Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial

Aims/hypothesis In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Methods Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed. Results A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups. Conclusions/interpretation Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR. Trial registration ClinicalTrials.gov NCT0198688

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

BACKGROUND Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events. METHODS We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P<0.001); the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P<0.001). The rates of additional ischemic end points, as assessed according to a prespecified hierarchical schema, were significantly lower in the icosapent ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs. 5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06). CONCLUSIONS Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361

Hypertensive phenotype signs in men with different genetic polymorphisms of aldosterone synthase and angiotensin II type 1 receptors

Tykhonova Susanna, Piskovatska Veronika. Ознаки гіпертензивного фенотипу у чоловіків із різними поліморфними алельними варіантами генів альдостеронової синтази та рецепторів до ангіотензину ІІ 1 типу = Hypertensive phenotype signs in men with different genetic polymorphisms of aldosterone synthase and angiotensin II type 1 receptors. Journal of Education, Health and Sport. 2015;5(6):123-130. ISSN 2391-8306. DOI 10.5281/zenodo.18398 http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%286%29%3A123-130 https://pbn.nauka.gov.pl/works/564165 http://dx.doi.org/10.5281/zenodo.18398 Formerly Journal of Health Sciences. ISSN 1429-9623 / 2300-665X. Archives 2011 – 2014 http://journal.rsw.edu.pl/index.php/JHS/issue/archive   Deklaracja. Specyfika i zawartość merytoryczna czasopisma nie ulega zmianie. Zgodnie z informacją MNiSW z dnia 2 czerwca 2014 r., że w roku 2014 nie będzie przeprowadzana ocena czasopism naukowych; czasopismo o zmienionym tytule otrzymuje tyle samo punktów co na wykazie czasopism naukowych z dnia 31 grudnia 2014 r. The journal has had 5 points in Ministry of Science and Higher Education of Poland parametric evaluation. Part B item 1089. (31.12.2014). © The Author (s) 2015; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland and Radom University in Radom, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 21.04.2015. Revised 28.05.2015. Accepted: 05.06.2015.   УДК 575.191:(616.12-008.331.1 +616.12-007.61)   ОЗНАКИ ГІПЕРТЕНЗИВНОГО ФЕНОТИПУ У ЧОЛОВІКІВ ІЗ РІЗНИМИ ПОЛІМОРФНИМИ АЛЕЛЬНИМИ ВАРІАНТАМИ ГЕНІВ АЛЬДОСТЕРОНОВОЇ СИНТАЗИ ТА РЕЦЕПТОРІВ ДО АНГІОТЕНЗИНУ ІІ 1 ТИПУ HYPERTENSIVE PHENOTYPE SIGNS IN MEN WITH DIFFERENT GENETIC POLYMORPHISMS OF ALDOSTERONE SYNTHASE AND ANGIOTENSIN II TYPE 1 RECEPTORS   С. А. Тихонова, В. П. Пісковацька Susanna Tykhonova, Veronika Piskovatska   Одеський національний  медичний університет Odessa National Medical University   Abstract. Single-nucleotide polymorphisms of renin-angiotensin-aldosterone system are widely discussed as the predictors of arterial hypertension, hypertensive target-organ damage, and antihypertensive treatment response. Controversies exist in numerous studies and meta-analyses of potential aldosterone synthase and angiotensin II type 1 receptors polymorphisms genes’ role in hypertension onset and target-organ damage progression. Current study aimed to evaluate relative risk of blood pressure elevation and left ventricle hypertensive remodeling in young men with various CYP11B2 and AGT1R polymorphic variants. Odds-ratio analysis showed that high blood pressure and hypertension were diagnosed in CYP11B2 C244T T-allele carriers, with the highest relative risk in T-homozygous patients, as compared to CC-variant. C-allelic variants of AGT1R A1166C were associated with elevated blood pressure levels, while A-allele was linked to left ventricle hypertrophy. 5 times higher left ventricle hypertrophy was also observed in TT CYP11B2 C244T males, comparing to C-homozygous men. Keywords: hypertension, genetic predisposition, SNP, CYP11B2 C244, AGT1R A1166C.   Резюме. Мононуклеотидні поліморфізми генів ренін-ангіотензин-альдостеронової системи розглядаються в якості предикторів виникнення артеріальної гіпертензії (АГ), особливостей її перебігу та також відповіді на антигіпертензивну терапію. Суперечливі дані, нерідко в межах однієї етнічної групи, існують щодо патогенетичної ролі поліморфізмів-кандидатів компонентів РААС у виникненні та прогресуванні АГ та ураження-органів мішеней. Метою дослідження було визначення відносного ризику підвищення артеріального тиску (АТ) та гіпертрофії лівого шлуночка (ГЛШ) у молодих чоловіків із різними поліморфними алелльними варіантами генів CYP11B2 та AGT1R. Дані обстеження 80 чоловіків віком від 18 до 35 років демонструють збільшення відносного шансу підвищення АТ до високого нормального рівня та діагностування АГ у носіїв Т-алелю поліморфізму 344 С/Т CYP11B2. Відносний шанс наявності ГЛШ у монозиготних за Т-алеллю чоловіків був у 5 разів вищим за С-монозиготних осіб. Носійство та монозиготність за С-алеллю AGT1R A1166C асоціювалися із підвищеним рівнем АТ, в той час як носії АА та АС варіантів генотипу AGT1R частіше мали ГЛШ. Ключові слова: артеріальна гіпертензія, генетична схильність, мононуклеотидні поліморфізми генів, ген альостеронової синтази CYP11B2, ген рецепторів до ангіотензину ІІ 1 типу AGT1R

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes