Gender Should Not Factor Into DAPT Choice After PCI
After PCI, men and women experience similar rates of bleeding and ischemic complications, a new study has confirmed, suggesting that gender may not be an important consideration in selection of short- or long-term DAPT.
Researchers led by Giuseppe Gargiulo, MD (Bern University Hospital, Bern, Switzerland), analyzed data from the PRODIGY study, which randomized patients with stable CAD or ACS to PCI with one of four stent types (bare-metal, zotarolimus-eluting, paclitaxel-eluting, or everolimus-eluting). At 30 days, patients were randomized to continue on antiplatelet therapy for 6 months (n = 983) or 24 months (n = 987).
The new findings from their prespecified sex-based analysis of PRODIGY “are consistent with the results of subgroup analysis of other major DAPT studies and support the concept that gender is not a treatment modifier with respect to DAPT duration,” Gargiulo and colleagues write in a JACC: Cardiovascular Interventions paper published online August 17, 2016, ahead of print.
Compared with men, women in the study were older and had more hypertension and reduced renal function. But at 2 years, there was no difference in risk of the primary efficacy endpoint of death, MI, or stroke for women compared with men (adjusted HR 0.91; 95% CI 0.65-1.26). The finding remained consistent for all other ischemic and bleeding endpoints. Additionally, there was no effect of gender or stent type on rates of MACE or net adverse clinical events, a composite that includes MACE and major bleeding, in an aged-matched sensitivity analysis.
When the long- and short-duration DAPT groups were compared, there was again no difference between men and women for the primary endpoint, nor any difference in event rates by DAPT duration, suggesting no benefit of prolonged therapy.
For the safety endpoint of BARC 2, 3, or 5 bleeding, however, men had an increased risk of bleeding events with longer-duration DAPT that was not seen in women. The difference was driven primarily by BARC 2 bleeds, with no differences in bleeding between genders when BARC 2 bleeds were excluded from analysis.
Consistent Lack of Gender Impact
Two years ago, the large-scale DAPT Study showed an advantage with 30-month versus 12-month therapy for the endpoints of stent thrombosis and major adverse cardiovascular and cerebrovascular events (MACCE), but these benefits came at the price of increased bleeding. Gargiulo and colleagues note, however, that the study also suggested prolonged therapy could reduce both MI and definite or probable stent thrombosis in men but not in women. Meanwhile, subgroup analyses from ARCTIC Interruption, DES-LATE, and PEGASUS all showed a consistent lack of impact of gender on primary endpoints similar to the latest PRODIGY analysis.
In an interview with TCTMD, Usman Baber, MD (Mount Sinai Hospital, New York, NY), who was not involved in the study, noted important limitations of PRODIGY, namely that it was relatively small in size and was underpowered. “Therefore, it is possible that the fact that they found no risk reduction with prolonged DAPT may be because of the small sample size compared with the much larger DAPT trial,” he said.
The most important message with respect to DAPT duration is tailoring therapy based on individual risk versus benefit scenarios, particularly knowing that comorbid risk factors in women have been shown to be the drivers of adverse events rather than “a unique effect of female sex per se,” Baber observed.
As for the increased bleeding in men in this gender-based analysis, Baber said it is somewhat surprising and may be spurious or subject to misinterpretation. “It’s important to remember that BARC 2 is self-reported and requiring some medical attention,” he stressed. “There may have been a difference in how those events were reported in men versus women, but that is just a personal hypothesis.”
Overall, Baber noted, the findings from the PRODIGY analysis reinforce the need for tools such as risk-prediction models that focus not only on the early periprocedural risk, but also on the long-term risk.
“The message we are seeing consistently is that what influences long-term bleeding risk may not be the same as short-term risk, and therefore we need dedicated tools,” he said. “We should not be unduly influenced by simply assuming that women alone are at excess risk for bleeding without looking at the individual risk factors those women carry and making our decisions based on that.”
Sorin Brener, MD (New York Methodist Hospital, Brooklyn, NY), agreed. “Women and men really are very similar and this analysis shows just that,” he said. “All of these comparisons of gender that we’ve seen including this one are underpowered, so whatever they find is most of the time simply a spurious finding that cannot be confirmed in any prospective, powered analysis.
“We’ve finally gotten away from the idea that a woman who presents with acute coronary syndrome should be treated differently than a man who presents with acute coronary syndrome. It’s nonsense to think otherwise,” he emphasized.
- Gargiulo G, Ariotti S, Santucci A, et al. Impact of gender on 2-year clinical outcomes in patients treated with a 6-month or 24-month DAPT duration: a pre-specified analysis from the PRODIGY trial. J Am Coll Cardiol Intv. 2016;Epub ahead of print.
- Gargiulo and Baber report no relevant conflicts of interest.
- Women More Often Than Men Report Lingering Angina After PCI, Raising More Questions
- Study Highlights Gender Differences in Bleeding Risk After PCI
- No More Gender Gap for Mortality After PCI, Complications Another Story