AIMS: People with diabetes are at high risk for cardiovascular events including heart failure (HF). We examined the effect of the glucagon-like peptide 1 agonist dulaglutide on incident HF events and other cardiovascular outcomes in those with or without prior HF in the randomized placebo-controlled Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. METHODS AND RESULTS: The REWIND major adverse cardiovascular event (MACE) outcome was the first occurrence of a composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes). In this post-hoc analysis, a HF event was defined as an adjudication-confirmed hospitalization or urgent evaluation for HF. Of the 9901 participants studied over a median follow-up of 5.4 years, 213/4949 (4.3%) randomly assigned to dulaglutide and 226/4952 (4.6%) participants assigned to placebo experienced a HF event (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.77-1.12; p = 0.456). In the 853 (8.6%) participants with HF at baseline, there was no change in either MACE or HF events with dulaglutide as compared to participants without HF (p = 0.44 and 0.19 for interaction, respectively). Combined cardiovascular death and HF events were marginally reduced with dulaglutide compared to placebo (HR 0.88, 95% CI 0.78-1.00; p = 0.050) but unchanged in patients with and without HF at baseline (p = 0.31). CONCLUSIONS: Dulaglutide was not associated with a reduction in HF events in patients with type 2 diabetes regardless of baseline HF status over 5.4 years of follow-up.

• MeSH
• diabetes mellitus 2. typu * komplikace   farmakoterapie   epidemiologie   MeSH
• hypoglykemika terapeutické užití   škodlivé účinky   MeSH
• inkretiny terapeutické užití   MeSH
• kardiovaskulární nemoci * epidemiologie   MeSH
• lidé MeSH
• srdeční selhání * farmakoterapie   epidemiologie   chemicky indukované   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: In patients with stable coronary heart disease, it is not known whether achievement of standard of care (SOC) targets in addition to evidence-based medicine (EBM) is associated with lower major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, and stroke. METHODS: EBM use was recommended in the STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY trial. SOC targets were blood pressure (BP) <140/90 mm Hg and low-density lipoprotein-cholesterol (LDL-C) <100 mg/dL and <70 mg/dL. In patients with diabetes, glycosylated hemoglobin A1c (HbA1c) < 7% and BP of <130/80 mm Hg were recommended. Feedback to investigators about rates of EBM and SOC was provided regularly. RESULTS: In 13,623 patients, 1-year landmark analysis assessed the association between EBM, SOC targets, and MACE during follow-up of 2.7 years (median) after adjustment in a Cox proportional hazards model. At 1 year, aspirin was prescribed in 92.5% of patients, statins in 97.2%, β-blockers in 79.0%, and angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers in 76.9%. MACE was lower with LDL-C < 100 mg/dL (70-99 mg/dL) compared with LDL-C ≥ 100 mg/dL (hazard ratio [HR] 0.694, 95% CI 0.594-0.811) and lower with LDL-C < 70 mg/dL compared with LDL-C < 100 mg/dL (70-99 mg/dL) (HR 0.834, 95% CI 0.708-0.983). MACE was lower with HbA1c < 7% compared with HbA1c ≥ 7% (HR 0.705, 95% CI 0.573-0.866). There was no effect of BP targets on MACE. CONCLUSIONS: MACE was lower with LDL-C < 100 mg/dL (70-99 mg/dL) and even lower with LDL-C < 70 mg/dL. MACE in patients with diabetes was lower with HbA1c < 7%. Achievement of targets is associated with improved patient outcomes.

• MeSH
• cévní mozková příhoda epidemiologie   etiologie   MeSH
• glykovaný hemoglobin analýza   MeSH
• infarkt myokardu epidemiologie   etiologie   MeSH
• Kaplanův-Meierův odhad MeSH
• koronární nemoc krev   komplikace   mortalita   MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• medicína založená na důkazech MeSH
• rizikové faktory MeSH
• senioři MeSH
• statiny terapeutické užití   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. METHODS: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p<0·0001), with HRs of 0·89 (0·78-1·01; p=0·066) for sustained decline in eGFR of 30% or more and 0·75 (0·39-1·44; p=0·39) for chronic renal replacement therapy. INTERPRETATION: Long-term use of dulaglutide was associated with reduced composite renal outcomes in people with type 2 diabetes. FUNDING: Eli Lilly and Company.

• MeSH
• albuminurie prevence a kontrola   MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• diabetické nefropatie prevence a kontrola   MeSH
• dvojitá slepá metoda MeSH
• glukagonu podobné peptidy analogy a deriváty   terapeutické užití   MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• hypoglykemika terapeutické užití   MeSH
• imunoglobuliny - Fc fragmenty terapeutické užití   MeSH
• kreatinin moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rekombinantní fúzní proteiny terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. METHODS: This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6-8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001). INTERPRETATION: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors. FUNDING: Eli Lilly and Company.

• MeSH
• cévní mozková příhoda prevence a kontrola   MeSH
• diabetes mellitus 2. typu komplikace   farmakoterapie   MeSH
• dvojitá slepá metoda MeSH
• glukagonu podobné peptidy analogy a deriváty   terapeutické užití   MeSH
• hypoglykemika terapeutické užití   MeSH
• imunoglobuliny - Fc fragmenty terapeutické užití   MeSH
• infarkt myokardu prevence a kontrola   MeSH
• kardiovaskulární nemoci mortalita   prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rekombinantní fúzní proteiny terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

The aim was to determine the effects of dulaglutide, a synthetic once-weekly, injectable human glucagon-like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non-fatal myocardial infarction or non-fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all-cause mortality. Follow-up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle-aged patient seen in general practice throughout the world.

• MeSH
• diabetes mellitus 2. typu krev   komplikace   farmakoterapie   metabolismus   MeSH
• diabetická kardiomyopatie epidemiologie   mortalita   prevence a kontrola   MeSH
• diabetické angiopatie epidemiologie   mortalita   prevence a kontrola   MeSH
• glukagonu podobné peptidy aplikace a dávkování   škodlivé účinky   analogy a deriváty   terapeutické užití   MeSH
• glykovaný hemoglobin analýza   MeSH
• hypoglykemika aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• imunoglobuliny - Fc fragmenty aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• injekce subkutánní MeSH
• inkretiny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• kardiovaskulární nemoci komplikace   epidemiologie   mortalita   prevence a kontrola   MeSH
• kombinovaná farmakoterapie škodlivé účinky   MeSH
• léky s prodlouženým účinkem aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mortalita MeSH
• multicentrické studie jako téma MeSH
• následné studie MeSH
• randomizované kontrolované studie jako téma MeSH
• receptor pro glukagonu podobný peptid 1 agonisté   metabolismus   MeSH
• rekombinantní fúzní proteiny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• rizikové faktory MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• výzkumný projekt MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS: In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS: The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS: The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).

• MeSH
• adherence k farmakoterapii MeSH
• antihypertenziva aplikace a dávkování   škodlivé účinky   MeSH
• benzimidazoly aplikace a dávkování   MeSH
• dvojitá slepá metoda MeSH
• hydrochlorthiazid aplikace a dávkování   MeSH
• hypertenze farmakoterapie   MeSH
• kardiovaskulární nemoci epidemiologie   prevence a kontrola   MeSH
• kombinovaná farmakoterapie MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rizikové faktory MeSH
• rosuvastatin kalcium aplikace a dávkování   škodlivé účinky   MeSH
• senioři MeSH
• statiny aplikace a dávkování   škodlivé účinky   MeSH
• tetrazoly aplikace a dávkování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH