Increased long-term bleeding complications in females undergoing endovascular revascularization for peripheral arterial disease

Abstract

Objective: Females with peripheral arterial disease (PAD) treated with endovascular interventions have increased limb-based procedural complications compared with males. Little is known regarding long-term bleeding risk in these patients who often require long-term antiplatelet or anticoagulation therapy. We hypothesize that females have a higher incidence of bleeding events compared with males in the year after endovascular intervention for PAD.

Methods: Adults (aged ≥65 years) who underwent endovascular revascularization for PAD between 2008 and 2015 in Medicare claims data were identified. Patients were allocated by prescribed postprocedural antithrombotic therapy, including (1) antiplatelet therapy, (2) anticoagulation therapy, (3) dual antiplatelet and anticoagulation therapy, and (4) no prescription antithrombotic therapy. Bleeding events were classified as gastrointestinal, intracranial, hematoma, airway, or other. Crude and covariate-standardized 30-, 90-, and 365-day cumulative incidence of bleeding events, overall and by sex, were estimated using Aalen-Johansen estimators accounting for death as a competing risk. Sex differences were identified using Gray's test.

Results: Of 31,593 eligible patients, 54% were females. Females were older (77.9 years vs 75.5 years) and tended to use antiplatelet therapy more often at 30, 90, and 365 days after the intervention. Clopidogrel was the most prescribed antiplatelet, and 32% of patients continued its use at 365 days. Anticoagulants were prescribed to 26.0% of patients at the time of the procedure, and only 8.8% continued anticoagulation at 365 days. Thirty-one percent of patients were diagnosed with a bleeding event within 1 year after the intervention. The cumulative incidence of any bleeding event during the postintervention period was higher in females compared with males with a risk difference of 3% between the sex cohorts (P < .01). Specifically, females had a higher incidence of gastrointestinal bleeding and hematoma (P < .01), but a lower incidence of airway-related bleeding at each time point as compared with males (P < .01).

Conclusions: Sex disparities in bleeding complications after endovascular intervention for PAD persist in the long term. Females are more likely to be readmitted with a bleeding complication up to 1 year after the procedure. Antithrombotic therapy disproportionately increases the risk of bleeding in females. Further research is necessary to understand the mechanisms responsible for abnormal coagulopathy in females after endovascular therapy.

Keywords: Anticoagulation; Bleeding; Endovascular; Peripheral arterial disease; Sex.

Fig 1.

Sex-based risk differences (RD) in short-term and long-term postoperative bleeding complications after endovascular intervention in females versus males prescribed antiplatelet therapy only. CI, Confidence interval; GI, gastrointestinal; ICH, intracranial hemorrhage.

Fig 2.

Sex-based risk differences (RD) in short-term and long-term postoperative bleeding complications after endovascular intervention in females versus males prescribed anticoagulation therapy only. CI, Confidence interval; GI, gastrointestinal; ICH, intracranial hemorrhage.

Fig 3.

Sex-based risk differences (RD) in short-term and long-term postoperative bleeding complications after endovascular intervention in females versus males prescribed dual antiplatelet and anticoagulation therapy. CI, Confidence interval; GI, gastrointestinal; ICH, intracranial hemorrhage.