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Arturo Cesaro: Lp(a) Lowered by 78% but Cardiovascular Outcomes Remain Unchanged
Arturo Cesaro/LinkedIn
Nov 11, 2026, 11:28

Arturo Cesaro: Lp(a) Lowered by 78% but Cardiovascular Outcomes Remain Unchanged

Arturo Cesaro, Assistant Professor of Cardiology at University of Campania “Luigi Vanvitelli”, shared a post on LinkedIn about a recent article by Steven Nissen et al, published in NEJM, adding:

“Lp(a)HORIZON: Lp(a) down 78%. No reduction in cardiovascular events

Published today in NEJM and presented by Steven Nissen at AHA 2026.

8,322 patients with established ASCVD and Lp(a) higher 70 mg/dL. Pelacarsen 80 mg monthly vs placebo. Median follow-up: 4.7 years.

  • Lp(a): 236-64 nmol/L at 1 year (−78%)
  • Primary MACE: 12.3% vs 12.1%; HR 1.02 (95% CI 0.90–1.15)
  • Lp(a) higher 90 mg/dL: HR 1.00 (0.87–1.15)
  • No benefit on any component or subgroup

This is not an underpowered miss. The trial was designed around a 20% relative risk reduction, and the confidence interval rules it out.

Tolerability was a concern. 20.6% stopped the drug because of adverse events (vs 7.5% on placebo).

Is the Lp(a) hypothesis dead? No. Genetic and Mendelian randomization data remain robust.

But, as Karol Watson argued, this population may have left little room for benefit:

  • In secondary prevention, Lp(a)-related risk appears attenuated
  • Median LDL-C was around 65 mg/dL
  • Starting therapy around 60 may be too late for a lifelong genetic exposure
  • The next answers will come from primary prevention, aortic stenosis and siRNA trials.

A causal risk factor is not automatically a modifiable one. At least not late, and not on top of excellent LDL control.

Will this change how you talk about Lp(a) with your patients?”

Title: Extended Analyses of Pelacarsen and Cardiovascular Outcomes in Patients with High Lipoprotein(a)

Authors: Steven Nissen, Leslie Cho, Seth Frndak, Kathy Wolski, Jing Wang, Brian Manning, Eran Leitersdorf, Ulf Landmesser, Jackie McCluskey, Michael Blaha, A. Michael Lincoff, Ziqiang Zhao, Bjorn Mueller-Edenborn, Thomas Nuehrenberg, Sotirios Tsimikas, Anastasia Lesogor, Hui Cao, Vidyasagar Kalahasti, Ulrich Laufs, Seth Baum, Eric Stroes, Michael Shapiro, Børge Nordestgaard, Stephen Nicholls

Arturo Cesaro: Lp(a) Lowered by 78% but Cardiovascular Outcomes Remain Unchanged

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A. Michael Lincoff Anastasia Lesogor Arturo Cesaro Bjorn Mueller-Edenborn Børge Nordestgaard Brian Manning Eran Leitersdorf Eric Stroes Health Hematology Hemostasis Hemostasis News Hemostasis Today Hui Cao Jackie McCluskey Jing Wang Kathy Wolski Leslie Cho Medicine Michael Blaha Michael Shapiro Seth Baum Seth Frndak Sotirios Tsimikas Stephen Nicholls Steven Nissen Thomas Nuehrenberg Ulf Landmesser Ulrich Laufs Vidyasagar Kalahasti Ziqiang Zhao
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