A pre-specified analysis of PRODIGY (Prolonging dual antiplatelet treatment after grading stent-induced intimal hyperplasia study), published in JACC: Cardiovascular Interventions, indicates that gender is not a treatment modifier with respect to duration of dual antiplatelet therapy (DAPT). Authors Giuseppe Gargiulo (Department of Cardiology, Bern University Hospital, Bern, Switzerland) and others comment that this finding suggests that, therefore, gender should not be a primary covariate when deciding DAPT duration.
Gargiulo et al write that gender is known to affect age, cardiovascular risk factors, clinical presentation and angiographic features, but state “the impact of gender on clinical outcomes after percutaneous coronary intervention (PCI) still remains debated”—noting that in some studies female gender is an independent predictor of worse outcomes after PCI but not in others. “Whether gender should be taken into account when selecting the DAPT regimen is still unknown. Female gender per se was recently proposed as a single covariate in order to identify patients in whom short DAPT duration should be advisable. Yet, the evidence appraising the role of gender in the choice of optimal DAPT duration is limited,” the authors add.
Therefore, in this pre-specified analysis of PRODIGY, they compared two-year clinical outcomes between male and female patients who either received DAPT (with clopidogrel or aspirin) for six months or for 24 months. In PRODIGY, an all-comer patient population were randomised to receive a short course of DAPT (six months) or a prolonged course (24 months) after undergoing PCI with a bare meal stent, zotarolimus-eluting stent, paclitaxel-eluting stent, or an everolimus-eluting stent. Overall, the study found that prolonged DAPT is not associated with ischaemic benefit.
Of the 1,970 patients in PRODIGY, 1,511 were male and 459 were female. Gargiulo et al note that female patients were “older, with a higher prevalence of hypertension, had a lower creatinine clearance, and presented with more frequently with acute coronary syndrome, but were less likely to be smokers, and had a lower prevalence of extension of coronary artery disease with lower need for multivessel intervention”. Furthermore, at two years, women had higher rates of death, myocardial infarction, and the composite of ischaemic events or ischaemic and bleeding events.
However, the authors report: “After multivariate adjustment for baseline imbalances, no significant difference was noted in the primary efficacy endpoint (the composite of death, myocardial infarction or cerebrovascular incident). Consistent results were observed across all other ischaemic or bleeding endpoints between genders.” They add that in both randomised groups (short and prolonged DAPT), the primary efficacy endpoint was similar in female and male patients after adjustment.
Male patients in the prolonged DAPT group had a significantly higher rate of bleeding events than male patients in the short DAPT group, but there was no such difference between prolonged DAPT and short DAPT female patients. Gargiulo et al state that this higher incidence of bleeding events in male patients mainly related to bleeding academic research consortium (BARC) 2 events. “Accordingly, when bleeding was assessed in terms of BARC 3 or 5, prolonged vs. short DAPT did not differ with respect to clinical outcomes in male or female patients,” they comment.
Reviewing the results from their study, and those of other studies, the authors suggest that decision-making about the duration of DAPT “should be a ‘patient-by-patient’ approach, aiming at balancing ischaemic vs. bleeding risks. With that respect, whether gender per se should be taken into account in tailoring a patient’s therapy is still unclear”. They add: “Compared with short-term DAPT, a prolonged DAPT regiment did not benefit both male and female patients suggesting that gender should not be a primary covariate to be considered in the decision-making on DAPT duration after coronary stenting.”
Study author Marco Valgimigli (Department of Cardiology, Bern University Hospital, Bern, Switzerland) told Cardiovascular News: “Female patients are traditionally regarded as high bleeding risk patients and in many instances they are deprived from potent or prolonged anti-thrombotic therapy due to this concern. In reality women are at higher risk for periprocedural bleeding (ie. those occurring at the time of intervention largely related to the access site). However, once you look into long-term bleeding risk, female patients carry a similar bleeding risk as compared to males especially if you correct for age. In fact, females patients who are on average six to seven years older age than men and age difference, more than gender accounts, for the difference in ischaemic and bleeding risk that has been reported on many occasions before.
In our study, BARC major bleeding were similar between males and females and actually BARC 2 was even higher in males than females once again confirming emerging evidence that female patients are not at high bleeding risk by definition as compared to men.
In summary, this analysis cautions clinicians who treat female patients differently compared to men with respect to DAPT duration as they seem to derive a very similar trade-off between ischaemic benefit and bleeding risk.”