The American journal of cardiology
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Review
The ongoing telmisartan alone and in combination with ramipril global endpoint trial program.
The renin-angiotensin system evolved to maintain volume homeostasis and blood pressure and to prevent ischemia during acute volume loss. But in the present age, these mechanisms are redundant, and the clinical significance of angiotensin II results from its pathologic effects, which are mediated by the angiotensin II type 1 (AT(1)) receptor. Activation of AT(1) receptors has been linked to pathologic processes that contribute to atherosclerosis and ischemic events, including oxidative stress, inflammatory processes, low-density lipoprotein cholesterol trafficking, and prothrombotic states. ⋯ Both trials will assess cardiovascular outcomes in patients at high risk using the same criteria as that of the HOPE study, with a single exception: the TRANSCEND trial will enroll patients who do not tolerate ACE inhibitor treatment. The primary end points in both ONTARGET and TRANSCEND are death caused by cardiovascular disease, acute MI, stroke, and hospitalization because of congestive heart failure. The secondary end points include newly diagnosed heart failure, revascularization, new-onset type 2 diabetes mellitus, nephropathy, cognitive decrease and dementia, and newly diagnosed atrial fibrillation; these will be used for hypothesis generation.
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Heart failure (HF) is a complex clinical syndrome resulting from any structural or functional cardiac disorder impairing the ability of the ventricles to fill with or eject blood. The approach to pharmacologic treatment has become a combined preventive and symptomatic management strategy. Ideally, treatment should be initiated in patients at risk, preventing disease progression. ⋯ Calcium antagonists, with the exception of amlodipine, oral or intravenous inotropes, and vasodilators, should be avoided in HF with reduced systolic function. Amiodarone should be used only if patients have a history of sudden death, or a history of ventricular fibrillation or sustained ventricular tachycardia, and should be used in conjunction with an implantable defibrillator [corrected]. Finally, anticoagulation is recommended only in patients who have concomitant atrial fibrillation or a previous history of cerebral or systemic emboli.
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Acute and chronic inflammation play a central role in the pathophysiology of atherosclerosis. Corticosteroids are the gold standard anti-inflammatory agent and may have a role in treating acute myocardial infarction. However, concern exists regarding the potential for impaired wound healing and wall thinning. ⋯ Sensitivity analyses limited to large studies and randomized controlled trials revealed odds ratios of 0.76 (95% CI 0.53 to 1.09) and 0.95 (95% CI 0.72 to 1.26), respectively. Two tests revealed no evidence for publication bias. Thus, the review of available clinical studies demonstrated no harm and a possible mortality benefit of corticosteroids in acute myocardial infarction.