgestrel. Overall, any use of combined oral contraceptives resulted in a three times increased risk for venous thromboembolism, compared with no use in the past year.

After accounting for smoking, obesity, a wide range of other health conditions, alcohol consumption, polycystic ovary syndrome and recent infections, surgeries, leg/hip fractures, and hospital admission, the researchers calculated an increased odds ratio for each hormone: desogestrel (4.28), cyproterone (4.27), drospirenone (4.12), gestodene (3.64), levonorgestrel (2.38), norgestimate (2.53), and norethisterone (2.56). The increased VTE risk in patients on these hormones was compared with no exposure to oral contraceptives in the previous year.

In terms of numbers needed to harm, the researchers estimated that use of levonorgestrel and norgestimate resulted in 6 extra cases of VTE each year per 10,000 treated women aged 15-49, and 7 extra cases for women aged 25-49.

Desogestrel and cyproterone each contributed 14 additional cases of VTE each year per 10,000 treated women aged 15-49, and drospirenone, desogestrel, and cyproterone each contributed to an extra 17 cases of VTE each year per 10,000 women aged 25-49.

“We believe this study has the statistical power and sufficient adjustment for relevant confounders to be regarded as an important clarifying study, which has produced the most reliable possible risk estimates using currently available U.K. prescription data,” the researchers wrote.

There was no external funding for the study. Julia Hippisley-Cox is the unpaid director of QResearch, a not-for-profit organization that is a joint partnership between the University of Nottingham and EMIS, a commercial IT supplier. She is also a paid director of ClinRisk, which produces clinical risk algorithm-related software.

The risk of developing venous thromboembolism is generally greater for women using oral contraceptives with newer types of progestogen hormones than for those taking older, second-generation birth control pills, study results showed.

“Women exposed to drospirenone, gestodene, cyproterone, and desogestrel within the last 28 days had around a four times increased risk of venous thromboembolism,” the investigators found. Women exposed to levonorgestrel, norethisterone, and norgestimate had about a 2.5 times greater risk of venous thromboembolism than did women not exposed in the past year, said Yana Vinogradova and her colleagues at the University of Nottingham (England) (BMJ. 2015 May 26 [doi:10.1136/bmj.h2135]).

The researchers conducted two nested case-control studies using data from 618 primary care practices in the Clinical Practice Research Datalink (CPRD) and 722 practices in the QResearch primary care database. A total of 5,062 cases from CPRD and 5,500 cases from QResearch were matched one to five with 19,638 and 22,396 controls, respectively.

areeya_ann/Thinkstock.com

Approximately 29% of CPRD patients and 26% of QResearch patients used oral contraceptives, most commonly levonorgestrel. Overall, any use of combined oral contraceptives resulted in a three times increased risk for venous thromboembolism, compared with no use in the past year.

After accounting for smoking, obesity, a wide range of other health conditions, alcohol consumption, polycystic ovary syndrome and recent infections, surgeries, leg/hip fractures, and hospital admission, the researchers calculated an increased odds ratio for each hormone: desogestrel (4.28), cyproterone (4.27), drospirenone (4.12), gestodene (3.64), levonorgestrel (2.38), norgestimate (2.53), and norethisterone (2.56). The increased VTE risk in patients on these hormones was compared with no exposure to oral contraceptives in the previous year.

In terms of numbers needed to harm, the researchers estimated that use of levonorgestrel and norgestimate resulted in 6 extra cases of VTE each year per 10,000 treated women aged 15-49, and 7 extra cases for women aged 25-49.

Desogestrel and cyproterone each contributed 14 additional cases of VTE each year per 10,000 treated women aged 15-49, and drospirenone, desogestrel, and cyproterone each contributed to an extra 17 cases of VTE each year per 10,000 women aged 25-49.

“We believe this study has the statistical power and sufficient adjustment for relevant confounders to be regarded as an important clarifying study, which has produced the most reliable possible risk estimates using currently available U.K. prescription data,” the researchers wrote.

There was no external funding for the study. Julia Hippisley-Cox is the unpaid director of QResearch, a not-for-profit organization that is a joint partnership between the University of Nottingham and EMIS, a commercial IT supplier. She is also a paid director of ClinRisk, which produces clinical risk algorithm-related software.

BOSTON– The already-firm evidence implicating obesity in boosting both the incidence and severity of atrial fibrillation grew even stronger with results from four meta-analyses that comprised 51 controlled studies involving a total of more than 600,000 people.

“We should pay more attention to using weight reduction strategies to prevent AF [atrial fibrillation] and to reduce its burden in patients with obesity and established AF,” Dr. Dennis H. Lau said at the annual scientific sessions of the Heart Rhythm Society.

Mitchel L. Zoler/Frontline Medical News

Physicians are increasingly aware of the strong evidence linking obesity and atrial fibrillation incidence and severity, said Dr. Christine M. Albert, director of the Center for Arrhythmia Prevention at Brigham and Women’s Hospital, Boston. The existence of this link is “really important because it is something we can offer patients,” Dr. Albert said in an interview. Obesity interventions provide a way to intervene in patients with, or at risk for, atrial fibrillation that goes beyond atrial ablation and antiarrhythmic drugs to reduce symptoms and help patients feel better, she noted.

Dr. Lau and his associates reviewed the published medical literature through January 2012 and identified 51 studies that examined the link between obesity and AF in a total of 626,603 people.

They found 16 studies with 5,864 patients that assessed the link between obesity and AF recurrence following atrial ablation treatment and found a statistically significant 13% increased rate of recurrent AF for every 5-unit rise in body mass index, Dr. Lau reported.

Mitchel L. Zoler/Frontline Medical News

They also identified 12 studies on the impact of obesity in 62,160 patients who underwent cardiac surgery that collectively showed a statistically significant 10% higher incidence of postoperative AF for every additional 5 BMI units.

The researchers found nine studies of the role of obesity in new-onset AF in cohort analyses with a total of 157,518 patients that showed an overall, statistically significant 29% rise in AF incidence for every 5 additional BMI units. And in 14 case-control studies with 401,061 patients, the rate of new-onset AF increased by a statistically significant 19% for every 5-unit rise in BMI.

These findings fit into an already substantial body of evidence documenting a significant link between obesity and AF, said Dr. Lau, director of the cardiac pacing unit at the Royal Adelaide (Australia) Hospital. For example, an analysis of 14,598 Americans enrolled in the Atherosclerosis Risk in Communities (ARIC) study found that 18% of the 1,520 new cases of AF that occurred in this cohort during an average 17 years of follow-up could be attributed to obesity or overweight (Circulation 2011;123:1501-8). Data collected from 34,309 women enrolled in the Women’s Health Study who had 834 cases of incident AF during an average 13-year follow-up showed that every 1-unit increase in BMI was linked to a 5% increased risk for AF, and that obese women had an overall 65% higher incidence of AF than did women with a normal BMI (J. Am Coll. Cardiol. 2010;55:2319-27).

And Dr. Lau and his associates recently published a review of 355 patients with AF and a baseline BMI of at least 27 kg/m² who participated in a weight-management program. After 5 years, patients who lost at least 10% of their baseline weight had an 86% rate of arrhythmia-free survival, compared with a 40% rate in patients who either lost less than 3% of their baseline weight or gained weight. In a multivariate analysis, weight loss of at least 10% linked with a statistically significant sixfold increase in arrhythmia-free survival, compared with all the other patients in the analysis (J. Am. Coll. Cardiol. 2015;65:2159-69).

Dr. Lau also cited findings from animal studies by his group that point to a direct role for obesity, and specifically deposits of epicardial fat in causing AF. Their model uses overfed sheep, and his group found that a higher burden of epicardial fat leads to fat infiltration into the myocardium, including atrial tissue. “We postulate that this fat contributes to conduction heterogeneity, increased re-entry, increased susceptibility to AF, and increased duration of AF episodes,” he said.

“It’s quite clear that obesity itself is important because, for example, the sheep do not develop sleep apnea, and they have only marginally elevated blood pressures. Using this animal model, we are quite convinced that obesity itself is an important risk factor.”

Dr. Lau added that results from recent sheep studies showed that after previously obese sheep lose their excess weight their atrial abnormalities revert to normal.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON– The already-firm evidence implicating obesity in boosting both the incidence and severity of atrial fibrillation grew even stronger with results from four meta-analyses that comprised 51 controlled studies involving a total of more than 600,000 people.

“We should pay more attention to using weight reduction strategies to prevent AF [atrial fibrillation] and to reduce its burden in patients with obesity and established AF,” Dr. Dennis H. Lau said at the annual scientific sessions of the Heart Rhythm Society.

Mitchel L. Zoler/Frontline Medical News

Physicians are increasingly aware of the strong evidence linking obesity and atrial fibrillation incidence and severity, said Dr. Christine M. Albert, director of the Center for Arrhythmia Prevention at Brigham and Women’s Hospital, Boston. The existence of this link is “really important because it is something we can offer patients,” Dr. Albert said in an interview. Obesity interventions provide a way to intervene in patients with, or at risk for, atrial fibrillation that goes beyond atrial ablation and antiarrhythmic drugs to reduce symptoms and help patients feel better, she noted.

Dr. Lau and his associates reviewed the published medical literature through January 2012 and identified 51 studies that examined the link between obesity and AF in a total of 626,603 people.

They found 16 studies with 5,864 patients that assessed the link between obesity and AF recurrence following atrial ablation treatment and found a statistically significant 13% increased rate of recurrent AF for every 5-unit rise in body mass index, Dr. Lau reported.

Mitchel L. Zoler/Frontline Medical News

They also identified 12 studies on the impact of obesity in 62,160 patients who underwent cardiac surgery that collectively showed a statistically significant 10% higher incidence of postoperative AF for every additional 5 BMI units.

The researchers found nine studies of the role of obesity in new-onset AF in cohort analyses with a total of 157,518 patients that showed an overall, statistically significant 29% rise in AF incidence for every 5 additional BMI units. And in 14 case-control studies with 401,061 patients, the rate of new-onset AF increased by a statistically significant 19% for every 5-unit rise in BMI.

These findings fit into an already substantial body of evidence documenting a significant link between obesity and AF, said Dr. Lau, director of the cardiac pacing unit at the Royal Adelaide (Australia) Hospital. For example, an analysis of 14,598 Americans enrolled in the Atherosclerosis Risk in Communities (ARIC) study found that 18% of the 1,520 new cases of AF that occurred in this cohort during an average 17 years of follow-up could be attributed to obesity or overweight (Circulation 2011;123:1501-8). Data collected from 34,309 women enrolled in the Women’s Health Study who had 834 cases of incident AF during an average 13-year follow-up showed that every 1-unit increase in BMI was linked to a 5% increased risk for AF, and that obese women had an overall 65% higher incidence of AF than did women with a normal BMI (J. Am Coll. Cardiol. 2010;55:2319-27).

And Dr. Lau and his associates recently published a review of 355 patients with AF and a baseline BMI of at least 27 kg/m² who participated in a weight-management program. After 5 years, patients who lost at least 10% of their baseline weight had an 86% rate of arrhythmia-free survival, compared with a 40% rate in patients who either lost less than 3% of their baseline weight or gained weight. In a multivariate analysis, weight loss of at least 10% linked with a statistically significant sixfold increase in arrhythmia-free survival, compared with all the other patients in the analysis (J. Am. Coll. Cardiol. 2015;65:2159-69).

Dr. Lau also cited findings from animal studies by his group that point to a direct role for obesity, and specifically deposits of epicardial fat in causing AF. Their model uses overfed sheep, and his group found that a higher burden of epicardial fat leads to fat infiltration into the myocardium, including atrial tissue. “We postulate that this fat contributes to conduction heterogeneity, increased re-entry, increased susceptibility to AF, and increased duration of AF episodes,” he said.

“It’s quite clear that obesity itself is important because, for example, the sheep do not develop sleep apnea, and they have only marginally elevated blood pressures. Using this animal model, we are quite convinced that obesity itself is an important risk factor.”

Dr. Lau added that results from recent sheep studies showed that after previously obese sheep lose their excess weight their atrial abnormalities revert to normal.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON– The already-firm evidence implicating obesity in boosting both the incidence and severity of atrial fibrillation grew even stronger with results from four meta-analyses that comprised 51 controlled studies involving a total of more than 600,000 people.

“We should pay more attention to using weight reduction strategies to prevent AF [atrial fibrillation] and to reduce its burden in patients with obesity and established AF,” Dr. Dennis H. Lau said at the annual scientific sessions of the Heart Rhythm Society.

Mitchel L. Zoler/Frontline Medical News

Physicians are increasingly aware of the strong evidence linking obesity and atrial fibrillation incidence and severity, said Dr. Christine M. Albert, director of the Center for Arrhythmia Prevention at Brigham and Women’s Hospital, Boston. The existence of this link is “really important because it is something we can offer patients,” Dr. Albert said in an interview. Obesity interventions provide a way to intervene in patients with, or at risk for, atrial fibrillation that goes beyond atrial ablation and antiarrhythmic drugs to reduce symptoms and help patients feel better, she noted.

Dr. Lau and his associates reviewed the published medical literature through January 2012 and identified 51 studies that examined the link between obesity and AF in a total of 626,603 people.

They found 16 studies with 5,864 patients that assessed the link between obesity and AF recurrence following atrial ablation treatment and found a statistically significant 13% increased rate of recurrent AF for every 5-unit rise in body mass index, Dr. Lau reported.

Mitchel L. Zoler/Frontline Medical News

They also identified 12 studies on the impact of obesity in 62,160 patients who underwent cardiac surgery that collectively showed a statistically significant 10% higher incidence of postoperative AF for every additional 5 BMI units.

The researchers found nine studies of the role of obesity in new-onset AF in cohort analyses with a total of 157,518 patients that showed an overall, statistically significant 29% rise in AF incidence for every 5 additional BMI units. And in 14 case-control studies with 401,061 patients, the rate of new-onset AF increased by a statistically significant 19% for every 5-unit rise in BMI.

These findings fit into an already substantial body of evidence documenting a significant link between obesity and AF, said Dr. Lau, director of the cardiac pacing unit at the Royal Adelaide (Australia) Hospital. For example, an analysis of 14,598 Americans enrolled in the Atherosclerosis Risk in Communities (ARIC) study found that 18% of the 1,520 new cases of AF that occurred in this cohort during an average 17 years of follow-up could be attributed to obesity or overweight (Circulation 2011;123:1501-8). Data collected from 34,309 women enrolled in the Women’s Health Study who had 834 cases of incident AF during an average 13-year follow-up showed that every 1-unit increase in BMI was linked to a 5% increased risk for AF, and that obese women had an overall 65% higher incidence of AF than did women with a normal BMI (J. Am Coll. Cardiol. 2010;55:2319-27).

And Dr. Lau and his associates recently published a review of 355 patients with AF and a baseline BMI of at least 27 kg/m² who participated in a weight-management program. After 5 years, patients who lost at least 10% of their baseline weight had an 86% rate of arrhythmia-free survival, compared with a 40% rate in patients who either lost less than 3% of their baseline weight or gained weight. In a multivariate analysis, weight loss of at least 10% linked with a statistically significant sixfold increase in arrhythmia-free survival, compared with all the other patients in the analysis (J. Am. Coll. Cardiol. 2015;65:2159-69).

Dr. Lau also cited findings from animal studies by his group that point to a direct role for obesity, and specifically deposits of epicardial fat in causing AF. Their model uses overfed sheep, and his group found that a higher burden of epicardial fat leads to fat infiltration into the myocardium, including atrial tissue. “We postulate that this fat contributes to conduction heterogeneity, increased re-entry, increased susceptibility to AF, and increased duration of AF episodes,” he said.

“It’s quite clear that obesity itself is important because, for example, the sheep do not develop sleep apnea, and they have only marginally elevated blood pressures. Using this animal model, we are quite convinced that obesity itself is an important risk factor.”

Dr. Lau added that results from recent sheep studies showed that after previously obese sheep lose their excess weight their atrial abnormalities revert to normal.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler