No abstract

HMG-CoA reductase inhibitors ('statins') represent the most effective and widely prescribed drugs currently available for the reduction of low-density lipoprotein cholesterol, a critical therapeutic target for primary and secondary prevention of cardiovascular atherosclerotic disease. In the face of the established lipid lowering and the emerging pleiotropic properties of statins, the patient population suitable for long-term statin treatment is expected to further expand. An overall positive safety and tolerability profile of statins has been established, although adverse events have been reported. Skeletal muscle-related events are the most common adverse events of statin treatment. Statin-induced myopathy can (rarely) manifest with severe and potentially fatal cases of rhabdomyolysis, thus rendering the identification of the underlying predisposing factors critical. The purpose of this review is to summarize the factors that increase the risk of statin-related myopathy. Data from published clinical trials, meta-analyses, postmarketing studies, spontaneous report systems and case reports for rare effects were reviewed. Briefly, the epidemiology, clinical spectrum and molecular mechanisms of statin-associated myopathy are discussed. We further analyse in detail the risk factors that precipitate or increase the likelihood of statin-related myopathy. Individual demographic features, genetic factors and co-morbidities that may account for the significant interindividual variability in the myopathic risk are presented. Physicochemical properties of statins have been implicated in the differential risk of currently marketed statins. Pharmacokinetic interactions with concomitant medications that interfere with statin metabolism and alter their systemic bioavailability are reviewed. Of particular clinical interest in cases of resistant dyslipidaemia is the interaction of statins with other classes of lipid-lowering agents; current data on the relative safety of available combinations are summarized. Finally, we provide an update of current guidelines for the prevention and management of statin myopathy. The identification of patients with an increased proclivity to statin-induced myopathy could allow more cost-effective approaches of monitoring and screening, facilitate targeted prevention of potential complications, and further improve the already overwhelmingly positive benefit-risk ratio of statins.

Background: To quantify the association between effects of interventions on carotid intimamedia thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. Methods: We systematically collated data from randomized controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were utilized. The primary outcome was a combined CVD endpoint defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the two using a Bayesian meta-regression approach. Results: We analyzed data of 119 randomized controlled trials involving 100,667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12,038 patients developed the combined CVD endpoint. Across all interventions, each 10 μm/year reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% credible interval 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/year would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74). Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary vs. secondary prevention trials, type of cIMT measurement, and proportion of female patients. Conclusions: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

Malnutrition has increasingly been acknowledged as an important prognostic factor which can influence the clinical outcome of patients suffering from end-stage liver disease (ESLD). Despite the fact that malnutrition is not included in the Child-Pugh classification, its presence should alert clinicians to the same extent as do other complications, such as ascites and hepatic encephalopathy. The pathophysiological mechanisms and the clinical conditions that drive cirrhotic patients to an ill-balanced metabolic state are multiple and they intertwine. Inadequate offer of nutrients, the hypermetabolic state in cirrhosis, the diminished synthetic capacity of the liver and the impaired absorption of nutrients are the main reasons that disrupt the metabolic balance in ESLD. Identifying patients that are approaching the state of malnutrition by simple and easily applied methods is necessary in order to provide nutritional support to those that need it most. According to the European Society for Clinical Nutrition and Metabolism, simple bedside methods such as Subjective Global Assessment and anthropometric parameters are reliable in assessing the nutritional state of cirrhotic patients. Correcting the nutrient deficit of the affected patients is mandatory. Avoidance of alcohol and excess fat and ingestion of 4-6 meals/day containing carbohydrates and protein are the most common recommendations. In severe malnutrition, initiation of enteral feeding and/or use of special formulae such as branched-chain amino acid-enriched nutrient mixtures are often recommended. Enteral nutrition improves nutritional status and liver function, reduces complications, prolongs survival and is therefore indicated.