Nonadherence to statins:individualized intervention strategies outside the pill box

Poor adherence to statin therapy is linked to significantly increased risk of cardiovascular events and death. Unfortunately, adherence to statins is far from optimal. This is an alarming concern for patients prescribed potentially life-saving cholesterol-lowering medication, especially for those at high risk of cardiovascular events. Research on statin adherence has only recently garnered broader attention; hence, major reasons unique to adherence to statin therapy need to be identified as well as suggestions for countermeasures. An integrated approach to minimizing barriers and enhancing facilitation at the levels of the patient, provider, and health system can help address adherence issues. Health care professionals including physicians, pharmacists, and nurses have an obligation to improve patient adherence, as routine care. In order to achieve sustained results, a multifaceted approach is indispensable

Pharmacogenetics of Cardiovascular Disease: Genetic Variation and Statin Intolerance

Statins are very effective for lowering low-density lipoprotein cholesterol for primary and secondary cardiovascular disease prevention. While statins are usually well tolerated, individual response to statin therapy varies and intolerance, predominantly muscle symptoms, may appear in a significant proportion of patients. Besides clinical factors, variation in genes coding for proteins with drug transporting, immune or enzymatic function have been implicated in the pathogenesis of statin intolerance. In this review, we will characterise the candidate gene variants for development of statin intolerance, describe their population distribution and summarise current knowledge on their biological plausibility. Clinical relevance and current guidelines/recommendations will be also discussed

Ethnicity and Response to Drug Therapy

Hypercholesterolemia is a complex disorder presenting in different forms, including the familial form (FH), with varying underlying aetiology, and contributing substantially to coronary artery disease. Particularly, the FH underlies monogenic changes in genes involved in cholesterol synthesis and transport, including the low density lipoprotein receptor, proprotein convertase sublitisin/kexin type 9 and apolipoprotein B. However, hyperlipidemia is largely a complex interaction of changes in multiple genes with environmental factors, such as diet, overweight and obesity that are controllable by adopting healthy eating habits and exercise, which may vary by ethnicity. Diet alone is often not adequate to achieve the desired lipid lowering effect in individuals harbouring very high cholesterol levels, necessitating the use of lipid lowering medication or other forms of therapy. Antilipidemic drugs fall into (a) bile acid sequestrants (b) cholesterol absorption inhibitors, (c) 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, (d) fibric acid derivatives (e) proprotein convertase subtilisin/kexin type 9 inhibitors, (f) miscellaneous agents and (g) drug combinations. Mutations in their various metabolizing enzymes, particularly the cytochrome P450 family, often lead to partially/non-functional, or even rapid metabolizing phenotypes, triggering great variations in the way individuals respond to drug therapy, which in turn depends on ethnicity. This may produce unexpected outcomes such as therapeutic failure, adverse side effects and toxicity in individuals of different ethnic origin. Hence, in-depth information of the impact of ethnicity on these relationships has the huge potential of achieving optimal quality use of drugs as well as improving the efficacy and safety of antilipidemic therapeutic agents

Dyslipidemia in Special Populations, the Elderly, Women, HIV, Chronic Kidney Disease and ESRD, and Minority Groups

This chapter discusses the management of dyslipidemia in special patient populations: the elderly, woman and pregnancy, renal disease, human immunodeficiency virus (HIV), and different racial/ethnic groups. In the elderly, dyslipidemia is often underdiagnosed and undertreated. Consideration for potential atherosclerotic risk-reduction benefits, risk of adverse effects, drug-drug interactions, and patient preferences should precede the initiation of statin therapy. Data on pregnant women are lacking and need future research. Dyslipidemia and its effects on the cardiovascular system in chronic kidney disease (CKD), end-stage renal disease (ESRD), and HIV are dynamic and multimodal. These conditions are states of chronic inflammation, where it is difficult to associate quantities of cholesterol types with outcomes. Among all racial groups, Asian Indians, Filipinos, and Hispanics are at a higher risk for dyslipidemia. Genetic differences in statin metabolism may explain this racial/ethnic difference

Pharmacogenetic implications in the management of metabolic diseases in Brazilian populations

Dyslipidemia, diabetes, obesity and hypertension are common metabolic diseases. In the last decades, unhealthy lifestyle and aging have leads to an increased incidence of these diseases, increasing morbidity and mortality by cardiovascular causes. The treatment of metabolic diseases includes lifestyle interventions as healthy diet and physical exercise, as well as pharmacological interventions. Several drugs are available for the management of metabolic diseases including among others lipidlowering antidiabetics and antihypertensive drugs. Variability in response to these drugs is influenced by both genetic and non-genetic factors. Polymorphisms in genes related to drug pharmacokinetics and pharmacodynamics have been shown to influence drug efficacy and safety. This review is focused on pharmacogenetic studies related to the management of metabolic diseases in samples of the Brazilian population. Associations of variants in drug metabolizing enzymes and transporters, drug target and metabolism-related genes with the efficacy and safety of lipid-lowering, antidiabetic and antihypertensive drugs are described. Most pharmacogenetic studies in Brazil have focused in pharmacological response to a small group of drugs, as statins and some antihypertensives, while there are almost no studies on antidiabetic and antiobesity drugs. Some studies reported significant associations of gene polymorphisms with drug response confirming previous data from other populations, whereas other works did not replicate, which may relay on the genetic admixture of our population. In conclusion, further studies are necessary considering larger sample sizes, new unexplored drugs and more genetic variants to obtain stronger conclusions to explore clinical applications of pharmacogenetic studies in our population

Safety and efficacy of laropiprant and extended-release niacin combination in the management of mixed dyslipidemias and primary hypercholesterolemia

Statins form the cornerstone of pharmaceutical cardiovascular disease prevention. However, despite very effective statin intervention, the majority of events remain unpreventable. In some cases statin therapy alone is insufficient to achieve adequate lipid levels whereas other patients are unable to tolerate statins. This calls for additional treatment options. Niacin has a long history of success in reducing low-density lipoprotein cholesterol and triglycerides, and increasing high-density lipoprotein cholesterol. It was the first lipid-lowering drug to demonstrate a reduction in cardiovascular events, and remains the only one that has consistently shown benefits on surrogate outcomes when added to background therapies of other lipid-lowering drugs, including statins. Niacin’s uptake in clinical practice has been less successful due to its side-effect profile, most notable being flushing. The uncovering of the mechanism by which flushing is induced, together with the development of a prostaglandin D2 receptor inhibitor (laropiprant) which reduces this downstream flushing effect of niacin, has sparked new promise in therapeutic lipid management. It provides an additional treatment option into managing lipid abnormalities. The uptake in clinical practice of the niacin–laropiprant combination will depend on the relative improvements experienced by the patient in the side-effect profile compared to other treatment options, as well as on the the keenly-awaited outcome studies currently underway. Until these data become available guidelines and recommendations are unlikely to change and niacin’s position in therapeutic cardiovascular risk prevention will be determined by clinician opinion and experience, and patient preferences