Coronary intervention for persistent occlusion after myocardial infarction

Abstract

Background: It is unclear whether stable, high-risk patients with persistent total occlusion of the infarct-related coronary artery identified after the currently accepted period for myocardial salvage has passed should undergo percutaneous coronary intervention (PCI) in addition to receiving optimal medical therapy to reduce the risk of subsequent events.

Methods: We conducted a randomized study involving 2166 stable patients who had total occlusion of the infarct-related artery 3 to 28 days after myocardial infarction and who met a high-risk criterion (an ejection fraction of <50% or proximal occlusion). Of these patients, 1082 were assigned to routine PCI and stenting with optimal medical therapy, and 1084 were assigned to optimal medical therapy alone. The primary end point was a composite of death, myocardial reinfarction, or New York Heart Association (NYHA) class IV heart failure.

Results: The 4-year cumulative primary event rate was 17.2% in the PCI group and 15.6% in the medical therapy group (hazard ratio for death, reinfarction, or heart failure in the PCI group as compared with the medical therapy group, 1.16; 95% confidence interval [CI], 0.92 to 1.45; P=0.20). Rates of myocardial reinfarction (fatal and nonfatal) were 7.0% and 5.3% in the two groups, respectively (hazard ratio, 1.36; 95% CI, 0.92 to 2.00; P=0.13). Rates of nonfatal reinfarction were 6.9% and 5.0%, respectively (hazard ratio, 1.44; 95% CI, 0.96 to 2.16; P=0.08); only six reinfarctions (0.6%) were related to assigned PCI procedures. Rates of NYHA class IV heart failure (4.4% vs. 4.5%) and death (9.1% vs. 9.4%) were similar. There was no interaction between treatment effect and any subgroup variable (age, sex, race or ethnic group, infarct-related artery, ejection fraction, diabetes, Killip class, and the time from myocardial infarction to randomization).

Conclusions: PCI did not reduce the occurrence of death, reinfarction, or heart failure, and there was a trend toward excess reinfarction during 4 years of follow-up in stable patients with occlusion of the infarct-related artery 3 to 28 days after myocardial infarction. (ClinicalTrials.gov number, NCT00004562 [ClinicalTrials.gov].).

Figure 1. Kaplan-Meier Curves for the Primary End Point, According to the Intention-to-Treat Analysis

The primary end point was the first centrally adjudicated occurrence of death from any cause, nonfatal reinfarction, or NYHA class IV heart failure requiring hospitalization or a stay in a short-stay unit. Kaplan-Meier estimates of the cumulative event rates in the PCI group and the medical therapy group, respectively, were 14.8% and 13.1% at 3 years, 17.2% and 15.6% at 4 years, and 21.2% and 16.4% at 5 years. The cumulative yearly adjusted hazard ratios for PCI versus medical therapy for years 1 through 5 were 1.13, 1.18, 1.14, 1.13, and 1.16, respectively. The P value was calculated with the use of the log-rank test.

Figure 2. Kaplan-Meier Curves for the Secondary End Points, According to the Intention-to-Treat Analysis

The secondary end points were the first adjudicated occurrences of the components of the primary end point (death from any cause, nonfatal reinfarction, or NYHA class IV heart failure requiring hospitalization or a stay in a short-stay unit). In Panel A, the estimated cumulative event rates for death from all causes in the PCI group and the medical therapy group, respectively, were 7.6% and 7.3% at 3 years, 9.1% and 9.4% at 4 years, and 13.4% and 12.1% at 5 years. In Panel B, the estimated cumulative event rates for fatal and nonfatal reinfarction in the two groups, respectively, were 5.9% and 4.3% at 3 years, 7.0% and 5.3% at 4 years, and 7.4% and 5.3% at 5 years. In Panel C, the estimated cumulative event rates for nonfatal reinfarction in the two groups, respectively, were 5.7% and 3.9% at 3 years, 6.9% and 5.0% at 4 years, and 7.2% and 5.0% at 5 years. In Panel D, the estimated cumulative event rates for NYHA class IV heart failure requiring hospitalization or admission for a stay in a short-stay unit in the two groups, respectively, were 4.2% and 4.5% at 3 years, 4.4% and 4.5% at 4 years, and 4.9% and 4.5% at 5 years. The P values for the estimated cumulative event curves at 5 years were calculated with the use of the log-rank test. The 4-year cumulative event rate for the adjudicated primary outcome in the PCI group was 16.8 for 937 patients in whom PCI was successful, 16.8 for 134 patients in whom PCI failed, and 48.6 for 11 patients who did not undergo PCI. The 4-year cumulative event rate for the adjudicated primary outcome in the medical therapy group was 18.8 for the 27 patients who crossed over to PCI within 30 days after randomization and 15.6 for the 1057 patients who did not cross over to PCI within 30 days after randomization.

Figure 3. Subgroup Analysis

Hazard ratios (black squares), 95% CIs (horizontal lines), P values for the interaction between the treatment effect and any subgroup variable, and cumulative estimated 4-year event rates for the primary outcome (death from any cause, nonfatal reinfarction, or NYHA class IV heart failure requiring hospitalization or a stay in a short-stay unit) for PCI versus medical therapy for the specified subgroups are shown. Age, sex, race or ethnic group, the location of the infarct-related artery, the ejection fraction, and the time from the index myocardial infarction (MI) to randomization were prespecified. Race was self-reported. Diabetes and the highest Killip class during the index MI were not prespecified for the subgroup analysis. Originally, the cutoff point for age was 70 years, but early during the trial monitoring and before any analyses were performed, it was changed to 65 years because of insufficient numbers of patients older than 70. There was no significant interaction between treatment and subgroup variable as defined according to the prespecified value for interaction (P<0.01). The use of a cutoff of 40% rather than the prespecified 50% for the ejection fraction did not alter the results. There was no interaction for the presence or absence of ST-segment elevation, Q-wave loss, or R-wave loss. LAD denotes left anterior descending artery.