New-generation anticoagulant agents pose risks in treatment of acute coronary syndromes

The potential ischemic benefits of novel oral antiplatelet therapy following an acute coronary syndrome (ACS) may be offset by a significant increase in major bleeding events, according to a meta-analysis recently published in the Archives of Internal Medicine.


“We are already exposing these patients to several drugs that can produce bleeding complications. Adding oral anticoagulants, albeit new generation, is expected to increase this risk further.”
-K. Sarat Chandra, MD, DM, cardiologist and a member of the mdCurrent-India Editorial Advisory Board, Hyderabad, India


India has the greatest number of ACS events in the world, according to a study published in 2008 in The Lancet. That study found that patients who experience ACS in India have a[s2If !is_user_logged_in()]…

[/s2If][s2If is_user_logged_in()] higher rate of elevated ST myocardial infarction (STEMI) vs patients in developed countries. The clinical trials included in the recently published meta-analysis did not differentiate among patients with specific types of ACS, so it is unknown whether the efficacy and safety of new-generation anticoagulants vary in patients with STEMI, non-ST-elevation MI, or unstable angina, according to a commentary that ran in the same issue of Archives of Internal Medicine.

Key Point: A meta-analysis of major clinical trials found that new-generation anticoagulant agents—anti-Xa or direct thrombin inhibitors—prescribed after an ACS increase by 3-fold the risk of major bleeding events. Although the therapy may result in a moderate decrease in ischemic events, the net clinical benefit is overshadowed by increased bleeding risk.

K. Sarat Chandra, MD, DM, cardiologist and a member of the mdCurrent-India Editorial Advisory Board, Punjagutta, Hyderabad, India, said that the results of the study reinforce current clinical practices. “We are already exposing these patients to several drugs that can produce bleeding complications,” Chandra said. “Adding oral anticoagulants, albeit new generation, is expected to increase this risk further. One needs to be very cautious while considering this therapy and we should await results from further studies.”

In the meta-analysis, investigators from Hungary examined 7 prospective randomized placebo-controlled clinical trials (N=31,286) conducted between 2000 and 2011. The analysis focused on evaluating the efficacy and safety of novel oral antiplatelet therapy, ie, orally activated Xa antagonist (anti-Xa) and direct thrombin inhibitors, compared with placebo in patients on antiplatelet therapy post-ACS.

Efficacy outcomes included overall mortality and stent thrombosis, with a composite end point of major ischemic events—MI, ischemic stroke, severe recurrent ischemia, and cardiovascular mortality. The safety end point was thrombolysis in MI-defined major bleeding.

While the new-generation oral anticoagulants were associated with a significantly lower risk for MI, those patients receiving the drug therapy had a 3-fold increase in major bleeding risk and a 2-fold increased risk for any bleeding. Patients taking an anti-Xa or direct thrombin inhibitor also had moderately decreased risks for ischemic outcomes and stent thrombosis, without impacting overall mortality.

Ultimately, when weighing the risk:benefit ratio based on the sum of composite ischemic events and major bleeding events, patients receiving novel oral antiplatelet therapy derived no net clinical benefit when compared with control groups.

Sources: Komocsi A, Vorobcsuk A, Kehl D, et al. Use of new-generation anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med. September 24, 2012 [epublication ahead of print].

Hernandez AD. No place for novel oral anticoagulants in current treatment of acute coronary syndromes. Arch Intern Med. September 24, 2012 [epublication ahead of print].

Xavier D, Pais P, Devereaux PJ, et al. Treatment and outcomes of acute coronary syndromes in India (CREATE): a prospective analysis of registry data. Lancet. 2008;371(9622):1435-1442.

Access the original journal information here:
http://www.ncbi.nlm.nih.gov/pubmed/23007264
Journal publishers are independent from mdCurrent-India and may require a subscription or charge a fee to download the full article.

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