Paradoxical decrease in HDL-cholesterol and apolipoprotein A1 with simvastatin and atorvastatin in a patient with type 2 diabetes

Abstract

Statins are agents widely used to lower LDL-cholesterol (LDL-C) in primary and secondary prevention of coronary heart disease. The five statins available in the UK (simvastatin, pravastatin, fluvastatin, atorvastatin and rosuvastatin) differ in many of their pharmacologic properties. In addition to lowering LDL-C, statins also increase HDL-cholesterol (HDL-C) moderately. There have been rare reports of significant HDL-C decreases in patients commenced on fibrates and when thiazolidinediones are added to fibrates. This is known as a 'paradoxical HDL-C decrease' as both groups of agents usually increase HDL-C. This phenomenon has never been clearly documented following statin therapy. We now describe a patient with type 2 diabetes who showed this paradoxical fall in HDL-C (baseline HDL-C: 1.8 mmol/L; on simvastatin 40 mg HDL-C 0.6 mmol/L; on atorvastatin 20 mg HDL-C 0.9 mmol/L) with a similar decrease in apolipoprotein A1. No similar decrease was observed with pravastatin and rosuvastatin therapy. This phenomenon appeared to be associated with statin treatment and not a statin/fibrate combination. Our patient clearly demonstrated a paradoxical HDL-C fall with simvastatin and atorvastatin, but not pravastatin or rosuvastatin. Simvastatin and atorvastatin share many pharmacokinetic properties such as lipophilicity while pravastatin and rosuvastatin are relatively hydrophilic and are not metabolized by cytochrome P450 3A4. However, these characteristics do not explain the dramatic reductions in HDL-C observed.

Upregulated expression of human alpha-defensins 1, 2 and 3 in hypercholesteremia and its relationship with serum lipid levels

“…This is in agreement with a study of Ramachandran [19]. The reason why HDL cholesterol decrease significantly following atorvastatin therapy is according to the study of Ansell [20].…”

A study in high-risk, maximally pretreated patients to determine the potential use of PCSK9 inhibitors at various thresholds of total and LDL cholesterol levels

“…Between April 2007 and March 2008, 271 patients were referred to the clinic and 72 of these patients were started on ezetimibe when not achieving target TC and/or LDL-c levels on maximal statin treatment (table 1). Data on these patients were collected as part of the lipid clinic audit programme carried out by the Department of Clinical Biochemistry, Heart of England Foundation NHS Trust to evaluate guideline compliance and efficacy of lipid-lowering agents (statins, fibrates, ezetimibe) 21 22. In the clinic we tried to achieve targets of TC: 4 mmol/L and/or LDL-c: 2 mmol/L.…”

Paradoxical decrease in serum high-density lipoprotein cholesterol with Tredaptive® (m/r nicotinic acid 1 g and laropiprant 20 mg)

“…I read with interest the recent case report 1 describing paradoxical decreases in high-density lipoprotein cholesterol (HDL-C) with simvastatin and atorvastatin in a patient with type 2 diabetes mellitus. The accompanying editorial 2 highlighted papers reporting paradoxical decreases in HDL-C by certain fibrates.…”