Re-evaluating DAPT Duration, Monotherapy Selection After PCI

Current guidelines recommend a 12-month-long dual antiplatelet therapy (DAPT) to reduce the risk for ischemic and thrombotic events following percutaneous coronary intervention (PCI).¹ Ischemic complications among patients who have undergone PCI have decreased considerably due to improvements in stent design and antiplatelet therapies. However, the rates of bleeding events after PCI remain high, prompting a shift toward shorter-term DAPT followed by monotherapy with aspirin or a P2Y12 inhibitor.²

In a review published in the American Journal of Cardiology, Yerasi et al. examined the results of randomized clinical trials (RCTs) in which DAPTs were assessed in this patient population.² In these RCTs, several DAPTs regimens were evaluated: 12- vs 6- or 3-month-long DAPT followed by aspirin monotherapy; 1-month DAPT followed by aspirin monotherapy for patients with high bleeding risk; or 3-month or 1-month DAPT followed by P2Y12 inhibitor monotherapy.

In RCTs in which all participants had acute coronary syndrome, strategies included DAPT for 3 or 6 months followed by aspirin monotherapy, or DAPT for 1 or 3 months followed by P2Y12 inhibitor monotherapy. 

Based on their review of the data, the authors developed a treatment algorithm to personalize the selection of DAPT and subsequent monotherapy after PCI, according to each patient’s risk for ischemic events and bleeding. They concluded that “while removing the P2Y12 inhibitor after a short DAPT appears to be safe in the low-risk population, removing aspirin and continuing the P2Y12 inhibitor as monotherapy would be the preferred strategy in intermediate- to high-risk patients to mitigate the bleeding risk.”²

We interviewed the following experts regarding this topic: Michelle L. O’Donoghue, MD MPH, associate professor of cardiovascular medicine at Harvard Medical School in Boston and senior investigator in the Thrombolysis in Myocardial Infarction (TIMI) Study Group, and Ori Ben-Yehuda, MD, cardiologist at the University of California, San Diego.

What are your thoughts about the conclusions drawn by Yerasi et al in this American Journal of Cardiology review?

Dr O’Donaghue: I agree with the authors that the weight of the evidence suggests that shorter durations of a P2Y12 inhibitor with continued aspirin may be possible without conferring excess risk in patients who are at low risk for ischemic events. This would include patients who have undergone elective PCI with newer generation stents.

However, more recent trial data has flipped this question around to ask whether we may actually be stopping the wrong therapy. We now have a growing number of studies that have shown that aspirin discontinuation with continued use of a P2Y12 inhibitor may not only be a safe strategy, but also an effective one.

Dr Ben-Yehuda: The authors’ conclusion is a reasonable one but is not based on RCT data –we do not have a trial in which patients, stratified by risk, are randomly assigned to continuing aspirin vs a P2Y12 inhibitor. There is also the concern that, particularly with clopidogrel, there may be patients with clopidogrel resistance who will be left unprotected.

Dr O’Donague, you co-authored a review and meta-analysis which was published in Circulation related to this issue.³ How do your findings compare or add to the conclusions by Yerasi et al.?

Dr O’Donague: In our meta-analysis of all randomized trials [to examine the safety and efficacy of aspirin discontinuation with continued use of a P2Y12 inhibitor], aspirin discontinuation in this setting reduced the risk for bleeding by approximately 40%. Importantly we did not see any signal toward an increased risk for cardiovascular events – if anything, this risk appeared to be lower for patients on P2Y12 inhibitor monotherapy. This may speak to the fact that bleeding can lead clinicians to stop therapies altogether, thereby putting patients at heightened risk.

Importantly, the findings appeared to be consistent from lower- to higher-risk patients with acute coronary syndrome. Of course, we always need to consider the patient populations that were enrolled in these clinical trials, but nonetheless, I think these findings have led many to rethink whether aspirin really should remain the cornerstone of antiplatelet therapy.

What are the relevant treatment recommendations or other important considerations for clinicians?

Dr O’Donague: Although guidelines have not yet had time to catch up with the latest evidence, I have become more comfortable with P2Y12 inhibitor monotherapy for my patients who are at increased risk for bleeding. My preference is to use ticagrelor or prasugrel in those instances since there exists substantial interpatient variability in response to clopidogrel. Again, clinicians always need to keep in mind who is enrolled in clinical trials when trying to extrapolate to their own practices.

Dr Ben-Yehuda: Overall, the field has been moving towards shorter DAPT duration, particularly for patients with high bleeding risk. The advancement in stent design with thinner struts and increasing use of intravascular imaging for optimal stent deployment makes us more comfortable with shorter DAPT duration.

What should be the focus of future research in this area?

Dr Ben-Yehuda: There are 2 main questions that require further investigation: Which is the optimal long-term single agent — aspirin or P2Y12? Should patients be switched after an initial month of potent P2Y12 inhibitor (ie, ticagrelor or prasugrel) to clopidogrel? There is a rationale for doing so as the greatest risk for stent thrombosis — the main impetus for DAPT and specifically for P2Y12 therapy — is markedly lessened after a month.

The main reason for maintaining DAPT is to prevent stent thrombosis. We need further research in identifying patients who are at risk for this event. The work by Yerasi et al. attempts to provide guidance in this regard but needs to be supported by ongoing prospective randomized trials.

References

1. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation. 2011;124(23):e574-651. doi:10.1161/CIR.0b013e31823ba622
2. Yerasi C, Case BC, Forrestal BJ, et al. Optimizing monotherapy selection, aspirin versus P2Y12 inhibitors, following percutaneous coronary intervention. Am J Cardiol. Published online August 15, 2020. doi:10.1016/j.amjcard.2020.07.061
3. O’Donoghue ML, Murphy SA, Sabatine MS. The safety and efficacy of aspirin discontinuation on a background of a P2Y₁₂ inhibitor in patients after percutaneous coronary intervention: a systematic review and meta-analysis. Circulation. 2020;142(6):538-545. doi:10.1161/CIRCULATIONAHA.120.046251