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VA NEPHRON-D Trial: Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy


The VA NEPHRON-D trial tackled an important question about the combination therapy of ACEi and ARBs. We know from the RENAAL trial that losartan has significant benefits in diabetic nephropathy. The authors of the VA NEPHRON-D tiral aimed to assess if the addition of an ACE inhibitor to ARB therapy prevent eGFR reduction, ESRD, or death in patients with T2DM, CKD stage 2-3, and elevated urine albumin: creatinine. The trial included a reasonable number of 1448 patients who were randomized to losartan + placebo group and combination group of losartan and lisinopril. The trial was ended earlier due to inconclusive results. The authors of VA NEPHRON-D trial concluded that combination therapy with an ACE inhibitor and an ARB was associated with an increased risk of adverse events among patients with diabetic nephropathy. Source: NEJM

VALIANT Trial (2003): Valsartan, Captopril, or Both in Myocardial Infarction

VALIANT Trial Summary visual abstract

VALIANT Trial Summary: Pfeffer et al. randomized 14,703 patients with acute MI within prior 10 days complicated by HF and/or LVEF ≤35% to either valsartan or captopril or combination of both. The objective was to assess the efficacy of ARBs compared with ACE-I in patients in the post-MI period complicated by HF and/or LV systolic dysfunction. The results of the trial showed similar mortality rates among both ACE and ARB groups along with similar rates in combination of both.  The authors of the VALIANT trial concluded that Valsartan was as effective as captopril in improving survival among patients with HF and/or LV dysfunction in the post-MI period.

Source: NEJM

RENAAL Trial: Losartan in Patients with Type 2 Diabetes and Nephropathy

RENAAL Trial Visual Abstract

Source: NEJM

RENAAL Trial Key Points
1. Losartan was found to have significant reno-protective role in patients with type II diabetes and nephropathy.
2. Losartan did not affect mortality in this patient population.
3. Proteinuria significant improved in patients taking losartan compared to placebo.
4. The IDNT trial tested irbesartan and reported similar renoprotective role in diabetic nephropathy.

Guideline Recommendations based on RENAAL Trial:

The JNC8 guidelines recommend: In patients who are diabetic with high levels of albuminuria, the medication regimen should include an ACE inhibitor or an ARB alone or in combination with medication from another drug class for treatment of HTN.

The KDIGO guidelines recommend use of an ACE or an ARB and a BP goal <130/80 mmHg in all patients with CKD and albuminuria irrespective of diabetes status.


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