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.
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.
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).
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.
Eli Lilly and Company.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
This is the second iteration of the European Society of Cardiology (ESC) and European Association for the Study of Diabetes (EASD) joining forces to write guidelines on the management of diabetes ...mellitus (DM), pre-diabetes, and cardiovascular disease (CVD), designed to assist clinicians and other healthcare workers to make evidence-based management decisions. The growing awareness of the strong biological relationship between DM and CVD rightly prompted these two large organizations to collaborate to generate guidelines relevant to their joint interests, the first of which were published in 2007. Some assert that too many guidelines are being produced but, in this burgeoning field, five years in the development of both basic and clinical science is a long time and major trials have reported in this period, making it necessary to update the previous Guidelines.
Specific criteria/considerations for inclusion of new data include the following: publication in a peer-reviewed journal; large, randomized, placebo-controlled trial(s); nonrandomized data deemed ...important on the basis of results affecting current safety and efficacy assumptions; strength/weakness of research methodology and findings; likelihood of additional studies influencing current findings; impact on current and/or likelihood of need to develop new performance measure(s); request(s) and requirement(s) for review and update from the practice community, key stakeholders, and other sources free of relationships with industry or other potential bias; number of previous trials showing consistent results; and need for consistency with a new guideline or guideline revisions. Ideal candidates for catheter ablation are younger patients with minimal structural abnormalities and multiple symptomatic episodes of paroxysmal AF over time despite appropriate pharmacological therapy. 70% of patients treated by catheter ablation remained free of symptomatic recurrent atrial arrhythmia versus 19% of patients treated with ADT. 95% CI: 0.15 to 0.39; p>0.001 HR: 0.24 63% of patients treated by catheter ablation were free of recurrent atrial arrhythmia versus 17% of patients treated with ADT. 95% CI: 0.18 to 0.45; p<0.001 HR: 0.29 Appendix 3 Summary Table ADT indicates antiarrhythmic drug therapy; AF, atrial fibrillation; ASA, aspirin; AV, atrioventricular; AVB, atrioventricular block; bid, twice a day; bpm, beats per minute; CABG, coronary artery bypass graft surgery; CAD, coronary artery disease; CHF, congestive heart failure; CI: confidence interval; CNS, central nervous system; CYP, cytochrome P; CV, cardiovascular; d, day; DCM, dilated cardiomyopathy; DM, diabetes mellitus; ECG, electrocardiogram; EF, ejection fraction; h, hour; HF, heart failure; HR, hazard ratio; HTN, hypertension; ICD, implantable cardioverter-defibrillator; IV, intravenous; LA, left atrial; LBBB, left bundle-branch block; LV, left ventricular; LVEF, left ventricular ejection fraction; MI, myocardial infarction; mm, millimeter; mo, month; ms, milliseconds; MSE, main safety endpoint; NYHA, New York Heart Association; PAD, peripheral arterial disease; PR interval, interval between onset of P wave and onset of QRS complex on an ECG; PVD, peripheral vascular disease; qd, once per day; RR, relative risk; s, seconds; SD, standard deviation; SOB, short of breath; SR, sinus rhythm; TIA, transient ischemic attack; wk, week; and y, year.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V in primary care was carried out by the European Society of Cardiology EURObservational Research ...Programme in 2016-2018. The main objective was to determine whether the 2016 Joint European Societies' guidelines on cardiovascular disease prevention in people at high cardiovascular risk have been implemented in clinical practice.
The method used was a cross-stional survey in 78 centres from 16 European countries. Patients without a history of atherosclerotic cardiovascular disease either started on blood pressure and/or lipid and/or glucose lowering treatments were identified and interviewed ≥ 6 months after the start of medication.
A total of 3562 medical records were reviewed and 2759 patients (57.6% women; mean age 59.0 ± 11.6 years) interviewed (interview rate 70.0%). The risk factor control was poor with 18.1% of patients being smokers, 43.5% obese (body mass index ≥30 kg/m2) and 63.8% centrally obese (waist circumference ≥88 cm for women, ≥102 cm for men). Of patients on blood pressure lowering medication 47.0% reached the target of <140/90 mm Hg (<140/85 mm Hg in people with diabetes). Among treated dyslipidaemic patients only 46.9% attained low density lipoprotein-cholesterol target of <2.6 mmol/l. Among people treated for type 2 diabetes mellitus, 65.2% achieved the HbA1c target of <7.0%.
The primary care arm of the EUROASPIRE V survey revealed that large proportions of people at high cardiovascular disease risk have unhealthy lifestyles and inadequate control of blood pressure, lipids and diabetes. Thus, the potential to reduce the risk of future cardiovascular disease throughout Europe by improved preventive cardiology programmes is substantial.
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.
A video related to the article is available on the journal's YouTube site: https://www.youtube.com/watch?v=vg_XhSPKxww&feature=youtu.be
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) IV in primary care was a cross-sectional survey carried out by the European Society of ...Cardiology, EURObservational Research Programme in 2014-2015 in 71 centres from 14 European countries. The main objective was to determine whether the 2012 Joint European Societies' guidelines on cardiovascular disease (CVD) prevention in people at high CVD risk have been followed in clinical practice. Methods Patients without a history of atherosclerotic disease started on either blood pressure and/or lipid and/or glucose-lowering treatments were identified and interviewed at least six months after the start of medication. Results Medical notes of 6700 patients were reviewed, and 4579 patients (58.7% women; mean age 58.8 (standard deviation (SD) 11.3) years) interviewed (interview rate 68.3%). Overall, 16.6% were smokers, 39.9% were overweight (body mass index (BMI)≥25 and <30 kg/m
), 43.5% obese (BMI ≥30 kg/m
) and 63.9% centrally obese (waist circumference of ≥88 cm for women, ≥102 cm for men). The medical risk factor control was very poor, with less than half (42.8%) of the patients on blood pressure lowering medication reaching the target of <140/90 mm Hg (<140/80 mm Hg in people with self-reported diabetes). Among treated dyslipidaemic patients only 32.7% attained the low-density lipoprotein (LDL)-cholesterol target of <2.5 mmol/l. Among people treated for type 2 diabetes mellitus, 58.5% achieved the glycated haemoglobin (HbA1c) target of <7.0%. Conclusion The EUROASPIRE IV survey shows that large proportions of patients at high CVD risk have unhealthy lifestyle habits and uncontrolled blood pressure, lipids and diabetes. The present data make it clear that more efforts must be taken to improve cardiovascular prevention in people at high CVD risk.
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