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Randomized Controlled Trial
. 2022 Jun 21;11(12):e024655.
doi: 10.1161/JAHA.121.024655. Epub 2022 Jun 14.

Sex-Based Differences in Outcomes Following Peripheral Artery Revascularization: Insights From VOYAGER PAD

Connie N Hess  1   2 , Iris Baumgartner  3 , Sonia S Anand  4 , Mark R Nehler  2   5 , Manesh R Patel  6 , E Sebastian Debus  7 , Michael Szarek  1   2   8 , Warren Capell  2   9 , Eva Muehlhofer  10 , Scott D Berkowitz  2   11 , Lloyd P Haskell  12 , Rupert M Bauersachs  13   14 , Marc P Bonaca  1   2 , Judith Hsia  1   2
Affiliations
Randomized Controlled Trial

Sex-Based Differences in Outcomes Following Peripheral Artery Revascularization: Insights From VOYAGER PAD

Connie N Hess et al. J Am Heart Assoc. .

Abstract

Background Despite high female prevalence of peripheral artery disease (PAD), little is known about sex-based outcomes after lower extremity revascularization (LER) for symptomatic PAD. The effects of rivaroxaban according to sex following LER have not been fully reported. Methods and Results In VOYAGER PAD (Vascular Outcomes Study of ASA [acetylsalicylic acid] Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease), low-dose rivaroxaban versus placebo on a background of aspirin reduced the composite primary efficacy outcome of cardiovascular and limb events in patients with PAD undergoing LER. Unplanned index limb revascularization was prespecified and prospectively ascertained. The primary safety outcome was Thrombolysis in Myocardial Infarction major bleeding. Analyses of outcomes and treatment effects by sex were performed using Cox proportional hazards models. Among 6564 randomly assigned patients followed for a median of 28 months, 1704 (26.0%) were women. Among patients administered placebo, women were at similar risk for the primary efficacy outcome (hazard ratio [HR], 0.90; [95% CI, 0.74-1.09]; P=0.29) as men, while female sex was associated with a trend toward higher risk of unplanned index limb revascularization (HR, 1.18; [95% CI, 1.00-1.40]; P=0.0499). Irrespective of sex, effects of rivaroxaban were consistent for the primary efficacy outcome (P-interaction=0.22), unplanned index limb revascularization (P-interaction=0.64), and bleeding (P-interaction=0.61). Women were more likely than men to discontinue study treatment (HR, 1.13; [95% CI, 1.03-1.25]; P=0.0099). Conclusions Among >1700 women with PAD undergoing LER, women and men were at similar risk for the primary outcome, but a trend for greater risk of unplanned index limb revascularization among women was observed. Effects of rivaroxaban were consistent by sex, though women more often discontinued treatment. Better understanding of sex-based outcomes and treatment adherence following LER is needed. Registration URL: http://clinicaltrials.gov; Unique identifier: NCT02504216.

Keywords: outcomes; peripheral artery disease; revascularization; sex.

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Figures

Figure 1
Figure 1. Primary composite outcome and unplanned index limb revascularization in placebo patients.
Shown are Kaplan‐Meier curves for the primary outcome (A) and unplanned index limb revascularization (B) by sex among patients administered placebo. Hazard ratios (HR) reflect stratification for endovascular or surgical revascularization.
Figure 2
Figure 2. Effects of rivaroxaban compared to placebo for the primary outcome by sex.
Shown are event rates, HR, and 95% CI for the primary composite outcome by sex in intention‐to‐treat and on‐treatment analyses. Analyses performed according to the intention‐to‐treat principle included all patients and events from randomization to the study efficacy cutoff date according to randomized treatment assignment. On‐treatment analyses included all patients and events from randomization until 2 days following permanent discontinuation of the study drug according to actual treatment received. Hazard ratios (HR) reflect stratification for endovascular or surgical revascularization. p‐y indicates patient‐years.
Figure 3
Figure 3. Study treatment discontinuation by sex.
Cumulative incidences of premature study treatment discontinuation are shown for women and men. HR indicates hazard ratio.
See this image and copyright information in PMC

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