Letter by Kan et al Regarding Article, “Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure: The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial”
To the Editor:
We read with interest the work by Massie et al,1 which reports that warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel and fewer admissions for worsening heart failure than aspirin in patients with reduced ejection fraction who are in sinus rhythm. Massie et al1 stated that a limitation relative to the higher number of diabetic patients in the warfarin group, with their higher risk, could have resulted in an underestimation of the ability of warfarin to reduce thromboembolic events. In our opinion, not only the composite of patients in each group but also the risk for occurrence of cardiac arrhythmia may influence the results of their second end point.
As we know, there are similar incidences of thromboembolic events in heart failure patients with paroxysmal atrial fibrillation (PAF) and sustained atrial fibrillation on antithrombotic therapy.2,3 Although the authors declared that PAF occurred without differences between treatment groups (10.3%, 10.3%, and 9.3% for aspirin, clopidogrel, and warfarin, respectively; P=0.57), we noticed that the incidence of PAF will increase more significantly in the aspirin or clopidogrel group than in the warfarin group if those who discontinued drug therapy during the study period are taken into account (13.2%, 13.0%, and 9.6% for aspirin, clopidogrel, and warfarin, respectively; P=0.08). Furthermore, the risk of developing PAF in patients with reduced left ventricular systolic function should be stressed. In recent studies, measurements of left atrial dimension, pressure, P-wave signal–averaged ECG, and atrial natriuretic peptide4 were reported to be predictors of PAF development in patients with heart failure. Because these objective variables were not obtained in the WATCH trial and because of the difficulty in documenting a PAF event completely, depending on the findings at follow-up, we recommend that the data of left atrial dimension estimated by echocardiography and left ventricular ejection fraction be available at baseline to reduce the potential difference for developing PAF in each group.
Finally, the more frequent hospitalizations for worsening symptoms of heart failure in the aspirin group could be explained in part by the fact that aspirin pharmacologically attenuates the cardiovascular protective effect of angiotensin-converting enzyme inhibitor,5 but the conclusion is still controversial. In addition, moderate to severe systolic cardiac function will precipitate heart failure in PAF and other cardiac arrhythmias that may not be detected on admission, reflecting the conflicts of the findings in this trial that more diabetic patients in the warfarin group were found to have fewer PAF events.
Massie BM, Collins JF, Ammon SE, Armstrong PW, Cleland JG, Ezekowitz M, Jafri SM, Krol WF, O'Connor CM, Schulman KA, Teo K, Warren SR, for the WATCH Trial Investigators. Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial. Circulation. 2009; 119: 1616–1624.
Hohnloser SH, Pajitnev D, Pogue J, Healey JS, Pfeffer MA, Yusuf S, Connolly SJ, for the ACTIVE W Investigators. Incidence of stroke in paroxysmal versus sustained atrial fibrillation in patients taking oral anticoagulation or combined antiplatelet therapy: an ACTIVE W Substudy. J Am Coll Cardiol. 2007; 50: 2156–2161.
Liao J, Khalid Z, Scallan C, Morillo C, O'Donnell M. Noninvasive cardiac monitoring for detecting paroxysmal atrial fibrillation or flutter after acute ischemic stroke: a systematic review. Stroke. 2007; 38: 2935–2940.