Cardiovascular outcomes in patients treated with sodium-glucose transport protein 2 inhibitors, a network meta-analysis of randomized trials

BackgroundGliflozins altering the sodium-glucose transport protein 2 (SGLT2) in the nephron, represent alone or in combination a promising treatment option for patients with type II diabetes mellitus. In addition to glucose control, these drugs provide benefits including reduced risk of long-term cardiovascular (CV) and renal complications. Several trials evaluated gliflozins in patients with various degrees of cardiac dysfunction with heterogeneous results.ObjectivesWe aimed to perform a comprehensive analysis of the effect of gliflozins on CV outcomes.MethodsSystematic searches of electronic databases were conducted until September 2022. Multiple treatment network meta-analysis was performed in R. Random-effects model was used to combine risk estimates across trials calculating risk ratio (RR) with 95% confidence intervals as summary statistics. The primary endpoint of interest was the rate of heart failure-related hospitalization (HHF) and the composite of HHF with CV mortality (HHF + CVD). Secondary outcomes included major adverse cardiac events (MACE), CV- and overall mortality, myocardial infarction (MI), and stroke.ResultsTwenty-nine studies randomizing 88,418 patients were identified. Gliflozins reduced the risk of HHF (RR: 0.72 [0.69; 0.76]) and HHF + CVD (RR: 0.78 [0.75; 0.82]). The risk of MACE and its component also improved significantly except for stroke. The network analyses did not explore major differences among the individual substances. The only exception was sotagliflozin which appeared to be more effective regarding HHF + CVD, stroke, and MI compared to ertugliflozin, in HHF + CVD and stroke compared to dapagliflozin, and in stroke endpoint compared to empagliflozin.ConclusionOur meta-analysis supports a group effect of gliflozins beneficial in a wide spectrum of patients with a risk of heart failure (HF) development. In addition to the improvement of HF-related outcomes, the risk of major adverse events is also reduced with SGLT2 inhibition.Systematic review registration[www.ClinicalTrials.gov], identifier [CRD42022358078]

Antithrombotic Therapy for Secondary Prevention in Patients with Non-Cardioembolic Stroke or Transient Ischemic Attack: A Systematic Review

Stroke embodies one of the leading causes of death and disability worldwide. We aimed to provide a comprehensive insight into the effectiveness and safety of antiplatelet agents and anticoagulants in the secondary prevention of ischemic stroke or transient ischemic attack. A systematic search for randomized controlled trials, comparing antiplatelet or anticoagulant therapy versus aspirin or placebo among patients with ischemic stroke or transient ischemic attack, was performed in order to summarize data regarding the different regimens. Keyword-based searches in the MEDLINE, EMBASE, and Cochrane Library databases were conducted until the 1st of January 2021. Our search explored 46 randomized controlled trials involving ten antiplatelet agents, six combinations with aspirin, and four anticoagulant therapies. The review of the literature reflects that antiplatelet therapy improves outcome in patients with ischemic stroke or transient ischemic attack. Monotherapy proved to be an effective and safe choice, especially in patients with a high risk of bleeding. Intensified antiplatelet regimens further improve stroke recurrence; however, bleeding rate increases while mortality remains unaffected. Supplementing the clinical judgment of stroke treatment, assessment of bleeding risk is warranted to identify patients with the highest benefit of treatment intensification

Data_Sheet_1_Combination of antiplatelet and anticoagulant therapy, component network meta-analysis of randomized controlled trials.docx

BackgroundDespite numerous randomized clinical trials (RCT), data regarding the efficacy of antiplatelet and anticoagulant combinations are still conflicting. We aimed to analyze treatment options tested in various fields of cardiovascular prevention, regarding their efficacy and bleeding risk.MethodsSystematic searches of electronic databases were conducted until June 2022. A component network meta-analysis was performed in R. Risk estimates across trials were pooled using random-effects model selecting risk ratio (RR) with 95% confidence intervals (95% CIs) as summary statistics. The primary endpoint of interest was the rate of major cardiac adverse events (MACE). Major bleeding events were assessed as main safety endpoint. Secondary outcomes included cardiovascular- and overall mortality, myocardial infarction (MI), stent thrombosis, and stroke.ResultsFifteen studies randomizing 73,536 patients were identified. The MACE risk reflected heterogeneity among the anticoagulants with dabigatran and apixaban significantly reducing the risk of MACE (RR 0.56; 95% CI 0.39–0.80 and RR 0.75; 95% CI 0.58–0.98, respectively). Vitamin K antagonist (VKA), rivaroxaban, or edoxaban did not reduced of MACE while it was associated with a significant increase of bleeding risk (RR 1.66; 3.66, and 5.47, respectively). The direct anticoagulant (DOAC) dose reduction resulted in tendencies of fewer bleeding but higher MACE risk, while combination with aspirin was followed with increased risk for bleeding, however, remained non-significant in these cases.ConclusionOur meta-analysis supports that the ischemic-bleeding balance is different among direct-acting oral anticoagulants (DOACs) while this is not significantly affected by the dose reduction approaches. Long-term aspirin treatment as part of the anticoagulant and dual antiplatelet regimen provides no ischemic benefit but may increase bleeding risk.Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [259703].</p

Data_Sheet_1_Cardiovascular outcomes in patients treated with sodium-glucose transport protein 2 inhibitors, a network meta-analysis of randomized trials.docx

BackgroundGliflozins altering the sodium-glucose transport protein 2 (SGLT2) in the nephron, represent alone or in combination a promising treatment option for patients with type II diabetes mellitus. In addition to glucose control, these drugs provide benefits including reduced risk of long-term cardiovascular (CV) and renal complications. Several trials evaluated gliflozins in patients with various degrees of cardiac dysfunction with heterogeneous results.ObjectivesWe aimed to perform a comprehensive analysis of the effect of gliflozins on CV outcomes.MethodsSystematic searches of electronic databases were conducted until September 2022. Multiple treatment network meta-analysis was performed in R. Random-effects model was used to combine risk estimates across trials calculating risk ratio (RR) with 95% confidence intervals as summary statistics. The primary endpoint of interest was the rate of heart failure-related hospitalization (HHF) and the composite of HHF with CV mortality (HHF + CVD). Secondary outcomes included major adverse cardiac events (MACE), CV- and overall mortality, myocardial infarction (MI), and stroke.ResultsTwenty-nine studies randomizing 88,418 patients were identified. Gliflozins reduced the risk of HHF (RR: 0.72 [0.69; 0.76]) and HHF + CVD (RR: 0.78 [0.75; 0.82]). The risk of MACE and its component also improved significantly except for stroke. The network analyses did not explore major differences among the individual substances. The only exception was sotagliflozin which appeared to be more effective regarding HHF + CVD, stroke, and MI compared to ertugliflozin, in HHF + CVD and stroke compared to dapagliflozin, and in stroke endpoint compared to empagliflozin.ConclusionOur meta-analysis supports a group effect of gliflozins beneficial in a wide spectrum of patients with a risk of heart failure (HF) development. In addition to the improvement of HF-related outcomes, the risk of major adverse events is also reduced with SGLT2 inhibition.Systematic review registration[www.ClinicalTrials.gov], identifier [CRD42022358078].</p