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).

The present analysis addresses the potential clinical and physiologic significance of discordance in severity of coronary artery disease between the angiogram and fractional flow reserve (FFR) in a large and unselected patient population. Between September 1999 and December 2011, FFR and percent diameter stenosis (DS) as assessed by quantitative coronary angiography were obtained in 2986 patients (n = 4086 coronary stenoses), in whom at least one stenosis was of intermediate angiographic severity. Fractional flow reserve correlated slightly but significantly with DS [−0.38 (95% CI: −0.41; −0.36); P < 0.001]. The sensitivity, specificity, and diagnostic accuracy of a ≥50% DS for predicting FFR ≤ 0.80 were 61% (95% CI: 59; 63), 67% (95% CI: 65; 69), and 0.64 (95% CI: 0.56; 0.72), respectively. In different anatomical settings, sensitivity and specificity showed marked variations between 35 to 74% and 58 to 76%, respectively, resulting in a discordance in 35% of all cases for these thresholds. For an angiographic threshold of 70% DS, the diagnostic performance by the Youden's index decreased from 0.28 to 0.11 for the overall population. The data confirm that one-third of a large patient population shows discordance between angiogram ≥50%DS and FFR ≤0.8 thresholds of stenosis severity. Left main stenoses are often underestimated by the classical 50% DS cut-off compared with FFR. This discordance offers physiologic insights for future trials. It is hypothesized that the discordance between angiography and FFR is related to technical limitations, such as imprecise luminal border detection by angiography, as well as to physiologic factors, such as variable minimal microvascular resistance.