Reassurance on the overall bleeding risks and intracranial hemorrhage rates associated with dabigatran (Pradaxa, Boehringer Ingelheim) use in patients with atrial fibrillation has come from a new real-world study comparing outcomes with the new direct oral thrombin inhibitor anticoagulant and warfarin. But questions over the risk for myocardial infarction (MI) still remain.
“This is one of the largest and most rigorously performed real-world studies of dabigatran with 25,000 patients in each group matched very carefully,” lead author, Alan S. Go, MD, Kaiser Permanente Northern California, Oakland, told Medscape Medical News. “We also covered all ages across all regions of the US, so I would say our results are very reliable and particularly relevant to clinical practice.”
The study was published online November 14 in Annals of Internal Medicine.
“Overall the results are reassuring — they tend to support what was seen in the randomized studies — that dabigatran is associated with a lower overall risk of stroke versus warfarin when considering both ischemic and hemorrhagic stroke together,” he added.
“The study found a comparable rate of ischemic stroke and overall bleeding with dabigatran and warfarin, but dabigatran was associated with a reduced rate of intracranial hemorrhage, a raised risk of GI [gastrointestinal] bleeding, and the possibility of an increased risk of MI,” Dr Go stated.
Expanding on the MI data, he noted that “the primary analysis showed an almost 2-fold higher risk of MI with dabigatran versus warfarin, but the absolute risk was very low — less than 1% per year for dabigatran versus less 0.5% per year for warfarin.”
And when the researchers conducted further sensitivity analyses, the increased MI risk with dabigatran decreased and became nonsignificant.
“For all the other outcomes — stroke and bleeding — we saw the same results in all the various analyses, but for MI risk the results differed in the various different analyses and not all of them were significant,” he said. “So, all we can really say is there may be an increased risk of MI but we need more definitive data to know for sure.”
Dr Go and his colleagues note that dabigatran was approved by the US Food and Drug Administration (FDA) in 2010 for patients with nonvalvular atrial fibrillation based on the RE-LY trial, which showed that the drug (at a dose of 150 mg twice daily) was superior to warfarin for reducing the combined rate of all stroke and systemic embolism, with similar rates of major bleeding, but less intracranial bleeding and more GI bleeding with dabigatran. In addition, there was a suggestion of a higher rate of MI with the new drug.
Since its use in clinical practice, there have been conflicting observational data about the balance of thromboembolic and safety risks with dabigatran vs warfarin, but relatively few studies have rigorously evaluated outcomes associated with dabigatran vs warfarin in populations more generalizable to clinical practice.
Because of this, Dr Go and colleagues conducted the current study using data from the FDA’s Sentinel national surveillance program, which includes 17 collaborating institutions and healthcare delivery systems.
They compared 25,289 patients who had atrial fibrillation and started dabigatran therapy with 25,289 propensity score–matched patients who started warfarin between November 2010 and May 2014.
Results showed that those receiving dabigatran did not have significantly different rates of ischemic stroke or extracranial hemorrhage but were less likely to have intracranial bleeding and more likely to have MI.
Table 1. Events per 100 Person-Years for Dabigatran vs Warfarin
| Event | Dabigatran | Warfarin | Hazard Ratio (95% Confidence Interval) |
|---|---|---|---|
| Ischemic stroke | 0.80 | 0.94 | 0.92 (0.65 – 1.28) |
| Extracranial hemorrhage | 2.12 | 2.63 | 0.89 (0.72 – 1.09) |
| Intracranial hemorrhage | 0.39 | 0.77 | 0.51 (0.33 – 0.79) |
| MI | 0.77 | 0.43 | 1.88 (1.22 – 2.90) |
However, the strength and significance of the association between dabigatran use and MI varied in sensitivity analyses and by exposure definition, with hazard ratios ranging from 1.13 (95% confidence interval [CI], 0.78 – 1.64) to 1.43 (95% CI, 0.99 – 2.08).
The results also showed that older patients and those with kidney disease had higher GI bleeding rates with dabigatran.
Table 2. Risk for GI Bleeding With Dabigatran vs Warfarin
| Patient Population | Hazard Ratio (95% CI) |
|---|---|
| Age 75 – 84 y | 1.47 (1.01 – 2.14) |
| Age ≥85 y | 1.84 (1.05 – 3.20) |
| Reduced kidney function | 1.91 (1.04 – 3.51) |
The researchers conclude that: “Collectively, these results provide reassurance about overall bleeding risks — particularly intracranial hemorrhage — associated with dabigatran use and give insights to potentially assist in decision making about stroke prevention strategies for certain patients with atrial fibrillation.
“However, given the variability of findings for the outcome of myocardial infarction based on the analytic approach we used and results from other studies, the association between dabigatran and myocardial infarction remains uncertain.”
The Sentinel Coordinating Center is funded by the FDA. Dr Go reports grants from the FDA during the conduct of the study.
Ann Intern Med. Published online on November 14, 2017. Abstract
For more Medscape Neurology news, join us on Facebook and Twitter
Tidak ada komentar:
Posting Komentar