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


Therapeutics

d-sotalol increased mortality in left ventricular dysfunction after myocardial infarction

ACP J Club. 1997 Jan-Feb;126:13. doi:10.7326/ACPJC-1997-126-1-013


Source Citation

Waldo AL, Camm AJ, deRuyter H, et al., for the SWORD Investigators. Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. Lancet. 1996 Jul 6;348:7-12.


Abstract

Objective

To determine the effectiveness of d-sotalol for reducing all-cause mortality in patients with previous myocardial infarction (MI) and left ventricular (LV) dysfunction.

Design

Randomized, double-blind, placebo-controlled trial (Survival with Oral d-Sotalol [SWORD] trial).

Setting

406 centers worldwide.

Patients

3121 patients who were ≥ 18 years of age (mean age 60 y, 86% men), had LV ejection fraction ≤ 40%, and had had either a recent MI (6 to 42 d previously) or a remote MI (> 42 d previously) with overt heart failure. Exclusion criteria were unstable angina; class IV heart failure; history of life-threatening arrhythmia unrelated to an MI, the sick sinus syndrome, or high-grade atrioventricular block; recent (within 14 d) coronary angioplasty or bypass surgery; abnormal electrolyte levels; creatinine clearance < 50 mL/min; corrected QT interval > 460 ms; or use of concomitant anti-arrhythmic drugs or drugs that prolonged the QT interval. Planned recruitment was 6374 patients with 2.3-year follow-up.

Intervention

Patients were allocated to oral d-sotalol, 100 mg twice daily (n = 1549), or to placebo (n = 1572) for 1 week. The dose was increased to 200 mg if the drug was well tolerated but was reduced if the corrected QT interval exceeded 560 ms at any time.

Main outcome measures

The primary end point was all-cause mortality; the secondary end point was cardiac mortality.

Main results

The study was terminated after recruitment of 3121 patients and a mean follow-up of 148 days because of increased mortality in patients allocated to d-sotalol: 78 patients (5.0%) who received d-sotalol died compared with 48 patients (3.1%) who received placebo (P = 0.006). {This absolute risk difference of 1.9% means that during a mean follow-up of 148 days, 1 additional death occurred for every 50 patients treated with d-sotalol (compared with placebo), 95% CI 29 to 164; the relative risk increase was 65%, CI 16% to 134%.}* Cardiac mortality was also higher in patients who received d-sotalol compared with placebo (4.7% vs 2.9%, P = 0.008) {absolute risk difference 1.8%; 1 additional cardiac death occurred for every 54 patients treated with d-sotalol, CI 31 to 193; the relative risk increase was 65%, CI 15% to 137%},* as was death presumed to have been caused by arrhythmia (3.6% vs 2.0%, P = 0.008). The groups did not differ for nonfatal cardiac events.

Conclusion

d-sotalol was associated with greater all-cause and cardiac mortality than was placebo in patients with previous myocardial infarction and left ventricular dysfunction.

Source of funding: Bristol-Myers Squibb.

For article reprint: Bristol-Myers Squibb Pharmaceutical Research Institute, Attention: Dr. Enrico Veltri, P.O. Box 4000, Princeton, NJ 08543-4000, USA.

*Numbers calculated from data in article.


Commentary

The risk for death among patients who have an MI is increased by LV dysfunction, frequent or repetitive ventricular premature depolarizations (VPDs), and extent of residual ischemia (1). At least half of the deaths are caused by ventricular arrhythmias, prompting many anti-arrhythmic drug trials. β-blockers (class II antiarrhythmic activity) have clearly been shown to reduce mortality (2, 3), whereas class I drugs, particularly those in class IC (encainide and flecainide) have an overall harmful effect (3). Calcium channel blockers (class IV effects) may also be harmful (3). Amiodarone, which has predominant class III effects, appears promising (3). In the SWORD trial, d-sotalol, a pure class III antiarrhythmic drug, was associated with an increase in all-cause cardiac and arrhythmic mortality. Although the harmful effect varied, it was seen in all 14 relevant subgroups. The results show that d-sotalol is not recommended for sur-vivors of MI who have impaired LV function. Reducing the incidence of arrhythmic death among survivors of MI is a challenge that persists. Apart from β-blockers, no antiarrhythmic drug is indicated except for use in patients who have survived sustained ventricular tachycardia or ventricular fibrillation. Great interest attends the publication of the recently presented evidence that amiodarone reduced the rate of arrhythmic deaths in patients who survived MI and had frequent or repetitive VPDs and LV dysfunction in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (4) and the European Myocardial Infarct Amiodarone Trial (5).

John Cairns, MD
University of British ColumbiaVancouver, British Columbia, Canada

John Cairns, MD
University of British Columbia
Vancouver, British Columbia, Canada


References

1. Risk stratification and survival after myocardial infarction. N Engl J Med. 1983; 309:331-6.

2. Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Cardiovasc Dis. 1985;27:335-71.

3. Teo KK, Yusuf S, Furberg CD. JAMA. 1993;270:1589-95.

4. Cairns JA, Connolly SJ, Roberts R, Gent M. Am J Cardiol. 1993;72:87F-94F.

5. Camm AJ, Julian D, Janse G, et al. Am J Cardiol. 1993;72:95F-8F.