The most common cause of death in North America is cardiac death and the most common cause of cardiac death is sudden death from ventricular arrhythmias. If patients have an arrhythmia and heart failure outside of the hospital, the chance of resuscitation is very low. If a patient is to survive sudden cardiac failure from serious ventricular arrhythmias (sustained ventricular tachycardia [VT] or ventricular fibrillation [VF]), they must be defibrillated with in a few minutes, at most. The underlying principle of the implantable cardioverter defibrillator (ICD) is the automatic delivery of life-saving defibrillation therapy within seconds from the onset of a life-threatening tachycardia arrhythmia.

Cardiac death and, in particular, sudden cardiac death from ventricular arrhythmia is one of the most common causes of death in Western society. Implanted cardioverter defibrillators (ICDs) have become mainstream therapy for the prevention of sudden cardiac death from ventricular tachyarrhythmias. A decade of studies has confirmed the superiority of ICDs over antiarrhythmic drug therapy in prolonging the life of patients with a prior history of sustained ventricular tachycardia (VT) or fibrillation (VF). In the 1990s, important advances in the treatment of heart disease were made with thrombolytic, anti-ischemic, and revascularization therapies. Now, the treatment challenge is focused on caring for patients with the chronic consequences of coronary artery disease (CAD), chiefly left ventricular dysfunction (LVD), prior myocardial infarction (MI), and the propensity for sudden arrhythmic death. New studies are examining the role of ICDs in these and other patient risk groups.

However, it is clearly established that patients with severe LV dysfunction, with or without symptomatic heart failure, are at high risk for out-of-hospital cardiac arrest and presumably arrhythmic sudden death. Therefore, prevention is a major therapeutic challenge. Each of the tests listed above have some prognostic value, but are not sufficiently accurate as predictors of sudden death. In addition, those patients with these markers represent only a small fraction of all the patients with ventricular scarring potentially at risk of sudden death.

In the 1960s and 70s, clinicians were optimistic that sudden death could be prevented by administering antiarrhythmic drug therapy. Several large trials examined the potential usefulness of amiodarone in preventing sudden death in high-risk patients with CAD and left ventricular dysfunction (LVD). The lack of demonstrated benefit in these studies suggests that there is little reason to prescribe amiodarone or other antiarrhythmic drugs as primary prophylaxis for VT or VF in patients with CAD or LVD and no symptoms of sustained ventricular arrhythmias. Beta-blockers, however, are of benefit in prolonging life in patients following MI, particularly in those with heart failure and extensive LVD. There is little optimism, however, that antiarrhythmic drugs can be even a partial solution to sudden cardiac death in susceptible coronary populations. EMIAT. Julian DG, et al. Lancet 1997;349:667-674. CHF-STAT. Deedwania PC, et al. Circulation 1998;98:2574-2579. CAMIAT. Cairns JA, et al. Lancet 1997;349:675-682. DIAMOND. Kober L, et al. Lancet 2000;356:2052-2058 DIAMOND-CHF. Moller M, et al. Congest Heart Fail 2001;7:146-150. ALIVE. Camm AJ, et al. Circulation 2001;104:1B

Studies such as AVID, CIDS, and CASH and their meta-analysis demonstrate that ICDs reduce all-cause mortality by 20%-30% in patients with a prior history of cardiac arrest or sustained VT (ie, secondary prophylaxis). The Canadian Implantable Defibrillator Study (CIDS) revealed a non-significant risk reduction in overall mortality from an ICD compared to amiodarone. A recent abstract examined the long-term survival of patients at a single centre in a subset of the CIDS study. This subset consisted of patients randomly assigned during the CIDS study to receive either amiodarone (n=60) or an ICD (n=60) and whose treatment was not altered after the trial ended. Over time, the study demonstrated an increase in the benefit from an ICD compared to amiodarone. There were 28 deaths in the amiodarone group versus 16 deaths in the ICD group; 49 patients (82%) had side effects related to amiodarone, of which 30 (50%) required discontinuation or dose reduction and 18 crossed over to ICD because of amiodarone failure (n=7) or adverse effects (n=11). The benefit of an ICD over amiodarone appears to increase over time, since most of the amiodarone-treated patients experienced recurrences or adverse effects or died during the 11 years of follow-up. Bokhari F, et al. Can J Cardiol 2002;18:185B.

The following studies assessed the usefulness of ICDs as primary prophylaxis. Initially, these trials of ICDs focused on patients who were at particularly high-risk of sudden cardiac death based on a low ejection fraction and an additional cardiac sudden death risk marker. The Multicenter UnSustained Tachycardia Trial (MUSTT) study demonstrated the superiority of an ICD versus antiarrhythmic therapy or no antiarrhythmic therapy. The risk of cardiac arrest or death from arrhythmia in patients who received an ICD was significantly lower than in patients who were treated with or without antiarrhythmic drugs and no ICD treatment (relative risk, 0.24; 95 % CI, 0.13 to 0.45; P<0.001). As a result, guidelines of the Canadian Cardiovascular Society Consensus concluded that patients should be treated with an ICD if they had: CAD, left ventricular ejection fraction (LVEF) < 40%, nonsustained VT, and inducible VT/VP at EP study. Other trials include: The Multicentre Automatic Defibrillator Implantation Trial (MADIT- I) was the first to document a potential benefit from prophylactic ICDs. Evidence showed a 54% reduction in mortality with an ICD compared to “conventional medical therapy.” This led to FDA approval of ICDs for the particular subset of patients meeting trial inclusion criteria. (Moss AJ, et al. N Engl J Med 1996;335:1933-40.) Patients in the Coronary Artery Bypass Graft study (CABG Patch) were randomized after surgery to an ICD or a control group without ICD. The device failed to show any benefit, but mortality after bypass surgery was very low for both groups suggesting that surgical revascularization has a protective effect. (Bigger JT Jr. N Engl J Med 1997;337:1569-75.)

The MADIT II trial tested the hypothesis that ICDs would reduce all-cause mortality in at-risk populations. The study examined the use of ICDs in a patient population relatively representative of a larger group of patients having chronic CAD, a prior MI, LVEF <30% and no requirement for an ICD or an electro-physiological (EP) study. In addition, the study population received “state-of-the-art” drug therapy (70% ACEIs, 20% ß-blockers, 57% digitalis, 66% statins) allowing generalization to the larger population. Over time, defibrillator therapy resulted in an increasing mortality benefit compared to conventional therapy, demonstrating an aggregate 31% reduction in the risk of death at any time interval. In addition, a further subgroup analysis showed that patients with QRS prolongation of >120 msec at baseline received a dramatic and particularly large benefit from implantation of an ICD. In these patients, mortality was reduced from 53% to 21% at 3 years. QRS prolongation on surface ECG is a particularly potent, simple marker for the probability of all-cause mortality and sudden death (Zareba W, et al. NASPE 2002. Late-breaking trials presentation).

There is compelling evidence that ICDs prolong life in patients susceptible to sudden cardiac death, particularly those with CAD. ICDs have demonstrated effective secondary prophylaxis in numerous studies of patients with a prior history of cardiac arrest or sustained VT. ICDs have also demonstrated effective primary prophylaxis in at-risk CAD populations. The greatest benefit, compared to amiodarone, occurs in those with severe LVD and in the elderly. No study has shown ICDs to be superior to medical therapy for dilated cardiomyopathy.

The reduction in mortality by defibrillator therapy compares very favourably to other cardiovascular therapies in common use in terms of the number needed to treat in order to prevent 1 death. The trials comparing ICDs with antiarrhythmic drug therapy (MUSTT, MADIT-I & II, AVID*), all show fewer numbers needed to treat than trials examining ACE inhibitors, beta-blockers, and statins. * The AVID Investigators. N Engl J Med 1997;337:1576-83.

Patients with very poor ventricular function benefit from ICD implantation even if they are receiving optimal medical therapy. An ICD will prolong the life of a patient with CAD and is superior to antiarrhythmic drug therapy. Thus, the patient should be informed about this treatment option. Despite the limitations of resources (device and implantation costs, and follow-up personnel), each patient should be considered for individual risk benefit in terms of using this therapeutic device to prevent a patient death. Any patient with a history of remote MI and an LVEF <30% should be given the opportunity of an ICD provided that they are receiving or considered for evidence-based pharmacological therapies and have no severe co-morbidities. Although nonsustained VT may have some prognostic significance, performing an EP study for risk stratification is not usually required in most patients. At present, ICD therapy is considered clearly superior to amiodarone therapy or no antiarrhythmic therapy for the prevention of sudden and all-cause mortality in susceptible populations.