Effect of insulin secretagogues on major cardiovascular events and all-cause mortality: A meta-analysis of randomized controlled trials

2020 ◽  
Vol 30 (10) ◽  
pp. 1601-1608
Author(s):  
Edoardo Mannucci ◽  
Matteo Monami ◽  
Riccardo Candido ◽  
Basilio Pintaudi ◽  
Giovanni Targher
Keyword(s):  
Randomized Controlled Trials ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
Major Cardiovascular Events ◽  
All Cause Mortality ◽  
Insulin Secretagogues

P6268Cardiovascular outcomes of new anti-diabetic agents - A meta-analysis of randomized controlled trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Lin ◽  
C Parco ◽  
M Brockmeyer ◽  
A Karathanos ◽  
V Schulze ◽  
...  
Keyword(s):  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Disease Status ◽  
Placebo Control ◽  
Diabetic Patients ◽  
Controlled Trials ◽  
Coronary Syndrome ◽  
Randomized Controlled ◽  
Major Cardiovascular Events ◽  
All Cause Mortality

Abstract Background and purpose The risk of major cardiovascular events (MACE) is increased in patients with diabetes mellitus. Recently published clinical trials of three different pharmacological classes (DPP4 inhibitors (DPP4i), SGLT2-inhibitors (SGLT2i), GLP-1-receptor-antagonists (GLP1RA)) of new anti-diabetic agents (ADA) showed potential benefits for cardiovascular (CV) outcomes. We thus aimed to perform a meta-analysis of randomized controlled trials (RCTs) of these ADA to elucidate benefits on CV outcomes in diabetic patients. Methods Following a systematic online database search, all RCTs reporting CV outcomes of DPP4i, SGLT2i or GLP1RA vs. Placebo in diabetic patients up until December 2018 were eligible for inclusion in the meta-analysis. Studies including patients with acute coronary syndrome (ACS) were excluded. Data were abstracted and analyzed with the inverse-variance method and a random-effects model, hazard ratios (HR) with 95% confidence intervals (CI) were used as summary statistics. CV outcomes of MACE, myocardial infarction (MI), stroke, heart failure (HF), CV death and all-cause mortality were analyzed. Results Eleven RCTs (DPP4i: SAVOR, TECOS, CARMELINA; GLP1RA: LEADER, SUSTAIN-6, EXSCEL, Harmony; SGLT2i: EMPA-REG OUTCOME, CANVAS Program, DECLARE) with 109,316 patients were selected for inclusion. ELIXA and EXAMINE were excluded due to their inclusion of patients with ACS, CAROLINA was excluded for lack of placebo-control. In the pooled meta-analysis of all trials, ADA significantly reduced the risk for MACE (Hazard ratio (HR) 0.91, CI 0.86–0.96, p=0.0004), MI (HR 0.91, CI 0.85–0.96, p=0.02), CV death (HR 0.9, CI 0.82–0.99, P=0.02) and all-cause mortality (HR 0.92, CI 0.85–0.99, p=0.03). There was no difference in the risk for stroke (HR 0.94, CI 0.87–1.02, p=0.16) and HF (HR 0.88, CI 0.76–1.02, p=0.08). In agent-specific subgroup analyses, GLP1RA and SGLT2i showed significant reductions in MACE (GLP1RA: HR 0.85, CI 0.78–0.92, p<0.0001; SGLT2i: HR 0.89, CI 0.83–0.96, p=0.001), MI (GLP1RA: HR 0.86, CI 0.76–0.98, p=0.02; SGLT2i: HR 0.88, CI 0.79–0.97, p=0.01) and all-cause mortality (GLP1RA: HR 0.88, CI 0.81–0.95; p=0.001; SGLT2i: HR 0.83, CI 0.70–0.99; p=0.03). GLP1RA significantly reduced risk for stroke (HR 0.85, CI 0.75–0.96, p=0.008) and CV death (HR 0.86, CI 0.78–0.95, p=0.002). SGLT2I were especially effective in the reduction of risk for HF (HR 0.69, CI 0.61–0.79; p<0.0001). DPP4i inhibitors however failed to show superiority in all analyzed outcomes. Conclusions This meta-analysis lends evidence to GLP1RA and SGLT2i benefits for MACE, MI and all-cause mortality, while DPP4i failed to show superiority in cardiovascular outcomes. Individualized medication for diabetic patients depending on CV disease status should be considered.

scholarly journals Intensive versus Usual Control of Hypertension in the Prevention of Cardiovascular and Renal Outcomes: A Cumulative Meta-Analysis of Randomized Controlled Trials

2019 ◽  
Vol 44 (3) ◽  
pp. 384-395 ◽  
Author(s):  
Li Li ◽  
Ling Li
Keyword(s):  
Myocardial Infarction ◽  
Randomized Controlled Trials ◽  
Cardiac Death ◽  
Cardiovascular Events ◽  
Treatment Effects ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Renal Outcomes ◽  
Randomized Controlled ◽  
Major Cardiovascular Events

Background/Aims: Previous studies have reported inconsistent results regarding the treatment effects of intensive blood pressure (IBP) control in the prevention of cardiovascular and renal outcomes. We conducted this cumulative meta-analysis to evaluate the treatment effects of IBP control on cardiovascular and renal outcomes. Methods: We systematically searched PubMed, EMBASE, and the Cochrane Library databases from the date of their inception to October 2017, to identify randomized controlled trials (RCTs). The relative risks (RRs) with corresponding 95% confidence intervals (CIs) were used to evaluate the treatment effects of IBP control by using a random-effects model. Results: The final analysis included 20 RCTs involving 56,687 individuals. The summary RRs indicated that IBP control treatment significantly reduced the risk of major cardiovascular events (RR: 0.85; 95% CI: 0.77–0.94; p = 0.001), including myocardial infarction (RR: 0.87; 95% CI: 0.76–1.00; p = 0.044), stroke (RR: 0.77; 95% CI: 0.66–0.89; p < 0.001), and albuminuria (RR: 0.90; 95% CI: 0.84–0.97; p = 0.007). However, IBP control had no significant effect on heart failure (RR: 0.80; 95% CI: 0.62–1.03; p = 0.077), all-cause mortality (RR: 0.91; 95% CI: 0.81–1.02; p = 0.112), cardiac death (RR: 0.91; 95% CI: 0.75–1.12; p = 0.390), non-cardiac death (RR: 0.98; 95% CI: 0.86–1.12; p = 0.773), end-stage renal disease (RR: 0.90; 95% CI: 0.77–1.06; p = 0.203), and retinopathy (RR: 0.81; 95% CI: 0.66–1.00; p = 0.052). Conclusion: The findings of this study suggest that IBP control plays a beneficial role in the prevention of some major cardiovascular events, including myocardial infarction, stroke, and albuminuria.

scholarly journals Is there value in prescribing colchicine in coronary artery disease for secondary prevention: a meta-analysis of over 5,000 patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.F Sunjaya ◽  
A.P Sunjaya
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Randomized Controlled Trials ◽  
Cardiovascular Events ◽  
Low Dose ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Randomized Controlled ◽  
All Cause Mortality ◽  
Artery Disease

Abstract Introduction Coronary Artery Disease (CAD) is the single greatest cause of mortality and loss of disability adjusted life years (DALYs) worldwide. Inflammation plays a central role in the pathogenesis of atherosclerosis, with numerous evidence from prospective studies indicating that increasing C-reactive protein levels (hs-CRP) are independently associated with increasing risk of cardiovascular events. Colchicine, is an inexpensive, potent anti-inflammatory drug considered as a staple therapy for gout. Recent studies have shown that colchicine use may prove to be useful in the prevention of cardiovascular events. Purpose In patients with coronary artery disease (CAD) does administration of low dose colchicine lead to reduced all-cause mortality, cardiovascular risk and morbidity. Methods A meta-analysis was performed based on randomized controlled trials obtained from Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Medline and Medline ahead of print published between 2000 and 2020. Main outcome measures include all-cause mortality, cardiovascular events, CRP levels and prevalence of CRP levels less than 2.0 mg/L. Data synthesis and analysis was done using RevMan 5.3 using a random effects model. Results A total of 5 randomized controlled trials, representing 5,430 patients were included in this meta-analysis. Three trials administered colchicine 1 mg/day while the rest were assigned colchicine. 5 mg/day. Administration of colchicine in CAD patients was found to reduce all-cause mortality (RR=0.66, 95% CI: 0.30 to 1.46, p=0.31) and major adverse cardiovascular events (MACE) (RR=0.61, 95% CI: 0.25 to 1.47, p=0.27), although results were non-significant. Reduced CRP levels (Mean difference = −0.88, 95% CI: −1.76 to 0.01, p=0.05) compared to control group as well as a higher prevalence of patients with CRP levels &lt;2.0 mg/L were found (RR=2.27, 95% CI: 0.45 to 11.33, p=0.32), although results were non-significant. Discussion Few studies are available evaluating the benefits of low dose colchicine in CAD patients. The beneficial effects of colchicine has been proposed due to its ability to inhibit neutrophil chemotaxis which may reduce the risk of plaque instability. The use of colchicine for secondary prevention of CAD will require long-term use, which will require the need for preparations that address its intolerance (mostly gastrointestinal) to prevent early discontinuation of the medication. Conclusion There's limited evidence on the benefit of low dose colchicine in CAD patients. Further large scale randomized-controlled trials are needed, and its dose-response relationship ascertained before consideration of its use could be given in CAD patients. Funding Acknowledgement Type of funding source: None

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