Rheumatic Heart Disease (RHD), the most common cardiovascular disease in those under 25, remains a significant public health problem in lower and middle-income countries (LMIC). Currently no proven treatment exists that prevents or delays the development and progression of cardiac sequelae in patients with RHD. Despite compelling biologic and observational data that suggests statin use delays progression of valvular heart disease, to date there has not been a randomized controlled trial to test this hypothesis. If statin therapy indeed delays progression of cardiac sequelae and improves clinical outcomes in patients with RHD, it will fundamentally shift RHD management strategies world-wide and importantly impact millions of lives, mostly in LMIC but also in Western countries. The largely benign safety profile of statins and their wide availability will further guarantee the usage and scalability of such therapy.
We aim to leverage our long-existing collaborations between colleagues at the University of Washington, Seattle, and institutions in Nepal (Manmohan Cardiothoracic, Vascular and Transplant Center; Dhulikhel Hospital Kathmandu University Hospital), an RHD endemic country, to conduct a pilot study to assess feasibility and gain implementation insights for conducting a larger RCT that will evaluate safety and efficacy of atorvastatin among RHD patients. The goal of this R34 application is to address specific implementation questions necessary and sufficient to ensure the feasibility of the larger RCT. With this study, we will build a registry of RHD patients in order to facilitate research on RHD subjects. We will then pilot a small feasibility study, administering low dose atorvastatin or placebo in a double blind randomized controlled fashion to 100 adult RHD patients, obtaining echocardiograms at baseline and end of study in 18 months, and following patients for RHD-related cardiovascular events. The feasibility study will address the following aims: (1) understand the recruitment, adherence, and retention rates and (2) evaluate the rate of valvular disease progression, and secondarily, composite cardiovascular endpoints in this population. The answers to the above questions are both necessary and sufficient to effectively design a larger trial to test the efficacy of statins in mitigating valvular damage.
Rheumatic Heart Disease (RHD) is a major public health problem world-wide and medications that delay the progression of valvular damage is needed. We will pilot a double-blind, placebo-controlled randomized controlled trial (RCT) in 100 adult RHD patients in Nepal to address specific implementation questions (availability of eligible patients, enrollment and retention rates, adherence, rate of progression of valvular pathology) necessary and sufficient to ensure the feasibility of the larger double-blinded placebo-controlled randomized clinical trial.
