Comparison of de-escalation of DAPT intensity or duration in East Asian and Western patients with ACS undergoing PCI: A systematic review and meta-analysis

Abstract

Abstract Background Guideline-recommended dual antiplatelet therapy (DAPT; aspirin plus prasugrel/ticagrelor) for 12 months in acute coronary syndromes (ACS) patients undergoing PCI, leads to an excess of bleeding. This led to studies to evaluate alternatives to 12 months of high-intensity DAPT, to balance thrombotic and bleeding risks. Several trials have investigated de-escalation strategies, either by reducing DAPT intensity, through switching from potent P2Y12 inhibitors prasugrel or ticagrelor to clopidogrel, or by shortening the duration of DAPT and continuing with single antiplatelet therapy. East Asian (EA) patients exhibit higher bleeding and lower ischaemic risk compared to non-East Asians (nEA) and most studies of "de-escalation" were conducted in EA patients. We sought to compare the safety and benefit of various DAPT "de-escalation" strategies in EA and nEA populations. Methods A systematic review and meta-analysis of randomized controlled trials assessing reduction of DAPT intensity or duration in ACS patients undergoing PCI, in EA and nEA, was performed using a non-random effects model. The study was registered on PROSPERO. The primary efficacy endpoint was the occurrence of net adverse cardiovascular events (NACE), namely the composite of ischaemic endpoints (including major adverse cardiovascular events [MACE] comprising all cause death, recurrent myocardial infarction [MI] and cerebrovascular accident); secondary endpoints were trial-defined MACE and major bleeding at longest follow-up. Results Twenty- trials assessed reduction of DAPT intensity (n=12) or duration (n=11). Of these 11 were conducted exclusively in EA patients while the remaining 7 were conducted predominantly in nEA patients. Overall, reduced DAPT intensity attenuated major bleeding (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.65-0.94, p=0.009), without impacting NACE or MACE. In nEA, this increased MACE (OR 1.20, 95% CI 1.09-1.31, p<0.0001) without impacting NACE or bleeding; whilst in EA, it reduced major bleeding (OR 0.71, 95% CI 0.53-0.95, p=0.02) without affecting NACE or MACE. Overall, DAPT abbreviation reduced NACE (OR 0.90, 95% CI 0.82-0.99, p=0.03) due to major bleeding (OR 0.69, 95% CI 0.53-0.99, p=0.006), without impacting MACE. In nEA, this strategy did not impact NACE, MACE or major bleeding; whilst in EA, it reduced major bleeding (OR 0.60, 95% CI 0.4-0.91, p=0.02) without impacting NACE or MACE. Conclusion In EA, reduction in DAPT intensity or duration can minimise bleeding, without safety concerns. In nEA, reduction in DAPT intensity may incur an ischaemic penalty, whilst DAPT abbreviation has no overall benefit. Although standard DAPT favours patients at high ischaemic risk, while shorter or less intense DAPT may benefit those at high bleeding risk, many patients have overlapping risk factors. Individualisation of DAPT strategy may be preferable to personalise care based on both ethnicity and prevailing risks.