Prevention Of Renin-Angiontensin System Inhibition On Coronary In-Stent Restenosis: A Meta-Analysis Of Randomized Controlled Trials

Objectives We reviewed published clinical trials about effects of renin-angiotensin system (RAS) inhibition on restenosis after coronary stent implantation, for purpose of looking for evidence of clinical practice.Background Coronary interventional procedures led to vascular intimal injury, compensating by inflammatory response which was supposed to induce restenosis. RAS inhibition has been proved to antiproliferative effect on neointimal hyperplasia so as to prevent in-stent restenosis (ISR) in animal models. However controversial results were continuing across human trials of whether RAS inhibition could prevent ISR.Methods A comprehensive search strategy was conducted to identify randomized controlled trials of coronary ISR prevention with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) treatment. We searched PubMed, Embase, Cochrane Library, Ovid, Clinical Trials and CBMdisc. Finally ten randomized controlled human studies were included. Study characteristics were extracted about study design, intervention, outcomes and study quality. We analyzed outcomes by the intention-to-treat (ITT) principle with Review Manager 5.1.0 used.Results A total of ten randomized controlled studies involving 1216 patients were analyzed. Random-effects model was used due to clinical and methodological heterogeneities across the trials (P=0.02, I2=52%). Overall, RAS inhibitors treatment was associated with no benefit or risk on preventing ISR (RR 0.84, 95%CI [0.61 to 1.17]; p=0.30). Similar results were seen in subgroup analysis of both ACEIs subgroup (p=0.79) and ARBs subgroup (p=0.26). Post-procedural subgroup shown significant reduction in ISR comparing with control group (p=0.006), which did not perform at pre-procedural subgroup (p=0.93). The following subgroup analysis of ACE D gene arm (p=0.61), diabetes mellitus arm (p=0.18) were with no statistical significance. The difference analyses of target lesion revascularizaion (ACEIs p=0.07 vs ARBs p=0.04), neonitimal area (ARBs p=0.38) and major adverse cardiac events (MACE) (ACEIs p=0.02 vs ARBs p=0.007) at 6 months follow-up were presented that ARBs reduced the risk of event accidents comparing with controlled group treatment.Conclusions It provides little evidence of RAS inhibition to reduce ISR. However ARBs were proposed to attenuate neointimal hyperplasia in some studies, and possibly reduced the incidence of secondary endpoints that presented by this meta analysis. Due to small sample sizes and low quality studies included, our conclusions are lacking of convincing. Other large-scale, prospective, randomized, double-blind, placebo-controlled clinical trials are expected to bring satisfactory answers.