Guideline-Based Statin Eligibility, Coronary Artery Stenosis and Cardiovascular Events in Patients with Stable Chest Pain: A Secondary Analysis of the PROMISE Randomized Clinical Trial

Background: Recommendations for preventive statin treatment in patients with stable chest pain may be difficult as symptoms can be unspecific. It is unclear if coronary CT angiography (CTA)-detected coronary artery disease (CAD) can optimize statin prescription.

Methods: In stable chest pain patients randomized to CTA in the PROMISE trial, statin eligibility was defined per 2018 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Primary outcome was a composite of death, myocardial infarction or unstable angina over 26 months median follow-up. Hazard ratios (HR) of non-obstructive (1-69% stenosis) and obstructive (≥70% stenosis) CAD for events were determined using Cox proportional hazard models. Calculated HR were then incorporated into the ACC/AHA pooled cohort equation (PCE) to revised ASCVD risk and assess re-classification of statin eligibility.

Results: Among 3986 patients (60.5 ± 8.2 years; 51% female), 72.9% (2904/3986) were statin eligible. Event rates in statin-eligible vs. ineligible patients were 3.3% vs. 2.3% (HR = 1.4 (95% CI 0.9-2.2), p = 0.142). Although the proportion of statin-eligible patients increased with CAD severity, 54% without CAD were statin eligible. Incorporating information on CAD into PCE reclassified 12.7% of patients (1.3% towards statin, 11.4% towards no statin). Similar results were found in stratified analysis of statin naïve patients (reclassification of 13.9%, 1.0% towards statin, and 12.9% towards no statin). As a result, revised ASCVD risk improved model discrimination in all patients (c-statistic: 0.59 (95 %CI 0.55-0.62) vs. 0.52 (95 %CI 0.49-0.56); p 0.001), while reducing statin use by 10.1% (62.7% vs. 72.9% statin eligible, p 0.001).

Conclusion: In stable chest pain patients, integration of CAD into guideline recommendations was associated with greater accuracy to reclassify those at increased risk for incident events and a more efficient use of statins.