Comprehensive stroke care is an interdisciplinary challenge. Close collaboration of cardiologists and stroke physicians is critical to ensure optimum utilisation of short- and long-term care and preventive measures in patients with stroke. Risk factor management is an important strategy that requires cardiologic involvement for primary and secondary stroke prevention. Treatment of stroke generally is led by stroke physicians, yet cardiologists need to be integrated care providers in stroke units to address all cardiovascular aspects of acute stroke care, including arrhythmia management, blood pressure control, elevated levels of cardiac troponins, valvular disease/endocarditis, and the general management of cardiovascular comorbidities. Despite substantial progress in stroke research and clinical care has been achieved, relevant gaps in clinical evidence remain and cause uncertainties in best practice for treatment and prevention of stroke. The Cardiovascular Round Table of the European Society of Cardiology together with the European Society of Cardiology Council on Stroke in cooperation with the European Stroke Organisation and partners from related scientific societies, regulatory authorities and industry conveyed a two-day workshop to discuss current and emerging concepts and apparent gaps in stroke care, including risk factor management, acute diagnostics, treatments and complications, and operational/logistic issues for health care systems and integrated networks. Joint initiatives of cardiologists and stroke physicians are needed in research and clinical care to target unresolved interdisciplinary problems and to promote the best possible outcomes for patients with stroke.

• MeSH
• Stroke diagnosis   epidemiology   therapy   MeSH
• Risk Assessment MeSH
• Delivery of Health Care, Integrated standards   MeSH
• Cardiology standards   MeSH
• Cardiovascular Diseases diagnosis   epidemiology   therapy   MeSH
• Comprehensive Health Care standards   MeSH
• Consensus MeSH
• Cooperative Behavior MeSH
• Humans MeSH
• Interdisciplinary Communication * MeSH
• Neurology standards   MeSH
• Prognosis MeSH
• Risk Factors MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Consensus Development Conference MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

BACKGROUND: Ezetimibe, when added to simvastatin, reduces cardiovascular events after acute coronary syndrome. We explored outcomes stratified by diabetes mellitus (DM). METHODS: In IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), 18 144 patients after acute coronary syndrome with low-density lipoprotein cholesterol 50 to 125 mg/dL were randomized to 40 mg ezetimibe/simvastatin (E/S) or 40 mg placebo/simvastatin. The primary composite end point was cardiovascular death, major coronary events, and stroke. DM was a prespecified subgroup. RESULTS: The 4933 (27%) patients with DM were more often older and female, had had a prior myocardial infarction and revascularization, and presented more frequently with non-ST segment elevation acute coronary syndrome compared with patients without DM (each P<0.001). The median admission low-density lipoprotein cholesterol was lower among patients with DM (89 versus 97 mg/dL, P<0.001). E/S achieved a significantly lower median time-weighted average low-density lipoprotein cholesterol compared with placebo/simvastatin, irrespective of DM (DM: 49 versus 67 mg/dL; no DM: 55 versus 71 mg/dL; both P<0.001). In patients with DM, E/S reduced the 7-year Kaplan-Meier primary end point event rate by 5.5% absolute (hazard ratio, 0.85; 95% confidence interval, 0.78-0.94); in patients without DM, the absolute difference was 0.7% (hazard ratio, 0.98; 95% confidence interval, 0.91-1.04; Pint=0.02). The largest relative reductions in patients with DM were in myocardial infarction (24%) and ischemic stroke (39%). No differences in safety outcomes by treatment were present regardless of DM. When stratified further by age, patients ≥75 years of age had a 20% relative reduction in the primary end point regardless of DM (Pint=0.91), whereas patients <75 years of age with DM had greater benefit than those without (Pint=0.011). When stratified by the TIMI (Thrombolysis in Myocardial Infarction) Risk Score for Secondary Prevention, all patients with DM demonstrated benefit with E/S regardless of risk. In contrast, among patients without DM, those with a high risk score experienced a significant (18%) relative reduction in the composite of cardiovascular death, myocardial infarction, and ischemic stroke with E/S compared with placebo/simvastatin, whereas patients without DM at low or moderate risk demonstrated no benefit with the addition of ezetimibe to simvastatin (Pint =0.034). CONCLUSIONS: In IMPROVE-IT, the benefit of adding ezetimibe to statin was enhanced in patients with DM and in high-risk patients without DM. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00202878.

• MeSH
• Acute Coronary Syndrome diagnosis   mortality   therapy   MeSH
• Biomarkers blood   MeSH
• Time Factors MeSH
• Diabetes Mellitus diagnosis   mortality   therapy   MeSH
• Dyslipidemias diagnosis   drug therapy   mortality   MeSH
• Risk Assessment MeSH
• Ezetimibe, Simvastatin Drug Combination adverse effects   therapeutic use   MeSH
• Comorbidity MeSH
• Cholesterol, LDL blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Risk Factors MeSH
• Aged MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Comparative Study MeSH

BACKGROUND: There is a direct relationship between bodyweight and risk of diabetes. Lorcaserin, a selective serotonin 2C receptor agonist that suppresses appetite, has been shown to facilitate sustained weight loss in obese or overweight patients. We aimed to evaluate the long-term effects of lorcaserin on diabetes prevention and remission. METHODS: In this randomised, double-blind, placebo-controlled trial done in eight countries, we recruited overweight or obese patients (body-mass index ≥27 kg/m2) with or at high risk for atherosclerotic vascular disease. Eligible patients were aged 40 years or older; patients at high risk for atherosclerotic vascular disease had to be aged 50 years or older with diabetes and at least one other risk factor. Patients were randomly assigned to receive either lorcaserin (10 mg twice daily) or matching placebo. Additionally, all patients had access to a standardised weight management programme based on lifestyle modification. The prespecified primary metabolic efficacy endpoint of time to incident diabetes was assessed in patients with prediabetes at baseline. The prespecified secondary outcomes for efficacy were incident diabetes in all patients without diabetes, achievement of normoglycaemia in patients with prediabetes, and change in glycated haemoglobin (HbA1c) in patients with diabetes. Hypoglycaemia was a prespecified safety outcome. Analysis was by intention to treat, using Cox proportional hazard models for time-to-event analyses. This trial is registered with ClinicalTrials.gov, number NCT02019264. FINDINGS: Between Feb 7, 2014, and Nov 20, 2015, 12 000 patients were randomly assigned to lorcaserin or placebo (6000 patients in each group) and followed up for a median of 3·3 years (IQR 3·0-3·5). At baseline, 6816 patients (56·8%) had diabetes, 3991 (33·3%) prediabetes, and 1193 (9·9%) normoglycaemia. At 1 year, patients treated with lorcaserin had a net weight loss beyond placebo of 2·6 kg (95% CI 2·3-2·9) for those with diabetes, 2·8 kg (2·5-3·2) for those with prediabetes, and 3·3 kg (2·6-4·0) for those with normoglycaemia (p<0·0001 for all analyses). Lorcaserin reduced the risk of incident diabetes by 19% in patients with prediabetes (172 [8·5%] of 2015 vs 204 [10·3%] of 1976; hazard ratio 0·81, 95% CI 0·66-0·99; p=0·038) and by 23% in patients without diabetes (174 [6·7%] of 2615 vs 215 [8·4%] of 2569; 0·77, 0·63-0·94; p=0·012). Lorcaserin resulted in a non-significant increase in the rate of achievement of normoglycaemia in patients with prediabetes (185 [9·2%] vs 151 [7·6%]; 1·20, 0·97-1·49; p=0·093). In patients with diabetes, lorcaserin resulted in a reduction of 0·33% (95% CI 0·29-0·38; p<0·0001) in HbA1c compared with placebo at 1 year from a mean baseline of 53 mmol/mol (7·0%). In patients with diabetes at baseline, severe hypoglycaemia with serious complications was rare, but more common with lorcaserin (12 [0·4%] vs four [0·1%] events; p=0·054). INTERPRETATION: Lorcaserin decreases risk for incident diabetes, induces remission of hyperglycaemia, and reduces the risk of microvascular complications in obese and overweight patients, supporting the role of lorcaserin as an adjunct to lifestyle modification for chronic management of weight and metabolic health. FUNDING: Eisai.

• MeSH
• Appetite Depressants therapeutic use   MeSH
• Atherosclerosis complications   drug therapy   MeSH
• Benzazepines therapeutic use   MeSH
• Diabetes Mellitus, Type 2 blood   complications   drug therapy   prevention & control   MeSH
• Double-Blind Method MeSH
• Glycated Hemoglobin analysis   MeSH
• Weight Loss drug effects   MeSH
• Hypoglycemic Agents therapeutic use   MeSH
• Remission Induction MeSH
• Middle Aged MeSH
• Humans MeSH
• Overweight complications   MeSH
• Obesity complications   MeSH
• Prediabetic State complications   drug therapy   prevention & control   MeSH
• Aged MeSH
• Body Weight drug effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH