bstract
BACKGROUND
Whether revascularization by percutaneous coronary intervention (PCI) can improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as compared with optimal medical therapy (i.e., individually adjusted pharmacologic and device therapy for heart failure) alone, is unknown.
METHODS
We randomly assigned patients with a left ventricular ejection fraction of 35% or less, extensive coronary artery disease amenable to PCI, and demonstrable myocardial viability to a strategy of either PCI plus optimal medical therapy (PCI group) or optimal medical therapy alone (optimal-medical-therapy group). The primary composite outcome was death from any cause or hospitalization for heart failure. Major secondary outcomes were left ventricular ejection fraction at 6 and 12 months and quality-of-life scores.
RESULTS
A total of 700 patients underwent randomization — 347 were assigned to the PCI group and 353 to the optimal-medical-therapy group. Over a median of 41 months, a primary-outcome event occurred in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the optimal-medical-therapy group (hazard ratio, 0.99; 95% confidence interval [CI], 0.78 to 1.27; P=0.96). The left ventricular ejection fraction was similar in the two groups at 6 months (mean difference, −1.6 percentage points; 95% CI, −3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, −1.7 to 3.4). Quality-of-life scores at 6 and 12 months appeared to favor the PCI group, but the difference had diminished at 24 months.
CONCLUSIONS
Among patients with severe ischemic left ventricular systolic dysfunction who received optimal medical therapy, revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure.
Discussion
We performed a randomized comparison of the efficacy and safety of a strategy of PCI plus optimal medical therapy, as compared with strategy of optimal medical therapy alone, among patients with severe left ventricular systolic dysfunction, extensive coronary artery disease, and demonstrable viable myocardium. The incidence of death from any cause or hospitalization for heart failure (the primary outcome) did not differ significantly between the trial groups. An apparent early benefit of PCI was observed with respect to quality of life, but the between-group difference diminished over time owing to the progressive improvement in scores in the optimal-medical-therapy group. Cardiac function appeared to improve in both groups over the course of follow-up, but this change was not affected by the trial-group assignment.
With the stipulation of a minimum number of dysfunctional segments that were viable and amenable to revascularization, our trial was designed to enroll an enriched cohort of patients who were most likely to show reverse remodeling after revascularization. However, PCI failed to produce recovery of global left ventricular function that was incremental to the improvement with optimal medical therapy alone. These findings challenge the paradigm of myocardial hibernation, which is classically defined according to improvement in left ventricular volumes and function after revascularization. Our observations mirror those in the STICH trial, in which revascularization by CABG did not affect left ventricular function, a finding that was consistent across the whole trial cohort, including the subgroup who underwent discretionary viability testing.16 We have not yet determined the concordance between the coronary arteries revascularized by PCI and the viable myocardial segments; hence, we cannot determine whether viability tests predict changes in segmental contractile function after medical therapy or revascularization or whether such changes are linked to clinical outcomes.17
In our trial, the incidences of death from any cause and the composite of death or hospitalization for heart failure were similar to the annualized rates observed in the medical-therapy groups of STICH and contemporary trials involving patients with left ventricular systolic dysfunction (Fig. S9), despite enrollment of a population with a more adverse risk profile. We enrolled older patients (mean age, 70 years) with a greater burden of coronary disease and included patients with left main coronary disease, a group that has traditionally been excluded from trials of revascularization as compared with medical therapy.18,19 The percentage of patients with ICD or cardiac resynchronization devices in our trial may be one reason why the clinical outcomes were similar despite higher baseline risk, and the serial improvement in left ventricular systolic function and reduction in NT-proBNP concentrations in both groups in our trial are objective markers of effective medical and device therapy.
Although the differences in the baseline characteristics of the patients enrolled in the STICH and REVIVED trials hamper direct comparison, the beneficial effect of CABG observed in the STICH trial was not seen with PCI in our trial.3 Incomplete revascularization by PCI has historically been a confounder in comparisons between PCI and CABG among patients with stable coronary disease.20 This factor is unlikely to be a consideration in the REVIVED trial, because the median percentage of completeness of revascularization was 71% in the PCI group, as measured by a coronary anatomical index, and the percentage of functional completeness of revascularization would be even higher, given that the protocol recommended revascularization for only coronary disease subtending viable myocardium.
Our trial has some limitations. First, we cannot rule out the possibility that the open-label design affected patient-reported outcomes. Any effect on the primary outcome was mitigated by ensuring that all hospitalizations for heart failure were adjudicated in a blinded fashion by an independent events committee, and the determination of death was robust to such bias; the left ventricular ejection fraction was assessed in a blinded fashion at the core laboratory. Second, most patients had little or no angina at enrollment, so the findings cannot be extrapolated to patients with angina that limits their quality of life or patients presenting with acute coronary syndromes. Third, there were 37 fewer primary-outcome events than what we estimated for the trial to have at least 85% power to address the primary hypothesis. Although this lower number of events had some effect on the prospective statistical power (263 events would provide the trial with 82% power if the other variables in our power calculation remained constant), the hazard ratio of 0.99 and the 95% confidence intervals observed with respect to the primary outcome suggest that the risk of a type II error was low.
In our trial involving patients with severe left ventricular systolic dysfunction, extensive coronary disease, and dysfunctional but viable myocardium who received optimal medical therapy, the addition of revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure, incremental improvement in the left ventricular ejection fraction, or a sustained difference in quality of life at a median of 3.4 years.
SOURCE: NEJM
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