What question did this study set out to answer?

To determine whether combining an ACE inhibitor with an ARB safely slows the progression of kidney disease and reduces mortality in patients with diabetic nephropathy.

November 9, 2013New England Journal of Medicine

Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy

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Why the study?

Does combination therapy with lisinopril and losartan reduce the progression of kidney disease or death in patients with type 2 diabetes and diabetic nephropathy?

Key Points

To determine whether combining an ACE inhibitor with an ARB safely slows the progression of kidney disease and reduces mortality in patients with diabetic nephropathy.
Randomized double-blind clinical trial (VA NEPHRON-D, NCT00555217) involving 1448 patients with type 2 diabetes, urinary albumin-to-creatinine ratio ≥300 mg/g, and eGFR 30.0–89.9 ml/min/1.73 m².
All patients received background losartan (100 mg/day) and were randomly assigned to receive lisinopril (10–40 mg/day) or placebo, with a median follow-up of 2.2 years before early study termination.
Combination therapy did not significantly reduce the primary composite endpoint of eGFR decline, ESRD, or death compared to monotherapy (132 vs. 152 events; HR 0.88, 95% CI 0.70 to 1.12; P=0.30) or all-cause mortality (HR 1.04, 95% CI 0.73 to 1.49; P=0.75).
Combination therapy significantly increased the incidence of hyperkalemia (6.3 vs. 2.6 events per 100 person-years; P<0.001) and acute kidney injury (12.2 vs. 6.7 events per 100 person-years; P<0.001).

Structured PICO

Does combination therapy with lisinopril and losartan reduce the progression of kidney disease or death in patients with type 2 diabetes and diabetic nephropathy?

Population

1448 patients with type 2 diabetes, a urinary albumin-to-creatinine ratio of at least 300 mg/g, and an estimated glomerular filtration rate (eGFR) of 30.0 to 89.9 ml/min/1.73m²

Intervention

Lisinopril (10 to 40 mg per day) added to background losartan (100 mg per day)

Comparator

Placebo added to background losartan (100 mg per day)

Outcome

First occurrence of a change in the estimated GFR (a decline of ≥ 30 ml/min/1.73m² if the initial estimated GFR was ≥ 60 ml/min/1.73m² or a decline of ≥ 50% if the initial estimated GFR was <60 ml/min/1.73m²), end-stage renal disease (ESRD), or deathcomposite

Combination therapy with an ACE inhibitor and an ARB in patients with diabetic nephropathy does not improve renal outcomes or survival but significantly increases the risk of hyperkalemia and acute kidney injury.

Limitations

Study was stopped early owing to safety concerns

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Avoid ACEi/ARB combination in diabetic nephropathy due to net harm; confirms no renal or survival benefit from dual blockade.

Cite This Study

Fried et al. (2013) studied this question.

synapsesocial.com/papers/69dff8f7ca6b6a2615860919 https://doi.org/10.1056/nejmoa1303154

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Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy

Key Points

Structured PICO

Limitations

Discussion

Implication

Cite This Study

Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy

Key Points

Structured PICO

Limitations

Discussion

Implication

Cite This Study

Also Consider

Also Consider