Drugs Xagena
A FDA ( Food and Drug Administration ) study of more than 134,000 Medicare patients found that Pradaxa ( Dabigatran etexilate mesylate ) was associated with significantly reduced risks of ischemic stroke, intracranial hemorrhage and death, and a significantly increased risk of major gastrointestinal hemorrhage, compared with Warfarin ( Coumadin ) in patients with non-valvular atrial fibrillation ( NVAF ).
The study found no difference in major bleeds or myocardial infarction with Dabigatran compared to Warfarin.
The study was published in Circulation.
The FDA study is based on data from elderly patients older than 65 years enrolled in Medicare who started therapy with Dabigatran or Warfarin between 2010 and 2012.
Each group comprised 67,207 patients.
The analysis showed that Dabigatran was generally associated with better patient outcomes compared to Warfarin.
The primary outcomes were: 20% reduced risk of ischemic stroke ( hazard ratio [ HR ] 0.80, 95% confidence interval [ CI ] 0.67-0.96; 205 vs 270 events ); no difference in major hemorrhage ( HR=0.97, CI 0.88-1.07; 777 vs 851 events ); 66% reduced risk of intracranial hemorrhage ( HR=0.34, CI 0.26-0.46; 60 vs 186 events ); 28% increased risk of gastrointestinal bleeding ( HR=1.28, CI 1.14-1.44; 623 vs 513 events ); no difference in acute myocardial infarction ( HR=0.92, CI 0.78-1.08; 285 vs 327 events ).
The study also found the following secondary outcomes: 14% reduced risk of mortality ( HR=0.86, CI 0.77-0.96; 603 vs 744 events ); no difference in all hospitalized bleeds ( HR=1.00, CI 0.92-1.09; 1079 vs 1139 events ).
This study was performed as part of the SafeRx Project, a joint initiative of the Centers for Medicare & Medicaid Services ( CMS ) and the FDA.
Pradaxa is approved to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation, for the treatment of deep venous thrombosis ( DVT ) and pulmonary embolism ( PE ) in patients who have been treated with a parenteral anticoagulant for five to 10 days and to reduce the risk of recurrent DVT and PE in patients who have been previously treated.
Nine million prescriptions for Pradaxa 150 mg and 75 mg have been filled for more than 935,000 patients with non-valvular atrial fibrillation in the United States since its approval in October of 2010.
Pradaxa 150 mg twice daily is the only oral anticoagulant to demonstrate superior reduction of ischemic stroke compared to warfarin in patients with non-valvular atrial fibrillation.
Pradaxa also demonstrated a similar rate of major bleeding events. Ischemic strokes are the most common type of stroke that NVAF patients experience.
The efficacy and safety of Dabigatran in NVAF were established in the RE-LY trial, one of the largest stroke prevention clinical studies ever conducted with NVAF patients.
The 18,113-patient RE-LY trial showed that, compared to well-controlled Warfarin ( n=6,022 ), Dabigatran 150 mg ( n=6,076 ) significantly reduced the risk of stroke and systemic embolism by 35% ( primary efficacy endpoint: 134 [ 2.2% ] vs 202 [ 3.4% ] events, HR: 0.65, 95% CI [ 0.52, 0.81 ], P=0.0001 ), ischemic stroke by 25% ( 103 [ 1.7% ] vs 134 [ 2.2% ] events, HR=0.75, 95% CI [ 0.58, 0.97 ], P=0.0296 ) and hemorrhagic stroke by 74% ( 12 [ 0.2% ] vs 45 [ 0.8% ] events, HR=0.26, 95% CI [ 0.14, 0.49 ], P less than 0.0001 ).
The rate of all-cause mortality was lower with Dabigatran 150 mg than with Warfarin ( 3.6% per year versus 4.1% per year ).
Dabigatran had a higher rate of total gastrointestinal bleeds ( 6.1% vs 4.0% ) and major GI bleeds ( 1.6% vs 1.1%; 50% increased risk with the 150 mg dose compared to Warfarin ).
Treatment with Dabigatran 150 mg led to a 59% reduction in intracranial hemorrhage, compared to Warfarin ( 38 vs 90 ), and showed numerically lower rates of fatal and life-threatening bleeds ( 28 vs 39 and 179 vs 218, respectively ). ( Xagena )
Source: Boehringer Ingelheim, 2014
XagenaMedicine_2014
