Atrial fibrillation, valvular heart disease, and use of target-specific oral anticoagulants for stroke prevention.

With the introduction of the target-specific oral anticoagulants (TSOAs), primary and secondary stroke prevention in atrial fibrillation (AF) has been revolutionized. Large randomized clinical trials and subsequent meta-analyses have clearly demonstrated that these agents have at least comparable if not superior efficacy and cause no more or even less major bleeding than vitamin K antagonists. 5 The improved safety profile of these new compounds is particularly reflected by the significantly reduced risk of intracranial bleeds in comparison with warfarin, a property which all TSOAs have in common. Because of the historical studies on stroke prevention in patients with AF, all of the pivotal trials of TSOAs were conducted in patients with non-valvular AF, defined as patients with AF without rheumatic valve disease (mainly severe/moderate mitral stenosis) and/or without prosthetic heart valves. All other types of valve disease such as mitral regurgitation, aortic regurgitation, or aortic stenosis, for example, were allowed to be included in these trials. However, the historical term ‘non-valvular AF’ recently used in TSOA studies has created some confusion and led to concerns about the use of the TSOAs in patients with AF and valvular abnormalities. The recently published European and North American recommendations for management of AF have defined valvular AF as AF related to rheumatic valve disease (predominantly mitral stenosis) or to prosthetic heart valves, or as AF occurring in the absence of rheumatic mitral stenosis, mechanical or bioprosthetic heart valves, or mitral valve repair. The rationale behind these definitions was the generally accepted higher risk of thrombo-embolic stroke associated with these conditions. Whereas rheumatic valvular disease is nowadays less frequently observed—at least in developed countries—many patients suffering from AF have other valve abnormalities. The ROCKET AF investigators have now presented their post-hoc analysis of AF patients with ‘significant valvular disease’ who were randomized to treatment with rivaroxaban or warfarin. Patients with valvular AF, defined as AF in patients with moderate/severe mitral stenosis and/or prosthetic heart valves, had been excluded from ROCKET AF. The authors are to be congratulated for their in-depth analysis of this important subset of patients. Their report represents the first full-length article on this topic which should be viewed in the light of two preliminary similar reports, one from the ARISTOTLE trial comparing apixaban with vitamin K antagonist therapy and one from the RE-LY trial comparing dabigatran with warfarin. The study by Breithardt et al. offers insights into three clinically important issues. The first issue relates to the clinical characteristics of subjects who had significant valvular disease. Overall, 14% of the ROCKET patients had some form of significant valvular disease compared with 26% in the ARISTOTLE trial and 22% in RE-LY. Not unexpectedly, valvular disease in the majority of patients consisted of mitral regurgitation (90%), followed by aortic regurgitation (25%) and aortic stenosis (11%; more than one valve could be affected). Similar numbers were seen in the dabigatran and the apixaban experience. In ROCKET AF, patients with valvular disease were older than individuals without, and had more comorbidities such as congestive heart failure, prior myocardial infarction, prior coronary artery bypass graft surgery, renal impairment, and peripheral arterial disease. The same differences in baseline characteristics between patients with and without valvular disease were observed in the other two trials. Despite these differences, in the ROCKET AF trial stroke rates were similar in patients with or without valvular disease after adjustment for important baseline criteria; similar to the findings in the RE-LY trial. In contrast, in the ARISTOTLE trial, the rate of stroke and systemic embolism