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Bempedoic acid, an ATP citrate lyase inhibitor, reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events; its effects on cardiovascular outcomes remain uncertain. We conducted a double-blind, randomized, placebo-controlled trial involving patients who were unable or unwilling to take statins owing to unacceptable adverse effects (\"statin-intolerant\" patients) and had, or were at high risk for, cardiovascular disease. The patients were assigned to receive oral bempedoic acid, 180 mg daily, or placebo. The primary end point was a four-component composite of major adverse cardiovascular events, defined as death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. A total of 13,970 patients underwent randomization; 6992 were assigned to the bempedoic acid group and 6978 to the placebo group. The median duration of follow-up was 40.6 months. The mean LDL cholesterol level at baseline was 139.0 mg per deciliter in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2 mg per deciliter; the observed difference in the percent reductions was 21.1 percentage points in favor of bempedoic acid. The incidence of a primary end-point event was significantly lower with bempedoic acid than with placebo (819 patients [11.7%] vs. 927 [13.3%]; hazard ratio, 0.87; 95% confidence interval [CI], 0.79 to 0.96; P = 0.004), as were the incidences of a composite of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction (575 [8.2%] vs. 663 [9.5%]; hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P = 0.006); fatal or nonfatal myocardial infarction (261 [3.7%] vs. 334 [4.8%]; hazard ratio, 0.77; 95% CI, 0.66 to 0.91; P = 0.002); and coronary revascularization (435 [6.2%] vs. 529 [7.6%]; hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = 0.001). Bempedoic acid had no significant effects on fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause. The incidences of gout and cholelithiasis were higher with bempedoic acid than with placebo (3.1% vs. 2.1% and 2.2% vs. 1.2%, respectively), as were the incidences of small increases in serum creatinine, uric acid, and hepatic-enzyme levels. Among statin-intolerant patients, treatment with bempedoic acid was associated with a lower risk of major adverse cardiovascular events (death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization). (Funded by Esperion Therapeutics; CLEAR Outcomes ClinicalTrials.gov number, NCT02993406.).

In this trial, patients with an acute coronary syndrome within the previous 10 days were randomly assigned to simvastatin plus either ezetimibe or placebo. At a median of 6 years, the rate of cardiovascular events was modestly but significantly lower with simvastatin–ezetimibe. The use of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) reduces both low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events in patients with and those without cardiovascular disease. 1 – 4 Intensive statin therapy, as compared with moderate-dose statin therapy, incrementally lowers LDL cholesterol levels and rates of nonfatal cardiovascular events. 5 – 9 Because of the residual risk of recurrent cardiovascular events and safety concerns associated with high-dose statin therapy, 10 additional lipid-modifying therapies have been sought. 11 – 14 Ezetimibe targets the Niemann–Pick C1–like 1 (NPC1L1) protein, thereby reducing absorption of cholesterol from the intestine. 15 , 16 When added to statins, ezetimibe reduces LDL cholesterol . . .

Among patients with recent MI, therapy with a polypill containing aspirin, ramipril, and atorvastatin led to a lower incidence of major adverse cardiovascular events at a median of 3 years than usual care.

In one comparison from a 2-by-2 factorial trial, 12,705 persons at intermediate cardiovascular risk were assigned to either rosuvastatin or placebo. At 5.6 years, there were significantly fewer participants with cardiovascular events in the rosuvastatin group than in the placebo group. Cardiovascular diseases cause 18 million deaths per year globally and a similar number of nonfatal cardiovascular events. 1 Elevated low-density lipoprotein (LDL) cholesterol levels account for approximately half the population-attributable risk of myocardial infarction 2 and approximately one quarter of the risk of ischemic stroke. 3 In previous trials, lowering LDL cholesterol levels with statins has been shown to reduce the risk of cardiovascular diseases, but most of the patients enrolled in those trials had vascular disease, elevated lipid levels, elevated inflammatory markers, hypertension, or diabetes. 4 , 5 The association between LDL cholesterol level and cardiovascular disease is graded and has no documented threshold. . . .

A genomewide screen of patients with myopathy who were taking high-dose simvastatin (80 mg per day) showed a strong association between myopathy and variants of SLCO1B1, which encodes an organic anion–transporting polypeptide. Approximately 60% of the cases of myopathy could be attributed to these variants. The association was replicated in an independent study. Genotyping SLCO1B1 variants may be helpful for tailoring the dosage of statins and safety monitoring. A genomewide screen of patients with myopathy who were taking high-dose simvastatin showed a strong association between myopathy and variants of SLCO1B1, which encodes an organic anion–transporting polypeptide. Evidence from large-scale, randomized studies shows that statin therapy reduces the incidence of heart attacks, strokes, and revascularization procedures by about one fifth for each reduction of 40 mg per deciliter (1 mmol per liter) in the low-density lipoprotein (LDL) cholesterol level. 1 In rare cases, statins can cause muscle pain or weakness in association with elevated creatine kinase levels (i.e., myopathy), and occasionally, this leads to muscle breakdown and myoglobin release (i.e., rhabdomyolysis), with a risk of renal failure and death. 2 The mechanisms by which statins cause myopathy remain unknown but appear to be related to statin concentrations in the . . .

Observational data had suggested that statin treatment may improve outcomes in patients with the acute respiratory distress syndrome from sepsis. This randomized trial showed no benefit to statin treatment in such patients. Despite progress in supportive care strategies for the acute respiratory distress syndrome (ARDS), mortality remains high, especially among patients with sepsis. 1 Inflammation leading to cellular damage and cellular death contributes to both pulmonary and nonpulmonary organ failure. Therapies that attenuate inflammation may improve outcomes in patients with ARDS. 2 Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, known collectively as statins, are commonly prescribed for hypercholesterolemia. However, statins also reduce inflammation and have been shown to prevent ARDS in murine models. 3 – 13 Several (but not all) large observational studies, a small randomized, controlled trial, and meta-analyses before study initiation have suggested that patients . . .

Patients undergoing cardiac surgery were randomly assigned to rosuvastatin or placebo. The groups did not differ significantly in the rate of postoperative atrial fibrillation or in the area under the troponin-release curve. Acute kidney injury was more common with rosuvastatin. Despite advances in surgical and perioperative care, postoperative complications after cardiac surgery remain frequent, leading to substantial increases in mortality, morbidity, and costs. 1 Inflammation and oxidative stress have been implicated in the pathogenesis of atrial fibrillation and other postoperative complications of cardiac surgery. 2 In particular, the incidence of postoperative atrial fibrillation coincides with the peak of the systemic inflammatory response after cardiac surgery, 2 is independently associated with atrial markers of oxidative stress, 3 , 4 and has been reported to be partially prevented by antiinflammatory drugs. 5 , 6 Statins have been shown to have rapid antiinflammatory and antioxidant effects 7 ; for example, 3 . . .

In this study, patients with acute respiratory distress syndrome who were not receiving statins were assigned to receive simvastatin or placebo. At 28 days, there were no significant between-group differences in survival or in the number of ventilator-free days. The acute respiratory distress syndrome (ARDS) is a common, devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and by multiple organ failure. In ARDS there is an uncontrolled inflammatory response that results in alveolar damage, with the exudation of protein-rich pulmonary-edema fluid in the alveolar space that results in respiratory failure. 1 The inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase with statins has been shown to modify a number of the underlying mechanisms implicated in the development of ARDS. 2 Statins decrease inflammation and histologic evidence of lung injury in murine models of ARDS. 3 Simvastatin reduced pulmonary and systemic . . .

The ODYSSEY COMBO I study (http://clinicaltrials.gov/show/NCT01644175) evaluated efficacy and safety of alirocumab as add-on therapy to stable maximally tolerated daily statin with or without other lipid-lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia. This multicenter, phase 3, randomized (2:1 alirocumab vs placebo), double-blind, 52-week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia. Alirocumab (75 mg every 2 weeks [Q2W]) or placebo Q2W was self-administered subcutaneously via 1 mL prefilled pen. The alirocumab dose was increased to 150 mg Q2W (also 1 mL) at week 12 if week 8 low-density lipoprotein cholesterol (LDL-C) was ≥70 mg/dL. The primary efficacy end point was percent change in LDL-C from baseline to week 24 (intention-to-treat analysis). At week 24, estimated mean (95% CI) changes in LDL-C from baseline were −48.2% (−52.0% to −44.4%) and −2.3% (−7.6% to 3.1%) for alirocumab and placebo, respectively, an estimated mean (95% CI) difference of −45.9% (−52.5% to −39.3%) (P < .0001). Low-density lipoprotein cholesterol <70 mg/dL was achieved by 75% alirocumab versus 9% placebo patients at week 24. At week 12, 83.2% of evaluable alirocumab-treated patients remained on 75-mg Q2W. Treatment-emergent adverse events were comparable between groups. Alirocumab treatment achieved a significantly greater reduction in LDL-C and allowed a greater proportion of patients to achieve LDL-C goals, versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid-lowering therapy. The frequency of treatment-emergent adverse events and study medication discontinuations were generally comparable between treatment groups.

In this study involving patients who were at high risk for exacerbations of chronic obstructive pulmonary disease but had no other indication for statin treatment, simvastatin at a daily dose of 40 mg did not affect the exacerbation rate. Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States. 1 It is characterized by acute exacerbations that are associated with increased hospitalizations and costs of care, worsened quality of life, and increased mortality. 2 – 9 Effective therapies for the treatment or prevention of exacerbations are limited. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that reduce the risks of acute cardiac events and death. 10 – 13 Although widely used for their lipid-lowering effects, statins are also reported to have antiinflammatory effects. 14 – 19 Multiple retrospective studies have shown that statins are beneficial in COPD. Reported benefits include . . .