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 low-density lipoprotein cholesterol (LDL-C) alone is unlikely to completely reduce atherosclerotic risk.
Prof. Paul Ridker (Brigham and Women’s Hospital, MA, USA) explained that the study 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 who were eligible for inclusion in these selected trials . This could then resolve the clinically highly relevant question of whether to add a second LDL-lowering agent or rather an agent that inhibits inflammation to a statin.
Prof. Ridker and colleagues performed a collaborative analysis of patients with (a high risk of) atherosclerotic disease receiving contemporary statins who participated in the PROMINENT (NCT03071692), REDUCE-IT (NCT01492361), or STRENGTH (NCT02104817) trials. Included were 9,988, 8,179, and 13,078 participants from these respective studies, totalling 31,245 participants. Assessed were quartiles of increasing baseline hsCRP and 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 3 trials, patients with elevated hsCRP were at high CV risk irrespective of their LDL-C levels, Prof. Ridker concluded. So, which options are available to prescribe in addition to a statin? Prof. Ridker mentioned colchicine (0.5 mg) for patients with stable atherosclerosis and normal eGFR; bempedoic acid, which reduces both LDL-C and hsCRP; or SGLT2i 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.”
- Ridker P, et al. Residual inflammatory risk in contemporary statin treated patients: A collaborative analyses of 31,197 participants in the PROMINENT, REDUCE-IT, and STRENGTH trials. Session 411-10, ACC Scientific Session 2023, 4–6 March, New Orleans, USA.
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Table of Contents: ACC 2023
Letter from the Editor
ACC 2023 Highlights Podcast
Pulmonary Arterial Hypertension
Sotatercept improves exercise capacity in patients with PAH
Fixed-dose macitentan plus tadalafil superior to either agent alone in PAH
Immediate complete revascularisation non-inferior to staged complete revascularisation
RENOVATE-COMPLEX-PCI results support intravascular-guided PCI for complex lesions
Heart Failure and Cardiomyopathy
No need to restrict vigorous exercise in selected HCM patients?
No difference in CV outcomes between PET or CMR and SPECT
Interventional and Structural Cardiology
Benefits of MitraClip sustained to 5 years in COAPT trial
Transcatheter repair for patients with tricuspid regurgitation
Minimally invasive versus conventional sternotomy for mitral valve repair
Durable benefits of TAVR versus surgical aortic valve replacement in aortic stenosis patients
PCI not better than GDMT in severe ischaemic cardiomyopathy
Anticoagulation in non-critically ill hospitalised COVID patients
Statins associated with reduced heart dysfunction from anthracyclines
Multifaceted strategy improves prescription of therapies for diabetes and ASCVD
Bempedoic acid benefits statin-intolerant patients at high cardiovascular risk
Evolocumab improves coronary plaque morphology in stable CAD
Inflammation stronger predictor of MACE than cholesterol levels
Oral PCSK9 inhibitor significantly lowers LDL-C
Baxdrostat in patients with uncontrolled hypertension
Hormone therapy for gender dysphoria associated with increased CV risk
Pulsed-field ablation appears safe and effective for atrial fibrillation
Key correlates of incident dementia identified in the MESA study
Alzheimer’s-like changes seen in COVID-19 patients’ brains
Predicting MCI and dementia by assessing worrying about memory