Prognosis of Myocardial Infarction With Left Ventricular Dysfunction in the Coronary Revascularization Era

– Subanalysis of the Japanese Coronary Artery Disease (JCAD) Study –

Abstract

Background: Indications of implantable cardioverter-defibrillator (ICD) for patients with an old myocardial infarction (OMI) and left ventricular dysfunction (LVD) were expanded in Western countries after the results of MADIT II. However, the prognosis of OMI patients with LVD and the merits of prophylactic implantation of ICD, based on evidence in Japan, have not yet been clarified. This subanalysis of the Japanese Coronary Artery Disease (JCAD) Study focused on MADIT II-compatible patients to clarify the prognosis of OMI patients with LVD in Japan.

Methods and Results: Consecutive 6,868 OMI patients were prospectively followed up for 3 years or until clinical events occurred. 291 patients had left ventricular ejection fraction (LVEF) ≤30%. Clinical events, congestive heart failure, cardiopulmonary arrest on arrival and vascular events were significantly more frequent in patients with LVEF ≤30% than in those with better LVEF. In the LVEF ≤30% group, cardiopulmonary arrest on arrival comprised 33% of all-cause deaths, and the survival curves at 2 years of the LVEF ≤30% group were almost compatible with those of the MADIT II ICD group.

Conclusions: In this subanalysis, LVD was less frequent than in Western countries. The annual death rate in JCAD was better than for the MADIT II ICD group. The prophylactic use of ICD seemed to be less effective than in Western countries but still expected to be useful for OMI patients with LVD in Japan. (Circ J 2014; 78: 2483–2491)

In Japan, the annual morbidity from myocardial infarction (MI) is approximately 80,000 and sudden cardiac death (SCD) accounts for approximately 50,000 in MI.^1,2 The mortality rate of patients with an old MI (OMI) with heart failure is 6.9–19%.^3–6 Many observational and interventional studies of OMI patients with left ventricular (LV) dysfunction have been performed in Western countries, revealing that the most significant prognostic factor for patients with OMI is LV dysfunction. The MADIT II study also revealed that prophylactic use of an implantable cardioverter-defibrillator (ICD) reduced all-cause death among OMI patients with advanced LV dysfunction.³ Accordingly, the indications for ICD implantation in patients with OMI and LV dysfunction were expanded and determined as class IIa in 2002⁷ and 2006,⁸ and subsequently updated in 2008 to a class I indication in the United States and Europe.⁹ In Japan, despite the limited clinical evidence concerning the prognosis of patients with OMI and LV dysfunction, the guidelines for the prophylactic use of ICDs for such patients (LV ejection fraction [LVEF] ≤30%) still class the indication as IIb,¹⁰ but this was extrapolated from the results of studies and guidelines published in the United States and Europe.

Editorial p 2384

Interventions in the early phase of MI improve the prognosis of OMI, and currently most patients with acute MI undergo primary angioplasty. However, even in this primary angioplasty era, LV function remains an important factor in the prognosis of OMI.¹¹

The Japanese Coronary Artery Disease (JCAD) study is a nationwide, large-scale, multicenter, prospective cohort study. In the present subanalysis, OMI patients with LV dysfunction, compatible with the MADIT II study, were selectively analyzed to clarify their clinical characteristics, risk factors, and prognosis, as well as to elucidate the indications for prophylactic ICD placement in such patients in Japan.

Methods

Protocol of the Trial

The protocol and major outcomes of the JCAD study have been previously published.^12–14 Of the 15,628 recruited individuals, 13,812 satisfied the criteria for eligibility and were followed up at 6-month intervals.

Data Registration and Follow-up Studies

All follow-up data were registered electronically over the Web, the details of which have been previously described.^12–14 LVEF was assessed by contrast ventriculography, radionuclide ventriculography, or echocardiography performed before hospital discharge. For those patients who underwent acute coronary interventions and in whom LVEF was measured before and after the intervention, the measurements of LVEF after the interventions were used. Registered patients were followed up for 3 years or until clinical events occurred. Clinical events included all-cause death (including cardiac, cerebral, and vascular deaths), cerebral events (including hemorrhage, infarction, and transient ischemic attack), cardiac events (fatal and nonfatal MI, unstable angina, congestive heart failure, coronary bypass graft surgery, resuscitated cardiac arrest, and cardiopulmonary arrest on arrival [CPAOA]), and vascular events.¹³ Treatments were registered in the categories of drug therapy, coronary interventional therapy, intracoronary thrombolysis or other treatments, including implantation of ICD.

Statistical Analysis

The methods used have been previously described.¹² During the observational period, none of the patients was treated with prophylactic ICD. Cumulative survival curves were determined by the Kaplan-Meier method, with a statistical comparison of cumulative mortality by the log-rank method.¹⁵ For comparison of groups, the chi-square test was used for qualitative data, and the t test was used for quantitative data.

Ethical Considerations

This study was approved by the Central Institutional Review Board of the University of Tokyo. After their attending physicians had explained the nature of the study to them, each patient provided written informed consent to participate. Patients were assigned a subject number to render their data anonymous.

Results

Patients With and Without MI

Of the 13,812 primary registered patients with coronary artery disease, 6,868 had MI and 6944 did not (Table 1). For all registered patients, the follow-up rate was 83.5%, and the mean follow-up period was 2.7 years.

Table 1. Clinical Characteristics of Patients With or Without MI

	Without MI (n=6,944)	With MI (n=6,868)	P value
Age (years)	66.0±9.3	65.0±10.2	<0.0001
Mean follow-up period (years)	2.7±0.7	2.7±0.8	0.1938
Male	5,098 (73.4)	5,528 (80.5)	<0.0001
NYHA class
I	58 (0.8)	172 (2.5)	<0.0001
II	146 (2.1)	469 (6.8)	<0.0001
III	71 (1.0)	256 (3.7)	<0.0001
IV	33 (0.5)	206 (3.0)	<0.0001
History of CHF	301 (4.5)	1,097 (16.8)	<0.0001
Low LVEF (≤30%)	64 (1.2)	291 (5.5)	<0.0001
Mean LVEF	64.9±11.6	53.8±13.8	<0.0001
Risk factors
Hyperlipidemia (%)	3,979 (57.3)	3,568 (52.0)	<0.0001
Impaired glucose tolerance (%)	2,761 (39.8)	2,809 (40.9)	0.1725
Hypertension (%)	4,291 (61.8)	3,660 (53.3)	<0.0001
Obesity (%)	2,303 (33.2)	2,139 (31.1)	0.011
Smoking habit (%)	2,441 (35.2)	2,996 (43.6)	<0.0001
Family history of CAD (%)	1,144 (16.5)	1,137 (16.6)	0.8988
1 risk factor	1,311 (18.9)	1,376 (20.0)	0.0863
>2 risk factors	3,274 (47.2)	3,051 (44.4)	0.0013
No. of risk factors	2.44±1.26	2.37±1.28	0.0027

Data are n (%) unless otherwise shown. CAD, coronary artery disease; CHF, congestive heart failure; LVEF, left ventricular ejection fraction; MI, myocardial infarction; NYHA, New York Heart Association.

In patients with OMI, male sex, incidence of congestive heart failure, and low ejection fraction, smoking habit were significantly more frequent than in those without OMI. Incidences of hyperlipidemia, hypertension, and obesity were lower, and the number of risk factors significantly smaller.

The mean LVEF with OMI was significantly lower than that in patients without OMI. Of the 10,591 patients in whom LVEF was measured, 355 had LVEF ≤30%, and of those, 291 had OMI. Of the 5,261 patients without OMI in whom LVEF was measured, 64 had LVEF ≤30% (Table 1). Of the 5,330 patients with OMI in whom LVEF was measured, 291 (5.46%) had LVEF ≤30%.

Characteristics of OMI Patients

The characteristics, laboratory findings, and treatments of OMI patients with LVEF ≤30% were compared with those of OMI patients with LVEF >30% (Table 2). Congestive heart failure and NYHA classes II, III, and IV occurred significantly more frequently in patients with LVEF ≤30% than in those with LVEF >30%.

Table 2. Clinical Characteristics of Patients With MI and EF ≤30% or >30%

	All patients (n=6,868)	EF >30% (n=5,039)	EF ≤30% (n=291)	P value (>30% vs. ≤30%)
Patients characteristics
Age (years)	65±10	64±10	65±10	0.0608
Male (%)		80	82	0.3968
Average follow-up (years)	2.7±0.8	2.7±0.7	2.5±1.0	0.0033
NYHA class (%)
I	3	2	7	<0.0001
II	7	6	25	<0.0001
III	4	3	21	<0.0001
IV	3	2	13	<0.0001
Mean LVEF (%)	54±14	56±12	25±4	<0.0001
History of CHF (%)	17	14	67	<0.0001
No. of affected arteries	1.78±0.80	1.79±0.79	2.05±0.85	<0.0001
LMT disease (%)	4	3	7	<0.0009
Underlying diseases (risk factors) (%)
Hyperlipidemia	52	53	46	0.0238
Impaired glucose tolerance	41	40	48	0.0101
Hypertension	53	54	44	0.0009
Obesity	31	32	27	0.0919
Smoking habit	44	43	45	0.5447
Family history of CAD	17	16	18	0.6443
1 risk factor	20	20	19	0.7836
>2 risk factors	44	44	42	0.4059
No. of risk factors	2.37±1.28	2.38±1.28	2.27±1.24	0.21
Laboratory findings
TC (mg/dl)	194±38	194±37	195±42	0.823
LDL-CHOL (mg/dl)	122±34	121±34	125±37	0.1252
HDL-CHOL (mg/dl)	46±15	46±14	46±17	0.4829
TG (mg/dl)	135±78	136±79	125±67	0.0328
FBS (mg/dl)	124±50	122±48	129±61	0.3924
HbA1c (%)	6.3±1.5	6.3±1.5	6.6±1.7	0.0023
SBP (mmHg)	130±21	130±20	125±21	<0.0001
DBP (mmHg)	74±13	74±13	72±14	0.0184
UA (mg/dl)	5.9±1.8	5.8±1.6	6.3±1.8	0.0019
CRP (mg/dl)	0.7±2.2	0.6±2.0	1.4±3.9	<0.0001
BMI (kg/m2)	23.7±3.2	23.8±3.1	23.0±3.4	<0.0001
Treatments
Coronary angioplasty (%)	66	63	55	0.0034
POBA	14	13	11	0.3102
Stenting	42	41	30	0.0003
Rotablator	2	2	1	0.627
DCA	1	1	1	0.151
CABG	5	5	11	0.0001
Medication at discharge (%)
Statins	39	39	35	0.1724
Fibrates	3	3	2	0.1924
Diuretics	22	20	69	<0.0001
CCB	44	45	24	<0.0001
ACEI	44	44	53	0.0025
ARB	16	16	18	0.268
β-blocker	32	31	44	<0.0001
Antithrombotic	89	94	94	0.9185
Warfarin	13	12	33	<0.0001
Nitrates	64	64	62	0.38
Class I antiarrhythmic drug	6	6	11	0.0003
Amiodarone	1	1	5	0.000004952
Digitalis	7	6	22	<0.0001
Insulin	3	3	6	0.0008
Antidiabetic drugs	26	27	37	0.5251

ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; BMI, body mass index; CABG, coronary artery bypass graft; CCB, calcium-channel blocker; CHOL, cholesterol; CRP, C-reactive protein; DBP, diastolic blood pressure; DCA, directional coronary atherectomy; EF, ejection fraction; FBS, fasting blood glucose; HDL, high-density lipoprotein; LDL, low-density lipoprotein; POBA, plain old balloon angioplasty; SBP, systolic blood pressure; TC, total cholesterol; TG, triglycerides; UA, uric acid. Other abbreviations as in Table 1.

As for risk factors, impaired glucose tolerance was significantly more frequent, and hyperlipidemia and hypertension were significantly less frequent in patients with LVEF ≤30% than in patients with LVEF >30%. There were no significant differences between the 2 groups for 1 or more than 2 risk factors or for the number of risk factors.

As for laboratory data, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and fasting blood glucose levels did not differ significantly between the 2 groups. However, triglycerides, systolic blood pressure, diastolic blood pressure, and body mass index were significantly lower, and HbA1c, uric acid and C-reactive protein levels were significantly higher in patients with LVEF ≤30% than in patients with LVEF >30%.

As for treatments, no patient had secondary ICD implantation. Coronary angioplasty and stenting were performed significantly less in patients with LVEF ≤30% than in patients with LVEF >30%. Coronary artery bypass graft, diuretics, angiotensin-converting enzyme inhibitors (ACEI), β-blockers, digitalis, warfarin, class I antiarrhythmic drugs, and amiodarone were prescribed significantly more frequently for patients with LVEF ≤30% than for patients with LVEF >30%. Angiotensin-receptor blockers (ARB) were used in only 16% of all patients with OMI.

Incidence of Clinical Events

The incidences of clinical events are expressed as percentages per year (Table 3). Composite endpoints were significantly more frequent in patients with LVEF ≤30% than in patients with LVEF >30%.

Table 3. Incidence of Clinical Events in Patients With MI and EF ≤30% or >30%

	Incidence in patients with MI (n=6,868)	Incidence in patients with EF >30% (n=5,039)	Incidence in patients with EF ≤30% (n=291)	P value (EF >30% vs. EF ≤30%)
Composite endpoints	1,077 (5.85)	742 (5.42)	88 (12.34)	0.0018
All-cause death	371 (2.02)	233 (1.70)	51 (7.15)	<0.0001
Cardiac death	176 (0.96)	99 (0.72)	36 (5.05)	0.0004
Cerebral death	17 (0.09)	11 (0.08)	2 (0.28)	0.0853
Vascular death	7 (0.04)	5 (0.04)	1 (0.14)	0.1833
Other causes of death	171 (0.93)	118 (0.86)	12 (1.68)	0.0432
Cardiac events	813 (4.42)	556 (4.06)	72 (10.10)	0.0082
Acute MI	171 (0.93)	114 (0.83)	10 (1.40)	0.4936
Unstable angina pectoris	323 (1.75)	238 (1.74)	11 (1.54)	0.329
Resuscitated cardiac arrest	10 (0.05)	7 (0.05)	1 (0.14)	0.659
Congestive heart failure	266 (1.45)	177 (1.29)	37 (5.19)	0.019
Bypass graft surgery	64 (0.35)	47 (0.34)	4 (0.56)	0.9554
CPAOA	61 (0.33)	33 (0.24)	17 (2.38)	0.0002
Cerebral events	112 (0.61)	78 (0.57)	5 (0.70)	0.5837
Stroke	94 (0.51)	64 (0.47)	5 (0.70)	0.4041
Transient ischemic attack	18 (0.10)	14 (0.10)	0 (0.00)	0.9975
Vascular events	11 (0.06)	6 (0.04)	2 (0.28)	0.0185
Aortic aneurysm rupture	7 (0.04)	4 (0.03)	1 (0.14)	0.1048
Aortic dissection	4 (0.02)	2 (0.01)	1 (0.14)	0.9998

The incidence of each clinical event is expressed as the number of events, and the percentages per year are expressed in parentheses. CPAOA, cardiopulmonary arrest on arrival. Other abbreviations as in Tables 1,2.

As for mortality, all-cause death, cardiac death, and other causes of death were significantly more frequent in patients with LVEF ≤30% than in patients with LVEF >30%. Cerebral and vascular death did not differ significantly between the 2 groups.

As for clinical events, cardiac events, congestive heart failure, CPAOA, and vascular events were significantly more frequent in patients with LVEF ≤30% than in patients with LVEF >30%. In contrast, acute MI, unstable angina, resuscitated arrest, bypass graft surgery, and cerebral events did not differ significantly between the 2 groups. In patients with LVEF ≤30%, CPAOA occurred in 17 patients and all-cause of death occurred in 51 patients. CPAOA comprised 33% of all-cause deaths.

Survival Curves

The Kaplan-Meier cumulative survival curves for the JCAD LV dysfunction group and the MADIT II ICD group were comparable until 1.5 years, but thereafter progressively separated (Figure).

Figure.

Kaplan-Meier estimates of the probability of survival in the JCAD study and the MADIT II study. The survival curves for the JCAD LV dysfunction group and the MADIT II ICD group were comparable until 1.5 years, but thereafter progressively separated. The survival curves of the JCAD LVEF ≤30% group were almost compatible with those of the MADIT II ICD group and markedly better than those of the MADIT II conventional-therapy group at 2 years. Thereafter, survival of the JCAD LVEF ≤30% group was slightly better than that of the MADIT II ICD group and significantly better than the MADIT II conventional-therapy group up to 3 years. LVEF, left ventricular ejection fraction.

The survival curves of the JCAD LVEF ≤30% group were almost compatible with those of the MADIT II ICD group and markedly better than those of the MADIT II conventional-therapy group at 2 years. Thereafter, survival of the JCAD LVEF ≤30% group was slightly better than that of the MADIT II ICD group and significantly better than the MADIT II conventional-therapy group up to 3 years.

Comparison of Survivors and Nonsurvivors

The baseline characteristics, laboratory findings, and treatments of OMI patients with LVEF ≤30% who died and of those who survived are shown in Table 4. Older age, higher NYHA class, left main trunk disease, and impaired glucose tolerance were significantly more frequent in the nonsurvivor group than in the survivor group, whereas LVEF did not differ significantly between the 2 groups. Fasting blood glucose was significantly higher and diastolic blood pressure significantly lower in the nonsurvivor group, but body mass index did not differ between the 2 groups. Other than the usage of nitrates and antidiabetic drugs, treatments did not differ significantly between the 2 groups.

Table 4. Clinical Characteristics of Survivors and Nonsurvivors Among Patients With Old MI

	EF ≤30% (n=291)	Survivor (n=240)	Nonsurvivor (n=51)	P value (Survivor vs. Nonsurvivor)
Patients characteristics
Age (years)	66±10	65±10	69±9	0.0151
Male (%)	82	83	76	0.2453
Average follow-up (months)	2.5±1.0	2.7±0.8	1.2±1.0	<0.0001
NYHA class (%)
I	7	7	4	0.5437
II	25	26	22	0.4794
III	21	21	20	0.8435
IV	13	10	27	0.0008
LVEF (%)	25±4	25±4	25±4	0.8306
History of CHF (%)	67	66	73	0.344
No. of affected arteries	2.1±0.9	2.0±0.8	2.4±0.8	0.0019
LMT disease (%)	7	5	16	0.0168
Underlying diseases (risk factors) (%)
Hyperlipidemia	46	46	43	0.6853
Impaired glucose tolerance (%)	48	45	61	0.0461
Hypertension (%)	44	45	39	0.4498
Obesity (%)	27	28	22	0.3526
Smoking habit (%)	45	46	39	0.388
Family history of CAD (%)	18	19	12	0.2334
1 risk factor	19	18	27	0.1016
>2 risk factors	42	42	41	0.9051
No. of risk factors	2.27±1.24	2.29±1.24	2.16±1.29	0.4275
Laboratory findings
TC (mg/dl)	195±42	194±43	196±35	0.3865
LDL-CHOL (mg/dl)	125±37	125±38	124±31	0.593
HDL-CHOL (mg/dl)	46±17	45±17	47±14	0.1814
TG (mg/dl)	125±67	125±64	124±82	0.4797
FBS (mg/dl)	129±61	122±48	167±97	0.0007
HbA1c (%)	6.6±1.7	6.6±1.7	6.9±1.5	0.1495
SBP (mmHg)	125±21	125±21	122±18	0.1804
DBP (mmHg)	72±14	73±14	68±12	0.0238
UA (mg/dl)	6.3±1.8	6.3±1.8	6.3±1.7	0.7648
CRP (mg/dl)	1.36±3.49	1.36±3.94	1.67±3.74	0.3783
BMI (kg/m2)	23.0±3.4	23.1±3.4	22.4±3.6	0.2048
Treatments
Coronary angioplasty (%)	55	55	53	0.7885
POBA	11	10	14	0.4335
Stenting	30	30	29	0.8872
Rotablator	1	1	0	1
DCA	1	2	0	1
CABG	11	11	10	0.8287
Medication at discharge (%)
Statins	35	37	22	0.066
Fibrates	2	2	0	1
CCB	69	69	73	0.5919
Diuretics	24	25	19	0.4388
ACEI	53	53	57	0.643
ARB	18	19	11	0.2063
β-blocker	44	44	43	0.9491
Antithrombotic	94	94	95	1
Warfarin	33	33	35	0.7744
Nitrates	62	59	78	0.0236
Class I antiarrhythmic drug	11	11	14	0.5874
Amiodarone	5	4	5	0.6791
Digitalis	22	21	32	0.1157
Insulin	6	7	5	1
Antithrombotic	18	16	30	0.0422

Abbreviations as in Tables 1,2.

Discussion

OMI With LV Dysfunction

MADIT II has brought about great advances in the prophylactic use of ICD and significantly influenced several guidelines on the indications of ICDs for patients with ischemic heart failure. In the AHA/ACC and ESC guidelines, prophylactic implantation of ICD for OMI patients with LV dysfunction was considered a class IIa indication^7,8 and subsequently updated to class I indication.⁹

In Japan, only a limited number of reports on the prognosis of OMI with LV dysfunction have been published,^16,17 and a nationwide, prospective, multicenter trial has been lacking. Because of the lack of clinical evidence, prophylactic use of ICD is still considered a class IIb indication.¹⁰ It was under these circumstances that the JCAD study, a nationwide, prospective, large-scale, multicenter cohort study, was conducted.

Angioplasty and LV Function in Patients With OMI

In the JCAD subanalysis, 5.46% patients with OMI had LVEF ≤30%. Other studies in Japan^16–19 also revealed fewer OMI patients with LVEF ≤30% than in Western countries.^20–22 The mean LVEF of patients with OMI was better preserved in Japan^17–19,23 than in Western countries.^4,24–26 In this JCAD subanalysis, angioplasty was performed in the acute phase of MI in 55% of patients. Other studies in Japan also reveal a higher rate of acute angioplasty^16,17,19,23 than in Western countries.^3,4,21 As Ohno et al described, patients who undergo acute revascularization show better long-term survival than those who do not.²³ Therefore, one explanation for the preserved LV function and better prognosis of patients in Japan seems to be that more patients undergo acute revascularization. This beneficial effect of acute revascularization on LV function was also observed in patients with MI and LV dysfunction (LVEF ≤30%).²⁷

Prognosis of OMI With LV Dysfunction

In this JCAD subanalysis, the annual rate of all-cause death was 7.15% and that of cardiac death was 5.05%. Tanno et al reported that all-cause death occurred in 16.67% of patients during a follow-up period of 37 months.¹⁶ In the OASIS study, all-cause death occurred in 14.5% of patients after 849 days of follow-up.¹⁹ In contrast, in studies from Western countries, although the inclusion and exclusion criteria varied, the annual rate of all-cause death was estimated as 8.52% in the ICD group and 11.88% in the conventional-therapy group in MADIT II,³ 6.9% in the control group and 7.5% in the ICD group in the DINAMIT trial,⁴ 19% in the pharmacologic therapy group in the COMPANION trial,⁵ 9% in the ICD for ischemic heart failure group in the SCD-HeFT study⁶ and 5.8% in the without-prophylactic-ICD group in the Zwolle study.²⁰ Thus, the prognosis for OMI patients with LV dysfunction given conventional therapy in Japan was better than that for the conventional-therapy groups and almost similar to that of the ICD groups of Western countries. Furthermore, the prognosis of OMI patients with preserved LV function was favorable, as shown in Figure, in Japan.

Prognosis of OMI Patients With and Without ICD

The survival curves of the JCAD subanalysis were almost compatible with those of the MADIT II ICD group and better than those of the MADIT II conventional-therapy group at 2 years (survival rates: 85%, 84%, and 78%, respectively).³ Thereafter, survival of the JCAD group was slightly better than that of the MADIT II ICD group and significantly better than that of the MADIT II conventional-therapy group up to 3 years. In the JCAD subanalysis, no patients received an ICD. Thus, the prognosis of the conventionally treated patients of the JCAD study was almost similar to that of the ICD-treated patients of MADIT II. The Kaplan-Meier cumulative survival curves for the JCAD subanalysis and the MADIT II ICD group were comparable until 1.5 years, but thereafter progressively separated. The reasons for this lack of early separation and the subsequent separation were not determined.

SCD in Patients With OMI and LV Dysfunction

SCD (ie, CPAOA) occurred in approximately 2.38% of patients in this JCAD substudy, in 2.9% of patients at 1 year and in 5.1% of patients at 3 years in the HIJAMI-II study,¹⁷ in 1.2% of patients during 849 days of follow-up in the OASIS study¹⁹ and in 2.2% of patients at 3 years in Tanno et al’s report.¹⁶ In Western countries, the annual rates of SCD were approximately 6% in the conventional-therapy group and 3% in the ICD group in MADIT II,²⁸ 15.5% at 3 years in the TRACE study²² and as high as 8% at 1 year in the VALIANT trial.²¹ The proportion of SCD among the total deaths comprised 51% of patients in the conventional-therapy group and 27% of patients in the ICD group in MADIT II,²⁸ 40% of patients in the Zwolle study²⁰ and 51% of patients in the DINAMIT study.⁴ The proportion of SCD (CPAOA) among the total deaths was 33% in this JCAD study, 13.3% in Tanno et al’s study¹⁶ and 12.1% in the HIJAMI-II study.¹⁷ From these studies, the annual rate of SCD, as well as the proportion of SCD among all causes of death in OMI patients with LV dysfunction, was smaller in Japan than in Western countries, but possibilities to rescue considerably more OMI patients with LV dysfunction by implanting an ICD still exist in Japan.

Drug Treatments

Many studies have indicated that “life-saving drugs” such as statins, β-blockers, ACEIs/ARBs, and amiodarone reduce the incidence of cardiac death among heart failure patients. Such drugs have also improved the prognosis in Japan.²⁹ In OMI patients with LV dysfunction, the proportion of patients given statins was 35% in the JCAD study and 27.1% in the HIJAMI study,¹⁷ which is significantly less than in Western studies.^3,6,20,30,31 The percentages of patients given ACEIs/ARBs were 71% in this study and 41.7/19.1% in the HIJAMI-II study,¹⁷ again significantly less than in Western countries.^3,5,6,20,31 The proportion of patients given β-blockers was 44% in the JCAD study, and 39.7% in the HIJAMI-II study,¹⁷ which is also significantly less than in Western countries.^3,5,6,20,31 In the Japanese guideline, β-blocker therapy is considered a class IIa indication for secondary prevention of OMI in low-risk patients.³² The proportion of patients given amiodarone was 5% in the JCAD study and 10–13% in MADIT II.³ Thus, although the use of “life-saving drugs” was significantly lower in the JCAD study, the prognosis of patients in Japan was better than that of patients in Western countries.

Study Limitations

Springeling et al³³ showed the time course of improvement of LVEF following PCI for acute MI. LVEF improved within the first 4 months, and thereafter became stable. In the present study, LVEF was measured before hospital discharge, which for most patients as within 4 months after PCI, and earlier than in MADIT II.³ Apprehension of underestimation of LVEF in the JCAD study still exists.

This study was a retrospective, observational subanalysis of the JCAD study, whereas MADIT II was a randomized controlled study, divided into a conventional therapy group and prophylactic ICD group. To certificate the merit of prophylactic ICD use in Japanese OMI patients with LV dysfunction, a similar study to MADIT II is required.

Conclusions

In the JCAD study, as in other studies in Japan, the LV function of patients with OMI was well preserved and fewer OMI patients had LV dysfunction than in Western countries. The annual rate of all-cause death in the JCAD study, as well as the annual rate of SCD, was almost the same as in other studies in Japan and better than those of studies from Western countries. The survival curves of MADIT II-compatible Japanese patients without ICD were almost the same as those of the MADIT II ICD group. Furthermore, prognosis of OMI patients with preserved LV function was favorable in Japan. One probable reason for the better prognosis for patients in Japan seems to be more frequent implementation of acute revascularization in Japan. The proportion of SCD among all causes of death was also less than in Western countries. Prophylactic use of ICD may be less effective but still useful for limited numbers of OMI patients with LV dysfunction in Japan. Therefore, the recent upgrade in the indications for prophylactic placement of ICD from IIb¹⁰ to IIa³⁴ in 2011 is reasonable.

Acknowledgments

We thank Mrs Flaminia Miyamasu for her advice in the preparation of the manuscript.

Disclosures

Dr Ryozo Nagai from the Japan Heart Foundation (No. 125003) from April 2000 to March 2004. All other authors report no conflicts of interest.

Supplementary Files

Supplementary File 1

Figure S1. Histogram of left ventricular ejection fraction (LVEF).

Figure S2. Kaplan-Meier curves according to strata of ejection fraction (EF).

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-14-0301

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