Danish Registry Suggests Aspirin Unnecessary in A-fib Patients After MI or PCI

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One year after myocardial infarction (MI) or percutaneous coronary intervention (PCI), patients with atrial fibrillation (A-fib) do just as well when they receive oral anticoagulants plus clopidogrel instead of triple therapy that includes aspirin. The findings, scheduled to be published online June 4, 2013, ahead of print in the Journal of the American College of Cardiology, were culled from a Danish nationwide registry study.

Morten Lamberts, MD, of Copenhagen University Hospital Gentofte (Hellerup, Denmark), and colleagues gathered data on 12,165 A-fib patients hospitalized with MI and/or undergoing PCI between 2001 and 2009 in Denmark.

Nearly two-thirds of patients (62.0%) received multiple antithrombotic drugs at baseline, though only 4,659 (38.3%) received oral anticoagulants, specifically warfarin or phenprocoumon. Neither prasugrel nor ticagrelor and none of the new oral anticoagulants were approved for routine use in A-fib or CAD patients in Denmark during the study period.

No Need for Triple Therapy

At 1 year, the rate of MI/coronary death was 18.5%, ischemic stroke was 5.6%, and bleeding 6.3%. All-cause death occurred at a rate of 19.4%.

Patients on oral anticoagulation plus either aspirin or clopidogrel, or on dual antiplatelet therapy (DAPT) with aspirin and clopidogrel, saw no increased risk of recurrent coronary events compared with triple therapy. Oral anticoagulation plus aspirin and DAPT both raised the risk of all-cause death while reducing the risk of bleeding. Oral anticoagulation plus clopidogrel showed a trend toward less bleeding (table 1).

Table 1. Outcomes at 1 Year: Various Regimens vs. Triple Therapy




95% CI

Recurrent Coronary Events
OAC + Clopidogrel
OAC + Aspirin





All-Cause Death
OAC + Clopidogrel
OAC + Aspirin





OAC + Clopidogrel
OAC + Aspirin





Abbreviations: OAC, oral anticoagulant; DAPT, dual antiplatelet therapy.

Among the various alternatives to triple therapy, only DAPT was associated with higher likelihood of ischemic stroke (HR 1.50; 95% CI 1.03-2.20).

Interestingly, the type of antithrombotic therapy prescribed at baseline did not reflect patients’ predicted risks of ischemic stroke (CHADS2) or bleeding (HAS-BLED).

Study Observational but Still Valuable

In an editorial accompanying the paper, Steven M. Markowitz, MD, of Weill Cornell Medical College (New York, NY), writes, "For patients with both [A-fib] and coronary disease, there is a paucity of information to guide rational decisions and very little evidence to support intensive anticoagulation with triple therapy."

The current study possesses the strengths and weaknesses of any retrospective registry, Dr. Markowitz notes. It provides what may be more realistic results than would be seen in a randomized trial but also lacks detail on clinical characteristics, such as the time course and indications for drug therapy and whether patients received DES or BMS during PCI. In addition, the "results cannot necessarily be extrapolated to the newer direct thrombin and factor Xa inhibitors, but it is probable that combining these new agents with dual antiplatelets would cause more bleeding than benefit," he adds.

Dr. Lamberts told TCTMD in an e-mail communication that, though the study is observational, it contributes important information. "[C]urrent recommendations [supporting] triple therapy are based on Level C evidence and selection of treatment in real-world practice seems largely random," he commented, adding that evidence continues to build showing the superiority of oral anticoagulation plus clopidogrel over triple therapy.

Time to Change?

Indeed, the Danish study dovetails with the randomized WOEST trial, published in the Lancet earlier this year, Dr. Markowitz notes in the editorial.

"The implication here is that physicians should have confidence to curtail triple therapy when [oral anticoagulation] is needed for [A-fib]," he concludes, adding that BMS should be used when possible in A-fib patients and that newer stent designs are apt to reduce the need for triple therapy even further. "Ultimately, the clinician must exercise judgment and integrate bleeding and thrombotic risks in prescribing anticoagulation regimens in such situations."

In an e-mail communication with TCTMD, Marco Valgimigli, MD, PhD, of the University of Ferrara (Ferrara, Italy), agreed that the evidence is now strong enough to shift clinical practice away from triple therapy.

"Aspirin has always been considered the unavoidable antithrombotic drug on top of which other compounds have to be added. But given the multiple options today, I think it is very reasonable to consider dropping aspirin in patients who have to take other concomitant antithrombotics, especially if a P2Y12 inhibitor is on board," Dr. Valgimigli said, acknowledging that it may be difficult to convince doctors to change.

Yet he stressed that dedicated studies are required before extending this message to the newer generation of oral anticoagulants.

As to why so few of the Danish patients received oral anticoagulants in the first place, Dr. Lamberts had no definitive answer. "Our findings . . . are very concerning but could be explained by what we know from other studies of A-fib patients [in that antithrombotic treatment is not necessarily dictated by guidelines]," he said. Moreover, it is possible that not all patients had indications for anticoagulation.

Looking forward, Dr. Lamberts highlighted the ongoing ISAR-TRIPLE trial, which is randomizing patients to 6 weeks vs. 6 months of triple therapy.

Study Details

Mean patient age was 75.6 years, with men comprising 60.7% of the cohort. Mean CHADS2, CHA2DS2-VASc, and HAS-BLED scores were 1.9, 4.0, and 2.0, respectively.



1. Lamberts M, Gislason GH, Olesen JB, et al. Oral anticoagulation and antiplatelets in atrial fibrillation patients after myocardial infarction and coronary intervention. J Am Coll Cardiol. 2013;Epub ahead of print.

2. Markowitz SM. Antithrombotic regimens in patients with atrial fibrillation and coronary disease: Optimizing efficacy and safety [editorial]. J Am Coll Cardiol. 2013;Epub ahead of print.


The paper and editorial contain no statements regarding potential conflicts of interest for Drs. Lamberts and Markowitz.

Dr. Valgimigli reports receiving research grants from Medtronic, Terumo, and The Medicines Company as well as speakers’ bureau or advisory board fees from Abbott, AstraZeneca, Biosensors, Boston Scientific, CID Vascular, Eli Lilly, Iroko, St. Jude, and Terumo.

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Caitlin E. Cox is News Editor of TCTMD and Associate Director, Editorial Content at the Cardiovascular Research Foundation. She produces the…

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