American Heart Journal
Volume 155, Issue 2 , Pages 197-199, February 2008

Atrial fibrillation in the setting of acute myocardial infarction —irregularly irregular treatment

  • Charles L. Campbell, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Charles L. Campbell, MD, FACC, Division of Cardiovascular Medicine, University of Kentucky, 900 S. Limestone, 326 CTW Building, Lexington, KY 40536‑0200.
    • ,
  • Steven R. Steinhubl, MD

Gill Heart Institute, University of Kenucky, Lexington, KY

Received 23 October 2007; accepted 25 October 2007. published online 13 December 2007.

Article Outline

 

The development of atrial fibrillation (AF) is a relatively common complication of acute myocardial infarction (AMI) present in ∼10% to 15% of AMIs and generally thought to be a marker of adverse prognosis.1, 2, 3, 4 Whether these worse outcomes are directly related to the development of AF or whether the development of AF is serving as a marker for greater myocardial dysfunction is unclear. However, what remains surprising is that despite the increased risk, clear guidelines regarding its treatment in this setting are unavailable. Although it might seem reasonable to treat these patients with oral anticoagulants (OACs), evidence suggests that patients who develop AF during an AMI are, in fact, frequently not discharged on an OAC.5, 6 This is somewhat surprising given the poor prognosis of the these patients and the broad evidence base that indicates moderate-intensity OAC (international normalized ratio 2.0-2.5) in the setting of AMI is at least as effective as aspirin in reducing recurrent ischemic events.7 There is also overwhelming evidence that OAC therapy is effective in reducing the embolic complications of chronic AF.7,8 It would seem logical therefore to err on the side of treatment.

The hesitancy to treat patients with transient AF in the setting of an AMI is likely born of several factors. First, there are simply no clinical trials specifically evaluating the efficacy of anticoagulation after an AMI complicated by AF, which is especially important because we too frequently look for reasons not to start our patients on anticoagulant therapies secondary to concerns of bleeding, poor compliance, or both.9,10 Second, in some of the retrospective analyses that helped delineate the risk of AF during an AMI, chronic AF was not distinguished from event-related AF, and it could be argued that the increase in risk might be confined to patients with chronic AF.3 Third, the development of AF is typically associated with comorbid conditions such as age, the presence of multivessel coronary disease, prior episodes of heart failure, and higher Killip class, raising the concern that AF may not really be an independent predictor of poor outcomes. Fourth, there are legitimate concerns about the potential for increased bleeding when OACs are combined with aspirin and clopidogrel as would be expected after percutaneous coronary intervention and stent placement. The current clinical guidelines are of little help, calling for OACs only in the setting of left ventricular thrombus, mechanical heart valves, and chronic AF.11

Two recently published articles promise to shed light on this issue and set the stage for future study. In the first, Siu et al retrospectively evaluated the impact of transient (sinus rhythm at admission and at discharge) AF on 1-year adverse events among a group of patients with an acute inferior myocardial infarction and no evidence of left ventricular dysfunction who were admitted to a single center over a 9-year period (1997-2005).6 This relatively healthy cohort of 431 patients provides an opportunity to evaluate transient AF in the absence of other risk factors for embolic events such as left ventricular dysfunction and anterior wall myocardial infarctions. In this cohort, transient AF was observed in 59 patients (13.7%) during the index hospitalization. When compared to patients without AF, those with transient AF were significantly more likely to experience an ischemic stroke over the next year (10.2% vs 1.8%, P < .01). None of these patients received OAC therapy at discharge. This work strongly suggests that new-onset AF is an important and independent finding in the peri-MI period, not just a manifestation of heart failure or shock.

In the second article, appearing in this issue of the Journal, Tangelder et al present a subgroup analysis from the ESTEEM trial involving patients who developed AF during their initial hospitalization. In the main trial, 1883 patients with a recent myocardial infarction were randomized to 1 of 4 doses of the oral direct thrombin inhibitor, ximelagatran plus aspirin, or aspirin alone. Randomization occurred within 14 days of the index event and was timed to coincide with the discontinuation of intravenous or subcutaneous anticoagulation. Follow-up occurred over 6 months. Patients who had recently undergone, or were expected to undergo a percutaneous coronary intervention, were excluded from the trial. Thus, most patients (1230/1883, 65%) had ST-segment elevation myocardial infarctions. With respect to the primary end point of death, nonfatal myocardial infarction, and recurrent ischemia, the combination of ximelagatran and aspirin was superior to aspirin alone. No dose response was noted in the ximelagatran groups. One hundred seventy-four patients in the trial developed AF before randomization, 73 from the placebo arm and 101 from the combined ximelagatran arms. Patients with AF were somewhat older but were otherwise similar to those that did not develop AF. Those randomized to ximelagatran experienced a significantly reduced risk of death, myocardial infarction, or stroke when compared to those receiving aspirin alone (7/101 = 6.9% vs 15/73 = 20.6%, adjusted hazard ratio 0.30, 95% CI 0.12-0.784. When analyzed independently, there was a trend toward a reduction in each of the individual end points, including stroke.

These results indicate that not only is AF in the setting of AMI a high-risk finding but that it also represents a potentially very treatable risk, even among patients receiving aspirin and clopidogrel. The time may now be especially right to consider a formal evaluation of this hypothesis as there are many new oral anticoagulant medications being developed and evaluated. The oral direct factor Xa inhibitors are a promising class of medications for this purpose. These drugs bind and inactivate factor Xa, thereby inhibiting the conversion of prothrombin to thrombin after initiation of the coagulation pathway by either the intrinsic or extrinsic pathway. Unlike heparinoids, and other indirect inhibitors of factor Xa such as fondaparinux, these drugs can bind free factor Xa molecules or those that are within developing clot or the prothrombinase complex.12 These medications also promise to be “cleaner” than the indirect factor Xa antagonists or the vitamin K antagonists because they should not activate platelets such as the heparinoids or inhibit the formation of vitamin K–dependent “anticoagulant” factors such as factor C and should have less rebound thrombin generation upon discontinuation.13 A number of oral factor Xa inhibitors are being developed, and at least one has entered into phase III clinical trials for the prevention of the complications of chronic AF.14,15 Fortunately, there are also plans for large-scale studies of these drugs in patients with an acute coronary syndrome, which gives us the opportunity to further explore the role of additional anticoagulation therapy in this contemporarily treated population.16 This information is critical as it has been demonstrated recently that clopidogrel and aspirin in combination are inferior to OAC for the prevention of embolic events among patients with AF.17 For too long now we have tolerated a lack of evidence as to how to best treat the patient with acute coronary syndrome and AF, and it is now clear that by doing so we are missing the opportunity to substantially improve patient outcomes.

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References 

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PII: S0002-8703(07)00871-X

doi:10.1016/j.ahj.2007.10.039

American Heart Journal
Volume 155, Issue 2 , Pages 197-199, February 2008

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