In 2011, the use of Dabigatran (Pradaxa) became commonplace in the anti-coagulation regimen for atrial fibrillation. In the US, FDA approval was based on the RELY Trial showing improved efficacy and safety compared with Warfarin in the setting of non-valvular atrial fibrillation (defined as valvular disease that was either insignificant or not meeting criteria for surgical correction). Dabigatran is an oral direct thrombin inhibitor and a twice daily regimen of 150 mg in patients with adequate renal clearance showing significant benefit in reducing stroke rates and reducing bleeding risk in patients compared with Warfarin.
Importantly, this study involved a higher percentage of patients with lower risk for CVA (CHADS 1), suggesting benefits even in lower risk patients. The ease of its use (no blood tests or dietary limitations) is a significant draw for patients, and it's no wonder that it's use is on a rapid upwards trajectory. In RELY, the primary subgroup that did not show benefit with Dabigatran were those with a history of GI bleeding. Their bleeding risks were substantially higher on Dabigatran. It should also be stated that there is no direct antidote for Dabigatran. Emergency management might require emergency dialysis which does clear the drug and eliminates most of the anticoagulant effect within an hour. For those with significant renal impairment (creatinine clearance less than 39ml), a reduced dose of Dabigatran 75 mg bid is available.
A recent report out of New Zealand, Harper et al, NEJM 3/1/12 meticulously reviewed dozens of serious bleeds on Dabigatran (Pradaxa). In nearly half of the cases, patients were noted to have significant renal impairment, and many of the bleeds occurred in octogenarians. It was felt that many of the bleeds might have been caused by poor patient selection, including very elderly patients with impaired creatinine clearance, and/or a history of GI bleeds.
With any new advance in medicine, excitement for adoption of its use must be tempered by knowledge and experience with its use. Understanding when to use a drug is only trumped by the knowledge of when not to use it. Dabigatran continues to offer significant advantages in most patient subsets. Understanding which subsets those are should help substantially in avoid untoward outcomes
POSTED BY STEVEN C. AJLUNI, MD
Symptoms of bleeding, one of the many adverse Pradaxa® side effects preceded many of the deaths linked to this anticoagulant drug. The FDA said it will be conducting the investigation to determine if the incidence of bleeding and deaths among patients prescribed Pradaxa® is higher than what would be expected based on observations in the clinical trial that was held before the FDA approved Pradaxa® (dabigatran).
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