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Aumentare le HDL è utile?

Elevati valori di colesterolo HDL come fattore di protezione cardiovascolare. Questo assioma radicato nel tempo ha portato la ricerca a studiare farmaci che possano aumentare il colesterolo HDL interferendo con uno degli enzimi chiave del loro metabolismo: il CETP (Cholesterol Ester Transfer Protein). I risultati degli studi finora intrapresi con varie molecole hanno dato risultati poco incoraggianti, se non controproducenti.
In questo lavoro Lincoff et al. hanno valutato l’efficacia di Evacetrapib, un inibitore del CETP, sugli eventi cardiovascolari in pazienti ad alto rischio. Anche se il farmaco aggiunto alla terapia standard si è dimostrato efficace nel migliorare il quadro lipidico con un aumento delle HDL del 133% ed una riduzione del colesterolo LDL del 31% rispetto al placebo questo miglioramento metabolico non ha portato ad una riduzione degli eventi cardiovascolari, riproponendo di nuovo il quesito se la misurazione della concentrazione di colesterolo HDL ci dica tutto sul reale ruolo di queste lipoproteine.

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

Lincoff AM, Nicholls SJ, Riesmeyer JS, Barter PJ, Brewer HB, Fox KAA, Gibson CM, Granger C, Menon V, Montalescot G, Rader D, Tall AR, McErlean E, Wolski K, Ruotolo G, Vangerow B, Weerakkody G, Goodman SG, Conde D, McGuire DK, Nicolau JC, Leiva-Pons JL, Pesant Y, Li W, Kandath D, Kouz S, Tahirkheli N, Mason D, Nissen SE; ACCELERATE Investigators

N Engl J Med 2017; 376: 1933-42

BACKGROUND: the cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease.
METHODS: in a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina.
RESULTS: at 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91).
CONCLUSIONS: although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998).

N Engl J Med 2017; 376: 1933-42