ADENOSINE DIPHOSPHATE RECEPTOR INHIBITOR MONOTHERAPY WITH TICAGRELOR OR CLOPIDOGREL FOLLOWING PERCUTANEOUS CORONARY INTERVENTION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Background and purpose In patients undergoing percutaneous coronary intervention (PCI) with implantation of coronary stents, the risk of stent thrombosis is mitigated with antiplatelet therapy. While current clinical practice is to treat patients with dual antiplatelet therapy (DAPT) combining aspirin with an adenosine diphosphate receptor inhibitor (ADPri), prolonged therapy is associated with heightened bleeding risk. Limiting DAPT to a shorter period after PCI, followed by ADPri monotherapy, may be an attractive strategy for optimizing the balance between thrombotic and bleeding risks. While several randomized controlled trials (RCTs) have been published examining this strategy, the optimal duration of abbreviated DAPT run-in and the ideal choice of ADPri remain uncertain. Methods We undertook a systematic review and meta-analysis of RCTs assessing abbreviated DAPT followed by ADPri monotherapy post coronary stenting. Our primary outcomes were defined as clinically important bleeding, major adverse cardiovascular events (MACE), and all-cause mortality. We searched Ovid MEDLINE and EMBASE from their inceptions to November 2019 with study selection and data extraction performed in duplicate. We pooled data at one year using random effects models; relative risks (RRs) with 95% confidence intervals (95% CIs) were generated using the inverse variance method. Pre-specified sub-group analyses were undertaken according to duration of DAPT and the primary ADPri employed. Results Four trials (n=29084) were eligible for inclusion. Mean age was 65 years and 51.5% of patients were recruited in the context of acute coronary syndrome. Following meta-analysis, the occurrence of clinically significant bleeding events was significantly lower in patients receiving ADPri monotherapy (4 studies; n=29084; RR=0.60; 95% CI, 0.43–0.83; I2=73%; Figure-A), with no significant difference in the rates of all-cause mortality (4 studies; n=29084; RR=0.87; 95% CI, 0.71–1.06; I2=0%; Figure-B) or MACE (4 studies; n=29084; RR=0.90; 95% CI, 0.79–1.03; I2=1%; Figure-C). In subgroup analysis, trends toward lower rates of both all-cause mortality (2 studies; n=23082 participants; RR=0.81; 95% CI, 0.65–1.01; I2=0%; Figure-B) and MACE (2 studies; n=23082 participants; RR=0.90; 95% CI, 0.79–1.03; I2=25%; Figure-C) were seen in the studies employing ticagrelor as opposed to clopidogrel; however, neither analysis reached statistical significance (p-values=0.06 and 0.19, respectively). There was no differential treatment effect based on the duration of abbreviated DAPT prior to ADPri monotherapy in sub-group analysis. Conclusions Following PCI in patients with coronary disease, an abbreviated course of DAPT followed by ADPri monotherapy significantly reduces rates of bleeding with no difference in rates of MACE or all-cause mortality. Future studies are required to conclusively determine whether the use of ticagrelor in this setting may also reduce rates of all-cause mortality. Meta-analysis of included studies Funding Acknowledgement Type of funding source: None