Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Nadolol and verapamil for symptomatic hypertrophic cardiomyopathy

ACP J Club. 1993 Nov-Dec;119:73. doi:10.7326/ACPJC-1993-119-3-073


Source Citation

Gilligan DM, Chan WL, Joshi J, et al. A double-blind, placebo-controlled crossover trial of nadolol and verapamil in mild and moderately symptomatic hypertrophic cardiomyopathy. J Am Coll Cardiol. 1993 Jun;21:1672-9.


Abstract

Objective

To evaluate the effectiveness of nadolol and verapamil in improving the functional capacity and quality of life in patients with mild or moderately symptomatic hypertrophic cardiomyopathy.

Design

Randomized, double-blind crossover trial.

Setting

Hospital in the United Kingdom.

Patients

18 consecutive outpatients (mean age 39 y, 10 men) with mild or moderately symptomatic hypertrophic cardiomyopathy. Exclusion criteria were New York Heart Association functional class III or IV, chronic atrial fibrillation, history of symptomatic bradycardia or heart rate < 60 beats/min at rest (without medication), systolic blood pressure < 100 mm Hg (without medication), or contraindication to β-blockers or calcium antagonists. 16 patients completed the study.

Intervention

Patients were randomly assigned to a 4-week treatment period of nadolol (80 mg/d for 1 wk with dose adjustment to 80 mg twice daily if required), verapamil (240 mg/d for 1 wk followed by 240 mg twice daily if required), or placebo. After a 1-week washout interval, patients crossed over to 1 of the remaining 2 treatments for 4 weeks. After a 1-week washout period, patients then crossed over to the last remaining treatment for 4 weeks.

Main outcome measures

Change in peak exercise capacity, symptoms, and quality of life.

Main results

2 of 16 patients received 80 mg/d of nadolol and the other 14 received 160 mg/d. 2 patients received 240 mg/d of verapamil and the remaining 14 received 480 mg/d. Mean levels of exercise duration, maximal oxygen consumption, and anaerobic threshold were not significantly changed by drug therapy. The peak exercise workload was reduced by ≥10 W in 13 patients (81%) during nadolol therapy and in 4 patients (25%) during verapamil therapy (absolute difference 56% {95% CI 28% to 85%}[numbers calculated from data in article], P = 0.005). The mean total symptoms score did not differ between treatment groups, but 81% of individual patients preferred drug treatment to placebo (P= 0.001).

Conclusion

Exercise capacity was not improved by nadolol or verapamil in patients with mild or moderately symptomatic hypertrophic cardiomyopathy but most patients preferred one or the other drug therapies over placebo.

Sources of funding: Squibb Limited and Knoll Limited.

For article reprint: Dr. D.M. Gilligan, Cardiology Branch, National Heart, Lung, and Blood Institute, Building 10, Room 7BI5, Bethesda, MD 20892, USA. FAX 301-402-0888.


Commentary

This well-done trial by Gilligan and colleagues compares nadolol and verapamil with placebo in a small number of mildly symptomatic patients with hypertrophic cardiomyopathy. Because the patients' symptoms may be related to the degree of outflow obstruction, amount of diastolic dysfunction associated with their cardiomyopathy, or psychological factors, it is not surprising that no differences were noted in the primary end point (mean level of exercise capacity) or secondary end points (such as symptom scores and quality-of-life indices). The most important finding in this double-blind study was that 81% of the patients preferred drug treatments (8 verapamil, 5 nadolol). This is an ideal situation for clinicians to institute N-of-1 trials to tailor drug therapy based on improvement in an individual patient's symptoms (1, 2). Controlled trials with larger numbers of patients designed to assess regression of hypertrophy, improvement in diastolic dysfunction, and protection against sudden death are needed to define the most effective treatment for hypertrophic cardiomyopathy.

Charles B. Eaton, MD
Memorial Hospital of Rhode Island Pawtucket, Rhode Island, USA