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Use of ACE Inhibitors in Patients with Type 2 Diabetes



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Am Fam Physician. 2000 May 1;61(9):2830-2832.

Angiotensin-converting enzyme (ACE) inhibitor therapy appears to be the most promising approach to slowing the development and progression of nephropathy in patients with type 2 diabetes (formerly known as non–insulin-dependent diabetes). Current recommendations for identifying early diabetic nephropathy by screening for microal-buminuria are not widely followed because the test is not uniformly available. Most screening involves testing for gross proteinuria with a dipstick or urinalysis. Many patients who might benefit from ACE inhibitor therapy do not receive it because some physicians are unaware of this clinical use for ACE inhibitors. Treating all patients with diabetes might be simpler, but the side effects associated with ACE inhibitors may affect compliance. Golan and associates created a decision model to evaluate the clinical outcomes and cost-effectiveness of three treatment strategies in patients with newly diagnosed type 2 diabetes mellitus: (1) treating all patients with ACE inhibitors; (2) screening for microalbuminuria and treating patients who have positive results, or (3) screening for gross proteinuria and treating patients who have positive results.

The target population included patients with newly diagnosed type 2 diabetes mellitus who were not taking ACE inhibitors. The starting age for patients in this base-case analysis was 50 years, which reflected the average age at diagnosis. Randomized trial data were used to model four health states in the progression of diabetic nephropathy, ranging from normoalbuminuria (albumin excretion less than 30 mg per day), to microalbuminuria (excretion of 30 to 300 mg per day), to gross proteinuria (excretion of more than 300 mg per day), and finally to end-state renal disease (ESRD). Initial analysis revealed that 79 percent of patients had normoalbuminuria, 18 percent had microalbuminuria and 3 percent had gross proteinuria. The analysis included only costs associated with ACE inhibitor therapy, screening or treatment of ESRD. Three outcomes were measured: average cost, life expectancy and quality-adjusted life expectancy.

In the analysis, the “treat all” strategy resulted in the lowest likelihood of ESRD or death and the highest likelihood of normoalbuminuria at 10 years. The “screen for gross proteinuria” strategy was the most expensive and had the least benefit. The “screening for microalbuminuria” strategy was the least expensive but offered a lower life expectancy. The marginal cost-effectiveness ratio (cost per additional quality-adjusted life years [QALY]) of the “treat all” strategy compared with the “screen for microalbuminuria” strategy was $7,500 per QALY gained. As patient age increased, so did the cost per QALY. The “treat all” strategy was clearly the least expensive and offered the highest benefit in patients younger than 44 years at diagnosis.

The authors conclude that adopting the “treat all” strategy would slow the progression to ESRD at a relatively low cost. The other strategies are associated with varying costs but are not as effective. Use of ACE inhibitors for the “treat all” strategy requires judicious monitoring of serum potassium levels and renal function. The authors also emphasize that the randomized trials on which much of these data were based used the older diagnostic criteria for diabetes (glucose level of greater than 140 mg per dL [greater than 7.8 mmol per L]). Therefore, the “treat all” strategy probably should not be extrapolated to patients whose diagnoses were based on the lower thresholds recommended by the American Diabetes Association.

Golan L, et al. The cost-effectiveness of treating all patients with type 2 diabetes with angiotensin-converting enzyme inhibitors. Ann Intern Med. November 2, 1999;131:660–7, and Cook DJ, Guyatt GH. Interpreting, integrating, and individualizing evidence about the prevention of diabetic nephropathy. Ann Intern Med. November 2, 1999;131:707–8.

editor's note:: In an editorial in the same journal, Cook and Guyatt note that a randomized trial assigning patients to one of the three strategies would be more accurate than an estimate based on evidence that may not be complete or accurate. Physicians with different perspectives and resources might come to different conclusions when presented with this evidence. Variations in patient age, anticipated quality of life and compliance might also influence individual decisions. Additional evidence, as well as a variety of other factors, must be considered before a conclusion is made about the right decision for any given situation.—r.s.

 

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