ApoB, Residual CV Risk After ACS, and Effects of Alirocumab

Jul 14, 2022
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Authors:
Hagström E, Steg G, Szarek M, et al.
Citation:
Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab. Circulation 2022;Jun 30:[Epub ahead of print].
Summary By:
Melvyn Rubenfire, MD, FACC

Quick Takes

  • In patients with recent ACS receiving optimized statin therapy, a decision to treat with a PCSK9 inhibitor may be better informed by the level of apoB than LDL-C and non–HDL-C.
  • Achieved apoB was predictive of MACE after adjustment for achieved LDL-C or non–HDL-C but not vice versa.
  • Achievement of an apoB level ≤35 mg/dL may reduce lipoprotein-attributable residual risk after ACS.

Study Questions:

Do the apolipoprotein B (apoB) level at baseline and apoB decline hold incremental predictive information on residual risk after acute coronary syndrome (ACS) treatment with alirocumab beyond that provided by low-density lipoprotein cholesterol (LDL-C)?

Methods:

The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab with placebo in 18,924 patients with recent ACS (1-12 months prior to randomization) and elevated atherogenic lipoproteins despite optimized statin therapy (LDL-C ≥70 mg/dL, non–high-density lipoprotein cholesterol [non–HDL-C] ≥100 mg/dL, and apoB ≥80 mg/dL). The primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score–matched models. ApoB values below the lower limit of detection were set to 35 mg/dL.

Results:

Average age was about 58 years, 25% were women, 79% were White, 76% were from Europe or North America, and 12% were Asian. Median follow-up was 2.8 years (interquartile range, 2.3-3.4 years). In proportional hazards analysis in the placebo group, MACE increased across increasing baseline apoB strata (3.2 [95% CI, 2.9–3.6], 4.0 [95% CI, 3.6–4.5], and 5.5 [95% CI, 5.0–6.1] events per 100 patient-years in strata <75, 75–<90, and ≥90 mg/dL, respectively; ptrend < 0.0001) and after adjustment for LDL-C (ptrend = 0.035). Higher baseline apoB stratum was associated with greater relative (p trend < 0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78–4.79], 3.09 [95% CI, 2.69–3.54], and 2.41 [95% CI, 2.11–2.76] events per 100 patient-years in strata ≥50, >35–<50, and ≤35 mg/dL, respectively). Compared with propensity score–matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved LDL-C or non–HDL-C but not vice versa.

Conclusions:

In patients with recent ACS and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved LDL-C or non–HDL-C, indicating that apoB provides incremental information. Achievement of an apoB level ≤35 mg/dL may reduce lipoprotein-attributable residual risk after ACS.

Perspective:

The study was conducted primarily in men from European countries with a small percentage of Asians and Blacks. Over 70% underwent revascularization for the index event. The concept of targeting to apoB is attractive but not generalizable unless validated in populations of Asians, Blacks, and Hispanics who may have different lipid and apolipoprotein responses to PCSK9 inhibition based on genetics, sex, drug metabolism, diet, stress, and alcohol, to name a few. There are differences in lipoprotein particle number and size and PCSK9 levels in Black versus White persons.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Diabetes and Cardiometabolic Disease, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Prevention, Vascular Medicine, Cardiac Surgery and Arrhythmias, Lipid Metabolism, Nonstatins, Novel Agents, Statins, Interventions and ACS, Interventions and Vascular Medicine

Keywords: Acute Coronary Syndrome, Angina, Unstable, Apolipoproteins B, Cholesterol, LDL, Coronary Disease, Dyslipidemias, Heart Disease Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Ischemic Stroke, Myocardial Infarction, Myocardial Revascularization, PCSK9 protein, human, Primary Prevention, Proprotein Convertase 9, Risk Factors, Stroke


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