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


Therapeutics

An implanted defibrillator reduced death in patients with coronary disease at high risk for ventricular arrhythmia

ACP J Club. 1997 May-Jun;126:60. doi:10.7326/ACPJC-1997-126-3-060

Related Content in this Issue
• Companion Abstract and Commentary: The cost of QALY gained was high for implantable cardioverter defibrillators compared with amiodarone for sudden cardiac death


Source Citation

Moss AJ, Hall WJ, Cannom DS, et al., for the Multicenter Automatic Defibrillator Implantation Trial Investigators. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med. 1996 Dec 26;335:1933-40.


Abstract

Objective

To compare the effectiveness of an implanted cardioverter-defibrillator (ICD) with conventional therapy in patients with coronary heart disease at high risk for ventricular arrhythmia.

Design

Randomized controlled trial with mean follow-up of 27 months (Multicenter Automatic Defibrillator Implantation Trial [MADIT]).

Setting

30 hospital centers in the United States and 2 in Europe.

Patients

196 patients (mean age 63 y, 92% men) were studied. Inclusion criteria were age 25 to 80 years; confirmed myocardial infarction (MI) ≥ 3 wk before entry; previously documented asymptomatic, unsustained ventricular tachycardia unrelated to acute MI; ejection fraction ≤ 0.35; New York Heart Association functional class I, II, or III; no current indications for coronary artery bypass grafting or angioplasty; and inducible sustained ventricular tachycardia or fibrillation not suppressed by intravenous procainamide. Exclusion criteria were cardiac arrest or ventricular tachycardia causing syncope not associated with acute MI, symptomatic hypotension while in stable rhythm, MI (< 3 wk), recent coronary artery bypass grafting (2 mo) or coronary angioplasty (3 mo), childbearing potential, cerebrovascular disease, a noncardiac condition reducing likelihood of survival, or participation in other trials. Follow-up was 98%.

Intervention

95 patients were allocated to an ICD and 101 to conventional therapy chosen by the attending physician.

Main outcome measure

Total mortality.

Main results

15 patients (16%) who received an ICD died compared with 39 patients (39%) who received conventional therapy (P = 0.009). {This absolute risk reduction of 23% means that 5 patients would need to be treated with an ICD (rather than conventional therapy) to prevent 1 additional death, 95% CI 3 to 9; the relative risk reduction was 59%, CI 32% to 76%.}* Regression analysis showed that mortality was not associated with anti-arrhythmic medications, including amiodarone, β-blockers, other cardiac medications, or any baseline characteristic (P > 0.2 for all interactions).

Conclusion

In high-risk patients with coronary artery disease, left ventricular dysfunction, asymptomatic unsustained ventricular tachycardia, and inducible sustained ventricular tachycardia, total mortality was reduced in patients who received an implanted defibrillator compared with those who received conventional therapy.

Source of funding: CPI/Guidant Corporation.

For article reprint: Dr. A.J. Moss, Heart Research Follow-up Program, Box 653, University of Rochester Medical Center, Rochester, NY 14642, USA. FAX 716-473-2751.

*Numbers calculated from data in article.


Commentary

The ICD aborts sudden cardiac death in patients with symptomatic ventricular tachyarrhythmias. The role of this device in preventing sudden death in patients with asymptomatic tachyarrhythmias is less clear. The landmark MADIT study found that ICD was an effective therapy for a select group of patients with asymptomatic unsustained ventricular tachycardia at very high risk for sudden death.

Patients in MADIT had previous MIs, mean ejection fractions of 25% to 27%, and electrophysiologically inducible sustained tachyarrhythmias that could not be suppressed with procainamide. These patients had a very high risk for sudden death and may represent the group that is least likely to respond to antiarrhythmic therapy (1). Despite very low ejection fractions, only 50% to 60% were treated with angiotensin-converting enzyme inhibitors. More optimal treatment of systolic dysfunction could decrease sudden death and overall mortality and lower the absolute benefits of ICD therapy. Whether participants received other therapies (such as aspirin and lipid-lowering agents), which could also decrease mortality and lower absolute benefits of ICD therapy, was not described.

MADIT compared ICD with conventional medical management determined by individual physicians. Most patients (92%) assigned to conventional therapy received antiarrhythmic agents, including β-blockers, at 1 month. Amiodarone is among the most promising pharmaceutical agents for ventricular arrhythmias. Although 74% of participants in MADIT who were assigned to conventional therapy received amiodarone, approximately 10% received class I antiarrhythmic agents; no patient received encainide, flecainide, or moricizine. Further, 23% of the conventional-therapy group were not taking any antiarrhythmic agents at the end of the trial. Of note is that 11% of the participants assigned to conventional therapy received a defibrillator during the trial, and 5% of those assigned to ICD never received a defibrillator. These factors could lead to underestimates of the benefits of ICD.

The elegant analysis done by Owens and colleagues elucidates important points that must be taken into consideration before ICD can be accepted as cost-effective for preventing sudden death in high-risk and intermediate-risk patients with asymptomatic ventricular arrhythmias. This analysis specifically compared ICD with amiodarone alone and amiodarone followed by ICD when necessary. It did not include costs of procedures, such as electrophysiologic testing, that are used by some cardiologists to identify patients likely to benefit from prophylaxis. The analysis found that cost-effectiveness strongly depended on the magnitude of reduction in total mortality associated with ICD and the frequency of generator replacements. ICD is estimated to cost more than U.S. $50 000 per QALY gained unless it reduces mortality by 30% or more compared with amiodarone. Although MADIT showed that mortality reductions as high as 50% can be achieved with ICD compared with conventional therapy in selected very high risk patients, the relative magnitude of reductions that are achievable in high-risk and intermediate-risk patients treated with ICD compared with amiodarone alone is not yet known. Further, estimates of the magnitude of mortality benefits in this relatively small study were not very robust (i.e., the CIs were wide).

In summary, MADIT showed that ICDs were more efficacious than physician-determined therapy that consisted of a heterogeneous mixture of antiarrhythmic agents for very high risk patients with tachyarrhythmias that could not be suppressed with procainamide. Actual costs of identifying and treating this select group of patients were not clearly defined and were likely to be high. The analysis by Owens and colleagues underscored the need to wait for the results of several ongoing trials before concluding that ICD is generally preferable to amiodarone. Clinicians should wait for the results of these trials before routinely recommending ICDs for their high-risk and intermediate-risk patients with asymptomatic unsustained ventricular tachyarrhythmias.

Domenic Marini, MD
Cynthia D. Mulrow, MD, MSc
Audie L. Murphy Memorial Veterans Administration HospitalSan Antonio, Texas, USA

Domenic Marini, MD
Audie L. Murphy Memorial Veterans Administration Hospital
San Antonio, Texas, USA

Cynthia D. Mulrow, MD, MSc
Audie L. Murphy Memorial Veterans Administration Hospital
San Antonio, Texas, USA


Reference

1. Waxman HL, Buxton AE, Sadowski LM, Josephson ME. The response to procainamide during electrophysiologic study for sustained ventricular tachyarrhythmias predicts the response to other medications. Circulation. 1983;67:30-7.