Do Japanese Patients With Myocardial Infarction and Left Ventricular Dysfunction Require Prophylactic Implantable Cardioverter-Defibrillator Implantation?

Myocardial infarction (MI) is a life-threatening event and its incidence is increasing worldwide. Survivors of acute MI may experience consequent cardiac complications, which are occasionally fatal. Previous studies revealed that the most powerful predictor of poor prognosis in patients with old MI (OMI) is left ventricular dysfunction (LVD). To overcome the poor prognosis of OMI patients with LVD, prophylactic implantable cardioverter defibrillator (ICD) implantation is being increasingly used clinically to prevent sudden cardiac death (SCD) based on positive results in clinical trials,^1,2 particularly in Western countries. However, it is challenging to determine the actual indication for each patient, because of several problems, including resistance to the implantation of a foreign body, the patient’s financial capabilities, and the socioeconomic benefit. The most fundamental way to address these difficulties is to weigh the risks vs. the benefits of the procedure based on the probability of mortality.

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In this issue of the Journal, Kuga et al report on the prognosis of MI with LVD in the Japanese population³ as a subanalysis of the Japanese Coronary Artery Disease (JCAD) study. The JCAD study commenced in 2000 and recruited 13,812 patients with coronary artery disease through 2001,⁴ and in the present study, 6,868 consecutive OMI patients were enrolled from the JCAD registry. The authors compared OMI patients with LVD (left ventricular ejection fraction (LVEF) ≤30%, n=291) and those without LVD (n=5,359) during 3 years of follow-up. They demonstrated that clinical events, congestive heart failure, cardiopulmonary arrest on arrival, and vascular events were significantly more frequent in the LVD group. Furthermore, the mortality and survival curves of this group, though none of them underwent ICD implantation, were comparable to those of the ICD group of the Multicenter Automatic Defibrillator Implantation Trial (MADIT-II).¹ The annual rate of total death was 7.15% for the present study vs. 8.52% for MADIT-II.

To date, 2 large-scale randomized trials, namely MADIT-II and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT),² have provided substantial evidence that positively supports the prophylactic use of ICD in patients with severe LVD. MADIT-II was conducted from 1997 until 2001 and enrolled 1,232 patients with OMI and reduced left ventricular (LV) function (LVEF ≤30%). The participants were randomly assigned to ICD therapy or conventional therapy. The investigators demonstrated that prophylactic ICD implantation resulted in a lower rate of death from any cause compared with conventional therapy alone (14.2% vs. 19.8% for 20 months, respectively). The risk of mortality was reduced by as much as 31% with ICD implantation. Of note, an electrophysiological study was not required for enrolment in MADIT-II. These findings suggest that ICD is a potential prophylactic therapy for OMI patients with reduced LV function regardless of evidence of fatal arrhythmia. SCD-HeFT also evaluated the effect of ICD implantation or amiodarone on the mortality of patients with heart failure of ischemic or non-ischemic cause and LVEF ≤35%, in comparison with placebo. The investigators demonstrated that ICD implantation resulted in a lower mortality compared with placebo and prescribed use of amiodarone; ICD implantation caused a decline in mortality of up to 23%. These core trials and other independent trials illustrate the clinical benefit of ICD implantation for patients with OMI and LVD, and the results of these trials have influenced guidelines for prevention and treatment of severe systolic heart failure.^5,6

However, despite strong evidence, ICD is still underused in the real-world clinical settings in Japan. One of the major reasons for this is the difficulty in estimating the “risk-benefit” of ICD implantation because it imposes a financial, emotional, and sometimes physical burden on the patient. In the current study, the authors demonstrated the mortality of a Japanese population who meet the criteria of the ICD group of MADIT-II. It provides a means of evaluating the risks and benefits of ICD implantation in the Japanese population.

Additionally, it is noteworthy that the mortality rate of Japanese OMI patients with reduced LV function tends to be lower than in comparable Western populations (Table). Although the study size was small, in a similar patient population, Tanno et al reported mortality of 5.4%.⁸ However, administration of life-saving drugs, such as angiotensin-converting enzyme inhibitors, β-blockers, statins, and amiodarone, was significantly underperformed (44% vs. 68%, 32% vs. 70%, 39% vs. 67%, 1% vs. 13%, respectively), whereas percutaneous coronary intervention (PCI) was significantly more performed (66% vs. 45%, respectively) in the present study compared with the MADIT-II ICD group. It is to be noted that we cannot simply compare the data from different studies. However, these findings highlight the existence of possible differences in the effect of medication as well as ICD implantation among ethnicities or races, which encourages us to obtain pertinent clinical information in Japan.

Table. Representative Studies Evaluating the All-Cause Mortality of Patients With CAD and Left Ventricular Dysfunction

Authors	Trial name	Enrolment period	No. of enrolled patients	Patients’ backgrounds	Annual rate of all-cause death
Buxton et al7	MUSTT	1990–1996	2,202	CAD+EF ≤40%+NSVT	9.6% (no arrhythmic therapy), 8.4% (arrhythmic therapy)
Kuga et al3	JCAD	2000–2001	291	OMI+EF ≤30%	7.2%
Tanno et al8	Tanno	1997–2001	90	OMI+EF ≤30%	5.4%
Bardy et al2	SCD-HeFT	1997–2001	2,521	Ischemic CHF+EF ≤35%	7.2% (ICD), 8.6% (placebo), 8.3% (amiodarone)
Solomon et al9	VALIANT	1998–2001	14,609	OMI+EF ≤40% and/or CHF	14.8%
Moss et al1	MADIT II	1997–2002	1,232	OMI+EF ≤30%	8.5% (ICD), 11.9% (conventional therapy)
Hohnloser et al10	DINAMIT	1998–2003	676	Recent MI+EF ≤35%	7.9% (ICD), 6.5% (control)
Ottervanger et al11	Zwolle	1994–2004	2,544	OMI+EF ≤30%	5.8%
Moss et al12	MADIT-CRT	2004–2008	1,820	Ischemic cardiomyopathy+EF ≤30%	3.6% (ICD), 3.7% (CRT-D)

CAD, coronary artery disease; CHF, congestive heart failure; CRT-D, cardiac resynchronization therapy with defibrillator; EF, ejection fraction; ICD, implantable cardiac defibrillator; MI, myocardial infarction; NSVT, non-sustained ventricular tachycardia; OMI, old myocardial infarction.

There are many issues that need to be investigated. Table demonstrates that the mortality rate of the indicated patient groups declines in later studies, which is strongly believed to be a consequence of improvement in pharmacological therapy and advanced revascularization strategies, largely supported by enhancements in the development of PCI devices and antiplatelet agents. Therefore, the actual mortality of Japanese patients today may be lower than that shown in the present study. Moreover, recent studies have pointed out that the benefits of ICD implantation may be less in the elderly¹³ and women.^14,15 Thus, the overall advantages of ICD implantation should be carefully determined by further study reflecting all the updated findings and current treatment strategies.

References

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