Reacción a "Results are presented from the unsuccessful first clinical trial that aimed to reduce cardiovascular risk by lowering lipoprotein(a) levels"

Lipoprotein(a) [Lp(a)] is known to be a significant risk factor for cardiovascular disease—comparable, in effect, to LDL cholesterol ("bad" cholesterol). There is no established "normal" value; the higher the blood levels, the greater the risk, although many laboratories set a desirable threshold at < 125 nmol/L (or 50 mg/dL).

Currently, no specific treatment aimed at lowering Lp(a) levels has demonstrated a clear clinical benefit—defined in clinical trials as a reduction in cardiovascular mortality, heart attack, or stroke.

The Lp(a) HORIZON study was designed to determine whether pelacarsen—a drug effective at lowering Lp(a) levels—could reduce the incidence of cardiovascular complications in patients already diagnosed with cardiovascular disease.

Contrary to expectations, the study yielded a neutral result; no significant difference was observed in cardiovascular mortality, heart attack, or stroke between patients who received the active drug and those who received a placebo.

The study is considered to be of the highest quality, designed by experts with extensive experience in conducting such clinical trials. It involved more than 8,000 patients, with a follow-up period of 4.7 years.

Because the study results did not meet expectations, the drug will not be approved for clinical use, due to a lack of proven efficacy. Nevertheless, the hypothesis that lowering Lp(a) levels could be beneficial remains. A well-designed study can yield negative results for various reasons, such as the criteria used for patient selection or the dosage of the drug. One potential shortcoming may have been the inclusion of patients with relatively low Lp(a) levels; such individuals naturally face a lower risk, making it more difficult to demonstrate a clinical benefit.

It is worth noting that, at present, the risk faced by individuals with cardiovascular disease has been progressively reduced thanks to modern treatment approaches. In the Lp(a)Horizon study, the annual incidence of the composite endpoint—cardiovascular mortality, heart attack, or stroke—was approximately 2.5% per year, a figure that is very difficult to improve upon with new treatments.

The positive contribution of this study lies in its meticulous data analysis, which helps identify the patients most likely to benefit—a finding that will need to be validated in a subsequent study.