Short DAPT May Be Especially Beneficial for Women at High Bleeding Risk

Women at high bleeding risk (HBR) do not seem to experience more ischemic or bleeding events than men and may especially benefit from a regimen of short dual antiplatelet therapy (DAPT) after PCI, according to a secondary analysis of the MASTER DAPT trial.

The authors acknowledge that there are likely no biological differences at play here; rather, they say, the hypothesis-generating findings are a result of the greater comorbidity burden present among women compared with men.

“At variance with previous studies, we did not observe higher risks of bleeding and ischemic events in female HBR patients compared with male patients despite several differences in baseline characteristics,” lead author Antonio Landi, MD, PhD (Ente Ospedaliero Cantonale, Lugano, Switzerland), told TCTMD in an email. “We speculated that the distribution of some comorbid conditions rather than other biological features may explain the increased bleeding risk in women reported in previous studies.”

With an abbreviated. 1-month course of DAPT, this subanalysis showed that men in the MASTER DAPT trial reported a 1% increase of MACCE rates compared with those taking a standard DAPT regimen of at least 3 months, whereas women saw more than a 2% decrease in MACCE.

Because of this, Landi said a short course of DAPT “should be considered as [the] default approach in women at HBR due to the relevant bleeding benefit and no discernible incremental ischemic risk compared with standard DAPT.”

Birgit Vogel, MD (Icahn School of Medicine at Mount Sinai, New York, NY), agreed. To TCTMD, she said the study validates the safety of using an abbreviated DAPT strategy in women, regardless of whether the benefit is due to independent biological factors or the higher prevalence of comorbidities. “In women, it is especially important to have strategies to reduce bleeding, and this is a good confirmation that shortening of DAPT is safe, especially when we look at the effect on ischemic events in this trial,” she stressed.

However, Sorin Brener, MD (NewYork-Presbyterian Brooklyn Methodist Hospital, NY), told TCTMD that the study findings should only be “only hypothesis-generating and nothing more,” because they are underpowered to change practice. “Whatever differences you see are just a manifestation of the baseline characteristics,” he said. “I do not think that people should base their decisions on the duration of DAPT on the gender of the patient.”

MACCE Difference Observed

For the prespecified subanalysis, published online last week in JAMA Cardiology, Landi and colleagues included 4,579 HBR patients (30.7% women; mean age 76.0 years) from the MASTER DAPT trial who were randomized at 1 month after PCI to abbreviated or standard DAPT.

Compared with men, women were older and had a greater prevalence of arterial hypertension, chronic kidney disease, and hematological or coagulation disorders. Women were also more likely to be treated with corticosteroids or nonsteroidal anti-inflammatory drugs, and they had a lower prevalence of previous ischemic events and concomitant comorbidities. The mean PRECISE-DAPT score was higher for women (28.96) than men (25.78).

The rates of both ischemic and bleeding events were comparable between men and women, overall. Among those randomized to abbreviated DAPT, rates of NACE—a composite of all-cause death, MI, stroke, or major bleeding—were similar for men (HR 0.97; 95% CI 0.75-1.24) and women (HR 0.87; 95% CI 0.60-1.26; P = 0.65 for interaction).

However, women on abbreviated DAPT saw a greater benefit regarding MACCE—defined as all-cause death, MI, or stroke—compared with men (HR 0.68; 95% CI 0.44-1.05 for women; HR 1.17; 95% CI 0.88-1.55 for men; P = 0.04 for interaction).

The risk of BARC 2, 3, or 5 bleeding was relatively greater in men (HR 0.65; 95% CI 0.50-0.84) compared with women (HR 0.77; 95% CI 0.53-1.12) on abbreviated DAPT, but there was no significant interaction between the sexes (P = 0.46 for interaction).

All results were maintained when looking only at ACS patients or those undergoing complex PCI.

Future Directions

Since the population was already a highly selected group of patients with HBR, Vogel said she wasn’t surprised not to see a difference in bleeding between men and women in this study. But because women are known to be at greater risk for bleeding than men more generally, conducting studies like this is important, she noted.

Vogel acknowledged that the study lacks the statistical strength to “derive definitive conclusions,” but said this bolsters the argument for increasing female participation in trials, perhaps even conducting a similar trial in women alone.

Landi agreed. Underscoring it all is an “impelling need for further research in the field of ischemic heart disease in women,” he said, adding that more focus should be placed on enrolling and retaining women in such studies. “Among many other aspects, the key grey zones to be prioritized include the different pathophysiology, clinical presentation, quality of care and clinical outcomes across sexes.”