Aims Although platelet reactivity during P2Y12-inhibitors is associated with stent thrombosis (ST) and bleeding, standardized and clinically validated thresholds for accurate risk stratification after percutaneous coronary intervention (PCI) are lacking. We sought to determine the prognostic value of low platelet reactivity (LPR), optimal platelet reactivity (OPR), or high platelet reactivity (HPR) by applying uniform cut-off values for standardized devices. Methods and results Authors of studies published before January 2015, reporting associations between platelet reactivity, ST, and major bleeding were contacted for a collaborative analysis using consensus-defined, uniform cut-offs for standardized platelet function assays. Based on best available evidence for each device (exploratory studies), LPR–OPR–HPR categories were defined as 208 PRU for VerifyNow, 46 U for the Multiplate analyser and 50% for VASP assay. Seventeen studies including 20 839 patients were used for the analysis; 97% were treated with clopidogrel and 3% with prasugrel. Patients with HPR had significantly higher risk for ST [risk ratio (RR) and 95% CI: 2.73 (2.03–3.69), P < 0.00001], yet a slight reduction in bleeding [RR: 0.84 (0.71–0.99), P = 0.04] compared with those with OPR. In contrast, patients with LPR had a higher risk for bleeding [RR: 1.74 (1.47–2.06), P < 0.00001], without any further benefit in ST [RR: 1.06 (0.68–1.65), P = 0.78] in contrast to OPR. Mortality was significantly higher in patients with HPR compared with other categories ( P < 0.05). Validation cohorts ( n = 14) confirmed all results of exploratory studies ( n = 3). Conclusions Platelet reactivity assessment during thienopyridine-type P2Y12-inhibitors identifies PCI-treated patients at higher risk for mortality and ST (HPR) or at an elevated risk for bleeding (LPR).

Optimizing outcomes after percutaneous coronary intervention (PCI) requires balancing between the risks of thrombotic and bleeding events in individual patients.^1–3 However, finding the optimal balance is not always straightforward since the risks of thrombotic and bleeding complications may differ extremely between individuals. In addition, the individual effects of anticoagulant and antiplatelet drugs are not uniform in patients.⁴

Dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is the standard treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). De-escalation of the potent P2Y12 inhibtor is an appealing concept to balance the ischaemic and bleeding risks after PCI. An individual patient data meta-analysis was performed to compare de-escalation versus standard DAPT in patients with ACS. Electronic databases, including PubMed, Embase, and the Cochrane database, were searched to identify randomised clinical trials (RCTs) comparing the de-escalation strategy with the standard DAPT after PCI in patients with ACS. Individual patient-level data were collected from the relevant trials. The co-primary endpoints of interest were the ischaemic composite endpoint (a composite of cardiac death, myocardial infarction, and cerebrovascular events) and bleeding endpoint (any bleeding) at 1-year post-PCI. Four RCTs (the TROPICAL-ACS, POPular Genetics, HOST-REDUCE-POLYTECH-ACS, and TALOS-AMI trials) including 10 133 patients were analysed. The ischaemic endpoint was significantly lower in the patients assigned to the de-escalation strategy than in those assigned to the standard strategy (2.3% vs. 3.0%, hazard ratio [HR] 0.761, 95% confidence interval [CI] 0.597-0.972, log rank P = 0.029). Bleeding was also significantly lower in the de-escalation strategy group (6.5% vs. 9.1%, HR 0.701, 95% CI 0.606-0.811, log rank P < 0.001). No significant intergroup differences were observed in terms of all-cause death and major bleeding events. Subgroup analyses revealed that compared to guided de-escalation, unguided de-escalation had a significantly larger impact on bleeding endpoint reduction (P for interaction = 0.007); no intergroup differences were observed for the ischaemic endpoints. In this individual patient data meta-analysis, DAPT-based de-escalation was associated with both decreased ischaemic and bleeding endpoints. Reduction in bleeding endpoints was more prominent for the unguided than the guided de-escalation strategy. This study was registered in the PROSPERO (ID: CRD42021245477). A total of 10 133 patients from four randomized clinical trials were analysed. During the first year after percutaneous coronary intervention, the de-escalation strategy was associated with a lower risk of the ischaemic and bleeding endpoints. The absolute risk difference of endpoints between the two astrategies was 0.69% for the ischaemic endpoint and 2.48% for the bleeding endpoint. CI, confidence interval; DAPT, dual antiplatelet therapy; HR, hazard ratio.