Heart failure and dipeptidyl peptidase‐4 inhibitors

Krum, Henry; Skiba, Marina; Wu, Shiying; Hopper, Ingrid

doi:10.1002/ejhf.90

Cited by 25 publications

(18 citation statements)

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“…However, significance was lost with sensitivity analysis looking only at trials at low risk of bias, so these findings should be interpreted with caution. In addition, there are no specific mechanistic reasons to attribute an increase in heart failure outcomes to the pharmacological properties of the DPP-4 inhibitors [68]. Indeed, among their many actions, these agents tend to augment circulating levels of glucagon-like peptide-1, which in itself has been shown to improve cardiac contractile function in the setting of systolic chronic heart failure [69].…”

Section: Discussionmentioning

confidence: 99%

“…However, as with all glucose-lowering agents, this class may cause hypoglycemia (particularly in combination with other hypoglycemic agents) which is associated with sympathetic activation, albeit short-term. Whether repeated episodes of hypoglycemia may contribute to deterioration in cardiac function and/or clinical heart failure is uncertain [68]. Moreover, an important component of the popularity of the DPP-4 inhibitors is the relatively low rates of hypoglycemia induced by their use.…”

Section: Discussionmentioning

confidence: 99%

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Dipeptidyl Peptidase‐4 Inhibitors and Cardiovascular Outcomes: Meta‐Analysis of Randomized Clinical Trials with 55,141 Participants

Hopper

Skiba

et al. 2014

Cardiovascular Therapeutics

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119

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Aims:The association between glucose lowering in diabetes mellitus and major cardiovascular (CV) outcomes is weak; indeed, some oral hypoglycemic agents are associated with increased CV events. Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are a new class of oral hypoglycemic agent that may have beneficial CV effects. We undertook a systematic review and meta-analysis to appraise the CV safety and efficacy of DPP-4 inhibitors. Methods: Comprehensive search for prospective trials involving DPP-4 inhibitors. Trials included reported at least one of the outcomes examined, recruited minimum 100 patients and minimum follow-up 24 weeks. The risk ratio (RR) was calculated using the MantelHaenszel random-effects model for mortality and major cardiovascular (CV) outcomes. Results: Fifty trials enrolling 55,141 participants were included. Mean follow-up 45.3 weeks. DPP-4 inhibitors compared with all comparators (placebo and active) showed no difference in all-cause mortality (n = 50,982, RR = 1.01, 95% CI 0.91-1.13, P = 0.83), CV mortality (n = 48,151, RR = 0.97, 95% CI 0.85-1.11, P = 0.70), acute coronary syndrome (ACS) (n = 53,034 RR = 0.97, 95% CI 0.87-1.08, P = 0.59), or stroke (n = 42,737, RR = 0.98, 95% CI 0.81-1.18, P = 0.80), and a statistically significant increase in heart failure outcomes (n = 39,953, RR = 1.16, 95% CI 1.01-1.33, P = 0.04). Discussion: Treatment with DPP-4 inhibitors compared with placebo shows no increase in risk with regards to all-cause mortality, CV mortality, ACS, or stroke, but a statistically significant trend toward increased risk of HF outcomes. Conclusion: These findings suggest no cardiovascular harm (or benefit) with DPP-4 inhibitors; further large-scale CV outcome studies will resolve the issue of excess HF risk.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase‐4 Inhibitors and Cardiovascular Outcomes: Meta‐Analysis of Randomized Clinical Trials with 55,141 Participants

Hopper

Skiba

et al. 2014

Cardiovascular Therapeutics

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119

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“…In the SAVOR-TIMI 53 (saxagliptin assessment of vascular outcomes recorded in patients with diabetes mellitus—thrombolysis in myocardial infarction 53) trial, patients taking saxagliptin were more likely to be hospitalized for heart failure (HF) than those in the placebo group (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.07–1.51). [4,5] In the EXAMINE (examination of cardiovascular outcomes with alogliptin versus standard of care) trial, patients taking alogliptin did not increase the risk of hospital admission for HF than those in the placebo group (HR, 1.07; 95% CI, 0.79–1.46). Alogliptin had no effect on composite events of cardiovascular death and hospital admissions for HF in the post hoc analysis (HR, 1.00; 95% CI, 0.82–1.21).…”

Section: Introductionmentioning

confidence: 99%

Comparative safety for cardiovascular outcomes of DPP-4 inhibitors versus glimepiride in patients with type 2 diabetes

et al. 2017

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Concerns about the cardiovascular safety of dipeptidyl peptidase-4 (DPP-4) inhibitors persist. This study sought to determine whether there is a differential risk of hospitalization for cardiovascular diseases (CVDs) between DPP-4 inhibitors and glimepiride.We conducted this retrospective cohort study by using the Korean National Health Insurance Service database from December 1, 2008, to December 31, 2013. The study subjects were new users of DPP-4 inhibitors or glimepiride for type 2 diabetes. Outcome was defined as hospitalization for CVDs, including angina pectoris, myocardial infarction, transient cerebral ischemic attack, heart failure, or cerebrovascular disease or any procedure involving coronary artery bypass grafting or percutaneous coronary intervention. We used a Cox proportional hazard model to estimate the adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs), to assess the risk of CVDs associated with the use of DPP-4 inhibitors compared with glimepiride.The cohort consisted of 1,045,975 patients, with 6504 in the DPP-4 inhibitors group and 13,447 in the glimepiride group. No significant increased risk of total CVDs was found (aHR, 0.87; 95% CI, 0.75–1.01) in the DPP-4 inhibitors versus glimepiride group. A decreased risk of hospitalization for CVDs was found among patients with a history of visit for CVDs (aHR, 0.73; 95% CI, 0.56–0.97) or with >2.5 years’ duration of type 2 diabetes (aHR, 0.77; 95% CI, 0.66–0.91) in the DPP-4 inhibitors versus glimepiride group.DPP-4 inhibitors did not increase cardiovascular risk compared with glimepiride regardless of CVD history and diabetes duration.

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“…DPP‐4 inhibition should direct BNP metabolism towards an increase in active BNP rather than biologically inactive BNP precursor fragments . There also seems to be interaction between DPP‐4 inhibitors and RAS inhibitors …”

Section: Discussionmentioning

confidence: 99%

Associations of dipeptidyl peptidase‐4 inhibitors with mortality in hospitalized heart failure patients with diabetes mellitus

et al. 2015

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BackgroundHeart failure (HF) and diabetes mellitus (DM) often co‐exist. Treatment of DM in HF patients is challenging because some therapies for DM are contraindicated in HF. Although previous experimental studies have reported that dipeptidyl peptidase‐4 (DPP‐4) inhibitors improve cardiovascular function, whether DPP‐4 inhibition improves mortality of HF patients with DM remains unclear. Therefore, we examined the impact of DPP‐4 inhibition on mortality in hospitalized HF patients using propensity score analyses.Methods and resultsWe performed observational study analysed by propensity score method with 962 hospitalized HF patients. Of these patients, 293 (30.5%) had DM, and 122 of these DM patients were treated with DPP‐4 inhibitors. Propensity scores for treatment with DPP‐4 inhibitors were estimated for each patient by logistic regression with clinically relevant baseline variables. The propensity‐matched 1:1 cohorts were assessed based on propensity scores (DPP‐4 inhibitors, n = 83, and non‐DPP‐4 inhibitors, n = 83). Kaplan–Meier analysis in the propensity score‐matched cohort demonstrated that cardiac and all‐cause mortality was significantly lower in the DPP‐4 inhibitor group than in the non‐DPP‐4 inhibitor group (cardiac mortality: 4.8% vs. 18.1%, P = 0.015; all‐cause mortality: 14.5% vs. 41.0%, P = 0.003, by a log‐rank test). In the multivariable Cox proportional hazard analyses, after adjusting for other potential confounding factors, the use of DPP‐4 inhibitors was an independent predictor of all‐cause mortality (pre‐matched cohort: hazard ratio 0.467, P = 0.010; post‐matched cohort: hazard ratio 0.370, P = 0.003) in HF patients with DM.ConclusionsOur data suggest that DPP‐4 inhibitors may improve cardiac and all‐cause mortality in hospitalized HF patients with DM.

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Heart failure and dipeptidyl peptidase‐4 inhibitors

Cited by 25 publications

References 18 publications

Dipeptidyl Peptidase‐4 Inhibitors and Cardiovascular Outcomes: Meta‐Analysis of Randomized Clinical Trials with 55,141 Participants

Dipeptidyl Peptidase‐4 Inhibitors and Cardiovascular Outcomes: Meta‐Analysis of Randomized Clinical Trials with 55,141 Participants

Comparative safety for cardiovascular outcomes of DPP-4 inhibitors versus glimepiride in patients with type 2 diabetes

Associations of dipeptidyl peptidase‐4 inhibitors with mortality in hospitalized heart failure patients with diabetes mellitus

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