No abstract

BACKGROUND: Some evidence-based therapies are underused in patients with a poor prognosis despite the fact that the survival gains would be highest among such patient subgroups. The extent to which this applies for acute, life-saving therapies is unknown. The impact of prognostic characteristics and pre-existing conditions on the use of reperfusion therapy among eligible patients with acute ST segment elevation myocardial infarction is examined. METHODS: Of 2829 acute myocardial infarction patients prospectively identified in 53 acute care hospitals across Ontario, 987 presented with ST segment elevation within 12 h of symptom onset and without any absolute contraindications to reperfusion therapy. The baseline prognosis for each patient was derived from a validated riskadjustment model of 30-day mortality. Multiple logistical regression was used to examine the relationships among reperfusion therapy, prognosis and the number of pre-existing chronic conditions after adjusting for factors such as age, sex, time since symptom onset and socioeconomic status. RESULTS: Of the 987 appropriate candidates, 725 (73.5%) received reperfusion therapy (70.8% fibrinolysis, 2.6% primary angioplasty). The adjusted odds ratio of reperfusion therapy fell 4% with each 1% increase in baseline risk of death (adjusted OR 0.96, 95% CI 0.92 to 1.00, P=0.04) and fell 18% with each additional pre-existing condition (adjusted OR 0.82, 95% CI 0.76 to 0.90, P<0.001). The number rather than the type of pre-existing conditions inversely correlated with the use of reperfusion therapy. While the impact of baseline risk and pre-existing conditions was additive, pre-existing conditions exerted a greater impact on the nonuse of reperfusion therapy than did baseline risk. CONCLUSIONS: A treatment-risk paradox is demonstrable even within a cohort of lower risk patients with ST segment elevation myocardial infarction. These findings are consistent with the view that these clinical decisions are more likely to be attributable to concerns about patient frailty or side effects than to a misunderstanding of treatment benefits.

This study demonstrates that therapy with GTN causes abnormal coronary vasomotor responses to the endothelium-dependent vasodilator acetylcholine, changes that were persistent for up to 3 hours after GTN discontinuation. This nitrate-associated vasomotor dysfunction has implications with respect to the development of nitrate tolerance and the potential for adverse events during nitrate withdrawal.

The objective of this study was to evaluate the effect of muscarinic receptor modulation on basal and ␤ -adrenergic stimulated left ventricular function in patients with heart failure. 21 heart failure patients and 14 subjects with normal ventricular function were studied. In Protocol 1 intracoronary acetylcholine resulted in a 60 Ϯ 8% inhibition of the left ventricular ϩ dP/dt response to intracoronary dobutamine in the normal group, and a similar 70 Ϯ 13% inhibition in the heart failure group. Acetylcholine also attenuated the dobutamine-mediated acceleration of isovolumic relaxation (Tau) in both groups. Acetylcholine alone had no effect on Tau in the normal group, while it prolonged Tau in the heart failure group. In Protocol 2 intracoronary atropine resulted in a 35 Ϯ 10% augmentation of the inotropic response to dobutamine in the normal group, versus a non-significant 12 Ϯ 15% augmentation of the dobutamine response in the heart failure group. In Protocol 3, in 6 heart failure patients, both effects of acetylcholine, the slowing of ventricular relaxation and the inhibition of ␤ -adrenergic responses, were reversed by the addition of atropine. Therefore, in the failing human left ventricle muscarinic stimulation has an independent negative lusitropic effect and antagonizes the effects of ␤ -adrenergic stimulation. ( J. Clin. Invest. 1996. 98:2756-2763.)