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Assistant Professor of Clinical Pharmacy Department of Pharmacy Practice and Pharmacy Administration Philadelphia College of Pharmacy University of the Sciences in Philadelphia 600 S. 43rd St. Philadelphia, PA 19104-4495 FAX 215/596-8586 E-mail e.vivian{at}usip.edu
Published Online, December 23, 2002. www.theannals.com, DOI
Brenner et al.2 evaluated the effects of losartan on renal and cardiovascular outcomes in 1513 type 2 diabetics with nephropathy. The primary composite endpoint of a doubling of the serum creatinine concentration, endstage renal disease, or death occurred in 43.5% (327) of patients treated with losartan, compared with 47.1% (359) of patients in the placebo treatment arm. Losartan also decreased the risk of endstage renal disease by 28% (p = 0.002).
Lewis et al.3 randomized 1715 hypertensive diabetic patients with nephropathy to 1 of 3 treatment arms: irbesartan, amlodipine, or placebo. Patients treated with irbesartan had a risk of reaching the primary point that was 20% lower than those in the placebo treatment arm (p = 0.02) and 23% lower than those in the amlodipine treatment arm (p = 0.006). Patients in the amlodipine group had poorer renal outcomes when compared with those taking irbesartan, although there was equal control of blood pressure in both groups.
The MARVEL (Microalbuminuria Reduction with Valsartan) study4 compared the effectiveness of valsartan with that of the calcium-channel blocker amlodipine in the reduction of UAE in 332 patients with type 2 diabetes mellitus and evidence of microalbuminuria. At the end of the 24-week study period, valsartan had a UAE reduction of 56% (95% CI 49.6% to 63.0%) from baseline that was a 44% reduction in UAE. Treatment with amlodipine resulted in a 92% (95% CI 81.7% to 103.7%) baseline reduction of UAE, an 8% reduction in UAE. No significant differences in blood pressure control between the groups were reported.
ARBs may play a role in attenuating the progression of diabetic nephropathy by reducing systemic blood pressure and slowing UAE. The American Diabetes Association (ADA)5 now recommends ARBs as initial agents of choice for hypertensive type 2 diabetic patients with microalbuminuria or clinical albuminuria. The ADA still supports the use of angiotensin-converting enzyme (ACE) inhibitors as first-line treatment for normotensive and hypertensive type 1 diabetic patients with evidence of microalbuminuria or clinical albuminuria.
It is reasonable to postulate that interruption of the renin–angiotensin system is a key factor in attenuating the progression of nephropathy. However, we cannot conclude that ACE inhibitors and ARBs are equivalent in the treatment of nephropathy in patients with type 2 diabetes, due to the complex pharmacologic activity of these agents. Until there are long-term studies that directly compare ARBs with ACE inhibitors in these patients, the use of both agents in normotensive as well as hypertensive type 2 diabetics with microalbuminuria or clinical albuminuria is warranted. Since the dihydropyridine calcium-channel blockers may have detrimental effects in some patients, these agents should be used with caution in patients at risk of developing diabetic nephropathy when other options are available.
References
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