An insufficient rise in pulse pressure (PP) at sub-maximal exercise may signify myocardial hypoxia and be a stronger and clinically useful marker for coronary artery disease (CAD) severity. However, the association between PP and severity of CAD has not been well-defined. PURPOSE: To determine the association between exercise PP and CAD severity. METHODS: We assessed exercise parameters and angiographic findings in 282 patients (62 ± 10 years) undergoing cardiac angiography subsequent to a positive exercise tolerance test. Severe CAD was defined as a diameter stenosis of: 1) 50% or greater in left main coronary artery; 2) 70% or greater in three vessels; and 3) 70% or greater in two vessels with the proximal left anterior descending artery involved. Multivariate logistic regression models were applied. Data were adjusted for age, body mass index, cardiac medications, baseline measurements and the conventional cardiovascular risk factors. RESULTS: Eighty-eight (31.2%) of the patients had severe CAD and 194 (68.8%) had moderate or mild CAD. An inverse association was noted between PP and CAD severity. More specifically, PP < 50 mm Hg at 3 minutes of exercise constituted a 5.2-fold increase in the likelihood for severe CAD (OR = 5.2; CI: 2.0-13.3; p <0.001). Furthermore, the risk of CAD severity was reduced by 19% (OR =0.81; p = 0.001) for every 5 mm Hg increase in PP beyond this threshold. Similarly, systolic BP at 5 METs was also a predictor of CAD severity (OR =0.97; p = 0.007). There was a 15% decrease in the risk of CAD severity for every 5 mm Hg increase in systolic BP at 5 METs. CONCLUSION: Failure of PP to rise above 50 mm Hg at 3 minutes of exercise constitutes a 7-fold increase in the likelihood of severe CAD. The risk of CAD severity is lowered by 19% for every 5 mm Hg increase in PP above this threshold.

Background-Both aspirin and warfarin when used alone are effective in the secondary prevention of vascular events and death after acute myocardial infarction. We tested the hypothesis that aspirin and warfarin therapy, when combined, would be more effective than aspirin monotherapy.Methods and Results-We conducted a randomized open-label study to compare the efficacy of warfarin (target international normalized ratio 1.5 to 2.5 IU) plus aspirin (81 mg daily) with the efficacy of aspirin monotherapy (162 mg daily) in reducing the total mortality in 5059 patients enrolled within 14 days of infarction and followed for a median of 2.7 years. Secondary end points included recurrent myocardial infarction, stroke, and major hemorrhage. Four hundred thirty-eight (17.3%) of 2537 patients assigned to the aspirin group and 444 (17.6%) of 2522 patients assigned to the combination group died (log-rank P=0.76). Recurrent myocardial infarction occurred in 333 patients (13.1%) taking aspirin and in 336 patients (13.3%) taking combination therapy (log-rank P=0.78). Stroke occurred in 89 patients (3.5%) taking aspirin and in 79 patients (3.1%) taking combination therapy (log-rank P=0.52). Major bleeding occurred more frequently in the combination therapy group than in the aspirin group (1.28 versus 0.72 events per 100 person years of follow-up, respectively; P<0.001). There were 14 individuals with intracranial bleeds in both the aspirin and combination therapy groups.Conclusions-In post-myocardial infarction patients, warfarin therapy (at a mean international normalized ratio of 1.8) combined with low-dose aspirin did not provide a clinical benefit beyond that achievable with aspirin monotherapy.

It is now agreed that the majority of acute myocardial infarctions result from intracoronary thrombosis at sites of atherosclerotic plaque that have been disrupted. In 1947 Nicol and Fassett published the first clinical paper suggesting that agents interfering with blood coagulation could prevent myocardial infarction in patients at risk. Scores of subsequent clinical trials were performed to assess the efficacy of anticoagulants and antiplatelet agents in preventing death and reinfarction in survivors of acute myocardial infarction. Despite these efforts no agreement exists on whether these strategies are beneficial and, if so, which is superior. The primary obstacle to progress in this field has been the failure of nearly all trials to enroll the large numbers of subjects required to demonstrate a survival benefit. The large sample size requirement derives from two inescapable facts: mortality rates following acute infarction, though variable, are generally low and the potential benefit of these agents in preventing mortality is small. Combining oral anticoagulants with antiplatelet agents (combination hemotherapy) may significantly enhance their antithrombotic effect. Clinical trials of combination hemotherapy have demonstrated superiority over anticoagulant monotherapy in the setting of stroke prevention in patients with prosthetic heart valves. Similar benefit was not observed in trials studying stroke prevention in nonvalvular atrial fibrillation and vascular morbidity in patients surviving an acute myocardial infarction. The failure of these latter studies may relate to the particularly low intensity of warfarin administered in combination with aspirin. This trial proposes to demonstrate that the combination of oral anticoagulation, administered in a moderate dose intensity, and antiplatelet therapy is superior to aspirin monotherapy in reducing overall mortality following acute myocardial infarction.