Functional Evaluation of Lipid-Lowering Therapy by Pravastatin in the Regression Growth Evaluation Statin Study (REGRESS)

Abstract

Background Lipid-lowering therapy during 2 years in the Regression Growth Evaluation Statin Study (REGRESS) was associated with less progression of coronary atherosclerosis in the pravastatin group compared with the placebo group. The effect of lipid-lowering therapy on the functional state of the coronary circulation is less well known. The purpose of this study was to evaluate this effect. Methods and Results In a substudy of REGRESS, 69 patients were randomized to pravastatin or placebo. Thirty-seven of these patients were allocated to the medical management stratum. Quantitative coronary angiography, regional myocardial perfusion, exercise testing, and classification of angina pectoris were assessed at baseline and after 2 years of therapy. Regional myocardial perfusion was assessed by digital subtraction angiography after intracoronary papaverine with videodensitometric calculation of the hyperemic mean transit time (HMTT) of contrast. In the medical management stratum, regional myocardial perfusion was assessed in 31 regions in the pravastatin group and 25 regions in the placebo group. The change in HMTT in the pravastatin group was −0.18 seconds (−5%) and in the placebo group +0.52 seconds (+18%), a difference of 0.70 seconds ( P =.004). The mean difference in change in classification of angina pectoris (scale, 1 to 4) between pravastatin and placebo was 0.7 ( P =.03) in favor of the pravastatin-treated patients. The change in HMTT was correlated with the change in exercise time ( r =−.65, P =.002). Conclusions In patients with symptomatic coronary artery disease, treatment with the HMG-coenzyme A reductase inhibitor pravastatin during 2 years resulted in a preserved regional myocardial perfusion, whereas patients on placebo deteriorated. The classification of angina pectoris improved only in patients receiving pravastatin. In lipid-lowering therapy, the evaluation of myocardial perfusion by assessment of the HMTT reveals a combined measure of functional and structural changes in the coronary circulation.

Anti-Atherosclerotic Effects of Statins: Lessons from Prevention Trials

“…The Regression Growth Evaluation Statin Study (RE-GRESS) [31] was a randomized, placebo-controlled trial to examine the effect of pravastatin on progression of coronary atherosclerosis. Compared to placebo, there was less progression of coronary atherosclerosis in the pravastatin group, as assessed by quantitative coronary angiography, regional myocardial perfusion, exercise testing, and angina classification.…”

Long term outcome in patients with silent versus symptomatic ischaemia during dobutamine stress echocardiography

“…29 30 Also, statins have been shown to decrease transient myocardial ischaemia, probably due to improved endothelial function. 31 Furthermore, myocardial revascularisation was previously shown in a prospective study to be associated with decreased asymptomatic ischaemia and improved clinical outcome compared with angina or ischaemia guided strategy. 32 In the present study, the decision to perform coronary angiography was made on clinical grounds by the treating cardiologist.…”

Broad-Spectrum Chemokine Inhibition Reduces Vascular Macrophage Accumulation and Collagenolysis Consistent with Plaque Stabilization in Mice

“…Recent work suggests that lipid lowering therapy (for example, using statins) alters the composition of human atherosclerotic plaques, consistent with stabilization [30]. However, clinical studies suggest that statin therapy needs to be maintained for a long period of time (months and years) for these changes to occur [31]. Our results suggest that strategies based on inhibiting macrophage accumulation (such as through chemokine inhibition) could provide a complementary therapeutic tool which is able to induce rapid changes in plaque composition providing almost immediate reductions in the risk of myocardial infarction.…”