Because of difficulties with quantitative measurement and with feasibility of follow-up, few controlled studies prior to SCRIP had been completed to determine the impact of risk factor modification directly on the progression of coronary atherosclerosis in humans. Suggestive evidence existed from animal studies, especially in primates, that diet and exercise altered atherosclerosis as a result of risk modification. But these animal models did not accurately represent the potential for modifying the coronary atherosclerotic process in humans. Some indirect evidence had been developed in humans by studying arteries more accessible than the coronaries. In the several preliminary studies reported using coronary arteriography to study the impact of risk modification on atherosclerosis, the results had been encouraging but far from definitive. One angiographic follow-up study of vein bypass grafts and severely atherosclerotic coronary arteries reported improvement with lipid lowering therapy. None of these studies had included randomization of patients to systematic, intense, long-term risk reduction versus usual care with prospectively identified coronary artery segments with mild disease.