(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Heart-Diseases

Renal-transplant recipients have shortened life expectancy primarily because of premature cardiovascular disease. Traditional and nontraditional risk factors for cardiovascular disease are prevalent in renal patients. In renal-transplant recipients, immunosuppressive therapy can be nephrotoxic and aggravate cardiovascular disease risk factors. Renal dysfunction has been established as a risk factor for cardiovascular disease and mortality in different populations. We evaluated the effects of baseline renal-transplant function on mortality and cardiovascular and renal endpoints in 1,052 placebo-treated patients of the Assessment of Lescol in Renal Transplantation trial.. All renal-transplant recipients were on cyclosporine-based immunosuppressive therapy. Follow-up was 5 to 6 years, and endpoints included cardiac death, noncardiovascular death, all-cause mortality, major adverse cardiac event (MACE), stroke, nonfatal myocardial infarction, and graft loss.. Baseline serum creatinine was strongly and independently associated with increased cardiac, noncardiovascular, and all-cause mortality, as well as MACE and graft loss. Serum creatinine was not a risk factor for stroke or nonfatal myocardial infarction.. Elevated baseline serum creatinine in renal-transplant recipients is a strong and independent risk factor for all-cause, noncardiovascular and cardiac mortality, MACE, and graft loss.

Topics: Adult; Antioxidants; Cardiovascular Diseases; Fatty Acids, Monounsaturated; Fluvastatin; Heart Diseases; Humans; Indoles; Kidney; Kidney Transplantation; Placebos; Risk Factors

Interleukin (IL)-33 is a member of the IL-1 family and is able to act cardioprotective. The aim of this study was to investigate the regulation of IL-33 by 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-CoA) reductase inhibitors (statins) and bisphosphonates (BPs) in human cardiac tissue. The lipophilic fluvastatin, simvastatin, atorvastatin, and lovastatin as well as the nitrogenous BPs alendronate and ibandronate, but not hydrophilic pravastatin increased IL-33 mRNA and intracellular IL-33 protein levels in both human adult cardiac myocytes (HACM) and fibroblasts (HACF). Additionally, fluvastatin reduced soluble ST2 secretion from HACM. IL-33 was also up-regulated by the general inhibitor of prenylation perillic acid, a RhoA kinase inhibitor Y-27632, and by latrunculin B, but statin-induced IL-33 expression was inhibited by mevalonate, geranylgeranyl pyrophosphate (GGPP) and RhoA activator U-46619. The IL-33 promoter was 2.3-fold more accessible in statin-treated HACM compared to untreated cells (P = 0.037). In explanted hearts of statin-treated patients IL-33 protein was up-regulated as compared with the hearts of non-statin-treated patients (P = 0.048). As IL-33 was previously shown to exert cardioprotective effects, one could speculate that such up-regulation of IL-33 expression in human cardiac cells, which might happen mainly through protein geranylgeranylation, could be a novel mechanism contributing to known cardioprotective effects of statins and BPs.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Amides; Apoptosis; Bridged Bicyclo Compounds, Heterocyclic; Cyclohexenes; Cytokines; Diphosphonates; Fibroblasts; Fluvastatin; Gene Expression Regulation; Heart; Heart Diseases; Humans; Interleukin-33; Lovastatin; Mevalonic Acid; Monoterpenes; Myocardium; Myocytes, Cardiac; Pravastatin; Pyridines; rhoA GTP-Binding Protein; Simvastatin; Thiazolidines

The French National Health Insurance and the Ministry of Health have introduced multiple reforms in recent years to increase prescribing efficiency. These include guidelines, academic detailing, financial incentives for the prescribing and dispensing of generics drugs as well as a voluntary pay-for-performance programme. However, the quality and efficiency of prescribing could be enhanced potentially if there was better understanding of the dynamics of prescribing behaviour in France.. To analyse the patient and general practitioner characteristics that influence patented versus multiple-sourced statin prescribing in France.. Statistical analysis was performed on the statin prescribing habits from 341 general practitioners (GPs) that were included in the IMS-Health Permanent Survey on Medical Prescription in France, which was conducted between 2009 and 2010 and involved 14,360 patients. Patient characteristics included their age and gender as well as five medical profiles that were constructed from the diagnoses obtained during consultations. These were (1) disorders of lipoprotein metabolism, (2) heart disease, (3) diabetes, (4) complex profiles and (5) profiles based on other diagnoses. Physician characteristics included their age, gender, solo or group practice, weekly workload and payment scheme.. Patient age had a statistically significant impact on statin prescribing for patients in profile 1 (disorders of lipoprotein metabolism) and profile 3 (complex profiles) with a greater number of patented statins being prescribed for the youngest patients. For instance, patients older than 76 years with a complex profile were prescribed fewer patented statins than patients aged 68-76 years old with the same medical profile (coefficient: -0.225; p = 0.0008). By contrast, regardless of the patient's age, the medical profile did not affect the probability of prescribing a patented statin except in young patients with heart diseases who were prescribed a greater number of patented statins (coefficient: 0.3992; p = 0.0007). Prescribing was also statistically influenced by physician features, e.g., older male physicians were more likely to prescribe patented statins (coefficient: 0.245; p = 0.0417) and GPs practicing in groups were more likely to prescribe multiple sourced statins (coefficient: -0.178; p = 0.0338), which is an important finding of the study. GPs with a lower workload prescribed a greater number of patented statins.. There is significant variability in the prescribing of different statins among patient and physician profiles as well as between solo and group practices. Consequently, there are opportunities to target demand-side measures to enhance the prescribing of multiple-sourced statins. Further studies are warranted, in particular in other therapeutic classes, to provide a counter-balance to the considerable marketing activities of pharmaceutical companies.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Atorvastatin; Diabetes Mellitus; Drug Prescriptions; Drugs, Generic; Fatty Acids, Monounsaturated; Female; Fluorobenzenes; Fluvastatin; France; General Practitioners; Heart Diseases; Heptanoic Acids; Humans; Indoles; Lipid Metabolism Disorders; Male; Middle Aged; Models, Statistical; Practice Patterns, Physicians'; Pravastatin; Prescription Drugs; Pyrimidines; Pyrroles; Rosuvastatin Calcium; Simvastatin; Sulfonamides

Topics: Fatty Acids, Monounsaturated; Fluvastatin; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Postoperative Period; Practice Guidelines as Topic; Vascular Surgical Procedures

The discontinuation of statin therapy in patients with acute coronary syndromes has been associated with an increase of adverse coronary events. Patients who undergo major surgery frequently are not able to take oral medication shortly after surgery. Because there is no intravenous formula for statins, the interruption of statins in the postoperative period is a serious concern. The objective of this study was to assess the effect of perioperative statin withdrawal on postoperative cardiac outcome. Also, the association between outcome and type of statin was studied. In 298 consecutive statin users who underwent major vascular surgery, detailed cardiac histories were obtained, and medication use was noted. Postoperatively, troponin levels were measured on days 1, 3, 7, and 30 and whenever clinically indicated by electrocardiographic changes. End points were postoperative troponin release, myocardial infarction, and a combination of nonfatal myocardial infarction and cardiovascular death. Multivariate analyses and propensity score analyses were performed to assess the influence of type of statin and the discontinuation of statins for these end points. Statin discontinuation was associated with an increased risk for postoperative troponin release (hazard ratio 4.6, 95% confidence interval 2.2 to 9.6) and the combination of myocardial infarction and cardiovascular death (hazard ratio 7.5, 95% confidence interval 2.8 to 20.1). Extended-release fluvastatin was associated with fewer perioperative cardiac events compared with atorvastatin, simvastatin, and pravastatin. In conclusion, the present study showed that statin withdrawal in the perioperative period is associated with an increased risk for perioperative adverse cardiac events. Furthermore, there seemed to be better outcomes in patients who received statins with extended-release formulas.

Topics: Aged; Atorvastatin; Electrocardiography; Fatty Acids, Monounsaturated; Female; Fluvastatin; Heart Diseases; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Male; Middle Aged; Myocardial Infarction; Postoperative Complications; Pravastatin; Pyrroles; Simvastatin; Substance Withdrawal Syndrome; Troponin T; Vascular Surgical Procedures

The Lescol Intervention Prevention Study (LIPS) was a multinational randomized controlled trial that showed a 47% reduction in the relative risk of cardiac death and a 22% reduction in major adverse cardiac events (MACEs) from the routine use of fluvastatin, compared with controls, in patients undergoing percutaneous coronary intervention (PCI, defined as angioplasty with or without stents). In this study, MACEs included cardiac death, nonfatal myocardial infarction, and subsequent PCI and coronary artery bypass graft. Diabetes was the greatest risk factor for MACEs.. This study estimated the cost-effectiveness of fluvastatin when used for secondary prevention of MACEs after PCI in people with diabetes.. A post hoc subgroup analysis of patients with diabetes from the LIPS was used to estimate the effectiveness of fluvastatin in reducing myocardial infarction, revascularization, and cardiac death. A probabilistic Markov model was developed using United Kingdom resource and cost data to estimate the additional costs and quality-adjusted life-years (QALYs) gained over 10 years from the perspective of the British National Health Service. The model contained 6 health states, and the transition probabilities were derived from the LIPS data. Crossover from fluvastatin to other lipid-lowering drugs, withdrawal from fluvastatin, and the use of lipid-lowering drugs in the control group were included.. In the subgroup of 202 patients with diabetes in the LIPS trial, 18 (15.0%) of 120 fluastatin patients and 21 (25.6%) of 82 control participants were insulin dependent (P = NS). Compared with the control group, patients treated with fluvastatin can expect to gain an additional mean (SD) of 0.196 (0.139) QALY per patient over 10 years (P < 0.001) and will cost the health service an additional mean (SD) of 10 pounds ( 448 pounds) (P = NS) (mean [SD] US $16 [$689]). The additional cost per QALY gained was 51 pounds (US $78). The key determinants of cost-effectiveness included the probabilities of repeat interventions, cardiac death, the cost of fluvastatin, and the time horizon used for the evaluation.. Fluvastatin was an economically efficient treatment to prevent MACEs in these patients with diabetes undergoing PCI.

Topics: Angioplasty, Balloon, Coronary; Cost-Benefit Analysis; Diabetes Complications; Fatty Acids, Monounsaturated; Fluvastatin; Heart Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Markov Chains; Models, Economic; Multicenter Studies as Topic; Multivariate Analysis; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; United Kingdom