Comment
PCSK9 inhibition and type 2 diabetes The focus of cardiovascular disease prevention has shifted from normalisation of risk factors to absolute risk reduction. Reducing LDL cholesterol concentration by 1 mmol/L for about 5 years is consistently associated with a 23–25% lowered risk of major cardiovascular events, with statin and non-statin therapies alike, irrespective of baseline LDL cholesterol concentration.1 In high-income and middle-income countries, statins are now routinely recommended as first-line LDL cholesterol-lowering therapy for people with 10-year modelled risk above, somewhat arbitrary, country-specific thresholds defined by economic and clinical considerations. This high-risk category includes most patients with type 2 diabetes. Statins achieve similar reductions in relative risk among people with and without diabetes.2 However, even among patients on maximum doses, with LDL cholesterol concentrations in the normal range, further reductions in LDL cholesterol and modelled risk are possible. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that catalyses the degradation of the LDL receptor, thereby reducing LDL cholesterol uptake by cells and increasing circulating concentrations. In The Lancet Diabetes & Endocrinology, Marc Sabatine and colleagues report on the efficacy and safety of PCSK9 inhibition in people with and without diabetes.3 The investigators undertook a prespecified secondary analysis of data from FOURIER,4 a randomised, placebocontrolled trial of subcutaneous injections of the antiPCSK9 monoclonal antibody evolocumab given every 2 or 4 weeks, in 27 564 patients with atherosclerotic disease who were on statin therapy. Evolocumab lowered LDL cholesterol similarly in people with diabetes (57%, 95% CI 56–58; p
PCSK9 inhibition and type 2 diabetes The focus of cardiovascular disease prevention has shifted from normalisation of risk factors to absolute risk reduction. Reducing LDL cholesterol concentration by 1 mmol/L for about 5 years is consistently associated with a 23–25% lowered risk of major cardiovascular events, with statin and non-statin therapies alike, irrespective of baseline LDL cholesterol concentration.1 In high-income and middle-income countries, statins are now routinely recommended as first-line LDL cholesterol-lowering therapy for people with 10-year modelled risk above, somewhat arbitrary, country-specific thresholds defined by economic and clinical considerations. This high-risk category includes most patients with type 2 diabetes. Statins achieve similar reductions in relative risk among people with and without diabetes.2 However, even among patients on maximum doses, with LDL cholesterol concentrations in the normal range, further reductions in LDL cholesterol and modelled risk are possible. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that catalyses the degradation of the LDL receptor, thereby reducing LDL cholesterol uptake by cells and increasing circulating concentrations. In The Lancet Diabetes & Endocrinology, Marc Sabatine and colleagues report on the efficacy and safety of PCSK9 inhibition in people with and without diabetes.3 The investigators undertook a prespecified secondary analysis of data from FOURIER,4 a randomised, placebocontrolled trial of subcutaneous injections of the antiPCSK9 monoclonal antibody evolocumab given every 2 or 4 weeks, in 27 564 patients with atherosclerotic disease who were on statin therapy. Evolocumab lowered LDL cholesterol similarly in people with diabetes (57%, 95% CI 56–58; p
