Pioglitazone for the Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with or at High Risk of Type 2 Diabetes Mellitus: A Meta-Analysis

2019 ◽  
Vol 105 (5) ◽  
pp. 1670-1681 ◽  
Author(s):  
Yue Zhou ◽  
Yajing Huang ◽  
Xiaoyun Ji ◽  
Xiang Wang ◽  
Liyan Shen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
High Risk ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Primary And Secondary Prevention ◽  
All Cause Mortality ◽  
History Of

Abstract Context The goal of the meta-analysis was to evaluate the effect of pioglitazone on the primary and secondary prevention of cardiovascular diseases (CVDs) and renal adverse events in patients with or at high risk of type 2 diabetes mellitus (T2DM). Design Randomized controlled trials (RCTs) comparing pioglitazone with any control were identified through PubMed, Embase, and the Cochrane Library. Cardiovascular outcomes included major adverse cardiovascular events (MACEs, defined as the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death), hospitalization for heart failure, and all-cause mortality. Renal outcomes included change in urinary albumin to creatinine ratio and 24-hour urinary protein excretion. Weighted mean difference (WMD) and risk ratio (RR) with 95% confidence intervals (CIs) were pooled. Results A total of 26 studies with 19 645 participants were enrolled. Pioglitazone reduced the risk of MACE (RR, 0.8 [95% CI, 0.7–0.9]), with benefit only seen in patients with a history of established CVDs (0.8 [0.7–0.9]) and not in those without (1.0 [0.7–1.3]). Regarding the individual components, pioglitazone reduced the risk of nonfatal myocardial infarction (0.8 [0.6–1.0]) and nonfatal stroke (0.8 [0.7–0.9]), which was confined to patients with a history of established CVDs, whereas no treatment effect was found on cardiovascular death (1.0 [0.7–1.2]) regardless of the presence of established CVDs. Pioglitazone increased the risk of hospitalization for heart failure (1.3 [1.1–1.6]) and had no treatment effect on all-cause mortality (1.0 [0.8–1.1]). Pioglitazone reduced albuminuria by 18.5% (WMD 18.5% [95% CI, 21.1-16.0]), with a similar benefit in patients with different renal function categories. Conclusions Pioglitazone should be considered in patients with or at high risk of T2DM for the prevention of cardiovascular endpoints, especially in those with a history of established CVD who might benefit the most. Robust reductions in progression of renal disease are seen regardless of baseline renal function degree.

scholarly journals GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Dario Giugliano ◽  
Lorenzo Scappaticcio ◽  
Miriam Longo ◽  
Paola Caruso ◽  
Maria Ida Maiorino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Significant Heterogeneity ◽  
Cardiovascular Outcome Trials ◽  
Receptor Agonists ◽  
All Cause Mortality

Abstract Background A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM). Methods We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease). Results GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR = 0.86, 95% CI 0.79–0.94, P = 0.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P = 0.127). GLP-1RA also reduced the risk of cardiovascular death by 13% (P = 0.016), nonfatal stroke by 16% (P = 0.007), hospitalization for heart failure by 10% (P = 0.023), all-cause mortality by 12% (P = 0.012), and the broad composite kidney outcome by 17% (P = 0.012), which was driven by a reduction in macroalbuminuria only (HR = 0.74, 0.67–0.82, P < 0.001). Conclusions GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria.

scholarly journals Metformin Use and Clinical Outcomes Among Patients With Diabetes Mellitus With or Without Heart Failure or Kidney Dysfunction

Circulation ◽  
2019 ◽  
Vol 140 (12) ◽  
pp. 1004-1014 ◽  
Author(s):  
Brian A. Bergmark ◽  
Deepak L. Bhatt ◽  
Darren K. McGuire ◽  
Avivit Cahn ◽  
Ofri Mosenzon ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Cardiovascular Death ◽  
Inverse Probability ◽  
All Cause Mortality

Background: Metformin is first-line therapy for type 2 diabetes mellitus, although its effects on the cardiovascular system are unproved. Methods: In this post hoc analysis, patients in SAVOR-TIMI 53 (Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus) with baseline biomarker samples (n=12 156) were classified as ever versus never taking metformin during the trial period. Associations between metformin exposure and outcomes were estimated with inverse probability of treatment weighting Cox modeling for the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke, as well as cardiovascular death and all-cause mortality, with biomarkers included as covariates. Additional sensitivity analyses included propensity score matching and Cox multivariable models. Results: Of the 12 156 patients with baseline biomarker samples, 8971 (74%) had metformin exposure, 1611 (13%) had prior heart failure, and 1332 (11%) had at least moderate chronic kidney disease (estimated glomerular filtration rate ≤45 mL·min −1 ·1.73 m −2 ). Metformin use was associated with no difference in risk for the composite end point (hazard ratio for inverse probability of treatment weighting, 0.92 [95% CI, 0.76–1.11]) but lower risk of all-cause mortality (hazard ratio for inverse probability of treatment weighting, 0.75 [95% CI, 0.59–0.95]). There was no significant relationship between metformin use and these end points in patients with prior heart failure or moderate to severe chronic kidney disease. Conclusions: In a cohort of 12 156 patients with type 2 diabetes mellitus and high cardiovascular risk, metformin use was associated with lower rates of all-cause mortality, including after adjustment for clinical variables and biomarkers, but not lower rates of the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. This association was most apparent in patients without prior heart failure or moderate to severe chronic kidney disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01107886.

scholarly journals P2Y12 Inhibitors Plus Aspirin Versus Aspirin Alone in Patients With Minor Stroke or High-Risk Transient Ischemic Attack

Stroke ◽  
2021 ◽  
Author(s):  
Zi-Xiao Li ◽  
Yunyun Xiong ◽  
Hong-Qiu Gu ◽  
Marc Fisher ◽  
Ying Xian ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
High Risk ◽  
Transient Ischemic Attack ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Controlled Trials ◽  
P2y12 Inhibitors ◽  
All Cause Mortality ◽  
Ischemic Attack

Background and purpose: We performed a systemic review and meta-analysis to elucidate the effectiveness and safety of dual antiplatelet (DAPT) therapy with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy in patients with mild ischemic stroke or high-risk transient ischemic attack. Methods: Following Preferred Reported Items for Systematic Review and Meta-Analysis standards for meta-analyses, Medline, Embase, Cochrane Central Register of Controlled Trials, and the Cochrane Library were searched for randomized controlled trials that included patients with a diagnosis of an acute mild ischemic stroke or high-risk transient ischemic attack, intervention of DAPT therapy with clopidogrel/ticagrelor and aspirin versus aspirin alone from January 2012 to July 2020. The outcomes included subsequent stroke, all-cause mortality, cardiovascular death, hemorrhage (mild, moderate, or severe), and myocardial infarction. A DerSimonian-Laird random-effects model was used to estimate pooled risk ratio (RR) and corresponding 95% CI in R package meta. We assessed the heterogeneity of data across studies with use of the Cochran Q statistic and I 2 test. Results: Four eligible trials involving 21 493 participants were included in the meta-analysis. DAPT therapy started within 24 hours of symptom onset reduced the risk of stroke recurrence by 24% (RR, 0.76 [95% CI, 0.68–0.83], I 2 =0%) but was not associated with a change in all-cause mortality (RR, 1.30 [95% CI, 0.90–1.89], I 2 =0%), cardiovascular death (RR, 1.34 [95% CI, 0.56–3.17], I 2 =0%), mild bleeding (RR, 1.25 [95% CI, 0.37–4.29], I 2 =94%), or myocardial infarction (RR, 1.45 [95% CI, 0.62–3.39], I 2 =0%). However, DAPT was associated with an increased risk of severe or moderate bleeding (RR, 2.17 [95% CI, 1.16–4.08], I 2 =41%); further sensitivity tests found that the association was limited to trials with DAPT treatment duration over 21 days (RR, 2.86 [95% CI, 1.75–4.67], I 2 =0%) or ticagrelor (RR, 2.17 [95% CI, 1.16–4.08], I 2 =37%) but not within 21 days or clopidogrel. Conclusions: In patients with noncardioembolic mild stroke or high-risk transient ischemic attack, DAPT with aspirin and clopidogrel/ticagrelor is more effective than aspirin alone for recurrent stroke prevention with a small absolute increase in the risk of severe or moderate bleeding.

scholarly journals Incident heart failure and myocardial infarction in sodium-glucose cotransporter 2 versus dipeptidyl peptidase-4 inhibitor users

2021 ◽  
Author(s):  
Jiandong Zhou ◽  
Sharen Lee ◽  
Keith Sai Kit Leung ◽  
Abraham Ka Chung Wai ◽  
Tong Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Population Based ◽  
Dipeptidyl Peptidase 4 ◽  
Sodium Glucose Cotransporter ◽  
All Cause Mortality ◽  
Incident Heart Failure ◽  
New Onset

Objectives: To compare the rates of major cardiovascular adverse events in sodium-glucose cotransporter-2 inhibitors (SGLT2I) and dipeptidyl-peptidase-4 inhibitors (DPP4I) users in a Chinese population. Background: SGLT2I and DPP4I are increasingly prescribed for type 2 diabetes mellitus patients. However, few population-based studies are comparing their effects on incident heart failure or myocardial infarction. Methods: This was a population-based retrospective cohort study using the electronic health record database in Hong Kong, including type 2 diabetes mellitus patients receiving either SGLT2I or DPP4I between January 1st, 2015, to December 31st, 2020. Propensity-score matching was performed in a 1:1 ratio based on demographics, past comorbidities, non-SGLT2I/DPP4I medications with nearest-neighbor matching (caliper=0.1). Univariate and multivariate Cox models were used to identify significant predictors for new onset heart failure, new onset myocardial infarction, cardiovascular mortality, and all-cause mortality. Sensitivity analyses with competing risk models and multiple propensity score matching approaches were conducted. Subgroup age and gender analyses were presented. Results: A total of 41994 patients (58.89% males, median admission age at 58 years old, interquartile rage [IQR]: 51.2-65.3) were included in the study cohorts with a median follow-up duration of 5.6 years (IQR: 5.32-5.82). After adjusting for significant demographics, past comorbidities, medication prescriptions and biochemical results, SGLT2I users have a significantly lower risk for myocardial infarction (hazard ratio [HR]: 0.34, 95% confidence interval [CI]: [0.28, 0.41], P < 0.0001), cardiovascular mortality (HR: 0.53, 95% CI: [0.38, 0.74], P = 0.0002) and all-cause mortality (HR: 0.21, 95% CI: [0.18, 0.25], P= 0.0001) under multivariate Cox regression. However, the risk for heart failure is comparable (HR: 0.87, 95% CI: [0.73, 1.04], P= 0.1343). Conclusions: SGLT2 inhibitors are protective against adverse cardiovascular events compared to DPP4I. The prescription of SGLT2I is preferred especially for males and patients aged 65 or older to prevent cardiovascular risks.

scholarly journals The Effects of Dapagliflozin in Patients With Heart Failure Complicated With Type 2 Diabetes: A Meta-Analysis of Placebo-Controlled Randomized Trials

2021 ◽  
Vol 2 ◽  
Author(s):  
Miaobo Zhai ◽  
Xin Du ◽  
Changmei Liu ◽  
Huipu Xu
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Meta Analysis ◽  
Cardiovascular Death ◽  
Major Adverse Cardiovascular Events ◽  
Significant Heterogeneity ◽  
Sodium Glucose Cotransporter ◽  
All Cause Mortality ◽  
Incidence Of Hospitalization

BackgroundCardiovascular disease threatens the health and quality of life of individuals, particularly those with type II diabetes. Recently, some studies have reported the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the rates of hospitalization or urgent visits, resulting in IV therapy for heart failure in patients with type 2 diabetes mellitus (T2DM).MethodsWe did a comprehensive search in electronic databases from inception through July 2020 for randomized-controlled trials, using the keywords “sodium-glucose cotransporter-2 inhibitor”, “dapagliflozin”, “heart failure”, “cardiovascular outcomes”, “major adverse cardiovascular events”, “all-cause mortality”, and “cardiovascular death”. Random-effects summary odds ratios (OR) were constructed using M-L heterogeneity model.ResultsFive trials with 5,252 patients were ultimately included. The incidence of hospitalization for heart failure (HHF) (n=4, OR=0.74; 95% CI, 0.61 to 0.88; I2 = 0%) and all-cause mortality (ACM, n=4, OR=0.76; 95% CI, 0.66 to 0.94; I2 = 0%); was reduced by dapagliflozin, respectively, in all heart failure patients, without obvious heterogeneity. The incidence of cardiovascular death in dapagliflozin was lower than that in placebo without statistically significant (CVD, n=5, OR=0.84; 95% CI, 0.69 to 1.03; I2 = 0%). In HFrEF subgroup, dapagliflozin was associated with a reduced incidence of hospitalization for heart failure (n=4, OR=0.74; 95% CI, 0.60 to 0.91; I2 = 0%), cardiovascular death (n=4, OR=0.72; 95% CI, 0.58 to 0.91; I2 = 8%), and all-cause mortality (n=3, OR=0.70; 95% CI, 0.50 to 0.99; I2 = 43%) without significant heterogeneity. In contrast, in the HFpEF subgroup, there was no difference in the incidence of cardiovascular death (n=2, OR=1.45; 95% CI, 0.95 to 2.22; I2 = 0%) and all-cause mortality (n=2, OR=1.04; 95% CI, 0.76 to 1.43; I2 = 0%) between dapagliflozin and placebo.ConclusionIn our study, dapagliflozin performed a statistical reduction in the rate of heart failure hospitalization, cardiovascular death, and all-cause mortality in patients with HFrEF and diabetes. However, in the HFpEF subgroup, dapagliflozin did not show a significant cardiovascular protective effect.

Sign in / Sign up

Export Citation Format

Share Document