Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Lp(a) Lowering for Reduction in CHD Risk

Lipoprotein(a) (Lp[a]) would have to be lowered by 65.7 mg/dL to reach the same potential effect on in coronary heart disease (CHD) clinical outcomes as lowering low-density lipoprotein cholesterol (LDL-C) by 38.67 mg/dL, a new study found. The mendelian randomization analysis estimated the required Lp(a)-lowering effect size that may be associated with a reduction of CHD outcomes compared with the effect size of LDL-C lowering therapies. Researchers found:

  • 13,781 individuals from the Lp(a)-GWAS-Consortium from 5 primarily population-based studies and 20,793 CHD cases and 27,540 controls from a subsample of the CHD Exome+ consortium were included.
  • 4 of the studies were similar in age distribution (means 51 to 59 years), and 1 cohort was younger.
  • The frequency of women was similar between 51% and 55%.
  • A required Lp(a)-lowering effect size of 65.7 mg/dL was estimated to reach the same effect as a 38.67 mg/dL lowering of LDL-C.

Citation:

Lamina C, Kronenberg F, for the Lp(a)-GWAS-Consortium. Estimation of the required lipoprotein(a)-lowering therapeutic effect size for reduction in coronary heart disease outcomes: A mendelian randomization analysis. [Published online ahead of print April 24, 2019]. JAMA Cardiol. doi:10.1001/jamacardio.2019.1041.

Commentary:

In a meta-analysis of 49 clinical trials, each 1 mmol/L (38.67 mg/dL) lowering in LDL-C level was associated with a 23 % relative risk reduction in major CVD events with statin therapy. Lipoprotein(a) or Lp(a) is a known CVD risk factor especially in individuals of European and South Asian descent. Until recently there were no effective therapies able to significantly reduce Lp(a) levels. This has changed with PCSK9 targeted therapy as well as antisense oligonucleotides in development that have achieved significant Lp(a) reduction in efficacy trials. Will Lp(a) treatment achieve similar reductions in CVD events as LDL reduction? This analysis estimated that the required Lp(a) reduction to achieve a similar CVD risk reduction observed with LDL-C treatment would be about 1.7 mmol/L (65.7 mg/dL). Outcome studies in process will help determine if the reduction in Lp(a) observed with newer therapies will be sufficient to achieve clinically significant CVD risk reduction. —Matthew Sorrentino, MD