JACC in a Flash | Understanding Antithrombotic Treatment in HF, Vascular Disease, and AF

A plethora of complications typically accompanies heart failure (HF), with two of the most common being vascular disease and atrial fibrillation (AF). In this "high-risk" scenario, patients are commonly prescribed combination oral anticoagulation and antiplatelet therapy. Uncertainty dogs the benefits of this approach, however, and a recent study by Lamberts et al. questions the merits of this antithrombotic therapy, as well as outlines potential problems.

The investigators included 37,464 patients (mean age 74.5 years; 36.3% female) with HF and co-existing vascular disease in the study cohort; over 3 years of follow-up, 20.7% had prevalent AF and 17.2% developed incident AF. During this period, 23,154 (61.8%) died; unsurprisingly, patients with prevalent AF were more likely to die than those with no AF.

In terms of cardiac events, recurrent HF hospitalization occurred most frequently:

  • Recurrent HF hospitalization = 17,889 (47.7%)
  • MI = 13,003 (34.7%)
  • Serious bleeding = 4,383 (11.7%)
  • Thromboembolism (TE) = 4,272 (11.4%)

Patients with incident and prevalent AF had similar risk for thromboembolism, serious bleeding, and HF hospitalization. However, patients with incident AF were found to have higher risk for MI than patients with prevalent or no AF (p < 0.001). In patients with prevalent or incident AF, the addition of an antiplatelet to a vitamin K antagonist (VKA) versus VKA monotherapy did not decrease risk of either TE (HR = 0.91 and 0.77, respectively) or MI (HR = 1.11 and 1.07) separately—or when the endpoints were combined for overall thrombosis risk (TABLE)—but did raise the risk of bleeding (HR = 1.31 and 2.71).

TABLE. Risk of Thromboembolism or MI According to Regimen and AF Status

Lamberts et al. also found no statistical differences between antithrombotic therapies regarding TE or MI risk in patients without AF, but bleeding risk was raised with VKA with or without single antiplatelet therapy. Ultimately, the presence of AF among patients with HF and vascular disease confers a greater risk for thromboembolism (which was always greater than for patients with no AF), but risk of serious bleeding was particularly high for AF patients when a single antiplatelet was added on top of VKA.

"No further beneficial effect on thromboembolism or coronary risk was apparent when adding a single antiplatelet drug to VKA in patients with AF (but with an increase in bleeding risk), whilst antiplatelet therapy only is inadequate," the authors concluded. "The use of antithrombotic therapy has to balance the reduction in thromboembolism against an increase in bleeding risk."

"Old habits die hard, as do old clinical precepts," Srijita Sen- Chowdhry, MA, MBBS, MRCP, and Richard J. Gordon, MD, wrote in an accompanying editorial. Perhaps the "white versus red thrombi" paradigm that has guided the pharmacological management of thrombosis should be replaced by a "continuous spectrum." They suggest that VKA might be the ideal weapon in the war against thrombus: VKA alone was more effective than antiplatelet therapy in attenuating TE risk, and combining the two failed to protect against the adverse outcomes while increasing the risk of serious bleeding.

Of course, they added, clinical decision making is individualized according to patients' stroke risk scores, coronary anatomy, and other factors, but these findings "add to accumulating evidence that optimal risk-benefit balance in some patients with AF and vascular disease may be achieved by VKA alone."

Lamberts M, Lip GYH, Ruwald MH, et al. J Am Coll Cardiol. 2014 April 16. [Epub ahead of print]
Sen-Chowdry S, Gordon RJ. J Am Coll Cardiol. 2014 April 16. [Epub ahead of print]

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