Ranolazine plus beta-blockers might prevent postop AF

PHOENIX – Twice-daily ranolazine following adult cardiac surgery seemed to protect against atrial fibrillation, based on a retrospective cohort study at the University of Florida Jacksonville Medical Center.

Ranolazine (Ranexa) was dosed orally at 1,000 mg the morning of surgery, and then resumed after extubation, generally the night of surgery. The goal was 1,000 mg orally twice a day, for a maximum of 7 hospital days; patients usually went home before then, so they received an average of nine doses. The drug was discontinued at discharge.

Six (10.5%) of 57 patients in the ranolazine group developed postoperative atrial fibrillation (POAF) versus 26 (45.6%) of 57 matched controls (P < .0001). The first case came at postop day 3 in the ranolazine group, but within 24 hours in the control group. One person in the ranolazine group and one in the control group had a history of AF.

There was no statistical difference in ICU length of stay, 30-day readmission for cardiac causes, or 30-day cardiovascular mortality; the one cardiovascular death was in the control group.

Two-thirds of the patients had coronary artery bypass grafts, and the rest had either valve surgery or a combination of both surgeries. Patients were 60 years old on average, and two-thirds were men, Drayton Hammond, Pharm.D., said at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

Ranolazine is indicated for chronic angina, not POAF prevention, but some previous investigations have suggested a possible benefit. A randomized, controlled clinical trial is currently looking into the matter.

At least retrospectively, the drug was “beneficial, definitely. There is about a 35% absolute-risk reduction,” said Dr. Hammond, who conducted the study while at the Jacksonville hospital.

Doctors there continue to use ranolazine for postop AF prophylaxis, as they see fit, said Dr. Hammond, now an assistant professor of pharmacy practice at the University of Arkansas for Medical Sciences, in Little Rock.

Gilead, the maker of the Ranexa, is also working on a ranolazine-dronedarone combination for paroxysmal AF.

More than half of the ranolazine patients in the study developed symptomatic hypotension within 72 hours of surgery, versus about a third in the control group (P = .0004). The drug was discontinued in one ranolazine patient because of hypotension. The problem resolved after 72 hours.

“We don’t have a good explanation” for the side effect. Perhaps there were differences in myocardial stunning or vasopressor use between the groups, but “we had the same three surgeons” for all the cases, Dr. Hammond said.

Ranolazine labeling notes the risk of hypotension and orthostatic hypotension. Labeling also warns of QT interval prolongation and renal failure in susceptible patients. The investigators found no between-group differences in bradycardia, new renal failure, or neurological events.

Overall, 53 (93%) patients in the ranolazine group were on postoperative beta-blockers, and 54 (94.7%) on postop statins; 48 (84.2%) in the control group were on beta-blockers postop and 47 (82.5%) on statins. Beta-blockers are first-line treatment to prevent postop AF; patients on any other antiarrhythmic were excluded from the trial, as were those who died during surgery.

aotto@frontlinemedcom.com

PHOENIX – Twice-daily ranolazine following adult cardiac surgery seemed to protect against atrial fibrillation, based on a retrospective cohort study at the University of Florida Jacksonville Medical Center.

Ranolazine (Ranexa) was dosed orally at 1,000 mg the morning of surgery, and then resumed after extubation, generally the night of surgery. The goal was 1,000 mg orally twice a day, for a maximum of 7 hospital days; patients usually went home before then, so they received an average of nine doses. The drug was discontinued at discharge.

Six (10.5%) of 57 patients in the ranolazine group developed postoperative atrial fibrillation (POAF) versus 26 (45.6%) of 57 matched controls (P < .0001). The first case came at postop day 3 in the ranolazine group, but within 24 hours in the control group. One person in the ranolazine group and one in the control group had a history of AF.

There was no statistical difference in ICU length of stay, 30-day readmission for cardiac causes, or 30-day cardiovascular mortality; the one cardiovascular death was in the control group.

Two-thirds of the patients had coronary artery bypass grafts, and the rest had either valve surgery or a combination of both surgeries. Patients were 60 years old on average, and two-thirds were men, Drayton Hammond, Pharm.D., said at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

Ranolazine is indicated for chronic angina, not POAF prevention, but some previous investigations have suggested a possible benefit. A randomized, controlled clinical trial is currently looking into the matter.

At least retrospectively, the drug was “beneficial, definitely. There is about a 35% absolute-risk reduction,” said Dr. Hammond, who conducted the study while at the Jacksonville hospital.

Doctors there continue to use ranolazine for postop AF prophylaxis, as they see fit, said Dr. Hammond, now an assistant professor of pharmacy practice at the University of Arkansas for Medical Sciences, in Little Rock.

Gilead, the maker of the Ranexa, is also working on a ranolazine-dronedarone combination for paroxysmal AF.

More than half of the ranolazine patients in the study developed symptomatic hypotension within 72 hours of surgery, versus about a third in the control group (P = .0004). The drug was discontinued in one ranolazine patient because of hypotension. The problem resolved after 72 hours.

“We don’t have a good explanation” for the side effect. Perhaps there were differences in myocardial stunning or vasopressor use between the groups, but “we had the same three surgeons” for all the cases, Dr. Hammond said.

Ranolazine labeling notes the risk of hypotension and orthostatic hypotension. Labeling also warns of QT interval prolongation and renal failure in susceptible patients. The investigators found no between-group differences in bradycardia, new renal failure, or neurological events.

Overall, 53 (93%) patients in the ranolazine group were on postoperative beta-blockers, and 54 (94.7%) on postop statins; 48 (84.2%) in the control group were on beta-blockers postop and 47 (82.5%) on statins. Beta-blockers are first-line treatment to prevent postop AF; patients on any other antiarrhythmic were excluded from the trial, as were those who died during surgery.

aotto@frontlinemedcom.com

PHOENIX – Twice-daily ranolazine following adult cardiac surgery seemed to protect against atrial fibrillation, based on a retrospective cohort study at the University of Florida Jacksonville Medical Center.

Ranolazine (Ranexa) was dosed orally at 1,000 mg the morning of surgery, and then resumed after extubation, generally the night of surgery. The goal was 1,000 mg orally twice a day, for a maximum of 7 hospital days; patients usually went home before then, so they received an average of nine doses. The drug was discontinued at discharge.

Six (10.5%) of 57 patients in the ranolazine group developed postoperative atrial fibrillation (POAF) versus 26 (45.6%) of 57 matched controls (P < .0001). The first case came at postop day 3 in the ranolazine group, but within 24 hours in the control group. One person in the ranolazine group and one in the control group had a history of AF.

There was no statistical difference in ICU length of stay, 30-day readmission for cardiac causes, or 30-day cardiovascular mortality; the one cardiovascular death was in the control group.

Two-thirds of the patients had coronary artery bypass grafts, and the rest had either valve surgery or a combination of both surgeries. Patients were 60 years old on average, and two-thirds were men, Drayton Hammond, Pharm.D., said at the Critical Care Congress, sponsored by the Society for Critical Care Medicine.

Ranolazine is indicated for chronic angina, not POAF prevention, but some previous investigations have suggested a possible benefit. A randomized, controlled clinical trial is currently looking into the matter.

At least retrospectively, the drug was “beneficial, definitely. There is about a 35% absolute-risk reduction,” said Dr. Hammond, who conducted the study while at the Jacksonville hospital.

Doctors there continue to use ranolazine for postop AF prophylaxis, as they see fit, said Dr. Hammond, now an assistant professor of pharmacy practice at the University of Arkansas for Medical Sciences, in Little Rock.

Gilead, the maker of the Ranexa, is also working on a ranolazine-dronedarone combination for paroxysmal AF.

More than half of the ranolazine patients in the study developed symptomatic hypotension within 72 hours of surgery, versus about a third in the control group (P = .0004). The drug was discontinued in one ranolazine patient because of hypotension. The problem resolved after 72 hours.

“We don’t have a good explanation” for the side effect. Perhaps there were differences in myocardial stunning or vasopressor use between the groups, but “we had the same three surgeons” for all the cases, Dr. Hammond said.

Ranolazine labeling notes the risk of hypotension and orthostatic hypotension. Labeling also warns of QT interval prolongation and renal failure in susceptible patients. The investigators found no between-group differences in bradycardia, new renal failure, or neurological events.

Overall, 53 (93%) patients in the ranolazine group were on postoperative beta-blockers, and 54 (94.7%) on postop statins; 48 (84.2%) in the control group were on beta-blockers postop and 47 (82.5%) on statins. Beta-blockers are first-line treatment to prevent postop AF; patients on any other antiarrhythmic were excluded from the trial, as were those who died during surgery.

aotto@frontlinemedcom.com