[angio]

Treatment with alirocumab (Sanofi/Regeneron Pharmaceuticals), an investigational proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, resulted in significant reductions in LDL cholesterol in various groups of patients who received the drug, including individuals at high risk for cardiovascular events currently taking a maximally tolerated statin dose.

In one analysis of the ODYSSEY Long-Term Study , a study consisting of 2341 patients at high risk for cardiovascular events, investigators conducted a post hoc analysis to investigate the effect of alirocumab on major cardiovascular events, the same end point being tested in the major morbidity and mortality ODYSSEY OUTCOMES study. After 65 weeks of treatment, the results suggested alirocumab significantly reduced the risk of major events compared with those who received placebo and a maximally tolerated statin.

ODYSSEY COMBO II : Testing the efficacy and safety of alirocumab in 720 patients at high risk for cardiovascular events despite treatment with a maximally tolerated statin. Patients received a 75-mg injection of alirocumab every two weeks, and the dose was increased to 150 mg every two weeks if their LDL-cholesterol levels remained >70 mg/dL at week 8. Patients in the control arm received a maximally tolerated statin, ezetimibe 10 mg/day, and a placebo injection.

ODYSSEY FH I and I: In total, 735 heterozygous familial hypercholesterolemia (FH) patients treated with a maximally tolerated statin who were not at the recommended LDL-cholesterol goal of <70 mg/dL (history of cardiovascular disease) or <100 mg/dL (no history of cardiovascular disease) were randomized to alirocumab 75 mg every two weeks or to placebo. Like the COMBO study, the dose was increased to 150 mg every two weeks if the patient's LDL-cholesterol level remained above 70 mg/dL at week eight.

ODYSSEY Long-Term: Evaluated the safety and efficacy of alirocumab in 2341 patients with heterozygous FH or at high risk for cardiovascular events who were receiving a maximally tolerated dose of statin but who had an LDL-cholesterol level >70 mg/dL. Patients were randomized to alirocumab 150 mg every two weeks or to placebo. The primary efficacy end point was the reduction in LDL-cholesterol levels at 24 weeks, but the study will continue to evaluate patients beyond one year.

As noted, the long-term study also evaluated major cardiovascular events at 65 weeks. Using the same end point as that used in the alirocumab outcomes study, which was the time to first coronary heart disease death, nonfatal MI, fatal and nonfatal ischemic stroke, or unstable angina requiring hospitalization, there was a benefit to treatment with the PCSK9 inhibitor. The absolute event rate of major cardiovascular events was 1.4% in the alirocumab arm and 3.0% in the placebo arm, a difference that translated into a relative risk reduction of 54%.

Asked about repeating history with another version of ezetimibe, that being the approval of alirocumab, evolocumab, or bococizumab (Pfizer) based on surrogate end points without any idea if the drugs reduce hard clinical end points, Ballantyne said the two scenarios are very different. When ezetimibe was approved based on LDL lowering, an outcomes study wasn't even in the works (the IMPROVE-IT study will finally be presented this November at the American Heart Association meeting, 12 years after the drug was approved by the FDA). With the PCSK9 inhibitors, the sponsors have all initiated outcomes studies, and enrollment has already begun in these large morbidity and mortality trials, he said

ищите на Medscape: Huge Decreases in LDL Cholesterol With Alirocumab: ODYSSEY.

Интересно сколько это будет стоить лет хотя бы через десять (не в абсолютных цифрах, а в отношении к стоимости максимальной дозы статинов)????