Moderne Lipidtherapie

Abstract

Primary and secondary prevention of cardiovascular diseases is tightly connected to the treatment of lipid disorders – primarily elevated LDL cholesterol levels. For decades the only drugs with proven benefit not only in the reduction of LDL serum levels but also concomitantly of cardiovascular adverse events were statins, supposedly due to their additional pleiotropic effects. This year this view shifted after the IMPROVE-IT study showed a decrease in cardiovascular events due to an additional LDL reduction using a non-statin drug, namely ezetimibe, on top of an existing statin therapy. Also with the novel PCSK9 inhibitors Evolocumab and alirocumab a supra-additive LDL lowering effect in combination with statin drugs has been determined not only in patients with acquired dyslipidemia but also with inherited familial hypercholesterolemia. Post hoc analyses of safety studies suggest a cardiovascular benefit of PCSK9 inhibitors. This review will provide an update on non-statin drugs in the treatment of dyslipidemia and the prevention of cardiovascular diseases.

• Literatur

• 1 Voight BF, Peloso GM, Orho-Melander M et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet 2012; 380: 572-580
• 2 Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG et al. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med 2014; 371: 32-41
• 3 Reiner Z, Catapano AL, De Backer G et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011; 32: 1769-1818
• 4 Baigent C, Blackwell L, Emberson J et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010; 376: 1670-1681
• 5 Stone NJ, Robinson JG, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 129: S1-S45
• 6 Jones PH, Davidson MH, Stein EA et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol 2003; 92: 152-160
• 7 Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med 2015; 372: 2387-2397
• 8 Cohen JC, Boerwinkle E, Mosley TH Jr. et al. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 2006; 354: 1264-1272
• 9 Urban D, Poss J, Bohm M et al. Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J Am Coll Cardiol 2013; 62: 1401-1408
• 10 Raal FJ, Stein EA, Dufour R et al. PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 385: 331-340
• 11 Kastelein JJ, Ginsberg HN, Langslet G et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J 2015;
• 12 Raal FJ, Honarpour N, Blom DJ et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 385: 341-350
• 13 Robinson JG, Colhoun HM, Bays HE et al. Efficacy and safety of alirocumab as add-on therapy in high-cardiovascular-risk patients with hypercholesterolemia not adequately controlled with atorvastatin (20 or 40 mg) or rosuvastatin (10 or 20 mg): design and rationale of the ODYSSEY OPTIONS Studies. Clin Cardiol 2014; 37: 597-604
• 14 Robinson JG, Farnier M, Krempf M et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372: 1489-1499
• 15 Sabatine MS, Giugliano RP, Wiviott SD et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015; 372: 1500-1509