September 5, 2014Circulation
Heart Failure, Saxagliptin, and Diabetes Mellitus: Observations from the SAVOR-TIMI 53 Randomized Trial
Why the study?
Does saxagliptin reduce the composite of cardiovascular death, myocardial infarction, or ischemic stroke in patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events?
Population
16,492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events
Comparison
Saxagliptin vs Placebo
Design
RCT, randomized
Follow-up
mean 2.1 years
Authors
Discussion
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Implication
Saxagliptin increases heart failure hospitalization risk in high-CV-risk type 2 diabetes; challenges DPP-4 inhibitor safety assumptions and warrants avoidance in prior heart failure.
Key Points
- To prospectively determine the effect of the DPP-4 inhibitor saxagliptin on the incidence of hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk.
- Randomized, placebo-controlled trial assigning 16,492 patients with type 2 diabetes and established cardiovascular disease or multiple risk factors to saxagliptin or placebo over a mean follow-up of 2.1 years (NCT01107886).
- Assessed hospitalization for heart failure as a predefined secondary end point component and measured baseline N-terminal pro B-type natriuretic peptide (NT-proBNP) in 12,301 participants.
- Hospitalization for heart failure occurred in 289 patients (3.5%) receiving saxagliptin compared with 228 patients (2.8%) receiving placebo (HR 1.27; 95% CI, 1.07–1.51; P=0.007).
- Heart failure hospitalization rates at 12 months were 1.9% with saxagliptin versus 1.3% with placebo (HR 1.46; 95% CI, 1.15–1.88; P=0.002), with no significant difference observed beyond 12 months (time-varying interaction P=0.017).
- The absolute excess risk was greatest among patients with preexisting heart failure, estimated glomerular filtration rate ≤60 mL/min, or baseline NT-proBNP in the highest quartile (2.1% excess).
Structured PICO
Does saxagliptin reduce the composite of cardiovascular death, myocardial infarction, or ischemic stroke in patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events?
P
Population
16,492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events
I
Intervention
Saxagliptin
C
Comparator
Placebo
O
Outcome
Composite of cardiovascular death, myocardial infarction, or ischemic strokecomposite
In patients with type 2 diabetes at high cardiovascular risk, saxagliptin increased the risk of heart failure hospitalization, especially among those with prior heart failure, chronic kidney disease, or elevated NT-proBNP.
Cite This Study
Scirica et al. (2014) studied this question.