Comprehensive review of statin-intolerance and the practical application of Bempedoic Acid.

Statin-intolerance (SI) has prevalence between 8.0 % and 10 %, and muscular complaints are the most common reason for discontinuation. Bempedoic acid (BA), an ATP citrate lyase inhibitor, decreases hepatic generation of cholesterol, upregulates low-density lipoprotein (LDL) receptor expression in the liver, and eventually clears circulating LDL-cholesterol from the blood. Multiple randomized clinical trials studying BA demonstrate a reduction in LDL levels by 17-28 % in SI. The CLEAR OUTCOME trial established significant cardiovascular benefits with BA. A dose of 180 mg/day of BA showed promising results. BA alone or in combination with ezetimibe is US Food and Drug Administration-approved for use in adults with heterozygous familial hypercholesterolemia and/or established atherosclerotic cardiovascular disease. BA reduced HbA1c by 0.12 % (p < 0.0001) in patients with diabetes. Adverse events of BA include myalgia (4.7 %), anemia (3.4 %), and increased aminotransferases (0.3 %). BA can cause up to four times higher risk of gout in those with a previous gout diagnosis or high serum uric acid levels. Reports of increased blood urea nitrogen and serum creatinine were noted. Current evidence does not demonstrate a reduction in deaths from cardiovascular causes. More studies that include a diverse population and patients with both high and low LDL levels should be conducted. We recommend that providers consider BA as an adjunct to statin therapy in patients with a maximally tolerated dosage to specifically target LDL levels.

Does Statin Use in Frail Patients Provide Survival Benefits? Insights From a Meta-Analysis.

Frailty is a complex syndrome that increases with age and predisposes older adults to adverse outcomes, including mortality. Statins are proven to lower the risk of atherosclerotic cardiovascular disease, but there is limited data on their survival benefit in frail older people. This meta-analysis was conducted to determine whether statins can lower mortality in frail persons. A comprehensive search of PubMed, Google Scholar, and SCOPUS was conducted until September 2022 to identify studies reporting mortality outcomes with statin therapy in adults aged 75 with a validated frailty assessment. The pooled odds ratio for all-cause mortality was calculated using a random effects model. Leave-one-out method was used for sensitivity analysis. Of 5 studies (2013-2022) included (Total = 14,324, 3 prospective and 2 retrospectives, Males: 49%, Mean follow-up duration: 4.7 years), 41.6% (5971/14,324) were frail. 52.7% of patients were on a moderate-dose/no-statin, while 47.2% took a high-dose statin. Nonstatin users were older (83.35 vs 81.5) than users. Frail patients often had diabetes, hypertension, hyperlipidemia, a history of Stroke/MI, and dementia. High-dose atorvastatin was the most used statin. Pooled analysis revealed that statins lower all-cause mortality in elderly adults, however, the association was not significant (OR 0.67, 95% CI 0.38-1.18; P = 0.17). The meta-analysis demonstrated that using statins to reduce mortality in frail patients does not appear justifiable. Further prospective studies are needed to guide statin use among frail older adults for survival benefits.