Risk for PAD Events May Be Related to Lipoprotein(a) Levels, Reduced by Alirocumab After ACS

peripheral artery disease
The risk for peripheral artery disease events was found to be associated with levels of lipoprotein(a) in patients with recent acute coronary syndrome.

The risk for peripheral artery disease events was found to be associated with levels of lipoprotein(a) in patients with recent acute coronary syndrome (ACS) on a maximally tolerated statin regimen, and to be reduced by alirocumab, according to study results published in Circulation.

Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce levels of lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). Investigators aimed to determine whether the PCSK9 inhibitor alirocumab reduces the risk for peripheral artery disease (PAD) or venous thromboembolism (VTE) in patients with recent ACS already on intensive/maximally tolerated statin treatment.

In this prespecified analysis of the ODYSSEY OUTCOMES trial (ClinicalTrials.gov Identifier: NCT01663402), in which 18,924 patients (25.2% women) were enrolled and randomly assigned 1:1 to receive alirocumab or placebo, the occurrence of PAD events and VTE was assessed. PAD events were amputation for ischemia, limb revascularization, or critical limb ischemia, and VTE were pulmonary embolism or deep vein thrombosis. Levels of LDL-C measured are corrected for cholesterol.

The median lipoprotein(a) level was 21 mg/dL and the median LDL-C level was 75 mg/dL at baseline. In patients treated with alirocumab, there was a 23.5% median reduction in lipoprotein(a) levels and a 70.6% median reduction in LDL-C levels. PAD events occurred in 246patients and VTE occurred in 92 patients.

In the placebo group, the risk for PAD events was related to the baseline quartile of lipoprotein(a) (Ptrend=.0021), but not of LDL-C levels.Treatment with alirocumab vs placebo was found to reduce the risk for PAD events (hazard ratio [HR], 0.69; 95% CI, 0.54-0.89; P =.0004), but not VTE events.

In the alirocumab group, the reduction in PAD events was associated with baseline quartile of lipoprotein(a) (Ptrend=.03). The change in lipoprotein(a) levels from baseline to 4 months was associated with a reduced risk for VTE (HR per 1 mg/dL decrease, 0.985; 95% CI, 0.972-0.999; P =.04) and the composite of VTE and PAD events (HR per 1 mg/dL decrease, 0.991; 95% CI, 0.982-1.000; P =.04).

“In patients with recent ACS on intensive statin treatment, the risk  [for] PAD events is substantial, related to levels of lipoprotein(a), and is reduced with PCSK9 inhibition with alirocumab,” the study authors concluded. “A mechanism of this effect may be alirocumab-induced reduction of lipoprotein(a) levels. Further study is required to confirm whether the risk [for] VTE is related to lipoprotein(a) concentration and modified by PCSK9 inhibition.”

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Disclosures: Funding for the study was provided by Sanofi and Regeneron Pharmaceuticals. Several authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.


Schwartz GG, Steg PG, Szarek M, et al. Peripheral artery disease and venous thromboembolic events after acute coronary syndrome: Role of lipoprotein(a) and modification by alirocumab: Prespecified analysis of a randomized clinical trial [published online March 29, 2020]. Circulation. doi:10.1161/CIRCULATIONAHA.120.046524