The GISSI-3 study examined the short-term effects of ACE inhibition when administered within 24 hours following an acute MI in a population of more than 18,000 patients, including 2790 patients who reported a history of diabetes (10). Retrospective analysis of results from this study revealed that ACE inhibitor treatment provided greater protective effects against 6-week mortality in diabetic patients compared with nondiabetics. The overall risk reduction by ACE inhibitor treatment for the diabetic group was 32%, compared with a risk reduction of 5% for nondiabetic patients. Within the diabetic group, ACE inhibitor treatment reduced mortality rates for both insulin-dependent (IDDM) and noninsulin-dependent diabetes mellitus (NIDDM) patients by 49% and 27%, respectively. Although this report indicates that the benefit of ACE inhibitor treatment in the diabetic group was greater than that for the nondiabetic group, the basis for this difference is unclear. Although the baseline characteristics for the treated and untreated groups were closely matched, the overall diabetic group appeared to have worse baseline characteristics than the nondiabetic group. The subgroup analyses performed in this report did not reveal an association between ACE inhibitor effects and baseline characteristics or physiological responses. Characterization of the diabetic population did not include measures of glycemic control, duration of diabetes, renal function, or for IDDM, classification of type 1 vs type 2 diabetes. Thus, although this provocative study suggests that the ACE inhibition provided selective protective effects for the diabetic subgroup, the absence of information regarding glycemic control and renal function among treated and placebo groups limit the interpretation of these results.
A retrospective analysis of data from the Trandolapril Cardiac Evaluation study compared the effects of ACE inhibitor therapy in diabetic and nondiabetic patients with left-ventricular dysfunction following acute MI. In this study, ACE inhibitor was given 3 to 7 days after acute MI with a mean follow-up time of 26 months. This study revealed that ACE inhibition reduced progression to severe heart failure in diabetic patients by nearly 40% compared with a nonsignificant effect in the nondiabetic group (11). ACE inhibitor treatment was associated with a trend for a greater relative risk reduction for cardiovascular and sudden death in the diabetic group compared with the nondiabetic group. As with the GISSI-3 study, the reason for the larger effects of ACE inhibitors for diabetics is unclear. Again, this could be related to worse baseline CVD in the diabetic group. Alternatively, differential responses for diabetic and nondiabetic groups may suggest that ACE inhibition normalizes or compensates for specific cardiovascular abnormalities associated with diabetes.
mechanisms of renin-angiotensin system-induced atherogenesis
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