Coronary lesion progression as assessed by fractional flow reserve (FFR) and angiography

Statin drugs reduce both atherogenic lipoproteins and cardiovascular morbidity and mortality. However, the optimal strategy and target level for lipid reduction remain uncertain. To compare the effect of regimens designed to produce intensive lipid lowering or moderate lipid lowering on coronary artery atheroma burden and progression. Double-blind, randomized active control multicenter trial (Reversal of Atherosclerosis with Aggressive Lipid Lowering [REVERSAL]) performed at 34 community and tertiary care centers in the United States comparing the effects of 2 different statins administered for 18 months. Intravascular ultrasound was used to measure progression of atherosclerosis. Between June 1999 and September 2001, 654 patients were randomized and received study drug; 502 had evaluable intravascular ultrasound examinations at baseline and after 18 months of treatment. Patients were randomly assigned to receive a moderate lipid-lowering regimen consisting of 40 mg of pravastatin or an intensive lipid-lowering regimen consisting of 80 mg of atorvastatin. The primary efficacy parameter was the percentage change in atheroma volume (follow-up minus baseline). Baseline low-density lipoprotein cholesterol level (mean, 150.2 mg/dL [3.89 mmol/L] in both treatment groups) was reduced to 110 mg/dL (2.85 mmol/L) in the pravastatin group and to 79 mg/dL (2.05 mmol/L) in the atorvastatin group (P<.001). C-reactive protein decreased 5.2% with pravastatin and 36.4% with atorvastatin (P<.001). The primary end point (percentage change in atheroma volume) showed a significantly lower progression rate in the atorvastatin (intensive) group (P =.02). Similar differences between groups were observed for secondary efficacy parameters, including change in total atheroma volume (P =.02), change in percentage atheroma volume (P<.001), and change in atheroma volume in the most severely diseased 10-mm vessel subsegment (P<.01). For the primary end point, progression of coronary atherosclerosis occurred in the pravastatin group (2.7%; 95% confidence interval [CI], 0.2% to 4.7%; P =.001) compared with baseline. Progression did not occur in the atorvastatin group (-0.4%; CI -2.4% to 1.5%; P =.98) compared with baseline. For patients with coronary heart disease, intensive lipid-lowering treatment with atorvastatin reduced progression of coronary atherosclerosis compared with pravastatin. Compared with baseline values, patients treated with atorvastatin had no change in atheroma burden, whereas patients treated with pravastatin showed progression of coronary atherosclerosis. These differences may be related to the greater reduction in atherogenic lipoproteins and C- reactive protein in patients treated with atorvastatin.

The purpose of this study was to investigate the 2-year outcome of percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) in patients with multivessel coronary artery disease (CAD). In patients with multivessel CAD undergoing PCI, coronary angiography is the standard method for guiding stent placement. The FAME (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) study showed that routine FFR in addition to angiography improves outcomes of PCI at 1 year. It is unknown if these favorable results are maintained at 2 years of follow-up. At 20 U.S. and European medical centers, 1,005 patients with multivessel CAD were randomly assigned to PCI with drug-eluting stents guided by angiography alone or guided by FFR measurements. Before randomization, lesions requiring PCI were identified based on their angiographic appearance. Patients randomized to angiography-guided PCI underwent stenting of all indicated lesions, whereas those randomized to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was 0.80, the rate of myocardial infarction was 0.2% and the rate of revascularization was 3.2 % after 2 years. Routine measurement of FFR in patients with multivessel CAD undergoing PCI with drug-eluting stents significantly reduces mortality and myocardial infarction at 2 years when compared with standard angiography-guided PCI. (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation [FAME]; NCT00267774). Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Plaque rupture, usually of a precursor lesion known as a 'vulnerable plaque' or 'thin-cap fibroatheroma', is the leading cause of thrombosis. Less-frequent aetiologies of coronary thrombosis are erosion, observed with greatest incidence in women aged <50 years, and eruptive calcified nodules, which are occasionally identified in older individuals. Various treatments for patients with coronary artery disease, such as CABG surgery and interventional therapies, have led to accelerated atherosclerosis. These processes occur within months to years, compared with the decades that it generally takes for native disease to develop. Morphological identifiers of accelerated atherosclerosis include macrophage-derived foam cells, intraplaque haemorrhage, and thin fibrous cap. Foam-cell infiltration can be observed within 1 year of a saphenous vein graft implantation, with subsequent necrotic core formation and rupture ensuing after 7 years in over one-third of patients. Neoatherosclerosis occurs early and with greater prevalence in drug-eluting stents than in bare-metal stents and, although rare, complications of late stent thrombosis from rupture are associated with high mortality. Comparison of lesion progression in native atherosclerotic disease, atherosclerosis in saphenous vein grafts, and in-stent neoatherosclerosis provides insight into the pathogenesis of atheroma formation in natural and iatrogenic settings.