Background-Aldosterone (ALD) has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that ALD was extracted through the infarct heart and extracting ALD-stimulated post-infarct left ventricular (LV) remodeling. Methods and Results-To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct LV remodeling, 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (nϭ65) or non-MRA (nϭ69) groups after revascularization. All patients were administered angiotensinconverting enzyme (ACE) inhibitor and study drug just after revascularization. Left ventriculography with contrast medium was performed at the acute stage and after 1 month to evaluate LV remodeling. ALD was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and LV performance between the two groups. However, LV ejection fraction was significantly improved in the MRA group compared with that in the non-MRA group (46.0Ϯ0.6% to 53.2Ϯ0.8% versus 46.5Ϯ0.8% to 51.0Ϯ0.8%, P interaction ϭ0.012). LV end-diastolic volume index was significantly suppressed in the MRA group compared with that in non-MRA group (86.5Ϯ1.0 to 90.6Ϯ2.4 versus 87.5Ϯ1.3 to 106.8Ϯ3.5 mL/m 2 , P interaction ϭ0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (P interaction ϭ0.001), and plasma procollagen type III aminoterminal peptide level, a biochemical marker of fibrosis, was significant lower in the MRA group compared with the non-MRA group (P interaction ϭ0.002). Conclusions-These findings indicate that MRA combined with ACE inhibitor can prevent post-infarct LV remodeling better than ACE inhibitor alone in association with the suppression of a marker of collagen synthesis. (Circulation.

These results indicate that downregulation of ANP receptors coupled to guanylate cyclase may occur in the peripheral vascular beds of patients with chronic severe CHF.

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We conducted a multicenter prospective, randomized, double-blind, placebo-controlled trial to test whether pravastatin, a hydroxymethyl glutaryl coenzyme A reductase inhibitor, can decrease restenosis after percutaneous transluminal coronary angioplasty (PTCA). Pravastatin 10 mg twice daily was begun at least 10 days prior to elective PTCA in patients with total cholesterol less than 280 mg/dl. The end-point was a between-group comparison of the frequency of restenosis defined as a more than 50% loss of the initial gain in diameter stenosis at the PTCA site at 3 months during follow-up by automated quantitative coronary arteriography. Of 207 patients randomly assigned to study groups, 139 patients underwent PTCA; 133 procedures were successful, and 124 patients underwent follow-up angiography at 3 months, and 179 lesions (85 pravastatin, 94 placebo) in 124 patients (62 pravastatin, 62 placebo) were analyzed. The two groups were comparable for baseline characteristics. Total cholesterol decreased by 19.6% in the pravastatin group (p < 0.001) but not in the placebo group. Although the restenosis rate was not different in the two groups (29.4% in pravastatin vs. 39.4% in placebo, p = 0.215) as a whole, it was reduced to about one fifth (8.8%) in the pravastatin group compared with 44.8% in the placebo group (p = 0.0011) when the comparison was restricted to high grade lesions (> or = 75% diameter stenosis, 34 lesions in pravastatin, 29 lesions in placebo). Pravastatin thus reduces restenosis after PTCA of high grade lesions.