Cochrane for Clinicians

Putting Evidence into Practice

ACE Inhibitors vs. ARBs for Patients with Diabetic Kidney Disease

JUSTIN BAILEY, CAPT, USAF, MC, David Grant Medical Center
Family Practice Residency Program, Travis Air Force Base, California

The Cochrane Abstract on the next page is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Dr. Bailey presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a critique of the review. The practice recommendations in this activity are available at http://www.cochrane.org/reviews /en/ab006257.html.

Clinical Scenario

A 57-year-old man presents with hypertension, diabetes, and early-stage diabetic kidney disease. His serum creatinine level is 1.6 mg per dL (140 µmol per L), and his blood pressure is in the 140s/80s mm Hg. An antihypertensive needs to be selected for this patient.

Clinical Question

Are angiotensin-converting enzyme (ACE) inhibitors or angiotensin-II receptor blockers (ARBs) better for all-cause mortality reduction and renal protection in patients with diabetic kidney disease?

Evidence-Based Answer

Studies comparing ACE inhibitors or ARBs with placebo found no mortality benefit in patients with diabetic kidney disease. A subgroup analysis of five studies (2,034 total patients) found that, when given at full or maximally tolerated doses, ACE inhibitors reduce all-cause mortality (relative risk = 0.78, 95% confidence interval, 0.61 to 0.98). Both classes of drugs are similarly effective at preventing the progression of diabetic kidney disease. However, there were too few trials comparing ACE inhibitors with ARBs to draw clear conclusions.1

Practice Pointers

Within two to three decades of diagnosis, roughly one third of patients with diabetes will have some degree of diabetic kidney disease.2 Patients with diabetic nephropathy are at a higher risk of mortality, mostly from cardiovascular complications, than other patients with diabetes.3 Drugs used to delay the progression of diabetic kidney disease include beta blockers, calcium channel blockers, diuretics, ACE inhibitors, and ARBs. Studies have shown that after a patient develops diabetic kidney disease, ACE inhibitors and ARBs are superior to the other drugs in reducing disease progression, making them the drugs of choice.4 The Cochrane review confirms this conclusion. Although the overall analysis did not find that ACE inhibitors and ARBs reduce mortality compared with placebo, a subgroup analysis found that full doses or maximally tolerated doses of ACE inhibitors had mortality benefit.

Progression to end-stage kidney disease is also an important clinical outcome for patients with diabetic kidney disease. ACE inhibitors reduced the incidence of end-stage renal disease by 40 percent, and ARBs reduced this progression by 22 percent. However, the absolute benefit was small (1.5 versus 0.8 percent over approximately one year; number needed to treat = 160). Both drug classes reduced the risk of disease-oriented renal outcomes such as doubling of creatinine concentration and progression of micro- to macroalbuminuria. Both classes also increased rates of regression from micro- to normoalbuminuria, with ACE inhibitors somewhat more effective than ARBs in placebo-controlled trials. Although these results suggest that ACE inhibitors are more effective than ARBs at reducing the progression of diabetic kidney disease, there are insufficient data directly comparing ACE inhibitors with ARBs.

Although this review found a mortality benefit with full doses or maximally tolerated doses of ACE inhibitors in patients with diabetic kidney disease, there were weaknesses in the included studies: suboptimal allocation concealment, incomplete blinding, and significant loss to follow-up. In addition, there is a risk of "data dredging" with subgroup analysis (i.e., if enough subgroup analyses are performed, some would be significant by chance alone).

Address correspondence to Justin Bailey, MD, at justinbailey2@hotmail.com. Reprints are not available from the author.

The opinions and assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the U.S. Air Force Medical Department or the U.S. Air Force Service at large.

Author disclosure. Nothing to disclose.

REFERENCES

1. Strippoli GF, Bonifati C, Craig M, Navaneethan SD, Craig JC. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev 2006(4):CD006257.

2. Ritz E, Orth SR. Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med 1999;341:1127-33.

3. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. Arch Intern Med 1997;157:1413-8.

4. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al., for the National High Blood Pressure Education Program Committee. The Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report [Published correction appears in JAMA 2003;290:197]. JAMA 2003;289:2560-72.

Cochrane Brief

Exercise for Older Patients Who Are Acutely Hospitalized

Clinical Question

What are the effects of exercise interventions for patients older than 65 years who are acutely hospitalized?

Evidence-Based Answer

The effects of exercise interventions on functional outcomes are unclear, but there is a trend toward functional improvement. Multidisciplinary interventions that include exercise also show several other benefits, including reduction in length of hospitalization and hospital costs; these benefits have not been shown with exercise-only interventions, however.

Practice Pointers

Older adults experience declines in physical strength, mobility, and functioning during and after acute hospitalization.1 Exercise training can improve functional outcomes in these patients.2

In this Cochrane review, the authors searched for studies evaluating the effectiveness of inpatient exercise programs for older patients admitted to the hospital with general medical problems. Nine studies with 4,223 total patients were included. Patients in specialized stroke, intensive care, or rehabilitation units or those with primarily orthopedic diagnoses were excluded. Interventions were started within three days of admission and were compared with usual hospital care. The exercise interventions ranged from increased physical activity to individually tailored walking and strengthening programs.

The review found that older patients benefited from a multidisciplinary intervention program that incorporated exercise. The benefits included a decrease in hospital costs of about $300 per hospital stay, an average one-day reduction in length of hospitalization, and a 6 percent increase in the proportion of patients discharged to home rather than to a nursing home or other facility (number needed to treat = 16). It is important to note that exercise-only programs did not demonstrate these outcomes. In addition, the exercise portion of the multidisciplinary interventions was not explained in detail, thus limiting the practical implication of the studies. The authors conclude that the benefits may be from the multidisciplinary effort rather than the exercise itself.

These data support including exercise in multidisciplinary programs initiated as early as hospital admission and continuing until discharge. Multidisciplinary programs generally include individually designed patient exercise plans, a specialized geriatric inpatient unit, and evaluation and treatment by physical and occupational therapists and a physician or nurse trained as a geriatrician. Small but important clinical outcomes can be expected with this multidisciplinary approach.

SUZANNE MEYER, MD

Source: de Morton NA, Keating JL, Jeffs K. Exercise for acutely hospitalised older medical patients. Cochrane Database Syst Rev 2007(1):CD005955.

Author disclosure: Nothing to disclose.

REFERENCES

1. Hirsch CH, Sommers L, Olsen A, Mullen L, Winograd CH. The natural history of functional morbidity in hospitalized older patients. J Am Geriatr Soc 1990;38:1296-303.

2. Gillespie LD, Gillespie WJ, Robertson MC, Lamb SE, Cumming RG, Rowe BH. Interventions for preventing falls in elderly people. Cochrane Database Syst Rev 2003(4):CD000340.

This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). See Clinical Quiz on page 29.

The series coordinator for AFP is Clarissa Kripke, MD, Department of Family and Community Medicine, University of California, San Francisco.

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