N Engl J Med 2019;381:1411-1421
Background Percutaneous coronary intervention (PCI) had been clearly established as the standard of care for ST elevation myocardial infarction. Yet many patients taken for PCI have multiple lesions in addition to the culprit. The benefit of routinely treating additional significant lesions has been unclear, with previous smaller trials showing reductions in composite outcomes primarily driven by reduced revascularization rates.
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The COMPLETE (Complete vs Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) trial investigated whether performing percutaneous coronary intervention (PCI) on non-culprit lesions reduces cardiovascular risk in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease.
Patients The trial enrolled 4,041 patients from 140 centers in 31 countries between February 2013 and March 2017. Eligible patients had STEMI with successful culprit-lesion PCI and at least one non-culprit coronary artery lesion with ≥70% stenosis (or 50-69% stenosis with FFR ≤0.80) in a vessel ≥2.5mm in diameter. Patients were randomized within 72 hours after successful culprit-lesion PCI. Exclusion criteria included planned surgical revascularization and previous coronary bypass surgery.
Baseline Characteristics The mean age was approximately 62 years, with about 80% being male. Approximately 19% had diabetes, 8% had previous MI, and 7% had previous PCI. Over 90% of patients underwent primary PCI (vs. pharmacoinvasive or rescue PCI), with 80% using radial access.
The groups were well-balanced, with similar SYNTAX scores at baseline and similar culprit and non-culprit lesion characteristics. About 76% had one residual diseased vessel and 24% had two or more. Guideline directed medical therapy was robust and balanced, including more than 99% on dual antiplatelet therapy, 98% on statins, 88% on beta blocker, and 85% on ACEi or ARB.
In patients in the complete revascularization group designated for non-culprit PCI during index hospitalization, the mean time to PCI was 1 day. In the group designated for non-culprit PCI after discharge, the mean time was 23 days.
Trial procedures Patients were randomized to complete revascularization (n=2,016) or culprit-lesion-only PCI (n=2,025). In the complete revascularization group, investigators specified before randomization whether non-culprit PCI would occur during index hospitalization or after discharge (within 45 days).
Everolimus-eluting stents were recommended for all procedures. Both groups received guideline-based medical therapy including dual antiplatelet therapy with aspirin and ticagrelor for at least one year.
Endpoints The first coprimary outcome was cardiovascular death or new myocardial infarction. The second coprimary outcome was cardiovascular death, myocardial infarction, or ischemia-driven revascularization. Secondary outcomes included individual components of the composite outcomes, all-cause mortality, and safety outcomes like major bleeding, stroke, and stent thrombosis.
Trialists estimated that a sample of 4000 patients would give 80% power to detect a 22% lower risk of the composite of cardiovascular death or myocardial infarction in the complete-revascularization group than in the culprit-lesion-only PCI group, assuming an event rate of 5% per year in the culprit-lesion-only PCI group. The first coprimary outcome was tested at a P value of 0.045 and the second at a P value of 0.0119.
The co-primary endpoints were analyzed according to the time to first event approach. Confidence intervals for secondary and exploratory efficacy outcomes were not adjusted for multiple comparisons, and therefore inferences drawn from these intervals may not be reproducible.
Results Over a median follow-up of 36.2 months, the first coprimary outcome occurred in 7.8% of the complete-revascularization group versus 10.5% of the culprit-lesion-only group (hazard ratio 0.74, 95% CI: 0.60-0.91; p= 0.004). Benefit was driven by reduced myocardial infarction rates (5.4% vs 7.9%) while cardiovascular death rates were similar (2.9% vs 3.2%).
The second coprimary outcome was also reduced with complete revascularization (8.9% versus 16.7%, HR: 0.51, 95% CI: 0.43-0.61; p<0.001). The benefit was consistent regardless of whether PCI was performed during index hospitalization or after discharge. There were no significant differences in major bleeding, stroke, or stent thrombosis between groups.
The Kaplan-Meier curves show that the benefit of complete revascularization seemed to have emerged over time, with continued divergence of the Kaplan–Meier curves for several years.
There was a trend toward higher contrast-induced kidney injury in the complete revascularization arm (Odds ratio: 1.59, 95% CI: 0.89 - 2.84; p= 0.11).
Conclusion Among STEMI patients with multivessel coronary artery disease, a strategy of complete revascularization was superior to culprit-lesion-only PCI in reducing the composite outcome of cardiovascular death or myocardial infarction. This benefit was driven by reduction in myocardial infarctions without significant reduction in cardiovascular death.
The benefit was consistent whether non-culprit PCI was performed during the index hospitalization or after discharge. The number needed to treat to prevent one cardiovascular death or myocardial infarction was 37 patients over 3 years.
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