At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks. (Funded by Amgen; DESCARTES ClinicalTrials.gov number, NCT01516879.).

No abstract

In the largest monotherapy trial using a PCSK9 inhibitor to date, evolocumab yielded significant LDL-C reductions compared with placebo or ezetimibe and was well tolerated in patients with hypercholesterolemia. (Monoclonal Antibody Against PCSK9 to Reduce Elevated LDL-C in Subjects Currently Not Receiving Drug Therapy for Easing Lipid Levels-2 [MENDEL-2]; NCT01763827).

Background: In FOURIER, the PCSK9 inhibitor evolocumab reduced LDL-C and risk of cardiovascular events and was safe and well-tolerated over 2.2 years median follow-up. However, large-scale, long-term data are lacking. Methods: The parent FOURIER trial randomized 27,564 patients with ASCVD and LDL-C ≥70mg/dl on statin to evolocumab versus placebo. Patients completing FOURIER at participating sites were eligible to receive evolocumab in two open-label extension studies (FOURIER-OLE) in the United States and Europe; primary analyses were pooled across studies. The primary endpoint was the incidence of adverse events. Lipid values and major adverse cardiovascular events were prospectively collected. Results: 6,635 patients were enrolled in FOURIER-OLE (3355 randomized to evolocumab and 3280 to placebo in parent study). Median follow-up in FOURIER-OLE was 5.0 years; maximum exposure to evolocumab in parent plus FOURIER-OLE was 8.4 years. At 12 weeks in FOURIER-OLE, median LDL-C was 30 mg/dl and 63.2% achieved LDL-C <40 mg/dl on evolocumab. Incidences of serious adverse events, muscle-related events, new-onset diabetes, hemorrhagic stroke, and neurocognitive events with evolocumab long-term did not exceed those for placebo-treated patients during parent study and did not increase over time. During the FOURIER-OLE follow-up period, patients originally randomized in the parent trial to evolocumab versus placebo had a 15% lower risk of cardiovascular death, MI, stroke, hospitalization for unstable angina or coronary revascularization (HR 0.85 [95% CI 0.75-0.96]; P=0.008), a 20% lower risk of cardiovascular death, MI or stroke of (HR 0.80 [0.68-0.93]; P=0.003), and a 23% lower risk of cardiovascular death (HR 0.77 [0.60-0.99]; P=0.04). Conclusions: Long-term LDL-C lowering with evolocumab was associated with persistently low rates of adverse events for over >8 years that did not exceed those observed in the original placebo arm during the parent study and led to further reductions in cardiovascular events compared with delayed treatment initiation.

Patients with suspected PAH were likely to initiate treatment with oral monotherapy, had high compliance rates, and received close ambulatory follow-up. PAH-related costs constituted the majority of all-cause healthcare costs.