A study investigated heart disease treatment strategies to determine the most effective strategy for reducing the risk of secondary heart problems.
Aspirin, commonly prescribed as a heart disease treatment, has been shown to reduce the risk of recurrent cardiovascular events such as coronary artery disease, stroke, and arrhythmias. Aspirin may also reduce the risk of certain types of cancer by 19% and reduce the risk of mortality risk from heart disease by 9%. Alternatively, many health care providers recommend long-term treatment with a vitamin K inhibitor.
Vitamin K inhibitors are anticoagulation therapies commonly known as blood thinners. These inhibitors can be used alone or in combination with aspirin and have been shown to be superior to aspirin alone. However, since vitamin K inhibitors are blood thinners, the patient is susceptible to the associated risks such as more bleeding, including bleeding inside your skull or brain. Therefore, this treatment is not generally recommended for patients at risk of recurrent cardiovascular events.
Hence, finding an alternative treatment is paramount for the long-term survival of heart disease patients. In an effort to discover a new treatment strategy, researchers from Canada designed the trial known as Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) which was carried out across 33 countries. The aim of the trial was to determine if the use of rivaroxaban alone or combined with aspirin increased the efficacy and safety in patients with heart disease whilst reducing the risk of recurrent cardiovascular events, compared to aspirin alone.
Rivaroxaban is an anticoagulant also, which is typically used to treat deep vein thrombosis and help prevent strokes. Previous studies have presented evidence that rivaroxaban has been effective in reducing the risk of cardiovascular death, stroke, and heart attacks in patients with acute coronary syndrome (an umbrella term for describing symptoms associated with a decrease in blood flow to the heart resulting in part of the heart being unable to function properly).
The results of this double-blind randomized trial were published recently in The New England Journal of Medicine. The researchers randomly assigned 27,395 participants who had stable atherosclerotic vascular disease (or heart disease) with either rivaroxaban alone, rivaroxaban in combination with aspirin, or aspirin alone. The primary outcome of this study was a combination of cardiovascular death, stroke, or heart attack.
The results clearly showed the superiority of the rivaroxaban in combination with aspirin treatment as the rate of the primary outcome was 24% lower than when compared to the aspirin-alone group. In addition, despite major bleeding events occurring in more patients receiving the rivaroxaban combined with aspirin treatment (which was higher by 70% in this group), there was no significant difference in bleeding inside their skull or brain or fatal bleeding. Also, there were fewer deaths in the group receiving the rivaroxaban combined with aspirin treatment (313) compared to aspirin alone group (378). Therefore, the overall clinical-benefit outcome was actually lower by 20% for the rivaroxaban combined with aspirin group in comparison to the aspirin-alone group. In fact, the trial was stopped early due to the evidence indicating the superior efficacy of the rivaroxaban-plus-aspirin treatment.
Furthermore, the patients receiving rivaroxaban alone did not experience a significant decrease in the occurrence of the primary outcome, but the results showed an increase in the number of patients which had a major bleeding event occur in comparison to the aspirin-alone group.
One limitation noted in the study was when trials are stopped early due to superior efficacy, an overestimation of the effectiveness of the treatment may occur. However, in this instance, before the trial was stopped the safety board observed data which provided evidence of the progressive increase in benefit for patients receiving this treatment for more than one year.
The comparison of these three heart disease treatments in patients diagnosed with stable heart disease showed that the rivaroxaban-plus-aspirin group suffered fewer adverse cardiovascular events, and the risk of major bleeding was significantly higher than those receiving only aspirin. Better cardiovascular outcomes were not observed for patients in the rivaroxaban-alone group and the risk of major bleeding events was much higher than in the aspirin-alone group. Therefore, the superior heart disease treatment for this study with the best net-clinical-benefit outcomes was the rivaroxaban in combination with aspirin.
Written by Lacey Hizartzidis, PhD
Reference: Eikelboom JW, Connolly SJ, Bosch J, et al; COMPASS Investigators. Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease. N Engl J Med. 2017 Oct 5;377(14):1319-1330. doi: 10.1056/NEJMoa1709118.