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Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58.
- Source :
-
Circulation . 8/25/2020, Vol. 142 Issue 8, p734-747. 14p. - Publication Year :
- 2020
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Abstract
- <bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *ANKLE brachial index
*PERIPHERAL vascular diseases
*SODIUM-glucose cotransporter 2 inhibitors
*DAPAGLIFLOZIN
*TYPE 2 diabetes
*KIDNEYS
*STROKE prevention
*STROKE-related mortality
*KIDNEY disease prevention
*BENZENE
*RESEARCH
*STROKE
*EXTREMITIES (Anatomy)
*RESEARCH methodology
*MYOCARDIAL infarction
*GLYCOSIDES
*MEDICAL cooperation
*EVALUATION research
*KIDNEY diseases
*COMPARATIVE studies
*RANDOMIZED controlled trials
MYOCARDIAL infarction-related mortality
Subjects
Details
- Language :
- English
- ISSN :
- 00097322
- Volume :
- 142
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 145300096
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.119.044775