Warfarin Quality, Adherence, Range, Determinants, and Events in Egyptian Rheumatic Heart Disease and Atrial Fibrillation

Overview

No Egyptian study has systematically quantified TTR, identified its predictors, or linked anticoagulation quality to clinical outcomes in the RHD-AF population. This knowledge gap directly impairs the ability of Egyptian cardiac centers to design effective anticoagulation clinic models.16 WARDEN-Egypt addresses a precisely defined evidence gap at zero marginal cost: the study relies entirely on INR logbooks already maintained in clinical practice and structured follow-up visits that replicate current standard of care. Its findings will provide the first Egyptian TTR benchmark, identify modifiable predictors of poor anticoagulation control amenable to targeted intervention, and generate hypothesis-forming data on the TTR-outcome relationship. This has direct implications for anticoagulation clinic design, national guideline development, and future interventional trials in Egyptian RHD.

Rheumatic heart disease (RHD) remains the most prevalent acquired cardiac condition in low- and middle-income countries (LMICs), disproportionately affecting young adults in sub-Saharan Africa, South Asia, and the Middle East.1-3 In Egypt, RHD continues to be a leading cause of cardiac morbidity, particularly among women of reproductive age and rural populations with limited access to primary prophylaxis.4,5 Atrial fibrillation (AF) is among the most frequent and clinically dangerous complications of RHD. Unlike non-valvular AF, RHD-AF carries a substantially higher thromboembolic risk - estimated at five to twenty times that of the general population.6 Mitral stenosis is the dominant lesion predisposing to AF and left atrial thrombus formation. For these patients, anticoagulation with vitamin K antagonists (VKAs) remains the standard of care.7 The INVICTUS trial (2022), the largest randomized controlled trial in RHD-AF, definitively established that warfarin is superior to rivaroxaban in patients with RHD-associated AF. The warfarin arm demonstrated significantly lower rates of the composite primary endpoint (stroke, systemic embolism, myocardial infarction, or death from vascular or unknown cause) compared to rivaroxaban (8.2% vs. 12.2% per 100 patient-years; HR 0.65, 95% CI 0.58-0.73; p\<0.001). Direct oral anticoagulants (DOACs) are therefore not recommended in RHD-AF, cementing the central role of warfarin in this population for the foreseeable future.5 Warfarin efficacy is critically dependent on the quality of anticoagulation control, best captured by time in therapeutic range (TTR) - the proportion of time that a patient's INR remains within the target range (typically 2.0-3.0 for RHD-AF). TTR calculated by the Rosendaal linear interpolation method is the accepted standard.9