LDL-C lowering and cardiovascular events in high risk patients

  • Vallejo-Vaz AJ & al.
  • Atherosclerosis
  • 12 Jul 2019

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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  • Patients with atherosclerotic cardiovascular disease (ASCVD) and comorbidities, such as diabetes mellitus (DM), chronic kidney disease (CKD) and polyvascular disease (PoVD), that increase cardiovascular diseaase (CVD) risk derived greater absolute benefits from achieving very low levels of low-density lipoprotein cholesterol (LDL-C) level with alirocumab.

Why this matters

  • Recent consensus statements and guideline updates specifically identified the presence of high-risk comorbidities as scenarios, in which the addition of a proprotein convertase subtilisin/kexin type 9 inhibitor should be considered if LDL-C levels remain high despite maximally tolerated statin therapy.

Study design

  • Post-hoc analysis of pooled data from 3505 patients with ASCVD included in 9 phase 3 ODYSSEY trials comparing alirocumab (n=2262) with control (placebo/ezetimibe; n=1243).
  • All patients were stratified into those with comorbidities (DM, n=981; CKD, n=660; PoVD, n=943) and without comorbidities (n=1573).
  • Funding: Sanofi and Regeneron Pharmaceuticals, Inc.

Key results

  • In the overall ASCVD population, the mean percentage change in LDL-C level during the study period was significantly lower with alirocumab compared with placebo (−57.4% vs 2.2%) or ezetimibe (−49.9% vs −17.2%).
  • Similar results were observed in those with and without comorbidities.
  • Reduction in LDL-C level (39 mg/dL) was associated with a lower risk for major adverse cardiovascular events (MACEs) in patients with ASCVD (HR, 0.75; 95% CI, 0.62-0.90; P=.0023).
  • Risk reduction was similar in all 3 very high-risk ASCVD subgroups:
    • DM (HR, 0.65; 95% CI, 0.49-0.87; P=.0034);
    • CKD (HR, 0.70; 95% CI, 0.48-1.01; P=.0571) and
    • PoVD (HR, 0.70; 95% CI, 0.49-1.00; P=.0516).
  • Absolute benefits were greater for very high-risk subgroups; lowering LDL-C from 120 to 40 mg/dL would result in 2.76-4.35 fewer MACEs/100 patient-years vs 0.3 for no comorbidities.


  • Post-hoc analysis.
  • Limited treatment duration.