L'obiettivo dello studio CLEAR Tranquility era di valutare l'efficacia e la sicurezza dell'acido bempedoico quando aggiunto alla terapia ipolipemizzante in pazienti con una storia di intolleranza alle statine che richiedessero un ulteriore abbassamento di LDL-C. In questo trial di fase 3, multicentrico, randomizzato, in doppio cieco, controllato con placebo, circa 270 pazienti sono stati randomizzati 2: 1 al trattamento con acido bempedoico 180 mg o a placebo una volta al giorno aggiunti a 10 mg/die di ezetimibe per 12 settimane. Il trattamento ha mostrato una riduzione del colesterolo LDL-C del 28,5% in più rispetto al placebo (p <0,001; -23,5% di acido bempedoico, + 5,0% di placebo). L'acido bempedoico era ben tollerato; i tassi di eventi avversi, tra cui eventi avversi muscolari e interruzioni del trattamento, erano simili nei due bracci.
BACKGROUND AND AIMS: Patients with hyperlipidemia who are unable to tolerate optimal statin therapy are at increased cardiovascular risk due to ongoing elevations in low-density lipoprotein cholesterol (LDL-C). The objective of CLEAR Tranquility (NCT03001076) was to evaluate the efficacy and safety of bempedoic acid when added to background lipid-modifying therapy in patients with a history of statin intolerance who require additional LDL-C lowering.
METHODS: This phase 3, multicenter, randomized, double-blind, placebo-controlled study enrolled patients with a history of statin intolerance and an LDL-C ≥100 mg/dL while on stable lipid-modifying therapy. After a 4-week ezetimibe 10 mg/day run-in period, patients were randomized 2:1 to treatment with bempedoic acid 180 mg or placebo once daily added to ezetimibe 10 mg/day for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C.
RESULTS: The study population comprised 269 patients (181 bempedoic acid, 88 placebo). Bempedoic acid added to background lipid-modifying therapy that included ezetimibe reduced LDL-C by 28.5% more than placebo (p < 0.001; -23.5% bempedoic acid, +5.0% placebo). Significant reductions in secondary endpoints, including non-high-density lipoprotein cholesterol (-23.6%), total cholesterol (-18.0%), apolipoprotein B (-19.3%), and high-sensitivity C-reactive protein (-31.0%), were observed with bempedoic acid vs. placebo (p < 0.001). Bempedoic acid was well tolerated; rates of treatment-emergent adverse events, muscle-related adverse events, and discontinuations were similar in the bempedoic acid and placebo treatment groups.
CONCLUSIONS: Bempedoic acid may provide an oral therapeutic option complementary to ezetimibe in statin intolerant patients who require additional LDL-C lowering.