Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Enalapril delayed end-stage renal failure in patients with chronic renal failure and hypertension

ACP J Club. 1995 Jan-Feb;122:2. doi:10.7326/ACPJC-1995-122-1-002


Source Citation

Hannedouche T, Landais P, Goldfarb B, et al. Randomised controlled trial of enalapril and β blockers in non-diabetic chronic renal failure. BMJ. 1994 Oct 1;309:833-7.


Abstract

Objective

To compare the effectiveness of enalapril with that of β-blockers in slowing the progression to end-stage renal failure in patients with chronic renal failure and hypertension but without diabetes.

Design

Randomized controlled trial with 3-year follow-up.

Setting

Outpatient departments of 6 hospitals in France.

Patients

100 patients (mean age 51 y, 53% men) with hypertension and chronic renal failure as defined by a serum creatinine concentration of 200 to 400 µmol/L. Exclusion criteria were diabetes; nephrotic syndrome; systemic diseases; malignant and renovascular hypertension; evolving obstructive nephropathy; serious disorders including malignancy, heart failure, and coronary artery disease; pregnancy or breast-feeding; receipt of angiotensin-converting enzyme (ACE) inhibitors in the previous 3 months; or contraindication to ACE inhibitors or β-blockers. 7 patients were lost to follow-up in the enalapril group and 4 in the β-blocker group.

Intervention

After a 1-month run-in period off antihypertensive drugs, 52 patients were allocated to enalapril, 5 to 10 mg/d, and 48 patients were allocated to β-blockers; acebutolol, 400 mg/d; or atenolol, 100 mg/d. If at 3 months diastolic blood pressure (BP) was not < 90 mm Hg, furosemide, 20 to 120 mg/d, was added. Then, if necessary, a calcium antagonist (nifedipine or nicardipine) or a central acting drug (methyldopa or clonidine) was added.

Main outcome measures

Progression to end-stage renal failure, and BP.

Main results

Analysis was by intention to treat. The progression to end-stage renal failure was 19% in the enalapril group compared with 35% in the β-blocker group. After adjusting for BP and the other treatment, the relative risk reduction for end-stage renal failure with enalapril treatment was 71% (Table). The cumulative renal survival rate was better with enalapril than with β-blockers (P < 0.05). No differences in BP were seen at any point during the follow-up between the 2 groups. 2 patients (4%) in the enalapril group were withdrawn because of hyperkalemia.

Conclusion

Enalapril slowed the rate of progression to end-stage renal failure in patients with chronic renal failure and hypertension but without diabetes.

Source of funding: Merck, Sharp and Dohme.

For article reprint: Not available.


Table. Enalapril vs β-blockers in patients with chronic renal failure and hypertension but without diabetes*

Outcomes at 3 y Enalapril β-blockers Adjusted RRR (95% CI)† NNT (CI)
End-stage renal failure 19% 35% 71% (33 to 87) 4 (3 to 8)

*Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.
†RRR was adjusted for blood pressure and other treatment.


Commentary

The treatment of systemic hypertension effectively delays the progression of most renal diseases. One class of anti-hypertensive drugs, ACE inhibitors, may be of special benefit because of their specific renoprotective effects (1). There is a dearth of clinical data comparing ACE inhibitors with conventional antihypertensive agents in nondiabetic renal disease.

This well-designed study by Hannedouche and colleagues provides support for the superiority of ACE inhibitors over β-blockers in delaying progression to end-stage renal disease. Although the study was unblinded and the primary end point was the development of end-stage renal disease (the timing of which may be subjective), the conclusions appear valid. The serum creatinine level was actually lower in the enalapril group at the time dialysis was initiated, allaying some concern about bias.

The patients in this study had renal diseases of varying causes. Although most renal diseases may follow a final common pathogenic pathway (perhaps related to intraglomerular hypertension) (1), this may not be true of all renal diseases. In a disease with a different pathogenesis of progression, there may be no incremental benefit in the use of an ACE inhibitor; further studies in individual renal diseases may be needed. Nonetheless, this and other recent studies (2) have added to a growing body of evidence showing that ACE inhibitors are associated with few adverse reactions and effectively delay progression in chronic renal diseases.

Steven Fishbane, MD
Winthrop University HospitalMineola, New York, USA


References

1. Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest. 1986;77: 1993-2000.

2. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group [published erratum appears in N Engl J Med. 1993;330:152]. N Engl J Med. 1993;329:1456-62.