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Nonantithrombotic medical options in acute coronary syndromes: old agents and new lines on the horizon.
Soukoulis, V, Boden, WE, Smith, SC, O'Gara, PT
Circulation research. 2014;(12):1944-58
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Abstract
Acute coronary syndromes (ACS) constitute a spectrum of clinical presentations ranging from unstable angina and non-ST-segment elevation myocardial infarction to ST-segment myocardial infarction. Myocardial ischemia in this context occurs as a result of an abrupt decrease in coronary blood flow and resultant imbalance in the myocardial oxygen supply-demand relationship. Coronary blood flow is further compromised by other mechanisms that increase coronary vascular resistance or reduce coronary driving pressure. The goals of treatment are to decrease myocardial oxygen demand, increase coronary blood flow and oxygen supply, and limit myocardial injury. Treatments are generally divided into disease-modifying agents or interventions that improve hard clinical outcomes and other strategies that can reduce ischemia. In addition to traditional drugs such as β-blockers and inhibitors of the renin-angiotensin-aldosterone system, newer agents have expanded the number of molecular pathways targeted for treatment of ACS. Ranolazine, trimetazidine, nicorandil, and ivabradine are medications that have been shown to reduce myocardial ischemia through diverse mechanisms and have been tested in limited fashion in patients with ACS. Attenuating the no-reflow phenomenon and reducing the injury compounded by acute reperfusion after a period of coronary occlusion are active areas of research. Additionally, interventions aimed at ischemic pre- and postconditioning may be useful means by which to limit myocardial infarct size. Trials are also underway to examine altered metabolic and oxygen-related pathways in ACS. This review will discuss traditional and newer anti-ischemic therapies for patients with ACS, exclusive of revascularization, antithrombotic agents, and the use of high-intensity statins.
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The vascular effects of doxazosin in hypertension complicated by metabolic syndrome.
Dell'Omo, G, Penno, G, Pucci, L, Pellegrini, G, Scotti, A, Del Prato, S, Pedrinelli, R
Coronary artery disease. 2005;(1):67-73
Abstract
AIMS: To evaluate the vascular effects of doxazosin, an alpha-1 antagonist, in hypertensive patients with metabolic syndrome in whom the drug has previously been shown to exert beneficial metabolic actions on lipids and insulin metabolism. EXPERIMENTAL PROTOCOL Twelve untreated non-diabetic hypertensive patients with National Cholesterol Education Program (NCEP) ATP-III defined metabolic syndrome were assigned to three-months of treatment with doxazosin (5.5 +/- 1.9 mg/die). Study variables were measured at baseline and after treatment. End-points: forearm blood flow (strain-gauge plethysmography) responses to graded intra-arterial acetylcholine and sodium nitroprusside infusion to test endothelium-dependent and independent vasodilatation respectively. Minimum forearm vascular resistance, the ratio of mean blood pressure and post-ischaemic maximal blood flow, as an index of arteriolar structure; transcapillary albumin escape rate (the 1-h decay rate of I-albumin, 6-8 microC ev) as a measure of systemic capillary permeability. Lipids, fasting and post-glucose insulin were measured at baseline and after treatment. RESULTS Doxazosin reduced blood pressure, augmented acetylcholine-mediated vasodilatation, decreased minimum resistance and, although not to a statistically significant extent, transvascular albumin leakage increased high-density lipoprotein (HDL) cholesterol while triglycerides and post-stimulative hyperinsulinemia decreased. CONCLUSIONS Doxazosin improved endothelial-mediated vasomotor function and reversed abnormal arteriolar structure in hypertensive patients with metabolic syndrome while improving lipid profile and blunting post-glucose hyperinsulinemia.