Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

Lipoprotein(a) and Cardiovascular Disease Prevention across Diverse Populations

“…In observational analyses for a 50 mg/dl (105 nmol/l) higher lipoprotein(a) level the age- and sex-adjusted hazard ratio for ischemic stroke was 1.20 (95% CI: 1.13 to 1.28), while the corresponding age- and sex-adjusted genetic causal risk ratio for KIV-2 number of repeats was 1.20 (95% CI: 1.02 to 1.43) and for rs10455872 was 1.27 (95% CI: 1.06 to 1.51). The highest absolute 10-year risk of ischemic stroke was 17% in active smoking individuals > 70 years of age with hypertension and lipoprotein(a) levels > 93 mg/dl (> 199 nmol/l: 96th to 100th percentile) Bittner et al (2020) [ 69 ] Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome 18,924 (15,024 white, 473 black, 2498 Asian) patients age 40 years or older who experienced an ACS 1–12 months before randomization and who had a LDL-C level of ≥ 70 mg/dl (1.81 mmol/l), non-high-density lipoprotein cholesterol (non-HDL-C) level of ≥ 100 mg/dl (2.59 mmol/l), or an apolipoprotein B level of ≥ 80 mg/dl on high-intensity statin therapy A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE) Composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina that required hospitalization Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI 0.990–0.999; p = 0.0081).…”

The dedicated “Lp(a) clinic”: A concept whose time has arrived?

“…1). The risk is small at Lp(a) of 50 mg/dL [5][6][7], but rises nearly linearly with increased Lp(a) levels. An estimated 1:10 subjects have Lp(a) levels > 90 mg/dL.…”

“…The evidence base for the potential causality of elevated Lp(a) for CVD and CAVD is composed of epidemiologic, mendelian randomization, genome-wide association and post-hoc studies of randomizedcontrolled clinical trials. A consistent conclusion is that elevated Lp(a) levels predict higher CVD event rates, both in primary care populations [3,4], as well as in subjects treated with statins [5] or PCSK9 inhibitors [6,7]. Although pharmacologic therapies that specifically target Lp(a) have not been tested in clinical outcomes trials, observational studies on apheresis performed specifically for elevated Lp(a) in subjects with recurrent events or progressive CVD have demonstrated 70-90% lower CV-event rates following initiation of apheresis [8][9][10][11].…”

“…In the JUPITER trial, elevated Lp(a) was a significant determinant of residual risk and rosuvastatin significantly reduced incident cardiovascular disease in subjects with low or high Lp(a) with no evidence of interaction, consistent with these findings. More recently, it was demonstrated that in intensively-treated statin patients in the FOURIER [6] and ODYSSEY OUTCOMES [7] trials allocated to the placebo group, Lp(a) remained an independent predictor of risk, with approximately a 25-30% higher event rate in the highest quartile (>~50-60 mg/dL). In ODYSSEY OUTCOMES, a 1 mg/dL reduction in Lp(a) with alirocumab was associated with a hazard ratio of 0.994.…”

“…If placed in a higher risk category, such patients are usually treated with a moderate/high dose statin to mitigate LDL-C driven risk aiming to reduce LDL-C to < 70 mg/dL. In subjects with established CVD, LDL-C is driven as low as possible below 70 mg/dL, even to 20-30 mg/dL as noted in PCSK9i trials [7,31]. These efforts are supported by recent EAS/ESC guidelines recommending an LDL-C < 55 mg/dL for very high risk individuals [22] and an LDL-C < 40 mg/dL for patients at extremely high risk.…”