As atherosclerosis is associated with a decrease in the HDL-C level, our observations reinforce the message that HDL-C should be measured before and after the commencement of rosiglitazone and also on increasing the dosage

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.

Disulfiram (tetraethylthiuram disulfide) has been used since decades in the treatment of alcohol addiction. It causes aversive behaviour towards alcohol due to Disulfiram Ethanol Reaction (DER

Abstract:Purpose of the study:Statins and ezetimibe reduce low density lipoprotein cholesterol (LDL-c) and cardiovascular disease (CVD) risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-c by 50-70% and might be useful in refractory patients. The National Institute for Health and Care Excellence (NICE) technology appraisal guidance (TAG) recommends use of these drugs in secondary prevention and familial hypercholestrolaemia (FH) at differing LDL-c thresholds. We have estimated the proportion of patients in whom this third-line drug might be useful. Study Design:We used data from a lipid lowering audit programme to study 72 with FH and/or CVD of 271 patients referred over 12 months who failed to achieve target total cholesterol (TC) and LDL-c levels. All 72 patients were treated with ezetimibe, 69 cases also received statins. We used LDL-c thresholds 1.5-5.5mmol/l to estimate how many of these refractory patients could benefit from PCSK9 inhibitors. Results:In the 72 patients, TC and LDL-c targets were not met by 64 and 53 patients respectively. We judged using the NICE TAG, that only 1 patient (1.4% ezetimibe requiring and 0.4% total referrals) required a PCSK9 inhibitor. Conclusion:We determined that the proportion of patients eligible for a PCSK9 inhibitor at various TC and LDL-c levels is modest. This may reflect the use of all available statins in UK lipid clinics often at non-daily frequency. We suggest that cost effective use of PCSK9 inhibitors requires prescribing being restricted to clinicians working in specialised lipid clinics. Introduction: