Although there were greater diuresis with the high-dose strategy and more favorable outcomes in a few secondary measures, there was also transient worsening of renal function.248 6.7.2. ACE Inhibitors ACE inhibitors are thought to reduce the remodeling that occurs after MI,249 to improve ischemic preconditioning,250 to reverse angiotensin II induced vasoconstriction and inotropy, to prevent the depletion of high-energy phosphate stores, to enhance nitric oxide release through prevention of bradyki- and to reduce blood coagulability through the endothelial release of tissue plasminogen ACE inhibitors have been shown in many trials to be ben- eficial in patients with LV dysfunction of ischemic origin. The Trandolapril Cardiac Evaluation (TRACE) trial showed a 7% absolute reduction in mortality rate.206.253 In the Acute Infarction Ramipril Efficacy (AIRE) trial,205 ramipril adminis- tered 3 to 7 days after MI reduced the relative mortality risk by 27% in the total cohort, by 15% in normotensive subjects, and by 41% in hypertensive subjects, which supports the particu- lar importance of ACE inhibition in hypertensive patients with LV dysfunction in the post-MI period. In the Assessment of Treatment With Lisinopril and Survival (ATLAS) trial, mor- tality was significantly lower in patients with HF who received a high dose of lisinopril (32.5 35 mg/d) than in those treated with a low dose of lisinopril (2.5 5 mg/d).254 Among patients with diabetes mellitus or other cardiovascular complica- ACE inhibitors have been most notable with respect to a reduction in the onset of HF and new-onset diabetes mel- litus. However, the message has not impacted clinicians as well as it should; in the IMPROVE-HF registry, only 80% of eligible patients with LV dysfunction were prescribed an ACE inhibitor/ARB at baseline.211 6.7.3. 