Statin Trials, Cardiovascular Events, and Coronary Artery Calcification: Implications for a Trial-Based Approach to Statin Therapy in MESA

Abstract

Objectives: This study sought to determine whether coronary artery calcium (CAC) could be used to optimize statin allocation among individuals for whom trial-based evidence supports efficacy of statin therapy.

Background: Recently, allocation of statins was proposed for primary prevention of atherosclerotic cardiovascular disease (ASCVD) based on proven efficacy from randomized controlled trials (RCTs) of statin therapy, a so-called trial-based approach.

Methods: The study used data from MESA (Multi-Ethnic Study of Atherosclerosis) with 5,600 men and women, 45 to 84 years of age, and free of clinical ASCVD, lipid-lowering therapy, or missing information for risk factors at baseline examination.

Results: During 10 years' follow-up, 354 ASCVD and 219 hard coronary heart disease (CHD) events occurred. Based on enrollment criteria for 7 RCTs of statin therapy in primary prevention, 73% of MESA participants (91% of those >55 years of age) were eligible for statin therapy according to a trial-based approach. Among those individuals, CAC = 0 was common (44%) and was associated with low rates of ASCVD and CHD (3.9 and 1.7, respectively, per 1,000 person-years). There was a graded increase in event rates with increasing CAC score, and in individuals with CAC >100 (27% of participants) the rates of ASCVD and CHD were 18.9 and 12.7, respectively. Consequently, the estimated number needed to treat (NNT) in 10 years to prevent 1 event varied greatly according to CAC score. For ASCVD events, the NNT was 87 for CAC = 0 and 19 for CAC >100. For CHD events, the NNT was 197 for CAC = 0 and 28 for CAC >100.

Conclusions: Most MESA participants qualified for trial-based primary prevention with statins. Among the individuals for whom trial-based evidence supports efficacy of statin therapy, CAC = 0 and CAC >100 were common and associated with low and high cardiovascular risks, respectively. This information may guide shared decision making aimed at targeting evidence-based statins to those who are likely to benefit the most.

Keywords: cardiovascular disease; guideline; lipoproteins; primary prevention; statin.

Figure 1. Enrollment criteria for primary prevention with statins under the trial-based approach

The figure summarizes the criteria for initiation of statin therapy in people free of ASCVD as defined by a trial-based approach to statin therapy. ASCVD=atherosclerotic cardiovascular disease;WOSCOPS=West of Scotland Coronary Prevention Study; AFCAPS/TexCAPS=Air Force/Texas Coronary Atherosclerosis Prevention Study;ASCOT-LLA=Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm;CARDS=Collaborative Atorvastatin Diabetes Study;MEGA=Management of Elevated Cholesterol in the Primary Prevention Group of Adult Japanese; JUPITER=Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; HOPE-3=Heart Outcomes Prevention Evaluation-3. TC=total cholesterol; LDL-C=low-density lipoprotein cholesterol; HDL-C=high-density lipoprotein cholesterol; SBP=systolic blood pressure; DBP=diastolic blood pressure; HTN=hypertension; hsCRP=high-sensitivity C-reactive protein; Cholesterol concentrations are shown in mg/dL(to convert to mmol/L, divide by 38.6). *Women 60–65 years of age were eligible for statins with HOPE-3 trial if they had at least two additional risk factors. **High waist/hip ratio, ≥0.90 in men and ≥0.85 in women; Low HDL-cholesterol, < 1.0 mmol/L in men and <1.3 mmol/L in women; Dysglycemia, impaired fasting glucose, impaired glucose tolerance or uncomplicated diabetes treated with diet only; Renal dysfunction, microalbuminuria, eGFR<60 ml/min/1.73m² or creatinine >124 μmol/L.

Figure 2. Statin eligibility in MESA using a trial-based approach

Diagram illustrating the fraction of individuals from MESA meeting enrollment criteria in RCT’s of statin therapy. Individuals were selected consecutively in chronological order clockwise starting 12 o’clock, that is, first we selected individuals according to WOSCOPS criteria(1995), then we selected additional individuals according to AFCAPS/TexCAPS criteria(1998), and so on. Abbreviations as in Figure 1.

Figure 3. Distribution of CAC among individuals eligible for statin therapy based on a trial-based approach

In individuals for whom trial-based evidence supports efficacy of statin therapy, 44% had no sign of CAC. CAC=coronary artery calcium score.

Figure 4. Cumulative incidence of ASCVD and CHD stratified by CAC burden, among individuals eligible for statin therapy under a trial-based approach

ASCVD=atherosclerotic cardiovascular disease; CHD=coronary heart disease; CAC=coronary artery calcium score.

Figure 5. Estimated number needed to treat in 10 years to prevent 1 ASCVD or CHD event stratified by CAC burden, among individuals eligible for statin therapy under a trial-based approach

ASCVD=atherosclerotic cardiovascular disease; CHD=coronary heart disease; CAC=coronary artery calcium score.