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Issue 91 Item 13 Why ACE inhibitors Remain Central to Management of Type 2 Diabe

Feb 12, 2002

In addition to hypoglycemia and antihyperten­sive agents—particularly ACE inhibi­tors—-play a central role in the man­agement of type 2 diabetes.   As a recent review of the subject points out, ACE inhibitors have earned this status not only because of their demonstrated potent antihypertensive properties but also because of reported protective effects on the kid­ney and heart, and to a lesser extent, on the eye and peripheral nerves. Moreover, cost-effectiveness studies indicate that these drugs provide such benefits at considerable indirect costs.

The reviewers noted that the best clinical evidence of ACE Inhibitor nephro-protection is exemplified by a 1993 report from the Cooperative Study Group showing that captopril reduced the risk of death, dialysis, or renal transplantation by 80%, com­pared with placebo, and more recently by the MICRO-HOPE Investigators, who reported a 24% reduction in the risk of overt nephropathy with ramipril, also compared with placebo, in addi­tion, the 1999 DIAB1OPSIES study showed that proteinuna increased in patients given a placebo but de­creased In those treated with perindo­pril; morphometric analysis revealed that cortical interstitial fractional volume Increased significantly in the placebo group but remain unchanged in the perlndopril group. 
ACE inhibitors, the reviewers pointed out, have not only markedly reduced the cardiovascular mortality in patients with diabetes but also reduced the incidence of heart failure and other cardiac events—with the same or better efficacy. Compared with beta-blockers or diuretics, and sometimes with better compliance. In the HOPE data, ramipril treatment was shown to reduce the risks of myocardial infarction, stroke, cardio­vascular death, and coronary revascularization by 22%, 33%. 37%, and 17%, respectively. These risk reductions were not accounted for by the 2 to 3 mm Hg fall in blood pressure produced by ramipril. 

As for the eye, progression of diabetic retinopathy in the EUCLID study (1997) was slowed by 50% in lisinopril-treated patients compared with placebo-treated patients, and MICRO-HOPE data showed a 16% reduction in the likelihood of laser therapy in ramipril-treated patients, even though the study was not designed to examine retinopathy. 

Finally, improved nerve conduc­tion velocity was noted in one 1996 study after 12 weeks of lisinopril therapy and after 12 months of tran­dolapril therapy In a 1995 study. 

The reviewers noted that contin­ued improvements in the use or ACE inhibitors will require studies involving various unexamined issues, includiung comparison of results in patients with the same risk factors, particularly hereditary cardiovascular risk factors, and head-to-head comparisons of different ACE inhibitors and of ACE inhibitors and other agents, such as angiotensin II receptor blockers. 
Cordonniar DJ et el. Role of ACE inhibitors in patients with diabetes. Drugs.