January 13, 2020
3 min read

LDL, Lp(a) reductions with alirocumab may predict CV events after ACS

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Vera A. Bittner

The risk for major adverse CV events after recent ACS could be predicted by baseline lipoprotein(a) and corrected LDL levels and their reductions with alirocumab, according to an analysis of the ODYSSEY Outcomes trial published in the Journal of the American College of Cardiology.

Results from this analysis were originally presented at the American College of Cardiology Scientific Session in March.

“The clinical message for the physician is that treatment with alirocumab (Praluent, Sanofi/Regeneron) reduces both LDL-C and Lp(a),” Cardiology Today Editorial Board Member Vera A. Bittner, MD, MSPH, professor of medicine and section head of general cardiology, prevention and imaging at University of Alabama at Birmingham, told Healio. “Both reductions contribute to treatment benefit based on our analysis, with reduction in LDL-C playing a larger role throughout the range of baseline Lp(a) levels. However, at higher baseline Lp(a) levels, the contribution of Lp(a) lowering becomes clinically meaningful. The type of evidence we provided is clearly not sufficient to result in guideline changes. We need the randomized trials for that.”

ODYSSEY Outcomes trial

Researchers analyzed data from 18,924 patients from the ODYSSEY Outcomes trial aged at least 40 years who had an ACS 1 to 12 months before randomization and a non-HDL level of at least 100 mg/dL, LDL level of at least 70 mg/dL or an apolipoprotein B level of at least 80 mg/dL on high-intensity statin therapy. Patients were assigned 75 mg alirocumab subcutaneously every 2 weeks or placebo. Measurements of Lp(a) mass were taken at randomization, 4 months and 12 months.

The primary endpoint was major adverse CV events, defined as a composite of nonfatal MI, CHD death, unstable angina requiring hospitalization and fatal or nonfatal ischemic stroke.

Major adverse CV events were predicted with baseline Lp(a) levels (median, 21.2 mg/dL) and LDL when corrected for cholesterol content in Lp(a). Patients assigned alirocumab had reductions in corrected LDL by 51.1 mg/dL and Lp(a) by 5 mg/dL. Alirocumab also reduced the risk for major adverse CV events (HR = 0.85; 95% CI, 0.78-0.93).

Reductions in Lp(a) and corrected LDL with alirocumab independently predicted a lower risk for major adverse CV events after adjusting for baseline concentrations of both lipoproteins, in addition to clinical and demographic characteristics. Each 1 mg/dL reduction in Lp(a) through alirocumab was linked to an HR of 0.994 (95% CI, 0.99-0.999).


“There are new medications in development that can lower Lp(a) by around 80%,” Bittner said in an interview. “At least one outcomes trial will start soon. Others won’t be far behind. These trials will give us the level of evidence to decide whether treatment with Lp(a) can make a significant contribution to reducing atherosclerotic CVD events.”

Further research

Samia Mora

In a related editorial, Samia Mora, MD, MHS, associate physician at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, wrote: “Future studies are needed to directly assess the impact of specifically lowering Lp(a) for potentially reducing residual risk. In the interim, one-time measurement of Lp(a) — even if imperfect — is better than no measurement in patients after the acute ACS period. This information could be useful for risk stratification clinical decision-making in selecting higher risk patients for novel therapies, including PCSK9 inhibitors, and for cascade screening of families with inherited Lp(a) disorders.” – by Darlene Dobkowski

For more information:

Vera A. Bittner , MD, MSPH, can be reached at University of Alabama at Birmingham, 701 19th St. South – LHRB 310, Birmingham, AL 35294; email: vbittner@uab.edu.

Disclosures: The ODYSSEY Outcomes trial was funded by Sanofi and Regeneron Pharmaceuticals. Bittner reports she serves on the executive steering committee of the ODYSSEY Outcomes trial by Sanofi; as the national coordinator for the STRENGTH trial by AstraZeneca, the DalGene trial by Dalcor, the CLEAR trial by Esperion; as site investigator for the ORION IV trial by The Medicines Company; previously served as a site investigator for the ARTEMIS trial by AstraZeneca and the COMPASS trial by Bayer Healthcare, and has consulted for Sanofi. Mora reports she is supported by the NHLBI and National Institute of Diabetes and Digestive and Kidney Diseases, received research support from Atherotech Diagnostics and has consulted for Pfizer and Quest Diagnostics. Please see the study for all other authors’ relevant financial disclosures.