A collaborative analysis of the PROMINENT, REDUCE-IT, and STRENGTH trials (N=31,245) showed that residual inflammatory risk is a better predictor of future major adverse cardiovascular events (MACE), cardiovascular (CV) death, and all-cause mortality than residual cholesterol risk in statin-treated patients. Thus, targeting LDL cholesterol (LDL-C) alone is unlikely to completely reduce atherosclerotic risk.
Paul Ridker, MD, MPH, explained at the American College of Cardiology 2023 Annual Scientific Sessions that he and colleagues aimed to determine the relative importance of high-sensitivity C-reactive protein (hsCRP) and LDL-C as determinants of risk for MACE, CV death, and all-cause death among patients receiving statins.1 This could then resolve the question of whether to add a second LDL-lowering agent or anti-inflammatory to a statin.
Dr. Ridker and colleagues performed a collaborative analysis of 31,245 patients with, or at high risk for, atherosclerotic disease receiving contemporary statins who participated in the PROMINENT (NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials. Assessed were quartiles of increasing baseline hsCRP and increasing baseline LDL-C.
Comparing the highest (4th) quartile to the first (referent) quartile, residual inflammatory risk measured by hsCRP was significantly associated with:
- incident MACE (HR, 1.31; 95% CI, 1.20–1.43; P<0.0001);
- CV mortality (HR, 2.68; 95% CI, 2.22–3.23; P<0.0001); and
- all-cause mortality (HR, 2.42; 95% CI, 2.12–2.77; P<0.0001).
Residual cholesterol risk was not associated with MACE (HR, 1.07; 95% CI, 0.98–1.17; P=0.11). It was associated with CV death and all-cause death, but HRs were much lower: 1.27 (95% CI, 1.07–1.50; P=0.0086) and 1.16 (95% CI, 1.03–1.32; P=0.025), respectively.
In all three trials, patients with elevated hsCRP were at high CV risk irrespective of their LDL-C levels, Dr. Ridker concluded. Regarding options available to add to a statin, Dr. Ridker mentioned colchicine (0.5 mg) for patients with stable atherosclerosis and normal eGFR; bempedoic acid, which reduces both LDL-C and hsCRP; or SGLT2is and GLP1RAs, both of which have concomitant anti-inflammatory effects. “We believe the combined use of aggressive LDL-lowering and inflammation-inhibiting therapies will become standard of care for almost all atherosclerotic patients,” Dr. Ridker said.
Copyright ©2023 Medicom Medical Publishers
