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RENIN-ANGIOTENSIN SYSTEM INHIBITORS
ACE Inhibitors & ARBs

Antihypertensive medications with well-established benefits in slowing the progression of chronic kidney disease (CKD) are renin-angiotensin system inhibitors, either ACE inhibitors (angiotensin-converting enzyme inhibitors) or ARBs (angiotensin receptor blockers).

This was demonstrated around the year 2001 through randomized controlled trials (RCTs) with medications such as losartan, among others.

STUDY DETAILS

Title: Effects of Losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy [see Ref. 1].

Year of Publication: 2001

Journal: The New England Journal of Medicine

Study type: randomized, double-blind study comparing losartan (50 to 100 mg once daily) with placebo. In the losartan group, 71% of patients received 100 mg per day.

Sponsored by: Merck and Company

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Number of Patients: 1,513 (751 in the losartan group and 762 in the placebo group)

Evaluation Period: Average of 3.4 years (range: 2.3 to 4.6 years)

Inclusion Criteria: Patients with type 2 diabetes and nephropathy

Exclusion Criteria: Diagnosis of type 1 diabetes or non-diabetic kidney disease

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Patient Characteristics:

  • Average age: 60 years (range: 31 to 70 years)

  • Losartan group: 61.5% men, 38.5% women  |  Placebo group: 64.8% men, 35.2% women

  • Baseline serum creatinine: 1.3 to 3 mg/dL (average: 1.9 mg/dL)

RESULTS

In the losartan group, 327 of 751 patients (43.5%) reached the primary composite endpoint, compared to 359 of 762 patients (47.1%) in the placebo group. This represents a 16% risk reduction with losartan for:

  1. Doubling of serum creatinine concentration

  2. End-stage renal disease

  3. Death

 

In other words, the losartan group experienced 15.9 events per 100 patients per year of follow-up, compared to 18.1 events in the placebo group.

 

More specifically:

  • Losartan reduced the risk of doubling serum creatinine by 25% (7.9 vs. 10 events per 100 patients per year)

  • It reduced the risk of end-stage renal disease by 28% (6.8 vs. 9.1 events per 100 patients per year)

The article concludes that this reduction corresponds to an average delay of 2 years in the need for dialysis or kidney transplantation.

Additionally, the losartan group showed a 35% reduction in proteinuria.

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eGFR Findings

The losartan group had an average eGFR annual decline of 4.4 ml/min/1.73 m², compared to 5.2 ml/min/1.73 m² in the placebo group.

Cited References

  1. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861-869. https://www.nejm.org/doi/full/10.1056/NEJMoa011161

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