What Regimen to Minimize Thromboembolic Risk and Bleeding?

May 9, 2014

Aging baby boomers will more frequently appear in primary care offices with cardiovascular diseases that place them at high risk for both clotting and bleeding. Many will also have atrial fibrillation. Is there a sure-fire therapeutic formula for all?

As the population grows ever older and the incidence of atrial fibrillation (AF) steadily rises worldwide, the confluence of atherosclerotic disease (which requires treatment with aspirin or other antiplatelet agent [APT]) and atrial fibrillation (for which a vitamin-K antagonist (VKA) is preferred] is encountered much more commonly in clinical practice.  Will either type of therapy decrease thromboembolic risk while minimizing bleeding risk?  Given the older population, it would prove ethically difficult to design a randomized controlled to trial to answer this question. Often, patients end up receiving both antiplatelet and anticoagulant. And while this combination is put forth in the ACC/AHA Acute Coronary Syndrome guidelines1, there is no clear evidence as to whether this is the preferred strategy.

Accompanying a study recently published in JACC2 that explored a similar "APT-VKA in CAD-AF" theme was an editorial3 entitled, “One weapon, two blows in the war against the thrombus.” The editorial author discussed the results of a large retrospective analysis of 37 464 patients who were hospitalized with HF between 1997 and 2009 and had co-existing vascular disease (coronary artery disease or peripheral vascular disease) and AF.  With a mean follow-up of 3 years, patients had an average age of 74.5 years, a mean CHADS2-Vasc score of 5 and a HAS-BLED bleeding risk score of 2; they were divided into thre groups: prevalent (previous) AF (21%), incident (new) AF (17%), or no AF (62%).

In all three groups, combination therapy with a VKA and single-agent APT increased the risk of serious bleeding compared with VKA alone (1.3 times greater risk in prevalent AF; 2.7 times greater in incident AF; 2.1 times greater without AF). With respect to efficacy, there was no difference in rates of thromboembolism in any of the groups taking combination APT and VKA compared to taking VKA alone.  VKA therapy was more efficacious than APT alone, but was also associated with more bleeding.

This large retrospective study provides solid observational evidence that both a VKA and APT may not be necessary and may only increase bleeding risk in AF patients with stable atherosclerotic disease. Notably, the participants  represented a very high-risk group (high scores on both CHADS2-Vasc and HAS-BLED), so achieving an optimal balance between clotting and bleeding was important and the population was well-selected to answer this question.

The results of this study will no doubt inform decisions about combination VKA and APT in AF patients who have concomitant high-bleeding and high-clotting risk. However, with several novel oral anticoagulants now available and an increasing number of patients receiving PCI (and therefore a Class I indication for dual antiplatelet therapy) the clinical application of these findings remains to be seen.


  • Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol 2004; 44:E1-E211.
  • Lamberts M, Gislason GH, Lip GYH, et al. Antiplatelet therapy for stable coronary artery disease in atrial fibrillation patients on oral anticoagulant: A nationwide cohort study. J Am Coll Cardiol 2014;129:1577-1585.
  •  Sen-Chowdhry S, Gordon RJ. One weapon, two blows in the war against the thrombus. J Am Coll Cardiol 2014; DOI:10.1016/j.jacc.2014.03.040.