PCSK9 inhibitors in hypercholesterolemia. New hope for patients with diabetes mellitus?

• Published in: Herz Vol. 41; no. 3; pp. 217 - 223
• Main Author: Parhofer, K G
• Format: Journal Article
• Language: German
• Published: Germany 01.05.2016
• Subjects: Anticholesteremic Agents - administration & dosage; Diabetes Complications - drug therapy; Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hypercholesterolemia - complications; Hypercholesterolemia - drug therapy; Proprotein Convertase 9 - antagonists & inhibitors; Treatment Outcome; PCSK9 inhibitors; Hypercholesterolemia; Cardiovascular diseases; Diabetes mellitus; Diabetic dyslipidemia
• ISSN: 0340-9937; 1615-6692
• DOI: 10.1007/s00059-016-4416-6

The interrelation between glucose and lipid metabolism is complex and comprises many aspects. In this context diabetic dyslipidemia is of utmost importance as it represents the crucial link between diabetes and cardiovascular disease. Although hypertriglyceridemia is usually the most prominent lipid abnormality in diabetic patients, reduction of low-density lipoprotein (LDL) cholesterol is the most important strategy to prevent cardiovascular disease. Statin trials and more recently the combination of statin with ezetimibe clearly showed that diabetic patients benefit from low LDL cholesterol levels. In this context the newly developed proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors are of great interest as they reduce LDL cholesterol by 50-70 % independent of co-medication and largely independent of the underlying dyslipidemia. Subgroup analyses of phase 2 and phase 3 studies indicated that diabetic patients show a similar response to PCSK9 inhibitors as non-diabetic patients. Furthermore, the overall very low rate of side effects seems to be comparable between diabetic and non-diabetic patients. In contrast to statins PCSK9 inhibitors do not lead to an increased rate of new onset diabetes. Although data from safety studies (post hoc analyses) are very promising concerning the prevention of cardiovascular events, data from outcome studies will only become available in 2016. Until then PCSK9 inhibitors should be restricted to patients with very high risk and a significant distance from the LDL cholesterol target values (despite maximum possible lipid-lowering therapy with statins and ezetimibe). This approach will most likely have to be adapted when outcome data are available.