scholarly journals GLUCOSE LOWERING DRUGS OR STRATEGIES, MAJOR ADVERSE CARDIOVASCULAR EVENTS AND HEART FAILURE OUTCOMES, AND ASSOCIATION WITH WEIGHT LOSS - META-ANALYSIS OF LARGE CARDIOVASCULAR OUTCOME TRIALS

2019 ◽  
Vol 35 (10) ◽  
pp. S78
Author(s):  
O. Ghosh-Swaby ◽  
S. Goodman ◽  
L. Leiter ◽  
A Cheng ◽  
K. Connelly ◽  
...  
Keyword(s):  
Heart Failure ◽  
Weight Loss ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Cardiovascular Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Glucose Lowering ◽  
Cardiovascular Outcome Trials

4113Glucose lowering drugs or strategies, major adverse cardiovascular events and heart failure outcomes, and association with weight loss - meta-analysis of large cardiovascular outcome trials

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O R Ghosh-Swaby ◽  
S G Goodman ◽  
L A Leiter ◽  
A Cheng ◽  
K Connelly ◽  
...  
Keyword(s):  
Heart Failure ◽  
Weight Loss ◽  
Risk Reduction ◽  
Cardiovascular Events ◽  
Cardiovascular Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Risk Reduction ◽  
Cardiovascular Outcome Trials ◽  
Lower Weight ◽  
Meta Regression

Abstract Background Glucose lowering drugs or strategies (GLDS) have varied effects on major adverse cardiovascular events (MACE) and heart failure (HF) in cardiovascular outcomes trials. Mechanisms driving cardiovascular risk reduction remain elusive. Methods We searched MEDLINE, PubMed, and meeting abstracts up to 11/21/2018 for large GLDS cardiovascular outcome trials (CVOTs) in patients with or at risk for type 2 diabetes. Primary endpoints of MACE and HF were evaluated with random effects risk ratios (RR) and explored by baseline CVD subgroups and meta-regression by weight change across treatment arms. Results In 27 GLDS CVOTs, a total 207,820 patients, median age 63 years, 64% male, 64% CVD and 11% with prior HF were studied over a mean 3.8 years with 20,118 (10%) patients having MACE and 7,212 (4%) a HF event. Compared with standard care, GLDS overall lowered MACE (RR 0.92, P<0.ehz745.01171) but not HF (RR 1.01, P=0.91). Across GLDS, the magnitude and directionality varied modestly for MACE RR (P-int=0.07) but markedly for HF (P-int<0.ehz745.01171). Meta-regression showed a change in HF RR by 6% (95% CI 3%-9%) per 1 kg weight gain/loss between treatment arms (P=0.0006; Figure). In 9 trials of GLDS that achieved marked weight loss (lifestyle, GLP1 agonists, SGLT2 inhibitors), MACE benefit was confined to patients with baseline CVD (RR 0.89 [0.84–0.95] versus without (RR 1.02 [0.91–1.15]; P-int=0.01) with consistent HF effect (RR 0.80 [0.72–0.88] vs RR 0.76 [0.56–1.03]; P-int=0.74). Heart Failure Risk and Changes in Weight Conclusion HF outcomes were improved with GLDS that lower weight. Among diabetes GLDS that lower weight, there was a robust risk reduction in atherothrombotic and heart failure events, with the MACE benefit confined to patients with established CVD. Acknowledgement/Funding Heart and Stroke Foundation

scholarly journals Series: Cardiovascular outcome trials for diabetes drugs Liraglutide and LEADER

2020 ◽  
Vol 20 (2) ◽  
pp. 142-144
Author(s):  
Miles Fisher
Keyword(s):  
Heart Failure ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Cardiovascular Outcome ◽  
Secondary Outcome ◽  
Major Adverse Cardiovascular Events ◽  
Cardiovascular Outcome Trials ◽  
Major Cardiovascular Events ◽  
Cardiovascular Outcome Trial ◽  
Outcome Trial

LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) was an FDA-mandated cardiovascular outcome trial with liraglutide and was the first trial with a glucagon-like peptide-1 (GLP-1) receptor agonist to demonstrate a significant reduction in cardiovascular events. It compared liraglutide and placebo in 9,340 people with type 2 diabetes and either existing cardiovascular disease or age >60 years with at least one cardiovascular risk factor. LEADER demonstrated superiority for major cardiovascular events (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke), and cardiovascular deaths were significantly reduced, as was all-cause mortality. Hospitalisation for heart failure, which was a secondary outcome, was not significantly reduced. Compared with the EMPA-REG OUTCOME trial, the curves for major adverse cardiovascular events in LEADER separated later, and the absence of a clear effect on hospitalisation for heart failure or on estimated glomerular filtration rate suggests that the mechanism of cardiovascular benefit for liraglutide was different from that for empagliflozin

scholarly journals Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: A real-world systematic review and meta-analysis

2020 ◽  
Author(s):  
Chun-xing Li ◽  
Shuo Liang ◽  
Lingyan Gao ◽  
Hua Liu
Keyword(s):  
Heart Failure ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Real World ◽  
Cardiovascular Events ◽  
Meta Analysis ◽  
Cardiovascular Outcome ◽  
Glucose Lowering

Abstract Background Glucose lowering agents that reduce the risk of major cardiovascular events would be considered a major advance. Despite the reduction of cardiovascular risk by sodium-glucose cotransporter 2 inhibitors (SGLT-2i) has been confirmed by some large randomized controlled studies and systematic reviews, exact indicators of cardiovascular risk remained controversial. Whether consistent results can be obtained in clinical practice is unclear. Therefore, in this meta-analysis, we examined the real-world effect of SGLT-2i on cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM).Methods We did a real-world systematic review and meta-analysis of cardiovascular outcome of SGLT-2i in patients with T2DM. We searched PubMed and Embase for trials published up to October 23, 2019. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. The primary outcome was major adverse cardiovascular events (MACE) and all-cause mortality (ACM). Secondary outcomes were hospitalization for heart failure (HHF), atrial fibrillation (AF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), unstable angina (UA), heart failure (HF). Odds ratio (OR) with 95% CIs were pooled across trials, and cardiovascular outcomes were stratified by baseline incidence of cardiovascular disease (CVD), usage rate of cardiovascular benefit drug, follow-up period and region.Results Fourteen trials enrolling 3,157,259 patients were included. SGLT-2i reduced MACE (OR, 0.71; 95% CI 0.67,0.75, P<0.001) and ACM (OR, 0.53; 95% CI 0.49,0.57, P<0.001) compared to other glucose lowering drugs (oGLD). Compared with oGLD, SGLT-2i had significantly lowered the risk of HHF (OR, 0.56; 95% CI 0.46,0.68, P<0.001), MI (OR, 0.77; 95% CI 0.73,0.81, P<0.001), stroke (OR, 0.75; 95% CI 0.72,0.78, P<0.001), CVM (OR, 0.58; 95% CI 0.49,0.69, P<0.001) and HF(OR, 0.56; 95% CI 0.48,0.67, P<0.001), but there was no benefit from UA or AF. Subgroup analysis showed SGLT-2i reduced the risk of MACE, ACM, HHF, MI, stroke, CVM and HF with a similar benefit regardless of the incidence of CVD was (20-30)% or < 15%, (15-30)% and <15% have been treated with GLP-1 receptor agonists (GLP-1RA), >80% and<70% have been treated with statins or both GLP-1RA and statins. SGLT-2i reduced the risk of ACM in low-risk population (P<0.001). No inconsistencies were found when stratification was performed at 1 or (3-4) years of follow-up. SGLT-2i showed similar cardiovascular benefits in the Nordic countries, Asia and the United States.Conclusions The predominant impact of SGLT-2i is on cardiovascular outcome driven predominantly by reduction in MACE, ACM, HHF, MI, stroke, CVM, HF, but not UA or AF. SGLT-2i have robust benefits on reducing MACE, ACM, HHF, MI, stroke, CVM and HF regardless of a history of usage rate of GLP-1RA and/or statins and /or metformin.

scholarly journals Cardiovascular outcomes associated with SGLT-2 inhibitors versus other glucose-lowering drugs in patients with type 2 diabetes: A real-world systematic review and meta-analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0244689 ◽  
Author(s):  
Chun-xing Li ◽  
Shuo Liang ◽  
Lingyan Gao ◽  
Hua Liu
Keyword(s):  
Heart Failure ◽  
Real World ◽  
Lower Limb ◽  
Meta Analysis ◽  
Severe Hypoglycemia ◽  
Cardiovascular Outcome ◽  
Limb Amputation ◽  
Glucose Lowering

Background and aims Glucose lowering agents that reduce the risk of major adverse cardiovascular events (MACE) would be considered a major advance. The reduction of cardiovascular risk by sodium-glucose cotransporter 2 inhibitors (SGLT-2i) has been confirmed by some large-scale randomized controlled studies (RCTs) and systematic reviews of RCTs, but exact indicators of cardiovascular risk remained controversial. Whether consistent results can be obtained in clinical practice is unclear. Therefore, in this meta-analysis, we analyzed the real-world effect of SGLT-2i on cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM). Methods We did a real-world systematic review and meta-analysis of cardiovascular outcome of SGLT-2i in patients with T2DM. We searched PubMed and Embase for trials published up to October 23, 2019. Data search and extraction were completed with a standardized data form and any discrepancies were resolved by consensus. The primary outcome was MACE and all-cause mortality (ACM). Secondary outcomes were hospitalization for heart failure (HHF), atrial fibrillation (AF), myocardial infarction (MI), stroke, cardiovascular mortality (CVM), unstable angina (UA), heart failure (HF). Odds ratio (OR) with 95% CIs were pooled across trials, and cardiovascular outcomes were stratified by baseline incidence of cardiovascular disease (CVD), usage rate of cardiovascular benefit drug, follow-up period and region. Results Fourteen trials enrolling 3,157,259 patients were included. SGLT-2i reduced MACE (OR, 0.71; 95% CI 0.67,0.75, P<0.001) and ACM (OR, 0.53; 95% CI 0.49,0.57, P<0.001) compared to other glucose lowering drugs (oGLD). Compared with oGLD, SGLT-2i had significantly lowered the risk of HHF (OR, 0.56; 95% CI 0.46,0.68, P<0.001), MI (OR, 0.77; 95% CI 0.73,0.81, P<0.001), stroke (OR, 0.75; 95% CI 0.72,0.78, P<0.001), CVM (OR, 0.58; 95% CI 0.49,0.69, P<0.001) and HF (OR, 0.56; 95% CI 0.48,0.67, P<0.001), but there was no benefit from UA or AF. SGLT-2i significantly reduced the risk of severe hypoglycemia (OR, 0.78; 95% CI 0.69,0.90, P<0.001) and lower limb amputation (OR, 0.83; 95% CI 0.71,0.98, P<0.001), but it may increase the risk of diabetic ketoacidosis. Subgroup analysis showed SGLT-2i reduced the risk of MACE, ACM, HHF, MI, stroke, CVM and HF with a similar benefit regardless of the incidence of CVD was (20–30)% or < 15%, (15–30)% or <15% have been treated with GLP-1 receptor agonists (GLP-1RA), >80% or <70% have been treated with statins or both GLP-1RA and statins. SGLT-2i reduced the risk of ACM in low-risk population (P<0.001). No inconsistencies were found when stratification was performed at 1 or (3–4) years of follow-up except for BKA followed up for 1 year. SGLT-2i showed similar cardiovascular benefits in the Nordic countries, Asia and the United States. Conclusions The predominant impact of SGLT-2i is on cardiovascular outcome driven predominantly by reduction in MACE, ACM, HHF, MI, stroke, CVM, HF, but not UA or AF. SGLT-2i has robust benefits on reducing MACE, ACM, HHF, MI, stroke, CVM and HF regardless of a history of usage rate of GLP-1RA and/or statins and /or metformin. SGLT-2i does not increase the risk of severe hypoglycemia and lower limb amputation.

scholarly journals Short-term risk of major adverse cardiovascular events or congestive heart failure in patients with psoriatic arthritis or psoriasis initiating a biological therapy: a meta–analysis of randomised controlled trials

RMD Open ◽  
2019 ◽  
Vol 5 (1) ◽  
pp. e000763 ◽  
Author(s):  
Bénédicte Champs ◽  
Yannick Degboé ◽  
Thomas Barnetche ◽  
Alain Cantagrel ◽  
Adeline Ruyssen-Witrand ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Events ◽  
Randomised Controlled Trials ◽  
Biological Therapy ◽  
Meta Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Controlled Trials ◽  
Short Term ◽  
Significant Difference ◽  
Randomised Controlled

ObjectiveThe objective was to investigate the short-term risk of major adverse cardiovascular events (MACEs) or congestive heart failure (CHF) in patients with psoriatic arthritis (PsA) or psoriasis initiating a biological therapy.MethodsScreening for the study was carried out using MEDLINE, Cochrane and Embase, from the inception of the database to December 2017. Randomised controlled trials (RCTs) of anti-tumour necrosis factor (TNF), anti-interleukin (IL)12/23, anti-IL23 and anti-IL17 agents for the treatment of PsA or psoriasis were included. Two investigators independently extracted MACEs or CHF data reported during the placebo-controlled phase. The primary outcome measures were the incidence of MACEs or CHF.ResultsOf 753 references screened, 62 articles were selected, and 12 articles were added by manual searches. Accordingly 77 RCTs were included in the meta-analysis (MA) (10 174 patient-years (P-Y)). No significant difference was observed in MACE incidences in patients receiving anti-TNF, anti-IL12/23, anti-IL23 or anti-IL17 agents in comparison to the placebo. However, 10 MACEs were observed in the anti-IL12/23 group (1150 P-Y) compared with 1 in the placebo group (652 P-Y), with 0.01 −0.00 to 0.02 event/P-Y risk difference, which is not statistically significant. This trend was not observed in the anti-IL23 group. No significant difference was observed in CHF incidence in patients receiving biological agents in comparison to placebo.ConclusionThis MA of 77 RCTs did not reveal any significant change in the short-term risk of MACE or CHF in patients with PsA or psoriasis initiating a biological therapy.

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