β-blockers no better than placebo in the treatment of vasovagal syncope

ABSTRACT

BACKGROUND: About half of syncopal episodes are vasovagal reactions. Empiric treatment with β-blockers is a common practice based on physiologic mechanisms of vasovagal syncope. Only 3 prospective, randomized controlled trials have been done to compare a β-blocker (atenolol) with placebo; no study showed reduced syncopal episodes. No studies have been published on β-blockers other than atenolol.

POPULATION STUDIED: The authors enrolled 30 consecutive patients with recurrent vasovagal syncope. The mean age of the subjects was 41 years; 17 (57%) were women. Investigators defined recurrent vasovagal syncope as at least 2 episodes in the past 3 months and a positive tilt test response. Patients had normal cardiovascular examinations and no electrocardiographic changes. Patients were excluded who had known or suspected autonomic failure (including diabetes), hypertension, chronic obstructive pulmonary disease, or peripheral vascular disease. Patients were recruited from an outpatient cardiology setting, potentially representing a different population than encountered in many primary care settings.

STUDY DESIGN AND VALIDITY: This study was an unblinded, crossover placebo-controlled trial. Patients were assigned to receive 3 drugs in random order for 3 months each. Study drugs were the maximum tolerated dose of propranolol (Inderal) 20 to 40 mg 3 times daily, nadolol (Corgard) 40 to 80 mg once daily, and placebo 1 capsule once daily. Investigators were not blinded but patients were. However, patients took propranolol 3 times daily compared with once daily for placebo and nadolol. To minimize the effect of dosing frequency, investigators advised patients that frequency had no relationship with efficacy. Concealed allocation was not performed. All 30 patients completed the study, although 1 patient withdrew from propranolol therapy due to fatigue. Results were analyzed by intention to treat.

OUTCOMES MEASURED: The primary outcome measured was the number of syncopal and presyncopal events during each study drug’s 3-month period. Additionally, patients’ assessed their quality of life and reported which therapies they preferred. Quality of life was scored from 0 to 4 based on vasovagal symptoms, drug side effects, and personal well being during therapy (0 = very dissatisfied and 4 = excellent).

RESULTS: Overall, no difference was noted in the number of syncopal episodes or quality of life scores during the 3 study periods. Propranolol, nadolol, and placebo equally improved outcomes as compared with baseline (0.25, 0.25, and 0.5 episodes during 3 months respectively vs 3.4 episodes per 3 months; P < .0001). Similar benefits were seen for presyncopal episodes (2.1, 1.3, and 2.6 episodes during 3 months, respectively vs 9.1 episodes per 3 months; P < .0001). Patients’ quality of life scores improved with propranolol, nadolol, and placebo as compared with baseline (3.1, 3.5, and 3.4 on a scale of 4, respectively vs 1.5; P < .0001). At the conclusion of the study, 4 patients preferred nadolol, 2 preferred placebo, and 3 preferred propranolol. Five patients were dissatisfied with propranolol due to fatigue. The remaining 70% of patients were satisfied with all 3 regimens.

ABSTRACT

BACKGROUND: About half of syncopal episodes are vasovagal reactions. Empiric treatment with β-blockers is a common practice based on physiologic mechanisms of vasovagal syncope. Only 3 prospective, randomized controlled trials have been done to compare a β-blocker (atenolol) with placebo; no study showed reduced syncopal episodes. No studies have been published on β-blockers other than atenolol.

POPULATION STUDIED: The authors enrolled 30 consecutive patients with recurrent vasovagal syncope. The mean age of the subjects was 41 years; 17 (57%) were women. Investigators defined recurrent vasovagal syncope as at least 2 episodes in the past 3 months and a positive tilt test response. Patients had normal cardiovascular examinations and no electrocardiographic changes. Patients were excluded who had known or suspected autonomic failure (including diabetes), hypertension, chronic obstructive pulmonary disease, or peripheral vascular disease. Patients were recruited from an outpatient cardiology setting, potentially representing a different population than encountered in many primary care settings.

STUDY DESIGN AND VALIDITY: This study was an unblinded, crossover placebo-controlled trial. Patients were assigned to receive 3 drugs in random order for 3 months each. Study drugs were the maximum tolerated dose of propranolol (Inderal) 20 to 40 mg 3 times daily, nadolol (Corgard) 40 to 80 mg once daily, and placebo 1 capsule once daily. Investigators were not blinded but patients were. However, patients took propranolol 3 times daily compared with once daily for placebo and nadolol. To minimize the effect of dosing frequency, investigators advised patients that frequency had no relationship with efficacy. Concealed allocation was not performed. All 30 patients completed the study, although 1 patient withdrew from propranolol therapy due to fatigue. Results were analyzed by intention to treat.

OUTCOMES MEASURED: The primary outcome measured was the number of syncopal and presyncopal events during each study drug’s 3-month period. Additionally, patients’ assessed their quality of life and reported which therapies they preferred. Quality of life was scored from 0 to 4 based on vasovagal symptoms, drug side effects, and personal well being during therapy (0 = very dissatisfied and 4 = excellent).

RESULTS: Overall, no difference was noted in the number of syncopal episodes or quality of life scores during the 3 study periods. Propranolol, nadolol, and placebo equally improved outcomes as compared with baseline (0.25, 0.25, and 0.5 episodes during 3 months respectively vs 3.4 episodes per 3 months; P < .0001). Similar benefits were seen for presyncopal episodes (2.1, 1.3, and 2.6 episodes during 3 months, respectively vs 9.1 episodes per 3 months; P < .0001). Patients’ quality of life scores improved with propranolol, nadolol, and placebo as compared with baseline (3.1, 3.5, and 3.4 on a scale of 4, respectively vs 1.5; P < .0001). At the conclusion of the study, 4 patients preferred nadolol, 2 preferred placebo, and 3 preferred propranolol. Five patients were dissatisfied with propranolol due to fatigue. The remaining 70% of patients were satisfied with all 3 regimens.

ABSTRACT

BACKGROUND: About half of syncopal episodes are vasovagal reactions. Empiric treatment with β-blockers is a common practice based on physiologic mechanisms of vasovagal syncope. Only 3 prospective, randomized controlled trials have been done to compare a β-blocker (atenolol) with placebo; no study showed reduced syncopal episodes. No studies have been published on β-blockers other than atenolol.

POPULATION STUDIED: The authors enrolled 30 consecutive patients with recurrent vasovagal syncope. The mean age of the subjects was 41 years; 17 (57%) were women. Investigators defined recurrent vasovagal syncope as at least 2 episodes in the past 3 months and a positive tilt test response. Patients had normal cardiovascular examinations and no electrocardiographic changes. Patients were excluded who had known or suspected autonomic failure (including diabetes), hypertension, chronic obstructive pulmonary disease, or peripheral vascular disease. Patients were recruited from an outpatient cardiology setting, potentially representing a different population than encountered in many primary care settings.

STUDY DESIGN AND VALIDITY: This study was an unblinded, crossover placebo-controlled trial. Patients were assigned to receive 3 drugs in random order for 3 months each. Study drugs were the maximum tolerated dose of propranolol (Inderal) 20 to 40 mg 3 times daily, nadolol (Corgard) 40 to 80 mg once daily, and placebo 1 capsule once daily. Investigators were not blinded but patients were. However, patients took propranolol 3 times daily compared with once daily for placebo and nadolol. To minimize the effect of dosing frequency, investigators advised patients that frequency had no relationship with efficacy. Concealed allocation was not performed. All 30 patients completed the study, although 1 patient withdrew from propranolol therapy due to fatigue. Results were analyzed by intention to treat.

OUTCOMES MEASURED: The primary outcome measured was the number of syncopal and presyncopal events during each study drug’s 3-month period. Additionally, patients’ assessed their quality of life and reported which therapies they preferred. Quality of life was scored from 0 to 4 based on vasovagal symptoms, drug side effects, and personal well being during therapy (0 = very dissatisfied and 4 = excellent).

RESULTS: Overall, no difference was noted in the number of syncopal episodes or quality of life scores during the 3 study periods. Propranolol, nadolol, and placebo equally improved outcomes as compared with baseline (0.25, 0.25, and 0.5 episodes during 3 months respectively vs 3.4 episodes per 3 months; P < .0001). Similar benefits were seen for presyncopal episodes (2.1, 1.3, and 2.6 episodes during 3 months, respectively vs 9.1 episodes per 3 months; P < .0001). Patients’ quality of life scores improved with propranolol, nadolol, and placebo as compared with baseline (3.1, 3.5, and 3.4 on a scale of 4, respectively vs 1.5; P < .0001). At the conclusion of the study, 4 patients preferred nadolol, 2 preferred placebo, and 3 preferred propranolol. Five patients were dissatisfied with propranolol due to fatigue. The remaining 70% of patients were satisfied with all 3 regimens.