DPP4 inhibitors and cardiovascular outcomes: safety on heart failure.
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ABSTRACT:
SUBMITTER: Xia C
PROVIDER: S-EPMC5491332 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
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DPP4 inhibitors and cardiovascular outcomes: safety on heart failure.
Xia Chang C Goud Aditya A D'Souza Jason J Dahagam CHanukya C Rao Xiaoquan X Rajagopalan Sanjay S Zhong Jixin J
Heart failure reviews 20170501 3
Diabetes is an important risk factor for cardiovascular disease. However, clinical data suggests intensive glycemic control significantly increase rather than decrease cardiovascular mortality, which is largely due to the fact that a majority of oral anti-diabetic drugs have adverse cardiovascular effect. There are several large-scale clinical trials evaluating the cardiovascular safety of DPP4 inhibitors, a novel class of oral anti-diabetic medications, which have been recently completed. They ...[more]
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Project description:BackgroundNo study has compared the cardiovascular outcomes for sodium-glucose cotransporter-2 inhibitors (SGLT2i) head-to-head against other glucose-lowering therapies, including dipeptidyl peptidase 4 inhibitor (DDP4i) or glucagon-like peptide-1 receptor agonist (GLP-1RA)-which also have cardiovascular benefits-in patients with heart failure with reduced (HFrEF) or preserved (HFpEF) ejection fraction.MethodsMedicare fee-for-service data (2013-2019) were used to create four pair-wise comparison cohorts of type 2 diabetes patients with: (1a) HFrEF initiating SGLT2i versus DPP4i; (1b) HFrEF initiating SGLT2i versus GLP-1RA; (2a) HFpEF initiating SGLT2i versus DPP4i; and (2b) HFpEF initiating SGLT2i versus GLP-1RA. The primary outcomes were (1) hospitalization for heart failure (HHF) and (2) myocardial infarction (MI) or stroke hospitalizations. Adjusted hazards ratios (HR) and 95% CIs were estimated using inverse probability of treatment weighting.ResultsAmong HFrEF patients, initiation of SGLT2i versus DPP4i (cohort 1a; n = 13,882) was associated with a lower risk of HHF (adjusted Hazard Ratio [HR (95% confidence interval)], 0.67 (0.63, 0.72) and MI or stroke (HR: 0.86 [0.75, 0.99]), and initiation of SGLT2i versus GLP-1RA (cohort 1b; n = 6951) was associated with lower risk of HHF (HR: 0.86 [0.79, 0.93]), but not MI or stroke (HR: 1.02 [0.85, 1.22]). Among HFpEF patients, initiation of SGLT2i versus DPP4i (cohort 2a; n = 17,493) was associated with lower risk of HHF (HR: 0.65 [0.61, 0.69]) but not MI or stroke (HR: 0.90 [0.79, 1.02]), and initiation of SGLT2i versus GLP-1RA (cohort 2b; n = 9053) was associated with lower risk of HHF (0.89 [0.83, 0.96]), but not MI or stroke (HR: 0.97 [0.83, 1.14]). Results were robust across range of secondary outcomes (e.g., all-cause mortality) and sensitivity analyses.ConclusionsBias from residual confounding cannot be ruled out. Use of SGLT2i was associated with reduced risk of HHF against DPP4i and GLP-1RA, reduced risk of MI or stroke against DPP4i within the HFrEF subgroup, and comparable risk of MI or stroke against GLP-1RA. Notably, the magnitude of cardiovascular benefit conferred by SGLT2i was similar among patients with HFrEF and HFpEF.
| S-EPMC9999503 | biostudies-literature
Project description:BACKGROUND:Incident heart failure (HF) is increased in persons with human immunodeficiency virus (PHIV). Protease inhibitors (PIs) are associated with adverse cardiac remodeling and vascular events; however, there are no data on the use of PIs in PHIV with HF. OBJECTIVES:This study sought to compare characteristics, cardiac structure, and outcomes in PHIV with HF who were receiving PI-based versus non-PI (NPI) therapy. METHODS:This was a retrospective single-center study of all 394 antiretroviral therapy-treated PHIV who were hospitalized with HF in 2011, stratified by PI and NPI. The primary outcome was cardiovascular (CV) mortality, and the secondary outcome was 30-day HF readmission rate. RESULTS:Of the 394 PHIV with HF (47% female, mean age 60 ± 9.5 years, CD4 count 292 ± 206 cells/mm3), 145 (37%) were prescribed a PI, whereas 249 (63%) were prescribed NPI regimens. All PI-based antiretroviral therapy contained boosted-dose ritonavir. PHIV who were receiving a PI had higher rates of hyperlipidemia, diabetes mellitus, and coronary artery disease (CAD); higher pulmonary artery systolic pressure (PASP); and lower left ventricular ejection fraction. In follow-up, PI use was associated with increased CV mortality (35% vs. 17%; p < 0.001) and 30-day HF readmission (68% vs. 34%; p < 0.001), effects seen in all HF types. Predictors of CV mortality included PI use, CAD, PASP, and immunosuppression. Overall, PIs were associated with a 2-fold increased risk of CV mortality. CONCLUSIONS:PI-based regimens in PHIV with HF are associated with dyslipidemia, diabetes, CAD, a lower left ventricular ejection fraction, and a higher PASP. In follow-up, PHIV with HF who are receiving a PI have increased CV mortality and 30-day HF readmission.
| S-EPMC6202063 | biostudies-literature
Project description:BACKGROUND:The effects of thyroid dysfunction in patients with preexisting heart failure have not been adequately studied. We examined the prevalence of thyroid dysfunction and associations with cardiovascular outcomes in a large, prospective cohort of outpatients with preexisting heart failure. METHODS AND RESULTS:We examined associations between thyroid dysfunction and New York Heart Association class, atrial fibrillation, and a composite end point of ventricular assist device placement, heart transplantation, or death in 1365 participants with heart failure enrolled in the Penn Heart Failure Study. Mean age was 57 years, 35% were women, and the majority had New York Heart Association class II (45%) or III (32%) symptoms. More severe heart failure was associated with higher thyroid-stimulating hormone (TSH), higher free thyroxine (FT4), and lower total triiodothyronine (TT3) concentrations ( P<0.001 all models). Atrial fibrillation was positively associated with higher levels of FT4 alone ( P?0.01 all models). There were 462 composite end points over a median 4.2 years of follow-up. In adjusted models, compared with euthyroidism, subclinical hypothyroidism (TSH 4.51-19.99 mIU/L with normal FT4) was associated with an increased risk of the composite end point overall (hazard ratio, 1.82; 95% CI, 1.27-2.61; P=0.001) and in the subgroup with TSH ?7.00 mIU/L (hazard ratio, 3.25; 95% CI, 1.96-5.39; P<0.001), but not in the subgroup with TSH 4.51-6.99 mIU/L (hazard ratio, 1.26; 95% CI, 0.78-2.06; P=0.34). Isolated low T3 was also associated with the composite end point (hazard ratio, 2.12; 95% CI, 1.65-2.72; P<0.001). CONCLUSIONS:In patients with preexisting heart failure, subclinical hypothyroidism with TSH ?7 mIU/L and isolated low T3 levels are associated with poor prognosis. Clinical trials are needed to explore therapeutic effects of T4 and T3 administration in heart failure.
| S-EPMC6352308 | biostudies-literature
Project description:AimsNo studies have comprehensively compared the efficacy of sodium-glucose cotransporter-2 (SGLT2) inhibitors, renin-angiotensin system (RAS) inhibitors, and angiotensin receptor neprilysin (ARN) inhibitors based on different type of heart failure, including heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). The aim of this network meta-analysis was to evaluate the relative efficacy of SGLT2 inhibitor (SGLT2i), RAS inhibitor (RASi) and ARN inhibitor (ARNI) in different types of heart failure.MethodsA systemic literature search was performed from inception to 19 November 2022 for randomized control trials assessing the risk of cardiovascular (CV) death or hospitalization for heart failure (HHF) of these drugs in HF. A network meta-analysis was performed. Risk ratio (RR) with 95% confidence intervals (CI) were synthesized.ResultsSeventeen studies were selected with a total of 61 489 patients. In patients with HFrEF, ARNI led to a reduced risk of a composite outcome of CV death or HHF when compared with placebo (RR = 0.83, 95% CI 0.77-0.89). Similar trends were observed when focusing on the outcome of CV death or HHF alone. In patients with HFpEF, SGLT2i showed the beneficial effects on the CV death or HHF events when compared with placebo and RASi (RR = 0.82, 95% CI 0.74-0.92; RR = 1.16, 95% CI 1.02-1.31). For CV death, all these three drugs could not show beneficial effects in HFpEF. For the incidence of HHF in HFpEF, both SGLT2i and ARNI demonstrated the beneficial effects but SGLT2i was superior to ARNI. There were no differences in the events of discontinuation under these drugs when compared with placebo or each other in either HFrEF or HFpEF patients. SGLT2i showed the least renal injury among these interventions in HFrEF and there were no differences in the incidence of renal injury of these interventions in HFpEF.ConclusionsAmong these drugs, ARNI showed the greatest ability to lower the incidence of CV death or HHF and SGLT2i exerted the least renal injury in patients with HFrEF. In patients with HFpEF, SGLT2i was associated with a reduction in the risk of CV death or HHF. There were no differences in the incidence of renal injury of these interventions in HFpEF. The intolerance of these drugs were comparable in both HFrEF and HFpEF.
| S-EPMC10053170 | biostudies-literature
Project description:BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the composite of heart failure (HF) hospitalizations or cardiovascular mortality among patients with HF. However, the efficacy of SGLT2 inhibitors in secondary endpoints of randomized trials and in subgroups of HF patients is not well known.MethodsWe performed a systematic review and meta-analysis of placebo-controlled, randomized trials of SGLT2 inhibitors in patients with HF. PubMed, Embase, and Cochrane databases were searched for trials published up to January 21, 2021. Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Hazard ratios (HRs) with 95% CI were pooled across trials. The primary endpoints of interest were all-cause and cardiovascular mortality.ResultsOut of 3969 database results, 15 randomized trials and 20,241 patients were included; 10,594 (52·3%) received SGLT2 inhibitors. All-cause mortality (HR 0·86; 95% CI 0·79-0·94; p = 0·0007; I2=0%) and cardiovascular mortality (HR 0·86; 95% CI 0·78-0·96; p = 0·006; I2=0%) were significantly lower in patients treated with SGLT2 inhibitors compared with placebo. The composite of cardiovascular mortality, HF hospitalizations, or urgent visits for HF was significantly reduced with SGLT2 inhibitors in all the following subgroups: male, female, age < 65, age ≥ 65, race - Black and White, estimated glomerular filtration rate (eGFR) <60, eGFR ≥60, New York Heart Association (NYHA) class II, NYHA ≥III, and HF with preserved ejection fraction.InterpretationIn patients with HF, SGLT2 inhibitors significantly reduce all-cause and cardiovascular mortality compared with placebo. In addition, the composite of cardiovascular mortality or HF hospitalizations/urgent visits is reduced with SGLT2 inhibitors across subgroups of sex, age, race, eGFR, HF functional class, and ejection fraction.
| S-EPMC8257984 | biostudies-literature
Project description:AimsThere is limited information on the association between left ventricular (LV) dimensions and cardiovascular (CV) outcomes in patients with heart failure (HF) with reduced LV ejection fraction (HFrEF) receiving recommended HF treatment. We investigated the association between LV dimensions and CV outcomes in HFrEF patients receiving recommended HF treatment.Methods and resultsWe investigated the association between LV echocardiographic dimensions and CV outcomes using conventional Cox models in 1138 HFrEF patients in sinus rhythm randomized to warfarin or aspirin treatment in the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial. LV enlargement, whether by diameter [LV end-diastolic diameter index (LVEDDI) and LV end-systolic diameter index (LVESDI)] or volume [LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI)], was independently associated with all-cause death [LVEDDI: hazard ratio (HR) per cm/m2 1.53, LVESDI: HR per cm/m2 1.65, LVEDVI: HR per 10 mL/m2 1.07, and LVESVI: HR per 10 mL/m2 1.10; all P values < 0.001], CV death (HR 1.68, 1.79, 1.09, and 1.12, respectively; all P values < 0.001), and HF hospitalization (HR 1.59, 1.79, 1.06, and 1.08, respectively; all P values < 0.001). No association was observed with myocardial infarction or stroke. The associations were independent of LV ejection fraction values, and incremental to them. LV volumes conferred additional predictive value over LV diameters.ConclusionsLeft ventricular enlargement is an independent predictor of CV events in patients with HFrEF and recommended HF treatment. LV dimensions should be considered in the risk assessment.
| S-EPMC8712869 | biostudies-literature
Project description:Background: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are an emerging class of glucose-lowering drugs that have become increasingly relevant for the treatment and prevention of heart failure (HF). Therefore, we aimed to investigate various SGLT2 inhibitors in patients with established HF at baseline and focused on the different types of HF. Methods: An extensive search of PubMed and Web of Science until January 2021 was done. Two reviewers, independently and in duplicate, applied the selection criteria. This meta-analysis was conducted according to the PRISMA guidelines. Data were pooled using a random-effects model. Randomized controlled trials (RCTs) of SGLT2 inhibitors vs. a comparator in patients with HF reporting clinical outcomes were included. The primary efficacy outcome was the composite of hospitalization for HF (HHF) or cardiovascular (CV) mortality. All-cause mortality, CV mortality, and HHF were considered as secondary endpoints. Subgroup analyses involving the status of diabetes, type of HF, administered type of SGLT2 inhibitor, sex, age, body mass index (BMI), estimated glomerular filtration rate (eGFR), cause of HF, and concomitant medication were performed. Results: Seventeen RCTs, comprising a total of 20,749 participants, were included (n = 10,848 treated with SGLT2 inhibitors and n = 9,901 treated with a comparator). Treatment with SGLT2 inhibitors in a HF population was associated with a 27% relative risk reduction (RRR) of HHF or CV mortality [risk ratio (RR) = 0.73, 95% CI = 0.68-0.78], 32% RRR of HHF (RR = 0.68, 95% CI = 0.62-074), 18% RRR of CV mortality (RR = 0.82, 95% CI = 0.73-0.91), and 17% RRR of all-cause mortality (RR = 0.83, 95% CI = 0.75-0.91). The effect of SGLT2 inhibitors on the primary endpoint was consistent among the different gliflozines. The effect of SGLT2 inhibitors on the primary endpoint was independent of underlying diabetes mellitus, age, sex, BMI, renal function, and HF type. Conclusions: SGLT2 inhibitors are associated with improved CV outcomes in patients with HF.
| S-EPMC8316592 | biostudies-literature
Project description:Sodium glucose contrasporter 2 inhibitors (SGLT2i) were initially introduced as a novel class of modestly effective antiglycemics. Over the last 5 years, multiple members of this class have been examined for their cardiovascular safety, effects on heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD) in diverse populations with or without diabetes type 2. The plethora of studies and outcomes examined make it difficult for the practitioner to track the entirety of the evidence. SGLT2i improve cardiorenal outcomes and have a beneficial risk benefit ratio across populations with cardiovascular disease, HFrEF and kidney disease. In this quantitative review, we synthesize the data from the large outcomes trials about the benefits and risks of SGLT2i. SGLT2i reduce all cause, cardiovascular mortality, heart failure hospitalizations, need for dialysis and acute kidney injury as a class effect across a broad range of populations with diabetes Type 2 at risk for cardiovascular disease, patients with HFrEF or CKD with or without diabetes. While certain adverse events for example, diabetic ketoacidosis and genital mycotic infections are reproducibly increased by SGLT2i, the absolute increase in the risk of these complications is smaller than the absolute risk reductions conferred by SGLT2i. Other complications such as amputations, fractures and urinary tract infections are increased to a lesser degree, or not at all (e.g., hypoglycemia). Overall, SGLT2is appear to have a favorable safety profile and thus should be used by cardiologists, nephrologists, endocrinologists, primary care physicians when managing the cardiorenal risk of their patients.
| S-EPMC7724239 | biostudies-literature
Project description:AimsWe sought to conduct a meta-analysis regarding the safety and efficacy of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with heart failure (HF).Methods and resultsMEDLINE, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched from their inception to November 2020 for placebo-controlled randomized controlled trials of SGLT2 inhibitors. Randomized controlled trials were selected if they reported at least one of the prespecified outcomes in patients with HF. Hazard ratios (HRs) or risk ratios and their corresponding 95% confidence intervals were pooled using a random-effects model. A total of seven trials including 16 820 HF patients (N = 8884 in the SGLT2 inhibitor arms; N = 7936 in the placebo arms) were included. In the overall HF cohort, SGLT2 inhibitors compared with placebo significantly reduced the risk of the composite endpoint of first HF hospitalization or cardiovascular death [HR: 0.77 (0.72-0.83); P < 0.001; I2 = 0%], time to first HF hospitalization [HR: 0.71 (0.64-0.78); P < 0.001; I2 = 0], cardiovascular mortality [HR: 0.87 (0.79-0.96); P = 0.005; I2 = 0%], and all-cause mortality [HR: 0.89 (0.82-0.96); P = 0.004; I2 = 0%]. Results remained consistent across HF-specific trials and according to diabetes mellitus status. A trend towards benefit was observed in patients with HF with preserved ejection fraction for the composite of HF hospitalization and cardiovascular death [HR: 0.80 (0.63-1.00); P = 0.05; I2 = 29%]. No increased risk of hypovolaemia, hyperkalaemia, and hypotension was seen with SGLT2 inhibitors compared with placebo.ConclusionsSGLT2 inhibitors significantly improve cardiovascular outcomes including cardiovascular and all-cause mortality in patients with HF without an increased risk of serious adverse events. A trend towards benefit was observed in patients with HF with preserved ejection fraction.
| S-EPMC7755023 | biostudies-literature
Project description:Type 2 diabetes is a debilitating disease that impacts the life expectancy, quality of life, and health of an individual. Cardiovascular disease (CVD) is a common diabetes-associated complication and a principal cause for death in diabetic patients. This review aims to investigate and summarize the effect of Type 2 diabetes mellitus (T2DM) medications on CVD issues. A comprehensive literature review mainly from level 1 evidence was performed. Thirty-seven articles were extracted from Google Scholar, ScienceDirect, ProQuest, and PubMed Database using a combination of keywords. The findings suggest that different glucose-lowering agents have been tested for their efficacy and safety in T2DM with CVD. Some of the recent trials such as the "United Kingdom Prospective Diabetes Study," "Empagliflozin (EMPA) Cardiovascular (CV) Outcome Event Trial in T2DM Patients-Removing Excess Glucose" (EMPA-REG OUTCOME), "Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results," and "Trial to Evaluate CV and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes" (SUSTAIN6) have shed important light on this vital clinical concern, thus demonstrating a convincing effect of liraglutide, semaglutide, and EMPA on CVD outcomes, while metformin is thought to be the first-line optimal oral agent to manage Type 2 diabetics. Some classes of drugs demonstrate CV protection, some of them may be a result of a class effect, and some differences might be based on the population enrolled individually. Most of the trials failed to show a significant benefit with regard to mortality and morbidity in spite of intensive glycemic control. This study, therefore, enabled us to develop a guide of potential antidiabetic medication that can influence or promote CV health. Health professionals in future should weigh the CV risk against possible advantages while prescribing antidiabetic medications.
| S-EPMC6124835 | biostudies-other