Abstract The leadership of the National Lipid Association convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. ...An Executive Summary of those recommendations was previously published. This document provides support for the recommendations outlined in the Executive Summary. The major conclusions include (1) an elevated level of cholesterol carried by circulating apolipoprotein B-containing lipoproteins (non–high-density lipoprotein cholesterol and low-density lipoprotein cholesterol LDL-C, termed atherogenic cholesterol) is a root cause of atherosclerosis, the key underlying process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events; (2) reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle and drug therapies; (3) the intensity of risk-reduction therapy should generally be adjusted to the patient's absolute risk for an ASCVD event; (4) atherosclerosis is a process that often begins early in life and progresses for decades before resulting a clinical ASCVD event. Therefore, both intermediate-term and long-term or lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies; (5) for patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk; (6) nonlipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus; and (7) the measurement and monitoring of atherogenic cholesterol levels remain an important part of a comprehensive ASCVD prevention strategy.
Abstract Various organizations and agencies have issued recommendations for the management of dyslipidemia. Although many commonalities exist among them, material differences are present as well. The ...leadership of the National Lipid Association (NLA) convened an Expert Panel to develop a consensus set of recommendations for patient-centered management of dyslipidemia in clinical medicine. The current Executive Summary highlights the major conclusions in Part 1 of the recommendations report of the NLA Expert Panel and includes: (1) background and conceptual framework for formulation of the NLA Expert Panel recommendations; (2) screening and classification of lipoprotein lipid levels in adults; (3) targets for intervention in dyslipidemia management; (4) atherosclerotic cardiovascular disease risk assessment and treatment goals based on risk category; (5) atherogenic cholesterol—non–high-density lipoprotein cholesterol and low-density lipoprotein cholesterol—as the primary targets of therapy; and (6) lifestyle and drug therapies intended to reduce morbidity and mortality associated with dyslipidemia.
Background Statin intolerance limits many patients from achieving optimal low-density lipoprotein cholesterol (LDL-C) concentrations. Current options for such patients include using a lower but ...tolerated dose of a statin and adding or switching to ezetimibe or other non-statin therapies. Methods ODYSSEY ALTERNATIVE ( NCT01709513 ) compared alirocumab with ezetimibe in patients at moderate to high cardiovascular risk with statin intolerance (unable to tolerate ≥2 statins, including one at the lowest approved starting dose) due to muscle symptoms. A placebo run-in and statin rechallenge arm were included in an attempt to confirm intolerance. Patients (n = 361) received single-blind subcutaneous (SC) and oral placebo for 4 weeks during placebo run-in. Patients reporting muscle-related symptoms during the run-in were to be withdrawn. Continuing patients were randomized (2:2:1) to double-blind alirocumab 75 mg SC every 2 weeks (Q2W; plus oral placebo), ezetimibe 10 mg/d (plus SC placebo Q2W), or atorvastatin 20 mg/d (rechallenge; plus SC placebo Q2W) for 24 weeks. Alirocumab dose was increased to 150 mg Q2W at week 12 depending on week 8 LDL-C values. Primary end point was percent change in LDL-C from baseline to week 24 (intent-to-treat) for alirocumab vs ezetimibe. Results Baseline mean (standard deviation) LDL-C was 191.3 (69.3) mg/dL (5.0 1.8 mmol/L). Alirocumab reduced mean (standard error) LDL-C by 45.0% (2.2%) vs 14.6% (2.2%) with ezetimibe (mean difference 30.4% 3.1%, P < .0001). Skeletal muscle-related events were less frequent with alirocumab vs atorvastatin (hazard ratio 0.61, 95% confidence interval 0.38–0.99, P = .042). Conclusions Alirocumab produced greater LDL-C reductions than ezetimibe in statin-intolerant patients, with fewer skeletal-muscle adverse events vs atorvastatin.
Background Statins substantially reduce the risk of cardiovascular disease and are generally well-tolerated. Despite this, many patients discontinue therapy. A better understanding of the ...characteristics of current and former statin users may be helpful for formulating strategies to improve long-term adherence. Objective The Understanding Statin Use in America and Gaps in Education (USAGE) survey assessed the attitudes, beliefs, practices, and behavior of current and former statin users. Methods Individuals 18 years or older who reported a history of high cholesterol and current or former statin use were identified within a registered consumer panel cohort in the United States and invited to participate in an Internet survey. Results Of the 10,138 respondents, 8918 (88%) were current statin users and 1220 (12%) were former users. Participants (mean age 61 years) were predominantly white (92%), female (61%), of middle income (median $44,504/yr), and had health insurance (93%). Among current users, 95% took a statin alone, and 70% had not missed a dose in the past month. Although ∼70% reported that their physicians had explained the importance of cholesterol levels for their heart health former users were less satisfied with the discussions (65% vs. 83%, P < .05). Muscle-related side effects were reported by 60% and 25% of former and current users, respectively ( P < .05). Nearly half of all respondents switched statins at least once. The primary reason for switching by current users was cost (32%) and the primary reason for discontinuation was side effects (62%). Conclusions This survey provides important insights into behavior and attitudes among current and former statin users and the results suggest that more effective dialogue between healthcare providers and patients may increase persistence of statin use, particularly when the patient has concerns about side effects and drug costs.
Background Although statins have been shown to reduce cardiovascular disease mortality, less than half of U.S. adults achieve their low-density lipoprotein cholesterol goal. In many patients ...initiated on a statin, adherence rates decrease over time. Objective To characterize current and former statin users, identify reasons for the discontinuation or switching of statins, and identify factors associated with adherence. Methods The USAGE survey is a cross-sectional, self-administered Internet-based survey of 10,138 U.S. adults fielded September to October 2011. The following statin users were identified and compared: adherent nonswitchers, adherent switchers, non-adherent switchers, and discontinuers. Univariate and multivariate models using a priori covariates for adherence and discontinuation were examined. Results Most participants were current statin users who adhered with their prescribed statin (82.5%, n = 8371). Former statin users or discontinuers (12%, n = 1220) cited muscle pain, a side effect, as the primary reason for discontinuation (60%), followed by cost (16%), and then perceived lack of efficacy (13%). Discontinuers were less satisfied with their physicians' explanation of cholesterol treatment, more likely to use the Internet to research statins, and less likely to undergo frequent cholesterol monitoring. Among adherent statin users, the primary reasons for switching were muscle side effects (33%) and cost (32%). Individuals at risk for non-adherence included those with low household income, those who experienced muscle pain as a side effect while on statin therapy, and those taking medication for cardiovascular disease. Conclusion Statin-related muscle side effects are common and contribute significantly to rates of discontinuation, switching, and non-adherence. Improved physician patient communication about side effects and benefits of statins are necessary to improve both adherence and outcomes.
Background Statin therapy has been shown to reduce cardiovascular morbidity and mortality, and the benefits of statin therapy are similar for men and women. Recent studies have shown that women are ...less likely to be treated with statin therapy, to be on higher doses of more potent statins, and to achieve their lipid goals as compared with men. Objectives To analyze results from the Understanding Statin Use in America and Gaps in Patient Education (USAGE) survey and to assess whether women differ from men with regard to reported side effects associated with statin use, clinician and patient interactions, as well as general attitudes and preferences regarding statin use. Methods The study population was derived from participants in the USAGE survey, a self-administered, Internet-based questionnaire. Results More women reported switching or stopping a statin because of side effects compared with men. New or worsening muscle symptoms were reported in 31% of women compared with 26% of men ( P < .01). More women, including high-risk women reported that their doctor did not give them information about their risk for heart disease compared with men. Women were more likely to try 3 or more statins, but less likely to use alternative low-density lipoprotein cholesterol–lowering drugs. Women were more likely to be dissatisfied with their statin, with how their clinician explained their cholesterol treatment, and less adherent to their statin than men. Conclusions Women are more likely to stop or switch their statin than men, and the main reason for this was new or worsening muscle symptoms. Improved communication between the clinician and the patient about the benefits and risks of statin therapy will improve adherence, lipid goal attainment, and outcomes in women with or at risk for cardiovascular disease.
Abstract An Expert Panel convened by the National Lipid Association was charged with updating the recommendations on the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody therapy ...that were provided by the 2015 National Lipid Association Recommendations for the Patient-Centered Management of Dyslipidemia: Part 2. Recent studies have demonstrated the efficacy of these agents in reducing low-density lipoprotein cholesterol and non–high-density lipoprotein cholesterol and have confirmed their excellent safety profile. A cardiovascular outcomes study has shown that these agents reduce incident atherosclerotic cardiovascular disease (ASCVD) events in patents with stable ASCVD and concomitant risk factors. The current update provides the Expert Panel's evidence-based recommendations on the clinical utility of PCSK9 inhibitors in patients with stable ASCVD, progressive ASCVD, LDL-C ≥ 190 mg/dL (including polygenic hypercholesterolemia, heterozygous familial hypercholesterolemia and the homozygous familial hypercholesterolemia phenotype) and very-high-risk patients with statin intolerance.
Abstract The National Cholesterol Education Program Adult Treatment Panel guidelines have established low-density lipoprotein cholesterol (LDL-C) treatment goals, and secondary non-high-density ...lipoprotein (HDL)-C treatment goals for persons with hypertriglyceridemia. The use of lipid-lowering therapies, particularly statins, to achieve these goals has reduced cardiovascular disease (CVD) morbidity and mortality; however, significant residual risk for events remains. This, combined with the rising prevalence of obesity, which has shifted the risk profile of the population toward patients in whom LDL-C is less predictive of CVD events (metabolic syndrome, low HDL-C, elevated triglycerides), has increased interest in the clinical use of inflammatory and lipid biomarker assessments. Furthermore, the cost effectiveness of pharmacological intervention for both the initiation of therapy and the intensification of therapy has been enhanced by the availability of a variety of generic statins. This report describes the consensus view of an expert panel convened by the National Lipid Association to evaluate the use of selected biomarkers C-reactive protein, lipoprotein-associated phospholipase A2 , apolipoprotein B, LDL particle concentration, lipoprotein(a), and LDL and HDL subfractions to improve risk assessment, or to adjust therapy. These panel recommendations are intended to provide practical advice to clinicians who wrestle with the challenges of identifying the patients who are most likely to benefit from therapy, or intensification of therapy, to provide the optimum protection from CV risk.
Abstract Plasma levels of lipids and lipoproteins are essential to the management of lipid disorders by generalists and by practitioners of the emerging specialty of clinical lipidology. The routine ...lipid panel consists of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Several additional lipid parameters are emerging as potentially valuable adjuncts to the standard panel, including measurements of apolipoproteins and LDL particle size and concentration, but most of these serve mainly as research tools at present. One major exception is non–HDL-C, which is readily available for routine clinical use. This review outlines some of the numerous research studies that clearly establish the clinical utility and even preeminence of non–HDL-C as a comprehensive measure of atherogenic lipoproteins. Non–HDL-C was highlighted as a key secondary goal of therapy several years ago in the National Cholesterol Education Program Adult Treatment Panel III national lipid treatment guidelines and recently was further emphasized as a major goal of therapy in the consensus guidelines for lipoprotein management in patients with cardiometabolic risk from the American Diabetes Association and the American College of Cardiology. Non–HDL-C is superior to LDL-C for the prediction of cardiovascular events and has many other compelling advantages over LDL-C and other traditional lipid parameters. Importantly, it can be calculated directly from values in routine lipid panels, at no added expense. It is our opinion that non–HDL-C should be reported on all routine lipid profiles and used regularly in the management of dyslipidemia for optimal prevention of atherosclerosis and cardiovascular disease.
Abstract Elevated lipoprotein(a) (Lpa) is a causal genetic risk factor for cardiovascular disease. To determine if current evidence supports both screening and treatment for elevated Lp(a) in ...high-risk patients, an English-language search of PubMed and MEDLINE was conducted. In population studies, there is a continuous association between Lp(a) concentrations and cardiovascular risk, with synergistic effects when low-density lipoprotein (LDL) is also elevated. Candidates for Lp(a) screening include patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL cholesterol (LDL-C) responses to statins. Given the comparative strength of clinical evidence, reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies. If the Lp(a) level is 30 mg/dL or higher in a patient who has the aforementioned characteristics plus residual LDL-C elevations (≥70-100 mg/dL) despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d). If, after these interventions, the patient has progressive coronary heart disease (CHD) or LDL-C levels of 160-200 mg/dL or higher, LDL apheresis should be contemplated. Although Lp(a) is a major causal risk factor for CHD, no currently available controlled studies have suggested that lowering it through either pharmacotherapy or LDL apheresis specifically and significantly reduces coronary risk. Further research is needed to (1) optimize management in order to reduce CHD risk associated with elevated Lp(a) and (2) determine what other intermediate- or high-risk groups might benefit from Lp(a) screening.
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