Impact of coronary stenting on top of medical therapy and of inclusion of periprocedural infarctions on hard composite endpoints in patients with chronic coronary syndromes: a meta-analysis of randomized controlled trials.

INTRODUCTION: Composite endpoints are pivotal when assessing rare outcomes over relatively short follow-ups. Most randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with stent implantation to optimal medical therapy (OMT) in chronic coronary syndromes (CCS) patients included both hard and soft outcomes in their primary endpoint, with periprocedural myocardial infarctions (MIs) systematically allocated to the PCI arm. We meta-analyzed the above RCTs for composite hard endpoints, with and without periprocedural MIs. EVIDENCE ACQUISITION: This study is registered in PROSPERO CRD42020166754 and follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Cochrane Collaboration reporting. Patients had inducible ischemia, no left main disease nor severe left ventricular dysfunction. EVIDENCE SYNTHESIS: Six RCTs involving 10,751 patients followed for a mean of 4.4 years were included. PCI+OMT versus OMT alone was associated with no difference in the two co-primary composite endpoints of all-cause death/MI/stroke and cardiovascular death/MI including all-MIs (IRR 0.99; 95% CI 0.90-1.08 and IRR 0.95; 95% CI 0.83-1.08 respectively). After inclusion of spontaneous rather than all-MIs (i.e., excluding periprocedural MIs), the odds showed benefit of PCI+OMT for both co-primary endpoints (IRR 0.88; 95% CI 0.80-0.97, P<0.01 and IRR 0.81; 95% CI 0.69-0.95, P=0.01 respectively) with numbers needed to treat of 42 in both cases. CONCLUSIONS: Among CCS patients with inducible myocardial ischemia without severely reduced ejection fraction or left main disease, adding PCI to OMT reduces hard composite outcomes only after exclusion of periprocedural MIs. Continued efforts to define periprocedural MIs reproducibly, to assess their prognostic relevance and to prevent them are warranted.