The consensus of evidence from angiographic trials demonstrates both coronary artery and clinical benefits from lowering of lipids by a variety of regimens. The findings of reduced arterial disease progression and increased regression have been convincing but, at best, modest in their magnitude. For example, among those treated intensively in FATS, the mean improvement in proximal stenosis severity per patient was < 1% stenosis, and only 12% of all lesions showed convincing regression. In view of these modest arterial benefits, the associated reductions in cardiovascular events have been surprisingly great. For example, coronary events were reduced 75% in FATS; this was entirely a result of a 93% reduction in the likelihood that a mildly or moderately diseased arterial segment would experience substantial progression to a severe lesion at the time of a clinical event. We believe that the magnitude of the clinical benefit is best explained in terms of this observation, according to the following lines of reasoning. Clinical events most commonly spring from lesions that are initially of mild or moderate severity and then abruptly undergo a disruptive transformation to a severe culprit lesion. The process of plaque fissuring, leading to plaque disruption and thrombosis, triggers most clinical coronary events. Fissuring is predicted by a large accumulation of core lipid in the plaque and by a high density of lipid-laden macrophages in its thinned fibrous cap. Lesions with these characteristics constitute only 10-20% of the overall lesion population but account for 80-90% of the acute clinical events. In the experimental setting, normalization of an atherogenic lipid profile substantially decreases the number of lipid-laden intimal macrophages (foam cells) and depletes cholesterol from the core lipid pool. In the clinical setting, intensive lipid lowering virtually halts the progression of mild and moderate lesions to clinical events. Thus, the reduction in clinical events observed in these trials appears to be best explained by the relation of the lipid and foam cell content of the plaque to its likelihood of fissuring and by the effects of lipid-lowering therapy on these "high-risk" features of plaque morphology. The composite of data presented here supports the hypothesis that lipid-lowering therapy selectively depletes (regresses) that relatively small but dangerous subgroup of fatty lesions containing a large lipid core and dense clusters of intimal macrophages. By doing so, these lesions are effectively stabilized and clinical event rate is accordingly decreased.

We found that CABG and PTCA did not differ significantly with respect to the occurrence of the composite primary end point. Consequently, the selection of one procedure over the other should be guided by patients' preferences regarding the quality of life and the possible need for subsequent procedures.

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The CREATE-ECLA Randomized Controlled TrialThe CREATE-ECLA Trial Group Investigators* See also pp 427 and 489.

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for the PRISM-PLUS InvestigatorsBackground-The present study describes the effects of tirofiban, a nonpeptide platelet glycoprotein (GP) IIb/IIIa receptor blocker, on the characteristics of culprit lesions in patients with unstable angina (UA) or non-Q-wave myocardial infarction (NQWMI). Methods and Results-Of 1915 patients enrolled in PRISM-PLUS, 1491 had a readable film obtained a median of 65 hours after randomization. A core laboratory examined the culprit lesions for intracoronary thrombus burden (primary end point) and for TIMI flow grade distribution and severity of the obstruction and of underlying coronary artery disease (secondary end points). The combination of tirofiban plus heparin compared with heparin alone significantly reduced the intracoronary thrombus burden of the culprit lesions (ORϭ0.77, Pϭ0.022), improved the perfusion grade (ORϭ0.65, Pϭ0.002), and decreased the severity of the obstruction (Pϭ0.037), but it did not influence the severity of the underlying plaque. Persistence of a thrombus in 45% of patients was associated with a 2.4-fold increase in the odds of death at 30 days (Pϭ0.005) and a 2-fold increase in the odds of myocardial infarction (Pϭ0.002). Conclusions-The addition of tirofiban to heparin reduced the thrombus burden of the culprit lesion and improved distal perfusion in patients with UA or NQWMI, which supports the clinical benefit observed with the combination treatment.

Abstract-During the past decade, the perception flourished that lipid and antioxidant therapy were 2 independent avenues for cardiovascular protection. However, studies have shown that commonly used antioxidant vitamin regimens do not prevent cardiovascular events. We found that the addition of antioxidant vitamins to simvastatin-niacin therapy substantially blunts the expected rise in the protective high density lipoprotein (HDL)2 cholesterol and lipoprotein(A-I) subfractions of HDL, with apparent adverse effects on the progression of coronary artery disease.

This study investigated whether a novel index of stress hyperglycemia might have a better prognostic value compared to admission glycemia alone in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The acute-to-chronic glycemic ratio was expressed as admission blood glucose (ABG) devided by the estimated average glucose (eAG), and eAG was derived from the glycated hemoglobin (HbA1c). A total of 1300 consecutive patients with STEMI treated with PCI were included. Baseline data and outcomes were analyzed. The study end point was a composite of in-hospital all-cause death, cardiogenic shock, and acute pulmonary edema. Accuracy was defined with area under the curve (AUC) by a receiver–operating characteristic (ROC) curve analysis. After multivariate adjustment, both ABG/eAG and ABG were closely associated with an increased risk of the composite end point in nondiabetic patients. However, only ABG/eAG (odds ratio = 2.45, 95% confidence interval: 1.24-4.82, P = .010), instead of ABG, was associated with the outcomes in diabetic patients. Compared to ABG, ABG/eAG had an equivalent predictive value in nondiabetic patients but a superior discriminatory ability in diabetic patients (AUC improved from 0.52-0.63, P < .001). Taken together, ABG/eAG provides more significant in-hospital prognostic information than ABG in diabetic patients with STEMI after PCI.