A study of new blood thinners, including Pradaxa®, has found that these novel drugs pose an elevated bleeding risk that cancels out their benefits in patients with Acute Coronary Syndrome (ACS). According to a report from MedPage Today, the study found that direct thrombin inhibitors, the class of drugs that includes Pradaxa®, and another new type of oral anticoagulant medication, factor Xa inhibitors, can increase the risk that an ACS patient will suffer a sever bleeding event by as much as 3-fold.
Pradaxa® was approved by the U.S. Food & Drug Administration (FDA) in October 2010 as a warfarin alternative to prevent blood clots and strokes in people with atrial fibrillation, and was the first direct thrombin inhibitor to come to market. Factor Xa inhibitors include Xarelto®, which was approved to prevent deep vein thrombosis in people who are having hip replacement or knee replacement surgery. The study, which appears in the Archives of Internal Medicine, also evaluated apixaban, a factor Xa inhibitor currently in development.
The study sought to compare the safety and efficacy of the new blood thinners in patients with ACS to those taking a placebo, according to MedPage Today. A total of 31,286 patients in seven randomized, placebo-controlled clinical trials conducted from 2000 to 2011 were included in the meta-analysis. All had been admitted to the hospital for unstable angina pectoris, ST-segment elevation myocardial infarction (STEMI), or non-STEMI. The Pradaxa® patients completed trials within 2 weeks, while those taking the factor Xa drugs complete trials within 1 week.
While a significant reduction in ischemic events was seen in all of the studies among patients taking the drug therapies compared to the placebo group, the study noted a threefold risk of major bleeding events in patients taking factor Xa inhibitors or direct thrombin inhibitor after an ACS. The bleeding risk, the researchers said, almost completely negated the drugs’ benefits.
“When both composite ischemic events and major bleeding events were taken into account, the use of new-generation oral anticoagulant agents showed no difference in net clinical benefit,” the study authors wrote.
The FDA launched a review of Pradaxa® this past December over reports of bleeding-related side effects, while regulators in Europe and Japan have directed Boehringer Ingelheim to strengthen warnings for the drug. According to the Institute for Safe Medicine Practices’ (ISMP) latest QuarterWatch report, the FDA received 3,781 adverse event reports associated with Pradaxa® in 2011. These included 541 deaths, 2,367 reports of hemorrhage, 291 reports of kidney failure and 644 reports of stroke. Pradaxa® was also a suspect in more than 15 cases of liver failure reported to the FDA.
Both Pradaxa® and warfarin can cause internal bleeding, but there are readily available antidotes for warfarin bleeding. A growing number of Pradaxa® bleeding lawsuits allege the drug caused serious, uncontrollable bleeding side effects, including gastrointestinal bleeding and cerebral hemorrhaging for which there is no reversal agent.