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A personalized approach to dual antiplatelet therapy (DAPT) duration after percutaneous coronary intervention (PCI) is recommended by international guidelines1 and the DAPT score (DS) was developed as a decision-making tool accounting for both ischemic and bleeding risk to identify patients who can benefit from prolonged DAPT beyond 12 months after PCI (►Fig. 1).2 Nonetheless, the DS showed a modest discrimination in individual, or pooled, validation studies but novel data are available and the impact of the run-in event-free DAPT period was not assessed.3 We searched electronic databases from 2016 up to March 2020 for studies that investigated the association of DS with the occurrence of ischemic and bleeding events. Results were reported according to the PRISMA4 guideline (►Supplementary Fig. S1 [available in the online version]). Ourmain analysis investigated the external validity of the DS by exploring the occurrence of an ischemic endpoint (composite of myocardial infarction [MI] and stent thrombosis [ST]) and of a bleeding endpoint (all events were included as reported by individual studies) according to DS stratum including all study types. We then performed two sets of sensitivity analysis: first, the outcomes of interest were analyzed in randomized clinical trials (RCTs) only or in registries only; second, we excluded the derivation cohort from our analysis as this may introduce bias. We also explored the same endpoints in patients treated with extended or standard DAPT according to DS stratum. Concordance statistics (c-stat) and observed:expected (O:E) ratios from individual studieswere pooled to assess discrimination and calibration power of the DS.5 Finally, in a meta-regression we assessed the effect of a longer uneventful run-in DAPT period before DS calculation on the score’s ability to predict ischemic and bleeding events. Treatment effect is reported as relative risk (RR) and 95% confidence interval (CI). Statistical analysis was performed using R environment. Overall, nine studies were included in our random-effect meta-analysis.2,6–13 Their characteristics are summarized in ►Supplementary Table S1 (available in the online version). Of the 100,211 patients included (►Supplementary Table S2, available in the online version), 42.5% had a DS 2 and when compared with those with lower DS, they experienced a significantly higher hazard of MI and ST combined (RR: 1.72; 95% CI: 1.50–1.97; p< 0.0001) and a significantly lowerhazard of bleeding (RR: 0.79; 95% CI: 0.70–0.89; p1⁄4 0.0001;►Fig. 2). These findings were confirmed by our secondary analysis including only RCTs (RR: 1.86; 95% CI: 1.45–2.39; p< 0.0001 for ischemic events; RR: 0.68; 95%CI: 0.55–0.84; p1⁄4 0.0004 for bleedings; ►Supplementary Fig. S2A [available in the online version]) or only registries (RR: 1.57; 95% CI: 1.43–2.43; p< 0.0001 for ischemic events; RR: 0.85; 95% CI: 0.74–0.98; p1⁄4 0.03 for bleedings; ►Supplementary Fig. S2B [available in the online version]). These results were confirmed also by excluding the derivation cohort from the analysis (►Supplementary Fig. S2C [available in the online version]). Only four studies separately reported outcomes of subjects according to DAPT duration and DS strata: in this secondary analysis of 27,462 patients, in the DS 2 stratum prolonged DAPTwas associated with a significantly lower occurrence of MI and ST combined (RR: 0.54; 95% CI: 0.43–0.67; p< 0.0001) without a significant increase in bleeding (RR: 1.26; 95% CI:

thrombosis and haemostasis

DAPT Score to Stratify Ischemic and Bleeding Risk after Percutaneous Coronary Intervention: An Updated Systematic Review, Meta-Analysis, and Meta-Regression of 100,211 Patients