LESS BLEEDING AND COMPARABLE ANTITHROMBOTIC EFFICACY WITH SHORTENED DURATION OF DUAL ANTIPLATELET THERAPY AFTER PERCUTANEOUS CORONARY INTERVENTION WITH 2ND GENERATION DRUG ELUTING STENTS

Abstract

Canadian guidelines recommend dual antiplatelet therapy (DAPT) with ASA and an ADP receptor inhibitor for 12 months after percutaneous coronary intervention (PCI) with drug eluting stents (DES). These recommendations are based upon a concern for late stent thrombosis (ST) with 1st generation sirolimus and paclitaxel eluting stents. Whether duration of DAPT can be safely shortened with use of thrombus resistant durable polymer everolimus, zotarolimus or biolimus eluting 2nd generation DES is unknown. We conducted a meta-analysis of randomized controlled trials comparing short duration (SD) (3-6 months) with longer duration (LD) (≥12 months) of DAPT in patients treated with 2nd generation DES for the outcomes of all-cause mortality, myocardial infarction (MI), definite or probable ST and clinical significant bleeding (CSB). Trials with >25% non-2nd generation DES use were excluded. Summary odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random effects model. Weighted random-effect meta-regression was performed to explore the relationship between PCI performed for acute coronary syndrome (ACS) and DAPT duration. A total of 6 studies comprising of 13,900 (SD 6,934; LD 6,966) patients were included; 12,737 (92%) patients received 2nd generation DES and 5,367 patients (39%) had PCI for ACS. The proportion of patients with ACS in these studies ranged from 23% to 55%. Clopidogrel was used in 13,851 (99.6%) patients and prasugrel or ticagrelor was used in 49 (0.3%) patients. There was no difference in mortality (1.1% vs. 1.2%, OR 0.86 95%CI 0.63-1.18, p=0.36), MI (1.5% vs. 1.3%, OR 1.17 95%CI 0.88-1.56, p=0.29), or ST (0.5% vs. 0.3%, OR 1.33 95% CI 0.75-2.34, p=0.33) (Figure 1) with SD compared with LD of DAPT. Clinically significant bleeding was lower with SD DAPT (0.9% vs. 1.4%, OR 0.64 95%CI 0.46-0.89, p=0.008). Meta-regression analysis showed no significant association between the proportion of ACS patients in trials and duration of DAPT for the outcomes of mortality (p=0.95), MI (p=0.98) or ST (p=0.89). In patients treated with contemporary 2nd generation DES, shortened 3-6 month duration of DAPT was associated with reduction in bleeding compared with the recommended 12 month duration, with comparable antithrombotic efficacy including stent thrombosis. However, a clinically significant difference in ischemic endpoints cannot be excluded and these findings require further confirmation with additional adequately powered randomized trials.