Meta-Analysis Suggests No Net Clinical Benefit With New Generation of Oral Anticoagulants Following ACS

A new meta-analysis published on Sept. 24 in the Archives of Internal Medicine concludes that new-generation oral anticoagulant agents (NOACs) are not appropriate for routine use in patients who are also on antiplatelet therapy following an acute coronary syndrome (ACS).

The conclusion is based on seven randomized placebo-controlled clinical trials with 31,286 patients.

NOACs, such as direct thrombin inhibitors and anti-Xa, do show a statistically significant reduction in the risk for stent thrombosis or composite ischemic events, noted lead author András Kómocsi, MD, PhD, University of Pecs, Pecs, Hungary. But the hazard ratio of 0.73 for stent thrombosis or composite ischemic events was offset by a hazard ratio of 2.26 for TIMI major bleeding events. There was no net clinical benefit to using NOACs compared to placebo (p=0.57) in patients receiving antiplatelet therapy following ACS.

"The benefit (of NOACs) is largely canceled by the harm; therefore, the routine use of NOACs among patients with ACS is unwarranted," said Adrian Hernandez, MD, PhD, Cleveland Clinic, Ohio, in an invited commentary. "Trials are needed to evaluate the use of NOACs in specific populations with ACS."

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Patients are clearly at significant risk for thrombotic events following ACS despite the common use of dual antiplatelet therapy with aspirin plus adenosine diphosphate receptor antagonists. Warfarin can significantly reduce the rate of thrombotic events, but anticoagulation therapy increases the rate of bleeding complications, has a high rate of interaction with foods and other drugs, and requires frequent monitoring. NOACs offer a more reliable therapeutic effect, as well as significant improvements in patient outcomes following atrial fibrillation and orthopedic surgery, suggesting similar reductions in thrombotic complications following ACS.

Researchers combined the results of NOAC trials reported between Jan. 1, 2000, and Dec. 31, 2011. The analysis included efficacy and safety outcomes in five dose-finding trials and two large phase III trials. They found that adding an NOAC to dual antiplatelet therapy in patients following ACS can prevent 13 major ischemic events at the cost of nine TIMI major bleeding events across the entire dataset. The lack of net benefit was even more apparent in phase III trials. Anti-Xa agents prevented 18 major ischemic events at the cost of 15 major bleeds while the use of apixaban, a direct thrombin inhibitor, prevented four major ischemic events at the cost of 15 major bleeds.

"This was translated into a net clinical benefit that was not significantly different compared with control group findings," Hernandez said. As the title of his commentary noted, there is "No Place for Novel Anticoagulants in Current Treatment of Acute Coronary Syndromes."

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