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Debate: Unstable angina - When should we intervene?
The prognosis of patients who present with non-ST segment elevation acute coronary syndromes (ACS) is guarded. These patients can be risk-stratified on the basis of symptom complex, electrocardiographic ST segment depression, obvious hemodynamic compromise and particularly on the basis of serum troponin level. An elevated troponin level determines risk and also predicts the degree of benefit from treatment with either low molecular weight heparin or platelet glycoprotein (GP) IIb/IIIa blockade. Higher risk patients should undergo early coronary angiography and myocardial revascularization as indicated and feasible. Although studies performed before the advent of coronary stenting and adjunctive platelet GP IIb/IIIa blockade suggested increased hazard for patients undergoing early intervention, recent experience cited herein supports an in-hospital and long-term clinical benefit for the aggressive approach. Here, I propose an algorithm for risk stratification and triage of appropriate patients for adjunctive pharmacotherapy and early revascularization.
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Debate: The slippery slope of surrogate outcomes
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Surrogate outcomes are frequently used in cardiovascular disease research. A concern is that changes in surrogate markers may not reflect changes in disease outcomes. Two recent clinical trials (Heart and Estrogen/Progestin Replacement Study [HERS], and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]) underscore this problem since their results contradicted what was expected based on the surrogate outcomes. The current regulatory policy to allow new therapies to be introduced onto the market based solely on surrogate outcomes may need to be reviewed.
Debate: does it matter how you lower blood pressure?
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The evidence base for drug treatment of hypertension is strong. Early trials using thiazide diuretics suggested a shortfall in prevention of coronary heart disease. The superiority of newer drugs has been widely advocated but trial evidence does not support an advantage of beta-blockers, angiotensin converting enzyme inhibitors, calcium channel blockers or alpha-blockers for this outcome. Even meta-analyses have failed to clarify matters. If this issue is to be settled, bigger and better trials of longer duration in high-risk patients are needed. Meanwhile, the importance of rigorous blood pressure control using multiple drugs has been established. This should be the focus of our attention rather than agonising over differences in cause-specific outcomes that may not be generalisable to all patient populations.
Debate: A subversive view of subsets - a dissident clinician's opinion
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Clinical trialists and statisticians are very wary of subgroup analysis, for good reasons. Clinicians have to deal with situations in which subgroups of patients differ widely from one another in their prognosis and response to treatment. Few trials are large enough to demonstrate convincingly these differences in outcome, but often provide suggestive evidence. Should we ignore this and treat all patients as the same, or should we allow dubious statistical evidence to buttress biological plausibility in making clinical decisions?