News | Peripheral Artery Disease (PAD) | May 17, 2021

Rivaroxaban Reduces First and Total Ischemic Events in Patients with Peripheral Artery Disease

Low dose of anticoagulant outperforms placebo when added to baseline aspirin

The anticoagulant rivaroxaban (Xarelto), in addition to low-dose aspirin, significantly reduced the occurrence of total severe events of the heart, limb or brain and issues related to other vascular complications in patients with symptomatic peripheral artery disease (PAD) who underwent lower extremity revascularization. The findings from the VOYAGER PAD trial were presented at the American College of Cardiology (ACC) 2021 Scientific Session.

May 17, 2021 — The anticoagulant rivaroxaban (Xarelto), in addition to low-dose aspirin, significantly reduced the occurrence of total severe events of the heart, limb or brain and issues related to other vascular complications in patients with symptomatic peripheral artery disease (PAD) who underwent lower extremity revascularization. The findings from the VOYAGER PAD trial were presented at the American College of Cardiology (ACC) 2021 Scientific Session, expand on earlier data and underscore the broad absolute benefits of this strategy in this high-risk patient population, researchers said.

“To our knowledge, this is the first time that the addition of low-dose rivaroxaban to aspirin has been clearly shown to reduce the occurrence of both first and total adverse events in patients with PAD who have undergone lower extremity revascularization but remain at high risk for a heart attack, stroke or recurrent arterial blockage in a limb,” said Rupert Bauersachs, M.D., director of vascular medicine at the Darmstadt Clinic in Germany and lead author of the study. “The benefits we saw in the trial for first events were statistically significant and entirely consistent with those for total events. Rivaroxaban 2.5 mg twice daily with aspirin should be considered as adjunctive therapy after revascularization to reduce first and subsequent adverse outcomes.”

An estimated 10 million U.S. adults and 200 million people worldwide have PAD, which is often associated with leg pain, difficulty walking and poor circulation that can lead to non-healing wounds and a high rate of limb loss. People with PAD are at very high risk for serious complications, including acute limb ischemia—similar to a heart attack or stroke of the leg—that can lead to limb amputation or death if not treated quickly. Patients with symptomatic PAD are commonly treated with procedures to open arteries in the leg to improve symptoms and prevent limb loss, but they remain at very high risk for adverse events. Overall, about 1 in 4 patients with symptomatic PAD require a repeat procedure to open a blocked leg artery.

“There is a need for greater awareness that PAD is a distinct disease state and that patients with PAD have a high risk for cardiovascular adverse events and are generally a very vulnerable population, especially in the post-revascularization setting,” Bauersachs said. “Care for these patients is often fragmented because the surgeon who performs the revascularization may not follow them for complications or recurrences. They deserve to receive optimal treatment to reduce the risk of recurrences.”

The randomized, double blind, international VOYAGER PAD trial, enrolled 6,564 patients in 34 countries who had PAD and had undergone lower extremity revascularization. The patients’ median age was 67 years and 74% were men. Patients were randomly assigned to receive rivaroxaban or a placebo in addition to daily aspirin. The trial was double blinded, meaning that neither the patients nor their doctors knew who was receiving rivaroxaban and who was receiving the placebo. The trial’s primary endpoint was timed to the first event of a composite of acute arterial blockage in the leg (called acute limb ischemia), leg amputation due to blood-vessel disease, heart attack, stroke or death due to cardiovascular causes. Another prespecified endpoint was the total number of vascular events, including recurrent primary endpoint events as well as other vascular events like blood clots in the leg veins or lungs or the need for repeat vascular procedures. The median follow-up time was 28 months after patients underwent revascularization.

The research team reported in a late-breaking clinical trial presented at ACC.20/WCC that the trial met its primary endpoint, with a 15% statistically significant reduction in the risk of a first major adverse limb or cardiovascular event seen in patients who received rivaroxaban compared with those who received the placebo. The current study reports on the total number of vascular events with over 4,700 occurring in the 6,564 randomized over three years.

“There were 342 fewer adverse events in the rivaroxaban group than in the placebo group, which translates to an absolute reduction in risk of 12.5%,” Bauersachs said. “In a high-risk population, that is a big gain in avoiding the need for patients to come back with vascular complications.”

The 6,564 study participants experienced a total of 4,714 vascular events during the study period with 2,301—or about one-third—experiencing at least one vascular event, Bauersachs said.

“So, during approximately three years of follow-up, about 2-3 out of 6 patients with PAD had a vascular event in spite of high utilization of background medical therapy. This overall rate of vascular events is eye-opening and speaks to the high vulnerability of this patient population,” Bauersachs said. “First events are just the tip of the iceberg.”

A limitation of the study is that the trial was designed to assess the occurrence of first adverse events following lower extremity revascularization, Bauersachs said. Therefore, in a double blinded trial, patients may come off study treatment or go on to other therapies after an event, which can attenuate the observed benefit. 

Assessment of the total number of adverse events, however, was a prespecified secondary endpoint and despite this limitation, the findings were statistically significant and robust in absolute terms.

This study was simultaneously published online in the Journal of the American College of Cardiology at the time of presentation. The study was funded by pharmaceutical companies Bayer and Janssen.

Find links to more ACC 2021 late-breakers

Fine more anticoagulantion news

Find more news on peripheral artery disease (PAD)

Related Content

Some of the top technology news from ACC 2021. Top left, the LAAOS III trial showed benefit when surgeons seal off the LAA during other open heart procedures. Bottom left, the ReCor Paradise renal denervation system helped lower blood pressure in patients who did not respond to medication. Top right, for patients with both heart failure and AFib it makes no differences is therapy is focused on controlling the heart rhythm or heart rate. Bottom right, the FLOWER-MI trial found no benefit to FFR-guided PCI.

Some of the top technology news from ACC 2021. Top left, the LAAOS III trial showed benefit when surgeons seal off the LAA during other open heart procedures. Bottom left, the ReCor Paradise renal denervation system helped lower blood pressure in patients who did not respond to medication. Top right, for patients with both heart failure and AFib it makes no difference if therapy is focused on controlling the heart rhythm or heart rate. Bottom right, the FLOWER-MI trial found no benefit to FFR-guided PCI in STEMI with multi-vessel disease.

Feature | ACC | June 08, 2021 | By Dave Fornell, Editor
Here are the top 10 takeaways from the late-breaking studies on cardiovascular technologies presented at the 2021 ...
AMERICAN COLLEGE OF CARDIOLOGY (ACC) Late-breaking clinical trial study presentations at ACC.21. @ACC21 @ACC2021
Feature | ACC | May 18, 2021 | Dave Fornell, Editor
The latest cardiology practice-changing scientific breakthrough, late-breaking study presentations have been announce
To help monitor the health of ACC 2021 in-person attendees for signs of COVID infection, the meeting will use BioIntelliSense's wearable BioButton continuous wireless temperature and vital signs monitoring. The wearable monitor is the size of a coin and is disposable.

To help monitor the health of ACC 2021 in-person attendees for signs of COVID infection, the meeting will use BioIntelliSense's wearable BioButton continuous wireless temperature and vital signs monitoring. The wearable monitor is the size of a coin and is disposable.

News | ACC | February 09, 2021 | By Dave Fornell, Editor
UPDATE Feb 22, 2021 — ...
The American College of Cardiology (ACC) released a list of the latest practice-changing presentations at the ACC.20 annual meeting March 28-30, 2020, in Chicago. This includes five late-breaking clinical trial (LBCT) sessions and three featured clinical research sessions. There also are two LBCT deep-dive sessions where the experts will break down the hottest trials and attendees can find out what the impact might be on the practice of cardiology and patients.
Feature | ACC | April 09, 2020 | Dave Fornell, Editor
Here is the list of American College of Cardiology (ACC) practice-
ACC Cancels 2020 Conference Amid Coronavirus Concerns. #COVID19 #coronavirus #2019nCoV
Feature | ACC | March 09, 2020 | Dave Fornell, Editor
March 9, 2020 — Less than week after the American College of Cardiolog...
American College of Cardiology Names Douglas Drachman Next Annual Scientific Session Vice Chair

Image courtesy of Massachusetts General Hospital

News | ACC | October 08, 2019
Douglas Drachman, M.D., FACC, has been selected as the next vice chair of the American College of Cardiology’s (ACC)...
SyncVision iFR Co-registration from Philips Healthcare maps pressure readings onto angiogram. Results from an international study presented at ACC 2019 indicates pressure readings obtained using iFR (instantaneous wave-free ratio, also referred to as instant wave-free ratio or instant flow reserve) in coronary arteries may localize stenoses that remain after interventions. FFR in the cath lab.

SyncVision iFR Co-registration from Philips Healthcare maps pressure readings onto angiogram. Results from an international study presented at ACC 2019 indicates pressure readings obtained using iFR (instantaneous wave-free ratio, also referred to as instant wave-free ratio or instant flow reserve) in coronary arteries may localize stenoses that remain after interventions.

Feature | ACC | March 27, 2019 | Greg Freiherr, Contributing Editor
The fingerprints of value-added medicine were all over products and works-in-progress on the exhibit floor of the a

The opening late-breaking trial at ACC 2019 is the Apple Heart Study, a large-scale, app-based study to identify atrial fibrillation using a smartwatch. Earlier, smaller trials showed this approach might be used in a population health application to proactively identify AFib patients earlier.

Feature | ACC | March 19, 2019
The American College of Cardiology (ACC) released a list of the late
A patient who received HeartMate III LVAD system at ACC.18. The HeartMate 3 was the topic of of the the key late-breaking trials at #ACC18

A patient who received the HeartMate III LVAD system showing off his external battery pack. He served as a patient ambassador in the Abbott booth at ACC.18. The HeartMate III, with its magnetic levitated pump, showed a big reduction in clotting over previous LVADs in a key late-breaking trial at this year's conference.

Feature | ACC | March 27, 2018 | Dave Fornell
There were several notable presentations of new data on cardiovascular technologies at the recent 2018 American Colle