Impact of Outcome Measure and Duration of Follow-up on the Reliability of Clinical Trials Assessing the Efficacy and Safety of Coronary Artery Stents

Abstract

Aim: Advances in coronary stent design have reduced rates of coronary restenosis and the need for further revascularisation. However, compared with second-generation(2ndGen) drug-eluting stents(DES), first-generation(1stGen) DES and bioresorbable coronary scaffolds(BVS) have an increased risk of stent thrombosis which may not be adequately assessed in individual studies. A meta-analysis was undertaken to evaluate the best choice of endpoint and follow-up duration to detect any increased risk of stent or scaffold thrombosis(ST). Methods: Medline, Embase and Central were searched for randomised coronary stent trials involving ≥100 patients and reporting clinical outcomes for ≥12months. Meta-analyses compared 1stGenDES with bare metal stents(BMS), 2ndGenDES with BMS, 2ndGenDES with 1stGenDES, 2ndGenDES with BVS. Landmark analysis evaluated clinical outcomes ≤1 year and >1 year. Results: 75 trials were analysed involving 78,491 patients. Compared with BMS, 1stGenDES decreased revascularisation[OR0.36(95%CI 0.25,0.53)] and myocardial infarction(MI)[OR0.65(95%CI 0.52,0.82)] ≤1 year, but increased ST[OR1.66(95%CI 1.21,2.29)] and MI[OR1.41(95%CI 1.07,1.87)] >1 year. 2ndGenDES vs BMS decreased revascularisation[OR0.51(95%CI 0.44,0.58)], MI[OR0.70(95%CI 0.58,0.85)], and ST[OR0.48(95%CI 0.31,0.72)], at ≤1 year with little impact on other and later end-points. Compared with 1stGenDES and BVS, 2ndGenDES reduced ST and MI at >1 year. Coronary revascularisation, and composite endpoints including death and revascularisation, did not reliably identify ST-related risk. Conclusion: Revascularisation rates ≤12 months can evaluate the efficacy of stents on reducing restenosis. Long-term safety can only be assessed in large study populations followed for several years, with the best endpoint a combination of MI and ST. A two-phased approach is required to evaluate the next generation of coronary stents and scaffolds.