Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Urgent Pericardiocentesis Is More Frequently Needed After Left Circumflex Coronary Artery Perforation.

Background: Coronary artery perforation (CAP) is a rare but potentially life-threatening complication of percutaneous coronary interventions (PCIs) due to the risk of cardiac tamponade. Strikingly, in contrast to numerous analyses of CAP predictors, only few studies were focused on the predictors of tamponade after PCI, once iatrogenic CAP has occurred. Our aim was to search for clinical and periprocedural characteristics, including the coronary artery involved, associated with the development of acute cardiac tamponade among patients experiencing CAP. Methods: From the medical records of nine centers of invasive cardiology in southern Poland, we retrospectively selected 81 patients (80% with acute myocardial infarction) who had iatrogenic CAP with a visible extravasation jet during angiography (corresponding to type III CAP by the Ellis classification, CAPIII) over a 15-year period (2005-2019). Clinical, angiographic and periprocedural characteristics were compared between the patients who developed acute cardiac tamponade requiring urgent pericardiocentesis in the cathlab (n = 21) and those with CAPIII and without tamponade (n = 60). Results: CAPIII were situated in the left anterior descending artery (LAD) or its diagonal branches (51%, n = 41), right coronary artery (RCA) (24%, n = 19), left circumflex coronary artery (LCx) (16%, n = 13), its obtuse marginal branches (7%, n = 6) and left main coronary artery (2%, n = 2). Acute cardiac tamponade occurred in 24% (10 of 41), 21% (4 of 19) and 37% (7 of 19) patients who experienced CAPIII in the territory of LAD, RCA and LCx, respectively. There were no significant differences in the need for urgent pericardiocentesis (37%) in patients with CAPIII in LCx territory (i.e., the LCx or its obtuse marginal branches) compared to CAPIII in the remaining coronary arteries (23%) (p = 0.24). However, when CAPIII in the LCx were separated from CAPIII in obtuse marginal branches, urgent pericardiocentesis was more frequently performed in patients with CAPIII in the LCx (54%, 7 of 13) compared to subjects with CAPIII in an artery other than the LCx (21%, 14 of 68) (p = 0.03). The direction of this tendency remained consistent regardless of CAP management: prolonged balloon inflation only (n = 26, 67% vs. 13%, p = 0.08) or balloon inflation with subsequent stent implantation (n = 55, 50% vs. 24%, p = 0.13). Besides LCx involvement, no significant differences in other characteristics were observed between patients according to the need of urgent pericardiocentesis. Conclusions: CAPIII in the LCx appears to lead to a higher risk of acute cardiac tamponade compared to perforations involving other coronary arteries. This association may possibly be linked to distinct features of LCx anatomy and/or well-recognized delays in diagnosis and management of LCx-related acute coronary syndromes.

Age may determine the effect of hypolipidemic agents on plasma adipokine levels in patients with elevated low-density lipoprotein cholesterol levels.

INTRODUCTION: Lipid-lowering agents affect adipose tissue function. No study has investigated the role of age in the effects of hypolipidaemic agents on plasma adipokines. MATERIAL AND METHODS: The study was a retrospective analysis of data of 65 hypercholesterolaemic patients treated for 90 days with simvastatin, ezetimibe, or simvastatin/ezetimibe combination therapy. Circulating levels of leptin, adiponectin, visfatin, and tumour necrosis factor alpha (TNF-alpha), as well as high-sensitivity C-reactive protein (hsCRP) were assessed separately for patients aged between 35 and 50 years and between 51 and 65 years, at the beginning and at the end of treatment. RESULTS: Patients in the age between 51 and 65 years had higher plasma levels of TNF-alpha and hsCRP, and lower plasma levels of adiponectin than patients aged between 35 and 50 years. In both age groups, simvastatin reduced plasma levels of hsCRP, leptin, visfatin, and TNF-alpha and increased circulating levels of adiponectin. This effect was particularly pronounced if simvastatin was administered in combination with ezetimibe. Ezetimibe alone increased plasma adiponectin and reduced plasma levels of leptin and hsCRP only in older adults. Irrespectively of age, ezetimibe administered alone did not affect visfatin and TNF-alpha. The effect of simvastatin on plasma hsCRP and the investigated adipokines did not differ between both groups. In turn, the effect of ezetimibe and simvastatin/ezetimibe combination therapy on leptin, adiponectin, and hsCRP was stronger in older than in younger adults. CONCLUSIONS: Our results show that age may partially determine the effect of ezetimibe, but not of simvastatin, on adipose tissue function. (Endokrynol Pol 2016; 67 (3): 271-276).

Comparison of the effects of short-term hypolipidaemic treatment on plasma adipokine levels in men and women with isolated hypercholesterolaemia.

INTRODUCTION: Hypolipidaemic agents were found to affect plasma adipokine levels, but no previous study has investigated whether this effect is sex-dependent. MATERIAL AND METHODS: We retrospectively analysed 61 patients participating in our previous studies, who because of isolated hypercholesterolaemia were treated with simvastatin (40 mg daily), ezetimibe (10 mg daily) or simvastatin (40 mg daily) plus ezetimibe (10 mg daily). Plasma levels of leptin, adiponectin, visfatin, tumour necrosis factor-alpha (TNF-alpha), free fatty acids (FFA), and high-sensitivity C-reactive protein (hsCRP) were assessed separately for men and women before and after 30 days of treatment. RESULTS: At baseline, plasma levels of adiponectin and leptin were lower, while plasma levels of TNF-alpha were higher in men than in women. Administration of simvastatin and statin/ezetimibe combination for 30 days reduced plasma levels of hsCRP, FFA, leptin, visfatin, and TNF-alpha but increased plasma levels of adiponectin, while the effect of ezetimibe was much more limited. The effect of simvastatin and ezetimibe, administered alone or in combination, on plasma hsCRP, FFA, leptin, adiponectin, visfatin, and TNF-alpha did not differ between men and women. Irrespectively of sex, the changes in plasma adipokines and systemic-anti-inflammatory effects were more expressed in simvastatin - than in ezetimibe-treated patients and were strongest when both these agents were administered together. CONCLUSIONS: Our results show that sex differences do not determine the effect of hypolipidaemic agents on adipose tissue and low-grade inflammation.

The effect of ezetimibe-statin combination on steroid hormone production in men with coronary artery disease and low cholesterol levels.

BACKGROUND: Aggressive statin treatment was found to slightly reduce testosterone production. The aim of this study was to compare the effects of ezetimibe-statin combination and high-dose statin therapy on testicular and adrenal cortex function in men with LDL cholesterol levels below 70 mg/dL. METHODS: The study included 26 adult men with coronary artery disease. Twelve of these patients did not tolerate high-dose statin therapy and were treated with lower doses of a statin plus ezetimibe. Fourteen patients tolerating high-dose simvastatin or rosuvastatin treatment continued high-dose statin therapy throughout the study period. Plasma lipids, glucose homeostasis markers and plasma levels of testosterone, cortisol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, gonadotropins and ACTH, as well as urine free cortisol were assessed at baseline and after 16 weeks of treatment. RESULTS: Replacing high-dose statin therapy with ezetimibe/statin combination therapy reduced plasma levels of LH by 32% (p=0.043), as well as increased plasma levels of testosterone by 20% (p=0.038). Ezetimibe/statin combination did not induce any significant changes in plasma levels or urine excretion of the remaining hormones. At the end of the study, plasma LH levels were higher, while plasma testosterone levels were lower in patients receiving the combination therapy than in those treated only with high-dose statin. CONCLUSIONS: Our results indicate that ezetimibe combined with moderate statin dose exerts a less pronounced effect on testicular function in comparison with high-dose statin therapy.

The effect of short-term combined treatment with simvastatin and ezetimibe on circulating adipokine levels in patients with isolated hypercholesterolemia.

INTRODUCTION: Although several studies have assessed plasma adipokines in patients treated with hypolipidemic agents, these studies have provided contrasting results. MATERIAL AND METHODS: This study included 19 high-risk patients with elevated total and LDL cholesterol levels treated with simvastatin (40 mg daily) and ezetimibe (10 mg daily). Plasma levels of leptin, adiponectin, visfatin, tumour necrosis factor-α, free fatty acids as well as C-reactive protein were measured before and after 30 days of treatment. High-risk hypercholesterolemic patients were compared with 17 age-, sex- and weight-matched healthy subjects who did not receive any treatment. RESULTS: Compared to the healthy subjects, hypercholesterolemic patients exhibited lower plasma levels of adiponectin, as well as higher plasma levels of the remaining adipokines. Administration of simvastatin and ezetimibe for 30 days reduced plasma levels of leptin, visfatin, TNF-α, as well as increased plasma levels of adiponectin. The treatment also reduced free fatty acids and C-reactive protein. CONCLUSIONS: High-risk hypercholesterolemic patients with elevated cholesterol levels are characterised by abnormal production of adipose tissue hormones. Short-term treatment with simvastatin and ezetimibe partially restores adipokine production and inhibits low-grade inflammation.

The effect of short-term simvastatin treatment on plasma adipokine levels in patients with isolated hypercholesterolemia: A preliminary report.

BACKGROUND: Apart from reducing plasma lipids, statins produce numerous non-lipid-related pleiotropic effects. The aim of this study was to investigate whether short-term simvastatin treatment affects plasma adipokine levels in patients with isolated hypercholesterolemia. METHODS: The study included 42 adult patients with untreated isolated hypercholesterolemia, complying throughout the study with lifestyle intervention, 23 of whom were treated with simvastatin (40 mg daily), as well as 18 healthy subjects with normal lipid profile. Plasma lipids, apolipoproteins, glucose metabolism markers, as well as plasma levels of C-reactive protein (CRP), free fatty acids (FFA), leptin, adiponectin, visfatin and tumor necrosis factor-α (TNF-α) were determined at baseline and after 30 days of treatment. RESULTS: Compared with the control age-, sex-, and weight-matched healthy subjects, isolated hypercholesterolemic patients exhibited higher plasma levels of leptin, visfatin, TNF-α, FFA and CRP, as well as lower plasma levels of adiponectin. Apart from decreasing plasma total cholesterol, LDL cholesterol and apolipoprotein B-100 levels, simvastatin reduced plasma levels of FFA, leptin and TNF-α, as well as increased plasma levels of adiponectin, which was accompanied by a reduction in plasma CRP. There were no differences in simvastatin action on plasma adipokines and CRP between insulin-resistant and insulin-sensitive subjects. CONCLUSIONS: Our results indicate that the presence of isolated hypercholesterolemia is associated with abnormal hormonal function of the adipose tissue. These changes are partially reversed by short-term simvastatin treatment, and this action may contribute to the clinical effectiveness of statins in the therapy of atherosclerosis-related disorders.

The effect of ezetimibe on androgen production in hypercholesterolemic women with polycystic ovary syndrome.

AIMS: Statin therapy was found to reduce circulating androgen levels in patients with polycystic ovary syndrome (PCOS). No similar data are available for ezetimibe. METHODS: The study included 14 women with PCOS and hypercholesterolemia, intolerant to statins or having contraindications to this treatment, who were treated with ezetimibe (10 mg daily). They were compared with 14 matched women with both of these disorders receiving simvastatin (40 mg daily). Plasma lipids, glucose homeostasis markers, and serum levels of androgens, sex hormone-binding globulin, and gonadotropins were assessed at baseline and after 3 months of treatment. RESULTS: Both simvastatin and ezetimibe decreased plasma levels of total and LDL cholesterol. Ezetimibe, but not simvastatin, slightly reduced insulin resistance. Simvastatin decreased serum levels of total testosterone (-23%, P < 0.001), free testosterone (-32%, P < 0.001), androstendione (-20%, P < 0.01), and dehydroepiandrosterone sulfate (-17%, P < 0.05), as well as tended to reduce the luteinizing hormone/follicle-stimulating hormone ratio (-23%, P = 0.095). Ezetimibe only insignificantly reduced serum levels of free testosterone (-14%, P = 0.098). There were no differences in the effects of simvastatin on circulating hormone levels between insulin-resistant and insulin-sensitive subjects. In turn, the effect of ezetimibe on free testosterone levels was stronger in insulin-resistant patients. CONCLUSIONS: Although ezetimibe and simvastatin are equipotent in lowering lipid levels in hypercholesterolemic patients with coexisting PCOS, simvastatin exhibits a more pronounced effect on circulating androgen levels in this group of patients.

The effect of ezetimibe on adipose tissue hormones in patients with isolated hypercholesterolemia.

BACKGROUND: Extra-lipid effects of ezetimibe, a new lipid-lowering agent, are so far poorly understood. METHODS: Twenty-two patients with elevated total and LDL cholesterol levels, statin-intolerant or having contraindications to statin therapy, were treated with ezetimibe (10mg daily) for 90 days. Plasma levels of lipids, apolipoproteins, glucose homeostasis markers, leptin, adiponectin, visfatin, tumor necrosis factor-α (TNF-α), free fatty acids (FFA) and high sensitivity C-reactive protein (hsCRP) were examined at the beginning of the study and after 30 and 90 days of treatment. RESULTS: Compared with the control age-, sex-, and weight-matched healthy subjects, isolated hypercholesterolemic patients exhibited higher plasma levels of leptin, visfatin and TNF-α and lower plasma levels of adiponectin. Their baseline FFA and hsCRP levels were also increased. Ezetimibe decreased circulating levels of total cholesterol, LDL cholesterol and apolipoprotein B-100. The drug significantly reduced plasma levels of visfatin and only tended to reduce plasma levels of leptin, TNF-α, visfatin, FFA and CRP. The effect of ezetimibe on these markers was lipid-independent but stronger in insulin-sensitive than in insulin-resistant patients. CONCLUSIONS: The obtained results indicate that the presence of isolated hypercholesterolemia is associated with abnormal hormonal function of the adipose tissue. They also show that ezetimibe induces relatively small changes in adipose tissue hormonal function and systemic inflammation in patients with elevated cholesterol levels.

The effect of simvastatin-ezetimibe combination therapy on adipose tissue hormones and systemic inflammation in patients with isolated hypercholesterolemia.

BACKGROUND: Pleiotropic effects of ezetimibe have only been investigated in a few studies. The aim of this article was to compare the effects of simvastatin and the combined treatment with simvastatin and ezetimibe on low-grade systemic inflammation and plasma levels of selected adipokines in patients with isolated hypercholesterolemia. METHODS: The study included 69 patients with elevated cholesterol levels, who were allocated to one of the three groups treated for 12 weeks, respectively, with simvastatin (40 mg daily), simvastatin (40 mg daily) plus ezetimibe (10 mg daily), or placebo. Plasma levels of lipids, apolipoproteins, glucose homeostasis markers, leptin, adiponectin, visfatin, tumor necrosis factor-α (TNF-α), free fatty acids (FFA), and high-sensitive C-reactive protein (hsCRP) were determined on the allocation day and after 12 weeks of therapy. RESULTS: Apart from improving lipid profile, simvastatin administered alone or in combination with ezetimibe, decreased plasma levels of hsCRP, FFA, leptin, visfatin, and TNF-α, as well as increased plasma levels of adiponectin. The combination therapy was superior to simvastatin in influencing plasma lipids/lipoproteins, hsCRP, FFA, and the investigated adipokines. The effect of the combination therapy, but not of simvastatin, on systemic inflammation and plasma adipokines was stronger in insulin-resistant than in insulin-sensitive subjects. CONCLUSIONS: The obtained results suggest that insulin-resistant patients with hypercholesterolemia and high cardiovascular risk may benefit the most from the combined treatment with simvastatin and ezetimibe.

[Peripartum cardiomyopathy, acute autoimmune pancreatitis and periadipose tissue inflammation - autoimmune reaction?]. / Kardiomiopatia pologowa a ostre zapalenie trzustki i tkanki tluszczowej - reakcja autoimmunologiczna?

A case of 26 year-old female with peripartum cardiomyopathy, acute pancreatitis, periadipose tissue inflammation due to unknown cause and multiple organ dysfunction syndrome complication is presented.

The effect of ezetimibe and simvastatin on hemostasis in patients with isolated hypercholesterolemia.

The aim of this study was to assess the strength of hemostatic effects of ezetimibe, administered alone or in combination with simvastatin, in patients with isolated hypercholesterolemia. One hundred and four patients with isolated primary hypercholesterolemia were randomized to one of four treatment groups, simultaneously treated for 90 days with ezetimibe (10 mg daily), simvastatin (40 mg daily), ezetimibe (10 mg daily) plus simvastatin (40 mg daily), or placebo. Plasma lipids/lipoproteins and hemostatic cardiovascular risk factors were assessed on the day of randomization and after 30 and 90 days of therapy. Despite improving lipid/lipoprotein profile by both simvastatin and ezetimibe, only simvastatin reduced plasma levels/activity of fibrinogen, factor VII, factor X, von Willebrand factor, and plasminogen activator inhibitor-1. The strongest effects on plasma lipids/lipoproteins and the assessed hemostatic variables were observed when patients were treated with both simvastatin and ezetimibe. With the exception of oxidized low-density lipoproteins, the hemostatic effects of simvastatin or simvastatin plus ezetimibe did not correlate with the changes in plasma lipids/lipoproteins. Our study shows that simvastatin is a more effective agent than ezetimibe in affecting coagulation and fibrinolysis in individuals with isolated hypercholesterolemia. It also suggests that the combined administration of simvastatin and ezetimibe may bring more benefits to patients than monotherapy with only one of these agents.

[Right atrial tumour and right ventricular failure - diagnostic role of echocardiography and cardiovascular magnetic resonance]. / Guz prawego przedsionka i ciezka niewydolnosc prawej komory w badaniu echokardiograficznym i rezonansie magnetycznym serca.

A case of a 66 year-old female with advanced right ventricular failure is described. Echocardiography and MRI revealed the presence of right atrial tumour. The patient underwent successful surgery and histological examination revealed lymphoma.