Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58

Background: Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular complications. The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduces the risk for hospitalization for heart failure (HHF) and kidney events in patients with type 2 diabetes mellitus. An increased risk of amputation has been observed with canagliflozin in 1 previous trial. We examined cardiovascular and kidney efficacy and the risk of limb-related events in patients with and without PAD in an exploratory analysis. Methods: A total of 17 160 patients with type 2 diabetes mellitus, including 1025 (6%) with PAD, were randomized. Key efficacy outcomes were MACE (cardiovascular [CV] death, myocardial infarction, stroke), CV death/HHF, and progression of kidney disease. Amputations, peripheral revascularization, and limb ischemic adverse events were site-reported and categorized by a blinded reviewer. Results: Patients in the placebo arm with PAD versus those without tended to have higher adjusted risk of CV death, myocardial infarction, or stroke (adjusted hazard ratio [HR], 1.23 [95% CI, 0.97–1.56], P =0.094) and significantly higher adjusted risk of CV death/HHF (adjusted HR, 1.60 [95% CI, 1.21–2.12], P =0.0010) and progression of kidney disease (adjusted HR, 1.51 [95% CI, 1.13 – 2.03], P =0.0058), and limb adverse events (adjusted HR, 8.37, P <0.001). The relative risk reductions with dapagliflozin for CV death/HHF (HR, 0.86, PAD; HR, 0.82, no-PAD; P -interaction=0.79) and progression of kidney disease (HR, 0.78, PAD; HR, 0.76, no-PAD; P -interaction=0.84) were consistent regardless of PAD. There were 560 patients who had at least 1 limb ischemic event, 454 patients with at least 1 peripheral revascularization, and 236 patients with at least 1 amputation, with a total of 407 amputations reported. Overall, there were no significant differences in any limb outcome with dapagliflozin versus placebo including limb ischemic adverse events (HR, 1.07 [95% CI, 0.90–1.26]) and amputation (HR, 1.09 [95% CI, 0.84–1.40]), with no significant interactions by a history of PAD versus not ( P -interactions=0.30 and 0.093, respectively). Conclusions: Patients with versus without PAD are at a higher risk of CV death of CV death, HHF, and kidney outcomes, and have a consistent benefits for CV death/HHF and progression of kidney disease with dapagliflozin. Patients with PAD had a higher risk of limb events, with no consistent pattern of incremental risk observed with dapagliflozin. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01730534.

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Clusterin, paraoxonase 1, and myeloperoxidase alterations induce high‐density lipoproteins dysfunction and contribute to peripheral artery disease; aggravation by type 2 diabetes mellitus

BioFactors ◽

10.1002/biof.1800 ◽

2021 ◽

Author(s):

Gabriela M. Sanda ◽

Laura Toma ◽

Teodora Barbalata ◽

Oriana E. Moraru ◽

Loredan S. Niculescu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Peripheral Artery Disease ◽

High Density ◽

Paraoxonase 1 ◽

High Density Lipoproteins ◽

Peripheral Artery ◽

Artery Disease

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Impact of diabetes type on treatment and outcome of patients with peripheral artery disease

Diabetes and Vascular Disease Research ◽

10.1177/1479164118793986 ◽

2018 ◽

Vol 15 (6) ◽

pp. 504-510 ◽

Cited By ~ 8

Author(s):

Lars Richter ◽

Eva Freisinger ◽

Florian Lüders ◽

Katrin Gebauer ◽

Matthias Meyborg ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Type 1 Diabetes Mellitus ◽

Peripheral Artery Disease ◽

Peripheral Artery ◽

Artery Disease

Background: The prevalence of diabetes mellitus and its associated complications such as peripheral artery disease is increasing worldwide. We aimed to explore the distinct impact of type 1 diabetes mellitus and type 2 diabetes mellitus on treatment and on short- and long-term outcome in patients with peripheral artery disease. Methods: Retrospective analysis of anonymized data of hospitalized patients covered by a large German health insurance. Assessment of patient’s characteristics (comorbidities, complications, etc.) and outcome using multivariable Cox regression and Kaplan–Meier curves. Results: Among 41,702 patients with peripheral artery disease, 339 (0.8%) had type 1 diabetes mellitus and 13,151 (31.5%) had type 2 diabetes mellitus. Patients with diabetes mellitus had more comorbidities and complications than patients without diabetes mellitus ( p < 0.001). Type 1 diabetes mellitus patients exhibited the highest risk for limb amputation at 4-year follow-up (44.6% vs 35.1%, p < 0.001), while type 2 diabetes mellitus patients had higher mortality than type 1 diabetes mellitus (43.6% vs 31.0%, p < 0.001). Conclusion: Although the fraction of type 1 diabetes mellitus among patients with peripheral artery disease and diabetes mellitus is low, it represents a subset of patients being at particular high risk for limb amputation. Research focused on elaborating the determinants of limb amputation and mortality in peripheral artery disease patients with diabetes mellitus is warranted to improve the poor prognosis of these patients.

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Single And Combined Effects Of Peripheral Artery Disease And Of Type 2 Diabetes Mellitus On The Risk Of Cardiovascular Events In Women

Atherosclerosis ◽

10.1016/j.atherosclerosis.2019.06.512 ◽

2019 ◽

Vol 287 ◽

pp. e169

Author(s):

C.H. Saely ◽

M. Schindewolf ◽

A. Vonbank ◽

C. Heinzle ◽

D. Purin ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Peripheral Artery Disease ◽

Cardiovascular Events ◽

Combined Effects ◽

Peripheral Artery ◽

Artery Disease

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P0751METFORMIN, A CLASSIC TREATMENT FOR TYPE 2 DIABETES WITH POSSIBLE RENOPROTECTIVE EFFECTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0751 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Adriana Acosta Barrios ◽

Marian Goicoechea ◽

Eduardo Verde ◽

Ángela González-Rojas ◽

Andres Delgado ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Kidney Disease ◽

Experimental Studies ◽

Diabetic Patients ◽

Metformin Treatment ◽

End Point ◽

Progression Of Kidney Disease

Abstract Background and Aims Metformin is the antidiabetic of choice in patients with type 2 diabetes mellitus. Experimental studies and clinical observations have shown that metformin could have a beneficial effect on the progression of kidney disease through the activation of cAMP due to its anti-inflammatory, antifibrotic, and anti-oxidative action. The objective was to compare the progression of CKD in diabetic patients with or without metformin as antidiabetic in their treatment and the prevalence of cardiovascular events in both groups. Method Unicentric retrospective observational analysis. Inclusion criteria: outpatients seen in nephrology consultation during the year of 2012 with diabetes mellitus and stage 3 CKD. Renal, cardiovascular outcomes and mortality were analyzed between patients treated with / without metformin. Median follow-up of 76.5 months (41-84). Renal end-point: estimated glomerular filtration rate drop (MDRD-4) by 50% and / or start of dialysis program. Cardiovascular end-point: ischemic heart disease, stroke, arterial revascularization and / or amputation. Cardiovascular or any cause mortality. Results 148 patients (96M, 52W) with a mean age of 75±9 years and an eGFR of 40±9 ml / min / 1.73 m2 were included. In relation to hypoglycemic therapy: 45 received metformin, 61 insulin and 31 DPP4i. 80% received treatment with RAAS blockers. After the follow-up, the progression of the renal disease was greater in patients who did not receive metformin: eGFR fall of -7.0±16 vs -0.15±16 ml / min in those treated with metformin (p = 0.019). 25 patients in the group without metformin suffered a renal event vs. 5 in the metformin group (logRank: 4.186, p = 0.045). In the Cox analysis, metformin treatment decreases the progression of kidney disease in a model adjusted for baseline renal function and treatment with RAASB (HR 0.368, p = 0.043), losing its predictive power in a proteinuria-adjusted model. During the follow-up, 45 patients died (20 metformin, 25 non-metformin) and 45 patients suffered a cardiovascular event (15 metformin, 30 non-metformin), with no differences between the two groups. Conclusion Metformin treatment in patients with stage 3 CKD could slow the progression of CKD, this effect should be demonstrated in randomized studies with larger sample size.

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