Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL...

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Biochemistry

Background:

• High-density lipoprotein cholesterol (HDL-C) is inversely associated with cardiovascular events, making it a therapeutic target.
• Previous CETP inhibitors like torcetrapib showed adverse effects, including increased blood pressure and CV mortality.
• Dalcetrapib, a novel CETP inhibitor, was investigated for its cardiovascular effects.

Purpose of the Study:

• To evaluate the effects of dalcetrapib on endothelial function, blood pressure, and inflammatory markers in patients with or at risk of coronary heart disease (CHD).
• To assess the safety and tolerability of dalcetrapib in this patient population.

Main Methods:

• A double-blind, randomized, placebo-controlled trial (dal-VESSEL) involving 476 patients with or at risk of CHD.
• Patients received dalcetrapib 600 mg/day or placebo for 36 weeks, alongside standard therapy.
• Primary outcomes included changes in flow-mediated dilatation (%FMD) and 24-hour ambulatory blood pressure monitoring (ABPM).

Main Results:

• Dalcetrapib significantly reduced CETP activity by 51-56% and increased HDL-C by 25-31% (placebo-corrected).
• No significant changes were observed in flow-mediated dilatation (%FMD) or blood pressure (ABPM) compared to placebo.
• Inflammatory markers, oxidative stress, and coagulation markers remained largely unchanged, except for a 17% increase in Lp-PLA(2) mass.

Conclusions:

• Dalcetrapib is well-tolerated and safe in patients with or at risk of CHD.
• CETP inhibition with dalcetrapib effectively increases HDL-C without negatively impacting endothelial function, blood pressure, or key inflammatory markers.
• Further trials, like dal-OUTCOMES, are needed to determine if dalcetrapib improves cardiovascular outcomes.