Triple Therapy With New Anticoagulants Suitable for Highest-Risk Patients

A literature review finds that triple therapy including newer anticoagulants, aspirin, and clopidogrel may increase the risk of bleeding and should be limited to patients at highest risk for thromboembolic events.

A therapeutic dilemma arises when patients who take anticoagulants experience acute coronary syndrome (ACS). If these patients receive a bare-metal stent, their risk for stent thrombosis is elevated for a month. If the stent is drug-eluting, the risk is elevated for 6 months following insertion. Currently accepted guidelines recommend dual antiplatelet therapy with aspirin and a thienopyridine. High-risk patients with concurrent atrial fibrillation (AF) and coronary stents should receive triple antithrombotic therapy. This consists of a vitamin K antagonist (usually warfarin) added to aspirin and a thienopyridine (usually clopidogrel) for the period of elevated risk.

Researchers at Midwestern University of Pharmacy in Arizona recently conducted a literature search focused on use of new oral anticoagulants in triple therapy and published their results online on April 2, 2013, in the Annals of Pharmacotherapy. They noted that previous studies had reported increased bleeding events with triple therapy compared with warfarin or aspirin monotherapy. Consequently, they advise clinicians to use the shortest possible duration when prescribing triple antithrombotic therapy to at-risk patients in order to reduce bleeding risk.

Newer anticoagulants—the direct thrombin inhibitor dabigatran and the factor Xa inhibitors rivaroxaban and apixaban—have been studied in classic situations. Their efficacy in preventing stroke and systemic embolism in patients with AF when compared with warfarin is clear. Since studies combining novel anticoagulants with dual antiplatelet therapy are limited to patients with recent ACS, but not with concomitant AF, the researchers evaluated the available evidence addressing bleeding risk.

Their publication, which covers 5 controlled clinical trials, acknowledges that the new agents have increased efficacy in some situations. However, the new agents may also increase the risk of bleeding in combination with dual antiplatelet therapy with aspirin and clopidogrel; available data consistently demonstrates a trend toward increased major and clinically relevant non-major bleeding. The researchers recommend limiting the use of dual antiplatelet agents with concurrent antithrombotics to patients at highest risk for thromboembolic events. Periodic evaluation to determine if all 3 agents are necessary is essential. They also urge clinicians to instruct patients to report any signs or symptoms of bleeding or recurrent thrombosis.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.