A new comparative study between dabigatran and warfarin finds similar ischemic stroke risks, but fewer brain bleeds for dabigatron compared with warfarin in US-based national drug surveillance network. More research is needed however, to determine whether dabigatran is associated with higher risk of heart attack or gastrointestinal bleeding in certain patients.
A study of two medications that can reduce risk of ischemic stroke in people with atrial fibrillation (AF) has shown that outcomes in typical patients with AF align well with those seen in clinical trials. The findings were published in Annals of Internal Medicine.
This research, led by Alan Go, director of the Comprehensive Clinical Research Unit within the Kaiser Permanente Division of Research, marks the first major study to examine outcomes of therapies for AF from the US Food and Drug Administration (FDA) Sentinel Initiative, a national multi-institution network to monitor the safety of new medical products after they reach the market.
The benefits of warfarin, which has been in use since the 1950s, are now increasingly surpassed in study outcomes by novel oral anticoagulant (NOAC) alternatives such as dabigatran, approved by the FDA in late 2010.
The analysis showed that both medications were associated with similar rates of ischemic stroke and overall bleeding. However, people taking dabigatran were less likely to experience bleeding in the brain, which can be dangerous or deadly. Brain bleeds occurred in 0.39 vs. 0.77 events per 100 person-years (HR, 0.51; CI, 0.33 to 0.79). These findings were consistent with the results of prior clinical trials that compared the two drugs.
“Our study provides reassurance that stroke-related outcomes seen with dabigatran in selected trial participants translate into usual clinical care for patients with atrial fibrillation,” Go says. “Importantly, while risks of ischemic stroke were similar for dabigatran and warfarin, dabigatran was safer from the standpoint of a lower risk of brain bleeds.”
The study also addressed myocardial infarction rates associated with each drug, but the results were inconclusive. Patients on dabigatran were more likely to experience a heart attack than patients on warfarin, but the statistical strength and consistency of this finding was unclear.
“The jury is still out,” Go says. “We need more research to rule out the possibility that there might be a higher risk of heart attack with dabigatran in certain patients, such as those who are older and men.”
The analysis incorporated data from 50,578 adults aged 21 and older with AF. Half of the patients started dabigatran and the other half started warfarin between November 2010 and May 2014. To ensure a fair comparison, patients taking dabigatran versus warfarin were statistically matched according to similar demographics, use of additional medications and many other characteristics.
Patient data was contributed by eight US-based Sentinel collaborators: Kaiser Permanente Northern California, Kaiser Permanente Washington, Aetna, Harvard Pilgrim Health Care Institute, HealthCore, HealthPartners Institute, Humana Comprehensive Health Insights, and Optum: Optum Epidemiology.
“The Sentinel program enabled us to look at adults of all ages—not just older patients—who received care across a variety of settings,” says study author Joshua Gagne of Harvard Medical School, Boston, USA. “Ours isn’t the first study to address this question outside of clinical trials, but it is the most wide-ranging and nationally representative.”
Future research should examine which types of patients benefit most from which stroke-prevention strategies, Go says. Indeed, the new study mirrored prior clinical trial results showing higher rates of gastrointestinal bleeding with dabigatran in older patients and those with kidney disease, emphasising that warfarin is likely still a better choice for some.
Go’s research is now looking at how different patient characteristics might affect ideal treatment choice to optimise outcomes for AF.