A major new study has found that the combination of two drugs — rivaroxaban and aspirin — is superior to aspirin alone in preventing further heart complications in people with vascular disease.
Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Image credit: Val-gb.
McMaster University researcher Dr. John Eikelboom and colleagues evaluated whether rivaroxaban (anticoagulant and blood thinner, often known by the brand name Xarelto) alone or in combination with aspirin (antiplatelet drug and blood thinner) would be more effective than aspirin in preventing heart attacks, strokes and death.
The study, called the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS), involved 27,395 participants with stable atherosclerotic vascular disease from 33 countries.
The scientists compared rivaroxaban at doses of 2.5 mg twice-daily combined with 100 mg of aspirin once-daily to rivaroxaban 5 mg twice-daily or to aspirin 100 mg once-daily. The patients were seen at one and six months, and then every six months.
The researchers found the drug combination reduces cardiovascular outcomes and improves survival in stable coronary or peripheral artery disease. They also found that the combination does increase the chance of a major bleeding. These bleeds were mainly gastroenterological, and not in critical organs such as the brain nor fatal.
“The results show that the combination of 2.5 mg of rivaroxaban twice daily plus 100 mg of aspirin once daily was significantly better than only aspirin or only rivaroxaban,” Dr. Eikelboom and co-authors said.
“The findings are significant because there are about 300 million people around the world living with cardiovascular disease, and every year as many as five to 10% have a stroke or heart attack.”
“Although aspirin reduces the risk of major cardiovascular events by 19%, a more effective antithrombotic strategy could have major benefits for the large population of patients with stable cardiovascular disease.”
“The clear result of this study — that the combination reduced strokes, heart attacks and cardiovascular death by practically 25% compared to either drug alone in both patients with stable coronary or peripheral artery disease — caused the clinical trial to be stopped early, after 23 months, in February 2017.”
“Efforts to improve aspirin have focused primarily on combining aspirin with another antiplatelet drug or replacing aspirin with another antiplatelet drug, but this has had only limited success,” Dr. Eikelboom added.
“Using a different approach, COMPASS showed that combining aspirin with a low dose of an anticoagulant was substantially more effective than aspirin alone. Even small improvements in the effectiveness of treatments that prevent stroke and heart attack are important because cardiovascular disease is very common. In COMPASS the treatment effect was unexpectedly large.”
These results are published in the New England Journal of Medicine.
A second paper from the same study, which is forthcoming in The Lancet, shows that the same drug combination is superior to aspirin for the risk of losing limbs or severe limb ischemia (limitation of blood flow to a limb), as well as decreasing cardiovascular events, among patients with peripheral artery disease (PAD).
The study looked at 7,470 patients with PAD who took part in the COMPASS study, and found the combination reduced heart attacks, stroke or cardiovascular death by 28% and damage to limbs by 46%.
Rivaroxaban alone was not superior to aspirin in preventing heart attacks, stroke, cardiovascular death, or limb events.
Both the combination and rivaroxaban alone had increased major bleeding, but not fatal nor critical organ bleeding.
“This is an important advance for patients with peripheral artery disease,” said McMaster University researcher Dr. Sonia Anand, who led the PAD component of the COMPASS trial.
“Until now we have only had aspirin for these patients, which is only modestly effective. To now have a therapy that both reduces major adverse cardiovascular events and major adverse limb events by one-third is going to be a great benefit for these high-risk patients.”
“The large size of the study, broad inclusion criteria and consistent results in all regions of the world means the results are widely applicable around the world,” said McMaster University Professor Salim Yusuf.
“The benefits seen in COMPASS are on the top of other effective therapies such as statins, aspirin, ACE inhibitors and beta blockers, and so their collective impact is substantial. It is likely the combination therapy will reduce the risk of recurrent cardiovascular events by well over two-thirds.”
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John W. Eikelboom et al. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. New England Journal of Medicine, published online August 27, 2017; doi: 10.1056/NEJMoa1709118
