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Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke.

ABSTRACT: The cardiovascular safety and efficacy of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-world cohort study was to evaluate the cardiovascular outcomes of linagliptin in patients with T2DM after ACS or AIS.An open observational noncrossover retrospective cohort study was conducted between June 1, 2012 and December 31, 2013 utilizing Taiwan National Health Insurance Research Database. A total of 1203 patients with T2DM after ACS or AIS were selected as the study cohort. Cardiovascular safety and efficacy of linagliptin were evaluated by comparing outcomes of 401 subjects receiving linagliptin after ACS or AIS to 802 matched control subjects not receiving any incretin-based therapy after ACS or AIS. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke.The primary composite outcome after 15-month follow-up was 7% (28 patients) in the linagliptin group compared with 6.1% (49 patients) in the control group [hazard ratio (HR) 1.06; 95% confidence interval (CI) .66-1.68]. The linagliptin group also had similar risks of all-cause mortality, hospitalization for heart failure, percutaneous coronary intervention and coronary artery bypass grafting compared to the control group in terms of the secondary outcomes.In T2DM patients after ACS or AIS, treatment with linagliptin was not associated with increased risks of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke.

SUBMITTER: Li YR

PROVIDER: S-EPMC5753457 | biostudies-other | 2018 Jan

REPOSITORIES: biostudies-other

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Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke.

Li Yan-Rong YR Tsai Sung-Sheng SS Chen Dong-Yi DY Chen Szu-Tah ST Sun Jui-Hung JH Chang Hung-Yu HY Liou Miaw-Jene MJ Chen Tien-Hsing TH

Cardiovascular diabetology 20180104 1

<h4>Background</h4>The cardiovascular safety and efficacy of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-world cohort study was to evaluate the cardiovascular outcomes of linagliptin in patients with T2DM after ACS or AIS.<h4>Methods</h4>An open observational noncrossover retrospective cohort study was conducted between June 1, 2012 and Decembe ...[more]

PMID: 29301579

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Project description:Type 2 diabetes (T2D) is an independent risk factor for acute ischemic stroke (AIS), but the underlying mechanisms remain elusive. Because the gut microbiota plays a causal role in both T2D and AIS, we wondered whether gut dysbiosis in T2D aggravates stroke progression. We recruited 35 T2D, 90 AIS, 60 AIS with T2D (AIS_T2D) patients, and 55 healthy controls and found that AIS and T2D had an additive effect on AIS_T2D patient gut dysbiosis by exhibiting the largest difference from the heathy controls. In addition, we found that the degree of gut dysbiosis associated with T2D was positively correlated with the National Institutes of Health Stroke Scale (NIHSS), modified Rankin score (mRS), and Essen stroke risk score in patients with AIS, including AIS and AIS_T2D patients. Compared with mice colonized with gut microbiota from healthy controls poststroke modeling, germfree (GF) mice colonized with gut microbiota from T2D patients showed exacerbated cerebral injury and impaired gut barrier function. Specifically, exacerbated brain injury and gut barrier dysfunction in T2D-treated GF mice were significantly associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. Our study showed that T2D and AIS have an additive effect on AIS_T2D patient gut microbiota dysbiosis. T2D-associated gut microbiota dysbiosis is associated with stroke severity in AIS patients and aggravates stroke progression in mice. IMPORTANCE We demonstrated an additive effect of type 2 diabetes (T2D) and acute ischemic stroke (AIS) on AIS with T2D (AIS_T2D) patient gut microbiota dysbiosis, and gut dysbiosis associated with T2D was positively correlated with stroke severity in AIS patients. Through animal experiments, we found that cerebral injury was exacerbated by fecal microbiota transplantation from T2D patients compared with that from healthy controls, which was associated with a reduction in short-chain fatty acid (SCFA)-producing bacteria. This study provided a novel view that links T2D and AIS through gut microbial dysbiosis.

Project description:BackgroundGuidelines have classified patients with acute coronary syndrome (ACS) and diabetes as a special population, with specific sections presented for the management of these patients considering their extremely high risk. However, in China up-to-date information is lacking regarding the burden of diabetes in patients with ACS and the potential impact of diabetes status on the in-hospital outcomes of these patients. This study aims to provide updated estimation for the burden of diabetes in patients with ACS in China and to evaluate whether diabetes is still associated with excess risks of early mortality and major adverse cardiovascular and cerebrovascular events (MACCE) for ACS patients.MethodsThe Improving Care for Cardiovascular Disease in China-ACS Project was a collaborative study of the American Heart Association and the Chinese Society of Cardiology. A total of 63,450 inpatients with a definitive diagnosis of ACS were included. Prevalence of diabetes was evaluated in the overall study population and subgroups. Multivariate logistic regression was performed to examine the association between diabetes and in-hospital outcomes, and a propensity-score-matched analysis was further conducted.ResultsAmong these ACS patients, 23,880 (37.6%) had diabetes/possible diabetes. Both STEMI and NSTE-ACS patients had a high prevalence of diabetes/possible diabetes (36.8% versus 39.0%). The prevalence of diabetes/possible diabetes was higher in women (45.0% versus 35.2%, p < 0.001). Even in patients younger than 45 years, 26.9% had diabetes/possible diabetes. While receiving comparable treatments for ACS, diabetes/possible diabetes was associated with a twofold higher risk of all-cause death (adjusted odds ratio 2.04 [95% confidence interval 1.78-2.33]) and a 1.5-fold higher risk of MACCE (adjusted odds ratio 1.54 [95% confidence interval 1.39-1.72]).ConclusionsDiabetes was highly prevalent in patients with ACS in China. Considerable excess risks for early mortality and major adverse cardiovascular events were found in these patients. Trial registration NCT02306616. Registered December 3, 2014.

Project description:Background and Purpose- Acute ischemic stroke patients with history of prior ischemic stroke plus concomitant diabetes mellitus (DM) were excluded from the ECASS III trial (European Cooperative Acute Stroke Study) because of safety concerns. However, there are few data on use of intravenous tissue-type plasminogen activator and symptomatic intracerebral hemorrhage or outcomes in this population. Methods- Using data from the Get With The Guidelines-Stroke Registry between February 2009 and September 2017 (n=1619 hospitals), we examined characteristics and outcomes among patients with acute ischemic stroke treated with tissue-type plasminogen activator within the 3- to 4.5-hour window who had a history of stroke plus diabetes mellitus (HxS+DM) (n=2129) versus those without either history (n=16 690). Results- Compared with patients without either history, those with both prior stroke and DM treated with tissue-type plasminogen activator after an acute ischemic stroke had a higher prevalence of cardiovascular risk factors in addition to history of stroke, DM, and more severe stroke (National Institutes of Health Stroke Scale: median, 8 [interquartile range, 5-15] versus 7 [4-13]). The unadjusted rates of symptomatic intracerebral hemorrhage and in-hospital mortality were 4.3% (HxS+DM) versus 3.8% (without either history; P=0.31) and 6.2% versus 5.5% ( P=0.20), respectively. These differences were not statistically significant after risk adjustment (symptomatic intracerebral hemorrhage: adjusted odds ratio, 0.79 [95% CI, 0.51-1.21]; P=0.28; in-hospital mortality: odds ratio, 0.77 [95% CI, 0.52-1.14]; P=0.19). Unadjusted rate of functional independence (modified Rankin Scale score, 0-2) at discharge was lower in those with HxS+DM (30.9% HxS+DM versus 44.8% without either history; P≤0.0001), and this difference persisted after adjusting for baseline clinical factors (adjusted odds ratio, 0.76 [95% CI, 0.59-0.99]; P=0.04). Conclusions- Among patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator within the 3- to 4.5-hour window, HxS+DM was not associated with statistically significant increased symptomatic intracerebral hemorrhage or mortality risk.

Project description:Background The aim of this prospective study was to determine the impact of elevated ANGPTL3 (angiopoietin-like protein 3) on cardiovascular events (CVEs) following acute coronary syndrome (ACS) in patients with or without obstructive sleep apnea (OSA). Methods and Results A total of 1174 patients with ACS underwent successful percutaneous coronary intervention were included in this prospective cohort study (NCT03362385). Patients were categorized according to the apnea-hypopnea index (≥15 events/h, OSA) and further classified by ANGPTL3 levels. We analyzed the incidence of CVEs in patients with ACS according to the status of OSA and ANGPTL3. During a median of 3.1 years of follow-up, 217 (18.48%) CVEs occurred. The patients with ACS with OSA had higher ANGPTL3 levels than those without OSA (30.4 [20.9-43.2] versus 27.80 [19.1-41.5] ng/mL; P<0.001). In all patients with ACS, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with an increased risk of CVEs with hazard ratios (HRs) of 1.555 (95% CI, 1.010-2.498) and 2.489 (95% CI 1.613-3.840), respectively. When the status of OSA or not was incorporated in stratifying factors, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with a significantly higher risk of CVEs in patients with ACS with OSA (HR, 1.916 [95% CI, 1.019-3.601] and HR, 2.692 [95% CI, 1.379-4.503]) but not without OSA. Moreover, adding ANGPTL3 to the Cox model increased C-statistic values by 0.035 and 0.029 in the OSA group and all patients with ACS, respectively, but was not statistically improved in patients with ACS without OSA. Conclusions In conclusion, our study demonstrates a predictive impact of plasma ANGPTL3 on cardiovascular risk in patients with ACS, especially in patients with ACS with OSA. It might be of clinical value in refining risk stratification and tailoring treatment of patients with ACS and OSA. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03362385.

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Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke.

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Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke.

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