Examinando por Autor "Rao-Melacini, Purnima"

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    Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial
    (ELSEVIER, 2019-07-13) Gerstein, Hertzel C.; Colhoun, Helen M.; Dagenais, Gilles R.; Diaz, Rafael; Lakshmanan, Mark; Pais, Prem; Probstfield, Jeffrey; Riesmeyer, Jeffrey S.; Riddle, Matthew C.; Rydén, Lars; Xavier, Denis; Messan Atisso, Charles; Dyal, Leanne; Hall, Stephanie; Rao-Melacini, Purnima; Wong, Gloria; Avezum, Alvaro; Basile, Jan; Chung, Namsik; Conget, Ignacio; Cushman, William C.; Franek, Edward; Hancu, Nicolae; Hanefeld, Markolf; Holt, Shaun; Jansky, Petr; Keltai, Matyas Matyas; Lanas, Fernando; Leiter, Lawrence A.; Lopez-Jaramillo, Patricio; Cardona-Munoz, Ernesto German; Pirags, Valdis; Pogosova, Nana; Raubenheimer, Peter J.; Shaw, Jonathan E.; Sheu, Wayne H-H.; Temelkova-Kurktschiev, Theodora; The REWIND Investigators; Everest
    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.
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    Dulaglutide and incident atrial fibrillation or flutter in patients with type 2 diabetes. A post hoc analysis from the REWIND randomized tria
    (2022-01-04) Raubenheimer, Peter J.; Cushman, William C.; Avezum, Alvaro; Basile, Jan; Conget, Ignacio; Dagenais, Gilles; Hoover, Anastasia; Jansky, Petr; Lanas, Fernando; Leiter, Lawrence A.; Lopez-Jaramillo, Patricio; Pogosova, Nana; Probstfield, Jeffrey; Rao-Melacini, Purnima; Rydén, Lars; Sheu, Wayne H.-H; Temelkova-Kurktschiev, Theodora; Gerstein, Hertzel C.; Masira
    Aim To assess the occurrence of atrial fibrillation or atrial flutter (atrial arrhythmias [AA]) in patients with type 2 diabetes treated with once-weekly subcutaneous dulaglutide versus placebo. Materials and Methods Patients without electrocardiographic (ECG)-confirmed AA at baseline and randomized in the REWIND trial were assessed for the development of AA based on an annual ECG. Additional analyses included whether dulaglutide compared with placebo reduced the composite outcome of AA or death, AA or cardiovascular death, AA or stroke and AA or heart failure. Results Among 9543 participants (mean age 66 ± 7 years, with cardiovascular risk factors and 31% with previous cardiovascular disease) without AA at entry in the trial, 524 patients (5.5%) had at least one episode of AA during the median 5.4 years of follow-up. Incident AA occurred in 269 of the 4769 participants allocated to dulaglutide (5.6%), at a rate of 10.7 per 1000 person-years, versus 255 of the 4774 allocated to placebo (5.3%), at a rate of 10.5 per 1000 person-years (P = .59). There was also no effect of dulaglutide on the composite outcome of AA and death or AA and heart failure. Conclusion This post hoc analysis of data from the REWIND trial showed that treatment with dulaglutide was not associated with a reduced incidence of AA in this at-risk group of patients with type 2 diabetes.
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    Dulaglutide and incident atrial fibrillation or flutter in patients with type 2 diabetes. A post hoc analysis from the REWIND randomized trial
    (Diabetes, Obesity and Metabolism, 2022-01-04) Raubenheimer, Peter J.; Cushman, William C.; Avezum, Alvaro; Basile, Jan; Conget, Ignacio; Dagenais, Gilles; Hoover, Anastasia; Jansky, Petr; Lanas, Fernando; Leiter, Lawrence A.; Lopez-Jaramillo, Patricio; Pogosova, Nana; Probstfield, Jeffrey; Rao-Melacini, Purnima; Ryden, Lars; Sheu, Wayne H.-H.; Temelkova-Kurktschiev, Theodora; Gerstein, Hertzel C.; Masira
    Aim To assess the occurrence of atrial fibrillation or atrial flutter (atrial arrhythmias [AA]) in patients with type 2 diabetes treated with once-weekly subcutaneous dulaglutide versus placebo. Materials and Methods Patients without electrocardiographic (ECG)-confirmed AA at baseline and randomized in the REWIND trial were assessed for the development of AA based on an annual ECG. Additional analyses included whether dulaglutide compared with placebo reduced the composite outcome of AA or death, AA or cardiovascular death, AA or stroke and AA or heart failure. Results Among 9543 participants (mean age 66 ± 7 years, with cardiovascular risk factors and 31% with previous cardiovascular disease) without AA at entry in the trial, 524 patients (5.5%) had at least one episode of AA during the median 5.4 years of follow-up. Incident AA occurred in 269 of the 4769 participants allocated to dulaglutide (5.6%), at a rate of 10.7 per 1000 person-years, versus 255 of the 4774 allocated to placebo (5.3%), at a rate of 10.5 per 1000 person-years (P = .59). There was also no effect of dulaglutide on the composite outcome of AA and death or AA and heart failure. Conclusion This post hoc analysis of data from the REWIND trial showed that treatment with dulaglutide was not associated with a reduced incidence of AA in this at-risk group of patients with type 2 diabetes.
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    Dulaglutide and renal outcomes in type 2 diabetes. An exploratory analysis of the REWIND randomised, placebo-controlled trial
    (The Lancet, 2019-07-13) Gerstein, Hertzel C.; Colhoun, Helen M.; Dagenais, Gilles R.; Diaz, Rafael; Lakshmanan, Mark; Pais, Prem; Probstfield, Jeffrey; Riesmeyer, Jeffrey S.; Riddle, Matthew C.; Rydén, Lars; Xavier, Denis; Messan Atisso, Charles; Dyal, Leanne; Hall, Stephanie; Rao-Melacini, Purnima; Wong, Gloria; Avezum, Alvaro; Basile, Jan; Chung, Namsik; Conget, Ignacio; Cushman, William C.; Franek, Edward; Hancu, Nicolae; Hanefeld, Markolf; Holt, Shaun; Jansky, Petr; Keltai, Matyas; Lanas, Fernando; Leiter, Lawrence A.; Lopez-Jaramillo, Patricio; Cardona-Munoz, Ernesto German; Pirags, Valdis; Pogosova, Nana; Raubenheimer, Peter J.; Shaw, Jonathan E.; Sheu, Wayne H-H.; Temelkova-Kurktschiev, Theodora; The REWIND Investigators; Everest
    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.
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    Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial
    (Elsevier, 2020-07-01) Cukierman-Yaffe, Tali; Gerstein, Hertzel C.; Colhoun, Helen M.; Diaz, Rafael; García-Pérez, Luis-Emilio; Lakshmanan, Mark; Bethel, Angelyn; Xavier, Denis; Probstfield, Jeffrey; Riddle, Matthew C.; Rydén, Lars; Messan Atisso, Charles; Hall, Stephanie; Rao-Melacini, Purnima; Basile, Jan; Cushman, William C.; Franek, Edward; Keltai, Matyas; Lanas, Fernando; Leiter, Lawrence A.; Lopez-Jaramillo, Patricio; Pirags, Valdis; Pogosova, Nana; Raubenheimer, Peter J.; Shaw, Jonathan E.; Sheu, Wayne H-H.; Temelkova-Kurktschiev, Theodora; Everest
    Background Diabetes is an independent risk factor for cognitive impairment. We aimed to investigate the association between the glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide and cognitive impairment as an exploratory analysis within the Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial. Methods REWIND is a randomised, double-blind placebo-controlled trial at 371 sites in 24 countries. We included men and women (aged ≥50 years) with either established or newly diagnosed type 2 diabetes and additional cardiovascular risk factors, glycated haemoglobin of up to 9·5% (80 mmol/mol) on a maximum of two oral glucose-lowering drugs with or without basal insulin, and a body-mass index of at least 23 kg/m2. Participants were randomly assigned (1:1) subcutaneous injections once a week of either dulaglutide (1·5 mg) or an equal volume of matching placebo. Randomisation was done using a computer-generated code with stratification by site. Participants and all study personnel were masked to treatment allocation until the database was locked. Participants were followed up at least every 6 months for the composite primary outcome of stroke, myocardial infarction, or death from cardiovascular or unknown causes. Cognitive function was assessed at baseline and during follow-up using the Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST). We present here the exploratory primary cognitive outcome, which was the first occurrence of a follow-up score on MoCA or DSST that was 1·5 SDs or more below the baseline mean score in the participant's country. All analyses were done using an intention-to-treat approach. The REWIND trial is registered with ClinicalTrials.gov, NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were randomly assigned to either dulaglutide (n=4949) or placebo (n=4952). During median follow-up of 5·4 (IQR 5·1–5·9) years, 8828 participants provided a baseline and one or more follow-up MoCA or DSST scores, of whom 4456 were assigned dulaglutide and 4372 were assigned placebo. The cognitive outcome occurred in 4·05 per 100 patient-years in participants assigned dulaglutide and 4·35 per 100 patient-years in people assigned placebo (hazard ratio [HR] 0·93, 95% CI 0·85–1·02; p=0·11). After post-hoc adjustment for individual standardised baseline scores, the hazard of substantive cognitive impairment was reduced by 14% in those assigned dulaglutide (HR 0·86, 95% CI 0·79–0·95; p=0·0018). Interpretation Long-term treatment with dulaglutide might reduce cognitive impairment in people with type 2 diabetes. Further studies of this drug focused on brain health and cognitive function are clearly indicated.
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    Erectile function in men with type 2 diabetes treated with dulaglutide: An exploratory analysis of the REWIND placebo-controlled randomised trial
    (The Lancet, 2021-08-01) Bajaj, Harpreet S.; Gerstein, Hertzel C.; Rao-Melacini, Purnima; Basile, Jan; Colhoun, Helen; Conget, Ignacio; Cushman, William C.; Dagenais, Gilles R.; Franek, Edward; Hanefeld, Markolf; Keltai, Matyas; Lakshmanan, Mark; Lanas, Fernando; Leiter, Lawrence A.; Lopez-Jaramillo, Patricio; Pirags, Valdis; Pogosova, Nana; Probstfield, Jeffrey; Raubenheimer, Peter; Ryden, Lars; Shaw, Jonathan E.; Sheu, Wayne H-H.; Xavier, Denis; Masira
    Background Diabetes is a major risk factor for erectile dysfunction, however, the effect of GLP-1 receptor agonists on erectile dysfunction is unknown. We aimed to assess the incidence, prevalence, and progression of erectile dysfunction in men treated with dulaglutide compared with placebo, and to determine whether dulaglutide's effect on erectile dysfunction was consistent with its effect on other diabetes-related outcomes. Methods The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial was a double-blind, placebo-controlled randomised trial of the effect of dulaglutide on cardiovascular outcomes. REWIND was done at 371 sites in 24 countries. Men and women aged older than 50 years with type 2 diabetes, who had either a previous cardiovascular event or cardiovascular risk factors, were randomly assigned (1:1) to receive either dulaglutide or placebo. Participating men were offered the opportunity to complete the standardised International Index of Erectile Function (IIEF) questionnaire at baseline, 2 years, 5 years, and study end. We did an exploratory analysis, in which we included participants who completed a baseline and at least 1 follow-up IIEF questionnaire. The primary outcome for these analyses was the first occurrence of moderate or severe erectile dysfunction following randomisation, assessed by the erectile function subscores on IIEF. This analysis was part of the REWIND trial, which is registered with ClinicalTrials.gov, NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 3725 (70·1%) of 5312 male participants with a mean age of 65·5 years (SD 6·4 years) were analysed, of whom 1487 (39·9%) had a history of cardiovascular disease, and 2104 (56·5%) had moderate or severe erectile dysfunction at baseline. The incidence of erectile dysfunction following randomisation was 21·3 per 100 person-years in the dulaglutide group and 22·0 per 100 person-years in the placebo group (HR 0·92, 95% CI 0·85–0·99, p=0·021). Men in the dulaglutide group also had a lesser fall in erectile function subscore compared with the placebo group, with a least square mean difference of 0·61 (95% CI 0·18–1·05, p=0·006). Interpretation Long-term use of dulaglutide might reduce the incidence of moderate or severe erectile dysfunction in men with type 2 diabetes.
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    Urinary Sodium and Potassium, and Risk of Ischemic and Hemorrhagic Stroke (INTERSTROKE). A Case-Control Study
    (Oxford Academic, 2021-04-01) Judge, Conor; O’Donnell, Martin J.; Hankey, Graeme J.; Rangarajan, Sumathy; Lim Chin, Siu; Rao-Melacini, Purnima; Ferguson, John; Smyth, Andrew; Xavier, Denis; Lisheng, Liu; Zhang, Hongye; Lopez-Jaramillo, Patricio; Damasceno, Albertino; Langhorne, Peter; Rosengren, Annika; Dans, Antonio; Elsayed, Ahmed; Avezum, Alvaro; Mondo, Charles; Ryglewicz, Danuta; Czlonkowska, Anna; Pogosova, Nana; Weimar, Christian; Diaz, Rafael; Yusoff, Khalid; Yusufali, Afzalhussein; Oguz, Aytekin; Wang, Xingyu; Lanas, Fernando; Ogah, Okechukwu S.; Ogunniyi, Adesola; Iversen, Helle K.; Malaga, German; Rumboldt, Zvonko; Oveisgharan, Shahram; Hussain, Fawaz Al; Yusuf, Salim; INTERSTROKE investigators; Masira
    BACKGROUND Although low sodium intake (<2 g/day) and high potassium intake (>3.5 g/day) are proposed as public health interventions to reduce stroke risk, there is uncertainty about the benefit and feasibility of this combined recommendation on prevention of stroke. METHODS We obtained random urine samples from 9,275 cases of acute first stroke and 9,726 matched controls from 27 countries and estimated the 24-hour sodium and potassium excretion, a surrogate for intake, using the Tanaka formula. Using multivariable conditional logistic regression, we determined the associations of estimated 24-hour urinary sodium and potassium excretion with stroke and its subtypes. RESULTS Compared with an estimated urinary sodium excretion of 2.8–3.5 g/day (reference), higher (>4.26 g/day) (odds ratio [OR] 1.81; 95% confidence interval [CI], 1.65–2.00) and lower (<2.8 g/day) sodium excretion (OR 1.39; 95% CI, 1.26–1.53) were significantly associated with increased risk of stroke. The stroke risk associated with the highest quartile of sodium intake (sodium excretion >4.26 g/day) was significantly greater (P < 0.001) for intracerebral hemorrhage (ICH) (OR 2.38; 95% CI, 1.93–2.92) than for ischemic stroke (OR 1.67; 95% CI, 1.50–1.87). Urinary potassium was inversely and linearly associated with risk of stroke, and stronger for ischemic stroke than ICH (P = 0.026). In an analysis of combined sodium and potassium excretion, the combination of high potassium intake (>1.58 g/day) and moderate sodium intake (2.8–3.5 g/day) was associated with the lowest risk of stroke. CONCLUSIONS The association of sodium intake and stroke is J-shaped, with high sodium intake a stronger risk factor for ICH than ischemic stroke. Our data suggest that moderate sodium intake—rather than low sodium intake—combined with high potassium intake may be associated with the lowest risk of stroke and expected to be a more feasible combined dietary target.
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    Variations in knowledge, awareness and treatment of hypertension and stroke risk by country income level
    (BMJ Journals, 2020-12-14) O’ Donnell, Martin; Hankey, Graeme J.; Rangarajan, Sumathy; Chin, Siu Lim; Rao-Melacini, Purnima; Ferguson, John; Xavier, Denis; Lisheng, Liu; Zhang, Hongye; Pais, Prem; Lopez-Jaramillo, Patricio; Damasceno, Albertino; Langhorne, Peter; Rosengren, Annika; Dans, Antonio L.; Elsayed, Ahmed; Avezum, Alvaro; Mondo, Charles; Smyth, Andrew; Judge, Conor; Diener, Hans-Christoph; Ryglewicz, Danuta; Czlonkowska, Anna; Pogosova, Nana; Weimar, Christian; Iqbal, Romana; Diaz, Rafael; Yusoff, Khalid; Yusufali, Afzalhussein; Oguz, Aytekin; Wang, Xingyu; Penaherrera, Ernesto; Lanas, Fernando; Ogah, Okechukwu Samuel; Ogunniyi, Adensola; Iversen, Helle K.; Malaga, German; Rumboldt, Zvonko; Oveisgharan, Shahram; AlHussain, Fawaz; Daliwonga, Magazi; Nilanont, Yongchai; Yusuf, Salim; Masira
    ABSTRACT Objective Hypertension is the most important modifiable risk factor for stroke globally. We hypothesised that country-income level variations in knowledge, detection and treatment of hypertension may contribute to variations in the association of blood pressure with stroke. Methods We undertook a standardised case-control study in 32 countries (INTERSTROKE). Cases were patients with acute first stroke (n=13 462) who were matched by age, sex and site to controls (n=13 483). We evaluated the associations of knowledge, awareness and treatment of hypertension with risk of stroke and its subtypes and whether this varied by gross national income (GNI) of country. We estimated OR and population attributable risk (PAR) associated with treated and untreated hypertension. Results Hypertension was associated with a graded increase in OR by reducing GNI, ranging from OR 1.92 (99% CI 1.48 to 2.49) to OR 3.27 (2.72 to 3.93) for highest to lowest country-level GNI (pheterogeneity<0.0001). Untreated hypertension was associated with a higher OR for stroke (OR 5.25; 4.53 to 6.10) than treated hypertension (OR 2.60; 2.32 to 2.91) and younger age of first stroke (61.4 vs 65.4 years; p<0.01). Untreated hypertension was associated with a greater risk of intracerebral haemorrhage (OR 6.95; 5.61 to 8.60) than ischaemic stroke (OR 4.76; 3.99 to 5.68). The PAR associated with untreated hypertension was higher in lowerincome regions, PAR 36.3%, 26.3%, 19.8% to 10.4% by increasing GNI of countries. Lifetime nonmeasurement of blood pressure was associated with stroke (OR 1.80; 1.32 to 2.46). Conclusions Deficits in knowledge, detection and treatment of hypertension contribute to higher risk of stroke, younger age of onset and larger proportion of intracerebral haemorrhage in lower-income countries.