What is the clinical evidence from this study?

Study design: Cohort. Population: Diabetes and Heart Failure with Preserved Ejection Fraction (HFpEF) (n=8466). Intervention: Insulin vs. Diabetes patients not on insulin. Primary outcome: Composite of cardiovascular death or HF hospitalization (aHR 1.41, 95% CI 1.23-1.63, p=< 0.001).

July 4, 2019Open Access

Insulin Treatment and Clinical Outcomes in Patients with Diabetes and Heart Failure with Preserved Ejection Fraction

Q: What are the key findings of this study?

Insulin use in diabetes and HFpEF was associated with a higher risk of cardiovascular death or HF hospitalization compared to other diabetes treatments (aHR 1.41; 95% CI 1.23-1.63; P<0.001).

Key Result

Insulin use in diabetes and HFpEF was associated with a higher risk of cardiovascular death or HF hospitalization compared to other diabetes treatments (aHR 1.41; 95% CI 1.23-1.63; P<0.001).

Study Design

Type

Cohort (n=8,466)

Multicenter

Yes

Structured PICO

Does insulin treatment increase the risk of cardiovascular death or HF hospitalization in patients with diabetes and HFpEF?

Population

8,466 patients with heart failure with preserved ejection fraction (LVEF ≥ 45%) pooled from CHARM-Preserved, I-Preserve, and TOPCAT (Americas) trials, including 2,653 (31%) with diabetes.

Intervention

Insulin treatment

Comparator

Patients with diabetes not receiving insulin, and patients without diabetes

Outcome

Composite of cardiovascular death or HF hospitalizationcomposite

In patients with HFpEF and diabetes, insulin use is observationally associated with a significantly higher risk of cardiovascular death or heart failure hospitalization compared to non-insulin treatments.

Main Result

Effect estimate: aHR 1.41 (95% CI 1.23-1.63)

Absolute Event Rate: 17.1% vs 10.2%

p-value: p=< 0.001

Limitations

Cannot conclude a causal association

Abstract

AIMS: Insulin causes sodium retention and hypoglycaemia and its use is associated with worse outcomes in heart failure (HF) with reduced ejection fraction. We have investigated whether this is also the case in HF with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We examined the association between diabetes/diabetes treatments and the risk of the primary composite of cardiovascular death or HF hospitalization, as well as other outcomes in adjusted analyses in CHARM-Preserved (left ventricular ejection fraction ≥ 45%), I-Preserve and TOPCAT (Americas) pooled. Of 8466 patients, 2653 (31%) had diabetes, including 979 (37%) receiving insulin. Patients receiving insulin were younger, had a higher body mass index, prevalence of ischaemic aetiology, N-terminal pro-B-type natriuretic peptide and use of diuretics, worse New York Heart Association class and signs and symptoms, and worse quality of life and renal function, compared to patients with diabetes not on insulin. Among the 1398 patients with echocardiographic data, insulin use was associated with higher left ventricular end-diastolic pressure and more diastolic dysfunction than in other participants. The primary outcome occurred at a rate of 6.3 per 100 patient-years in patients without diabetes, and 10.2 and 17.1 per 100 patient-years in diabetes patients without and with insulin use, respectively fully adjusted hazard ratio (aHR) insulin-treated diabetes vs. other diabetes: 1.41, 95% confidence interval (CI) 1.23-1.63, P < 0.001. The adjusted HR is 1.67 (95% CI 1.20-2.32, p = 0.002) for sudden death (insulin-treated diabetes vs. other diabetes). CONCLUSIONS: Insulin use is associated with poor outcomes in HFpEF. Although we cannot conclude a causal association, the safety of insulin and alternative glucose-lowering treatments in HF needs to be evaluated in clinical trials.