The introduction of direct oral anticoagulants (DOACs) in 2010 significantly changed clinical algorithms for prevention of VTE and stroke, as well as management of atrial fibrillation. In this report, which was initially published March 29, 2020, researchers presented findings that support a role for rivaroxaban in revascularization procedures in patients with PAD. BreakingMED is republishing this report as part of its year end clinical review series.
Findings from a trial of more than 6,564 patients undergoing revascularization procedures for peripheral artery disease are likely to change clinical practice, signaling a death knell for dual antiplatelet therapy while boosting the use of direct oral anticoagulant (DOAC) therapy in these patients.
In the VOYAGER-PAD (Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) trial, patients randomized to rivaroxaban 2.5 mg twice daily plus aspirin achieved a 20% reduction in the relative risk of the primary efficacy outcome of acute limb ischemia, myocardial infarction, ischemic stroke, amputation, or death from cardiovascular disease at 12 months, said VOYAGER-PAD principal investigator Marc P. Bonaca, MD, MPH.
Bonaca, who is the executive director of CPC Clinical Research and Community Health, Director of Vascular Research, and Associate Professor of Medicine at the University of Colorado Anschutz Medical Campus, reported the findings in the opening late-breaking clinical trials session at the ACC.20 World Congress of Cardiology Virtual Meeting.
The results were also published online in The New England Journal of Medicine.
The study, which was hailed as practice-changing during a virtual press conference, randomized 3,286 patients to rivaroxaban and 3,274 to placebo. The median age of patients was 67 and 26% were women.
Among the findings:
- 508 patients in the rivaroxaban group had a primary efficacy outcome.
- 584 control patients had a primary efficacy outcome.
- Kaplan-Meier estimates of the incidence of events at 3 years was 17.3% in the rivaroxaban group versus 19.9% in controls (P=0.009).
Since dual antiplatelet therapy (DAPT) is recommended for one to three months for PAD patients who undergo revascularization via endovascular procedures such as stenting, the VOYAGER-PAD substudy looked at patients who were on background clopidogrel — 51% of the patients in each arm — and found clopidogrel did not improve the efficacy outcome but did increase the rate of bleeding, a risk that increased with the duration of clopidogrel.
William R. Hiatt, MD, a co-investigator who reported the VOYAGER-PAD substudy, said the findings “cast doubt on what role, if any, DAPT would have in these patients.” Hiatt noted that recommendations for DAPT are “based on the experience in CAD, which has been well-characterized,” but efficacy in peripheral disease has not been well-studied.
Sahil Parihk, MD, a member of the ACC Peripheral Vascular Disease Council, commended the VOYAGER-PAD investigators, noting that “this is the largest vascular intervention trial ever attempted, and it is practice-changing.”
Serving as ACC discussant during the press briefing, Parihk said the question of bleeding risk with clopidogrel was “over-arching… the value of clopidogrel is questionable, but the hazard is not questionable… This brings into question if one should use DAPT at all, and I think the guidelines committees will have to look seriously at these studies.”
Bonaca did caution that there is clearly more bleeding, even with rivaroxaban alone. He noted that the TIMI major bleeding rate was 27% in the rivaroxaban arm versus 1.9% in the placebo group, a difference that didn’t reach statistical significance (P =0.0694), “but it probably didn’t reach significance because the numbers were so small,” he added. There were 62 TIMI major bleeding events in the rivaroxaban arm versus 44 in the control group.
But he added that, when comparing risks and benefits, it is noteworthy that there were 181 fewer primary events in the rivaroxaban-treated patients.
Interventional cardiologist Roxana Mehran, MD, an incoming member of the ACC Board of Trustees, agreed that the findings are likely to change practice. Mehran, who served as a press briefing discussant, said the trial, which was investigator-initiated, “was well-designed, with hard endpoints… this was an unmet need, as we had no proven best strategy for these patients.” She added that the trial was also well-balanced, with about a third of patients treated surgically and two-thirds by endovascular or hybrid revascularization.
Peggy Peck, Editor-in-Chief, BreakingMED™
Bonaca reported grants from Bayer AG, grants from Janssen Pharmaceuticals, grants from American Heart Association , during the conduct of the study; grants from Amgen, grants from AstraZeneca, grants from Merck, grants from NovoNordisk, grants from Pfizer, grants from Sanofi, outside the submitted work.
Cat ID: 103
Topic ID: 74,103,730,103,206,192,925,168