Significance of Persistent Inflammation in Patients With Chronic Coronary Syndrome: Insights From the REAL-CAD Study

Background The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS. Objectives This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients. Methods The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP. Results Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP. Conclusions The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730)