Critical review of high-sensitivity C-reactive protein and coronary artery calcium for the guidance of statin allocation: head-to-head comparison of the JUPITER and St. Francis Heart Trials.

Statins have been shown to be effective in primary prevention even among patients at low cardiovascular risk.1 However, statins are associated with moderate medical costs and have potential side effects.2 As a result, various biomarkers have been proposed for use in a tailored treatment strategy aimed at decreasing the number needed to treat (NNT), increasing the number needed to harm, and maximizing the cost-effectiveness of statin therapy. High-sensitivity C-reactive protein (hsCRP) and coronary artery calcium (CAC) are the leading novel markers of cardiovascular risk and are most commonly suggested for use in a tailored treatment approach. Despite the theoretical benefits of these 2 biomarkers, there has been a dearth of definitive randomized trials specifically designed to test the efficacy of these, or any, novel biomarker for statin allocation. To date, only 2 randomized control trials have explored the potential use of these tests in improving outcomes with statin therapy: hsCRP in the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial2a and CAC in the St. Francis Heart trial (Table).2b View this table: Table. Systematic Comparison of the JUPITER and the St. Francis Heart Trials In this article, we perform a comprehensive review of these trials from several different viewpoints: study rationale, study design, funding source, study population, pharmacological intervention, overall trial result, and overall trial interpretation. Our goal is to critically assess the level of evidence that these 2 randomized control trials provide, to suggest additional secondary analyses of the existing trial data, and to lay out a framework for performing true biomarker randomized control trials in the future. ### JUPITER Trial hsCRP is an acute phase inflammatory protein shown to predict the likelihood of future cardiovascular events regardless of baseline Framingham risk score, low-density lipoprotein-cholesterol (LDL-C) level, or presence of metabolic syndrome.5, …