A meta-analysis of 24 randomised controlled trials assessing dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents shows a net clinical benefit in favour of short-term DAPT followed by P2Y12 inhibitor monotherapy, instead of aspirin, in select patients. The analysis, published in Circulation, notes that extended-term DAPT “has a role” in patients at low risk of bleeding but with a higher ischaemic risk, and adds that a “personalised approach” considering each patient’s relative and absolute risk of ischaemia and bleeding should be considered when deciding upon the optimal intensity and duration of DAPT after PCI.
Writing in the study’s introduction, authors Safi Khan (West Virginia University, Morgantown, USA), Deepak Bhatt (Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, USA) et al note that the optimal duration of DAPT following PCI remains unsettled, with guidelines from both the American College of Cardiology (ACC) and American Heart Association (AHA), updated in 2016, as well as from the European Society of Cardiology (ESC), updated in 2017, recommending differing lengths of DAPT based upon patient bleeding risk. The analysis sought to include data from more recent clinical trials, comparing different durations of DAPT and strategies focused on different types of antiplatelet monotherapy—aspirin versus P2Y12 inhibitor—after DAPT discontinuation in patients undergoing PCI.
Twenty-four trials, including data from 79,073 patients, were included in the study and involved either short-term (less than six-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; mid-term (six-month) DAPT; 12-month DAPT; and extended-term (more than 12-month) DAPT after PCI with a drug-eluting stent. The co-primary endpoints were myocardial infarction (MI) and major bleeding, which constituted the net clinical benefit.
Analysis of the results of the 24 trials showed that at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of MI compared with 12-month DAPT (absolute risk difference [ARD], -3.8 incident cases per 1,000 person-years; relative risk (RR), 0.68 [95% CI, 0.54–0.87]); mid-term DAPT (ARD, -4.6 incident cases per 1,000 person-years; RR, 0.61 [0.45–0.83]); and, short-term DAPT followed by aspirin monotherapy (ARD, -6.1 incident cases per 1,000 person years; RR, 0.55 [0.37–0.83]), or P2Y12 inhibitor monotherapy (ARD, -3.7 incident cases per 1,000 person-years; RR, 0.69 [0.51–0.95]).
Additionally, the analysis showed that extended-term DAPT was associated with a higher risk of major bleeding compared with all other DAPT groups. Compared with 12-month DAPT, Khan, Bhatt et al found no significant differences in the risks of ischaemic endpoints or major bleeding compared with mid-term or short-term DAPT followed by aspirin monotherapy, except noting that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding.
The study team found that there were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term compared with 12-month DAPT was associated with a reduced risk of MI without a significant increase in the risk of major bleeding.
Khan, Bhatt and colleagues write that the principal results of the analysis are that, among patients undergoing PCI with a drug-eluting stent, short-term DAPT followed by P2Y12 inhibitor monotherapy was non-inferior for MI, major adverse cardiovascular events and mortality, and was superior for major bleeding and net adverse clinical events compared with 12-month DAPT. However, DAPT longer than 12 months, reduced myocardial infarction.
“Both mid-term and short-term DAPT followed by aspirin monotherapy had a similar safety and effectiveness profile compared with 12-month DAPT, and a better safety profile compared with extended-term DAPT; however, these strategies had a higher risk of MI and stent thrombosis compared with extended-term DAPT,” Khan, Bhatt and colleagues note, adding: “Extended-term DAPT reduced ischaemic endpoints but at the cost of more frequent major bleeding events, except in the setting of acute coronary syndrome (ACS). Importantly, none of the DAPT durations and strategies were associated with differences in either cardiovascular or all-cause mortality.”
The results showed that one-month DAPT followed by P2Y12 monotherapy was superior to three-month DAPT followed by aspirin monotherapy in limiting the bleeding risk. Khan, Bhatt et al add that the current study also provides evidence favouring extended-term therapy for ischaemic events, which may be appropriate for certain patients who are at a higher risk of cardiovascular events after PCI and low risk of bleeding, such as those presenting with acute coronary syndrome or with diabetes mellitus, or at high ischaemic risk. Nonetheless, the study’s authors advocate a “personalised approach considering each patient’s relative and absolute risks of ischaemia and bleeding when deciding upon the optimal duration of DAPT after PCI”.
Commenting on the study’s significance to Cardiovascular News, Bhatt said: “These results are the most up-to-date look at the totality of data on this topic, and pending further trials, should provide physicians with confidence in assessing the benefits and risks of different durations of DAPT.”
On the relevance of the findings to clinical practice, he said: “Careful patient selection is key. For patients at high ischemic risk and low bleeding risk, durations of DAPT longer than 12 months are generally warranted, assuming that they have already tolerated DAPT without a problem. For patients, at high bleeding risk, even if at high ischemic risk (as many are), a shorter duration of DAPT followed by ADP receptor antagonist monotherapy seems to strike the best balance.”