Male and female patients had different outcomes, but before recommendations can be made, trials only in women are needed.
The safety and efficacy of strategies for dual antiplatelet therapy (DAPT) de-escalation following PCI may vary depending on patient sex, especially when switching to a single antiplatelet agent, according to a new network meta-analysis.
Several trials have now shown most patients benefit from a short course of DAPT, thanks to bleeding advantages without a sacrifice in ischemic risk, although few have stratified patients by sex.
The meta-analysis, published online recently in the European Heart Journal, with first author Giovanni Occhipinti, MD (University of Barcelona, Spain), comprised more than 71,000 patients from 20 trials, of whom almost one-quarter were female. DAPT discontinuation—followed by either aspirin or P2Y12 monotherapy—lowered MACE in female but not male patients, and it reduced major bleeding in male but not female patients compared with standard DAPT.
“In the field of precision medicine, we now know that there are several factors that affect the response to antiplatelet therapy, but sex was not very well established among them,” study co-author Mattia Galli, MD (Sapienza University of Rome, Latina, Italy), told TCTMD.
When trying to individualize antiplatelet therapy, sex should be taken into account, he said. Clinical presentation as well as ethnicity also play important roles, but patient sex is potentially something that some physicians might not have taken into account before, said Galli.
In an accompanying editorial, Dirk Sibbing, MD (Ludwig-Maximilians-Universität München, Germany), agrees.
“The situation for the treating physician has become much more complex, given the increasing number of recommendations and DAPT modulation strategies,” he writes. “Despite all of these improvements, a significant residual risk for adverse events post-PCI still remains for our patients. To a significant extent, this remaining risk could be related to not adjusting for individual characteristics of our patients, including sex, age, BMI, cardiovascular risk factors, and co-medication. Also, genetic profiling to improve outcomes for cardiovascular drug treatment is still in the early stages of investigation.”
The “next stop” on continuing to improve individualized antiplatelet therapy regimens, Sibbing adds, will require “a better understanding and implementation of intrinsic and extrinsic factors that impact” drug efficacy and safety.
More Than 70,000 Patients
For the network meta-analysis, Occhipinti and colleagues included 71,272 patients (mean age 64.7 years; 23.3% female; 62.2% presenting with ACS) from 20 trials looking at different DAPT de-escalation strategies after PCI. Fifteen were studies of DAPT discontinuation (either aspirin or P2Y12 inhibitor) and five evaluated switching the P2Y12 inhibitor or reducing drug doses. Female participants, as compared to male, were older and reported more hypertension and diabetes.
Compared with standard DAPT, DAPT discontinuation had a different treatment effect depending on patient sex in regard to both MACE (P = 0.028 for interaction) and major bleeding (P = 0.015 for interaction). The risk of MACE was lower with DAPT discontinuation in females (HR 0.86; 95% CI 0.75-0.98) but not in males (HR 1.04; 95% CI 0.93-1.16). However, the risk of major bleeding was lower in men (HR 0.60; 95% CI 0.44-0.82) but not women (HR 1.04; 95% CI 0.76-1.43).
The researchers found no similar interactions by sex with a P2Y12 inhibitor switch or dose reduction strategy compared with standard DAPT.
In a treatment ranking analysis, females had the best outcomes with aspirin discontinuation and males fared best when their P2Y12 inhibitor was switched to clopidogrel.
In another recent paper cited by Galli, one that took a closer look at the pharmacodynamics behind sex-based responses to antiplatelet therapy, it seems that “females have different pathways through which platelets activate,” he said. “This may explain the fact that if you use a P2Y12 inhibitor, that could be more effective in females because we have found that the females have an increased platelet relativity mediated by that pathway.”
This also could explain why female patients might have had a reduced response to aspirin in the current analysis, Galli added.
Their meta-analysis points to the need for a study of DAPT de-escalation strategies done exclusively in women, he said. “That is very, very important because you need a very solid evidence [base] in females to be 100% sure that your findings and your clinical practice can change.”