Publications by authors named "Beat Knusel"
Background: Olpasiran, a small interfering RNA (siRNA), blocks lipoprotein(a) (Lp(a)) production by preventing translation of apolipoprotein(a) mRNA. In phase 2, higher doses of olpasiran every 12 weeks (Q12W) reduced circulating Lp(a) by >95%.
Objectives: This study sought to assess the timing of return of Lp(a) to baseline after discontinuation of olpasiran, as well as longer-term safety.
Background: Lipoprotein(a) is a presumed risk factor for atherosclerotic cardiovascular disease. Olpasiran is a small interfering RNA that reduces lipoprotein(a) synthesis in the liver.
Methods: We conducted a randomized, double-blind, placebo-controlled, dose-finding trial involving patients with established atherosclerotic cardiovascular disease and a lipoprotein(a) concentration of more than 150 nmol per liter.
Background: Data support lipoprotein(a) (Lp[Lp(a)]) being a risk factor for atherosclerotic cardiovascular disease (ASCVD). Olpasiran is a small interfering RNA molecule that markedly reduces Lp(a) production in hepatocytes.
Study Design: The Olpasiran trials of Cardiovascular Events And lipoproteiN(a) reduction-DOSE finding study is a multicenter, randomized, double-blind, placebo-controlled dose-finding study in 281 subjects with established ASCVD and Lp(a) > 150 nmol/L.
Aims: Some trials have reported diminished efficacy for statins in the elderly, and in women compared with men. We examined the efficacy and safety of evolocumab by patient age and sex in the FOURIER trial, the first major cardiovascular outcome trial of a PCSK9 inhibitor.
Methods And Results: FOURIER was a randomised, double blind trial, comparing evolocumab with placebo in 27,564 patients with atherosclerotic cardiovascular disease receiving statin therapy (median follow-up 2.
Background: Lipoprotein apheresis (LA) can effectively lower lipoproteins but is an invasive procedure.
Objective: The objective of this study was to evaluate whether evolocumab can reduce LA requirement in patients undergoing chronic LA.
Methods: Patients on regular weekly or every-2-week LA and moderate- to high-intensity statin (if tolerated) with pre-LA low-density lipoprotein cholesterol (LDL-C) levels ≥2.
Background: Omecamtiv mecarbil (OM) is a selective cardiac myosin activator that increases myocardial function in healthy volunteers and in patients with chronic heart failure.
Objectives: This study evaluated the pharmacokinetics, pharmacodynamics, tolerability, safety, and efficacy of OM in patients with acute heart failure (AHF).
Methods: Patients admitted for AHF with left ventricular ejection fraction ≤40%, dyspnea, and elevated plasma concentrations of natriuretic peptides were randomized to receive a double-blind, 48-h intravenous infusion of placebo or OM in 3 sequential, escalating-dose cohorts.
Objectives: This study sought to evaluate the efficacy and safety of subcutaneous evolocumab compared with oral ezetimibe in hypercholesterolemic patients who are unable to tolerate effective statin doses.
Background: Statin intolerance, which is predominantly due to muscle-related side effects, is reported in up to 10% to 20% of patients. Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), demonstrated marked reductions in plasma low-density lipoprotein cholesterol (LDL-C) in a phase 2 study in statin-intolerant patients.
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases serum LDL-cholesterol (LDL-C) concentrations. We assessed the effects of AMG 145, a human monoclonal antibody against PCSK9, in patients with hypercholesterolaemia in the absence of concurrent lipid-lowering treatment.
Methods: In a phase 2 trial done at 52 centres in Europe, the USA, Canada, and Australia, patients (aged 18-75 years) with serum LDL-C concentrations of 2·6 mmol/L or greater but less than 4·9 mmol/L were randomly assigned equally through an interactive voice response system to subcutaneous injections of AMG 145 70 mg, 105 mg, or 140 mg, or placebo every 2 weeks; subcutaneous AMG 145 280 mg, 350 mg, or 420 mg or placebo every 4 weeks; or oral ezetimibe 10 mg/day.
Lowering low-density lipoprotein cholesterol (LDL-C) is a cornerstone for the prevention of atherosclerotic heart disease, improving clinical outcomes and reducing vascular mortality in patients with hypercholesterolemia. The clinical benefits of LDL-C reduction appear to extend even to patients starting with LDL-C as low as 60-80 mg/dL prior to initiating therapy. Statins are the first-line agents for treating hypercholesterolemia and are effective in reducing LDL-C, but many patients are unable to achieve their optimal lipid targets despite intensive statin therapy.
View Article and Find Full Text PDFAims: To assess the safety and tolerability of darbepoetin alfa (DA) in the treatment of anaemia in heart failure (HF).
Methods And Results: In this pooled analysis of three randomized, double-blind, placebo-controlled studies of anaemic [haemoglobin (Hb) < or =12.0 g/dL or < or =12.
Background: Substantial evidence suggests that anemia is an independent risk factor for worse outcomes in patients with heart failure (HF). The Study of Anemia in Heart Failure Trial (STAMINA-HeFT) is the largest multicenter, randomized, double-blind, placebo-controlled trial to date evaluating the effect of treating anemia in HF.
Methods And Results: Patients (N=319) with symptomatic HF, left ventricular ejection fraction < or = 40%, and hemoglobin > or = 9.