Statin-Associated Muscle Symptoms Among New Statin Users Randomly Assigned to Vitamin D or Placebo.

Importance: Statin-associated muscle symptoms (SAMS) are common and may lead to discontinuation of indicated statin therapy. Observational studies suggest that vitamin D therapy is associated with reduced statin intolerance, but no randomized studies have been reported. Objective: To test whether vitamin D supplementation was associated with prevention of SAMS and a reduction of statin discontinuation. Design, Setting, and Participants: Men 50 years or older and women 55 years or older, free of cancer and cardiovascular disease, were enrolled in a randomized, placebo-controlled, double-blind clinical trial of vitamin D supplementation. Participants who initiated statin therapy after randomization were surveyed in early 2016. The data were analyzed in early 2022. Interventions: Daily cholecalciferol (2000 international units) or placebo with assessment of statin prescriptions during follow-up. Main Outcomes and Measures: Muscle pain or discomfort lasting several days (primary outcome) and discontinuation of a statin due to SAMS (secondary outcome). Results: Statins were initiated by 1033 vitamin D-assigned participants and 1050 placebo-assigned participants; mean (SD) age was 66.8 (6.2) years and 49% were women. Over 4.8 years of follow-up, SAMS were reported by 317 participants (31%) assigned vitamin D and 325 assigned placebo (31%). The adjusted odds ratio (OR) was 0.97 (95% CI, 0.80-1.18; P = .78). Statins were discontinued by 137 participants (13%) assigned to vitamin D and 133 assigned to placebo (13%) with an adjusted OR of 1.04 (95% CI, 0.80-1.35; P = .78). These results were consistent across pretreatment 25-hydroxy vitamin D levels (interaction P value = .83). Among participants with levels less than 20 ng/mL, SAMS were reported by 28 of 85 vitamin D-assigned participants (33%) and 33 of 95 placebo-assigned participants (35%). For those with levels less than 30 ng/ml, SAMS were reported by 88 of 330 vitamin-D assigned participants (27%) and 96 of 323 of placebo-assigned participants (30%). Conclusions and Relevance: Vitamin D supplementation did not prevent SAMS or reduce statin discontinuation. These results were consistent across pretreatment 25-hydroxy vitamin D levels. Trial Registration: ClinicalTrials.gov Identifier: NCT01169259.

Comparing eligibility for statin therapy for primary prevention under 2022 USPSTF recommendations and the 2018 AHA/ACC/ multi-society guideline recommendations: From National Health and Nutrition Examination Survey.

INTRODUCTION: The United States Preventive Services Taskforce (USPSTF) recently released recommendations for statin therapy eligibility for the primary prevention of cardiovascular disease (CVD). We report the proportion and the absolute number of US adults who would be eligible for statin therapy under these recommendations and compare them with the previously published 2018 American Heart Association (AHA)/ American College of Cardiology (ACC)/ Multisociety (MS) Cholesterol guidelines. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES) 2017-2020 of adults aged 40-75 years without prevalent self-reported atherosclerotic CVD (ASCVD) and low-density lipoprotein-cholesterol <190 mg/dL. The 2022 USPSTF recommends statin therapy for primary prevention in those with a 10-year ASCVD risk of ≥10% and ≥ 1 CVD risk factor (diabetes mellitus, dyslipidemia, hypertension, or smoking). The 2018 AHA/ ACC/ MS Cholesterol guideline recommends considering statin therapy for primary prevention for those with diabetes mellitus, or 10-year ASCVD risk ≥20% or 10-year ASCVD risk 7.5 to <20% after accounting for risk-enhancers and shared decision making. Survey recommended weights were used to project these proportions to national estimates. RESULTS: Among 1799 participants eligible for this study, the weighted mean age was 56.0 ± 0.5 years, with 53.0% women (95% confidence interval [CI] 49.7, 56.3), and 10.6% self-reported NH Black individuals (95% CI 7.7, 14.3). The weighted mean 10-year ASCVD risk was 9.6 ± 0.3%. The 2022 USPSTF recommendations and the 2018 AHA/ ACC/ MS Cholesterol guidelines indicated eligibility for statin therapy in 31.8% (95% CI 28.6, 35.1) and 46.8% (95% CI 43.0, 50.5) adults, respectively. These represent 33.7 million (95% CI 30.4, 37.2) and 49.7 million (95% CI 45.7, 53.7) adults, respectively. For those with diabetes mellitus, 2022 USPSTF recommended statin therapy in 63.0% (95% CI 52.1, 72.7) adults as compared with all adults with diabetes aged 40-75 years under the 2018 AHA/ ACC/ MS Cholesterol guidelines. CONCLUSION: In this analysis of the nationally representative US population from 2017 to 2020, approximately 15% (~16.0 million) fewer adults were eligible for statin therapy for primary prevention under the 2022 USPSTF recommendations as compared to the 2018 AHA/ ACC/ MS Cholesterol guideline.

Update on the omega-3 fatty acid trial landscape: A narrative review with implications for primary prevention.

Residual risk mediated by hypertriglyceridemia among statin-treated individuals is an important clinical and public health challenge. Niacin, fibrates and omega-3 FA are three classes of non-statin agents with demonstrated TG-lowering effects. Randomized controlled trials of niacin and fibrates have been consistently negative, but the trial landscape for two key sources of omega-3 FAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is more complex. Clinical trials evaluating omega-3 FA can be differentiated into those that studied mixed formulations (EPA + DHA) and those that studied EPA alone. Those assessing the impact of mixed formulations have not consistently demonstrated CVD risk reduction, whereas trials of EPA alone have been successful. Two recent trials of mixed formulations - STRENGTH (Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia) and OMEMI (Omega-3 fatty acids in Elderly patients with Myocardial Infarction) - studied contemporarily treated patients with mixed EPA + DHA formulations at higher doses than before and showed no benefit, thus adding valuable information to our overall understanding of this evolving therapeutic class. In this review, we contextualize the findings of STRENGTH and OMEMI within the existing omega-3 FA clinical trial landscape and look ahead to how future trials can inform existing knowledge gaps, particularly with regards to the applicability of these agents within the primary prevention realm.

The 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk: a new paradigm supported by more evidence.

AIMS: The 2013 American College of Cardiology/American Heart Association cholesterol guideline was a major paradigm shift and heavily criticized by some experts. A better understanding of the methodology used to develop the guideline, the guideline recommendations, and the evidence supporting them addresses many of criticisms. METHODS AND RESULTS: An extensive body of evidence from randomized clinical trials supports the new risk-based approach. The emphasis is on the appropriate intensity of statin therapy in patients most likely to benefit. The National Institute for Health and Care Excellence guidelines have taken a similar approach. Recent studies have found the 2013 guideline outperforms earlier cholesterol guidelines recommending low-density lipoprotein cholesterol (LDL-C) treatment thresholds and targets. The 2013 cholesterol guideline better identifies high-risk patients with a greater burden of atherosclerosis and avoids treating those at lower risk with little atherosclerosis; its application would prevent up to 450 000 more atherosclerotic cardiovascular disease (ASCVD) events over 10 years. The 2013 cholesterol guideline also recommends regularly monitoring LDL-C levels to assess adherence to lifestyle and drug therapy, and adjusting treatment based on response to therapy and adverse events. Non-statins shown to reduce ASCVD events when added to statin therapy, and that have an acceptable margin of safety in randomized, controlled clinical trials, are preferred. Ezetimibe has now been shown to meet this standard. CONCLUSIONS: The concept of net benefit introduced in the 2013 ACC/AHA cholesterol guideline identifies patients most likely to benefit from statin therapy to reduce ASCVD risk. Net benefit, incorporating the absolute ASCVD risk of a patient and the relative reduction in ASCVD risk based on the magnitude of LDL-C reduction from the addition of a non-statin, can be used when considering whether to add ezetimibe or another LDL-C lowering drug.

Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids.

Omega-3 fatty acids from both marine and plant sources have been shown to reduce the risk of coronary artery disease death. Although their beneficial cardiovascular effects are thought to be due to their antiarrhythmic properties, omega-3 fatty acids also have been shown to have a wide range of antiatherosclerotic and antithrombotic effects in animal and human studies. Review of the findings of randomized, controlled trials published through August 2005 shows that omega-3 fatty acids of marine origin consistently lower elevated plasma triglyceride levels in a dose-dependent fashion, with greater efficacy at higher triglyceride levels. Smaller effects on lowering blood pressure, improving endothelial function, and increasing plasma levels of high-density lipoprotein cholesterol were also found. No consistent effects on other lipid, hemostatic, inflammatory, glucose tolerance, or plaque stabilization parameters were found. Epidemiologic studies show more consistent reductions in the incidence of nonfatal myocardial infarction and ischemic stroke than do the clinical trials of increased omega-3 fatty acid intake, which suggests important confounding factors in observational studies. Ongoing clinical trials may clarify the non-antiarrhythmic benefits of omega-3 fatty acid supplementation.

Therapeutic lifestyle change and Adult Treatment Panel III: evidence then and now.

The Third Report of the National Cholesterol Education Program's Adult Treatment Panel (ATP III) has an extensive section on nonpharmacologic therapy for those with abnormal blood lipids. ATP III focused on the high-saturated fat atherogenic diet, obesity, and sedentary lifestyle and recommended a program of therapeutic lifestyle change (TLC). This review discusses several issues, including 1) why ATP III changed from the Step I and Step II diets to TLC; 2) the benefits of keeping trans fatty acid intake low and the addition of viscous fiber and plant stanol/sterol esters to reduce low-density lipoprotein cholesterol beyond that seen with the Step II diet; 3) the de-emphasis on total fat and a sharper focus on the kinds of fat ingested in the new guidelines; 4) the endorsement of regular physical activity and weight loss as important first steps in reversing the unwanted metabolic effects of the metabolic syndrome; and 5) the emphasis of health-promoting aspects of the diet that include, among other things, fish and omega-3 fatty acids. At all stages of TLC, ATP III encourages the referral to registered dietitians or other qualified nutritionists for medical nutrition therapy. TLC and the ATP III guidelines should provide guidance to practitioners who wish to get low-density lipoprotein cholesterol to goal (whether or not drugs are used), prevent or treat the metabolic syndrome, and improve the overall health of the patient.