Ricerc@Sapienza

Abstract: Optimal timepoint for the discontinuation of dual antiplatelet therapy (DAPT) after an acute coronary syndrome is still debated. In fact, despite a shortening of DAPT duration should be advocated, based on the negligible risk of thrombotic complications observed with newer generations of drug-eluting stents (DES), in order to reduce the hemorrhagic risk, a more prolonged anti-ischemic protection would be suitable for certain higher-risk patients, rendering the traditional 12 months strategy outdated. We performed an updated meta-analysis and indirect comparison of randomized trials comparing shorter vs extended DAPT duration in ACS patients undergoing percutaneous coronary interventions with DES. Literature and main scientific session abstracts were searched for studies comparing 3–6 (short-term) or prolonged (> 12 months) DAPT vs traditional 12 months in ACS patients treated with DES. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were myocardial infarction and stent thrombosis. We included three randomized clinical trials and six study sub-analysis comparing alternative (short-term or prolonged) DAPT vs 12 months in post-ACS, with a total of 15,738 patients. Mortality occurred in 1.8% of patients, with no difference according to DAPT duration (short-term vs standard DAPT: OR [95% CI] 1.00 [0.72–1.39], p = 0.99; > 12 vs 12 months: OR [95% CI] 0.87 [0.61–1.22], p = 0.41). No difference in the risk of recurrent myocardial infarction and stent thrombosis was observed between short-term and standard DAPT, while a significant reduction was achieved only when extending the duration beyond 12 months (MI: OR [95% CI] 0.49 [0.36–0.67], p < 0.00001; ST: OR [95% CI] 0.40 [0.23–0.70], p = 0.001). However, prolonged DAPT was associated with a significant increase in major bleedings (OR [95% CI] 1.69 [1.17–2.45], p = 0.006). In fact, indirect comparison confirmed a significant interaction between short-term vs prolonged DAPT and the risk of myocardial infarction (p < 0.001), stent thrombosis (p = 0.0006) and major bleeding complications (p = 0.02). Based on the current meta-analysis, among ACS patients treated with percutaneous coronary interventions with DES, a shorter-term (3 or 6 months) DAPT can be safely considered, offering a non-inferior protection from major cardiovascular ischemic events as compared to the standard 12 months strategy. Extending DAPT therapy beyond 12 months enhances the antithrombotic protection, although paying the fee of increasing major bleeding complications, therefore resulting in a null effect on mortality. Graphic abstract: [Figure not available: see fulltext.].