Cardiac Ischemic Events In Patients Research Articles

Pharmacological characterization of tegaserod at the wild type and 124Cys variant of the human 5-HT1B receptor

Sumatriptan, an antimigraine drug, causes contraction of human coronary arteries through activation of 5-HT1B receptors which couple to Gi/Go inducing inhibition of adenylate cyclase. At a rare, naturally occurring human receptor variant (124Cys-h5-HT1B), sumatriptan has previously been shown to act as a more potent agonist than at wild-type receptor. Tegaserod, a 5-HT4-receptor agonist, developed for the treatment of functional gastrointestinal disorders, has been suspected to be involved in very rare cardiac ischemic events in patients with cardiovascular risk factors. In this study, we examined the potential agonist-like effects of tegaserod in comparison with sumatriptan at heterologously expressed human wild type and 124Cys-variant 5-HT1B receptors, using assays addressing G-protein coupling and inhibition of forskolin-stimulated cyclic AMP accumulation. Sumatriptan exhibited agonist effects as previously reported, whereas tegaserod acted as partial agonist at both wild type and 124Cys-variant h5-HT1B receptors (expressed in rat C6 glioma cells). Sumatriptan and tegaserod were more potent at the 124Cys-variant h5-HT1B receptor. It remains to be shown whether the very rare cardiovascular side effects reported with these drugs are predominantly observed in patients homozygously expressing the variant receptor.

Clinical and Angiographic Predictors of Short- and Long-Term Ischemic Events in Acute Coronary Syndromes

Background— Contemporary adjunctive pharmacology and revascularization strategies have improved the prognosis of patients with acute coronary syndromes (ACSs). We sought to identify the clinical and angiographic predictors of cardiac ischemic events in patients with ACSs treated with an early invasive strategy. Methods and Results— Multivariable logistic regression was used to analyze the relation between baseline characteristics and 30-day and 1-year composite ischemia (death, myocardial infarction, or unplanned revascularization) among the 6921 ACS patients included in the prespecified angiographic substudy of the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial. Of the 6921 patients, 3826 (55.3%) were treated with percutaneous coronary intervention, 755 (10.9%) with coronary artery bypass grafting, and 2340 (33.8%) with medical therapy. Composite ischemia occurred in 595 (8.6%) patients at 30 days and in 1153 (17.4%) at 1 year. Renal insufficiency, biomarker elevation, ST-segment deviation, nonuse of aspirin or thienopyridine, insulin-treated diabetes, older age, baseline lower hemoglobin value, history of percutaneous coronary intervention, and current smoking were independently associated with 30-day or 1-year ischemic events. Angiographic characteristics predicting ischemic events included number of diseased vessels, moderate/severe calcification, worst percent diameter stenosis, jeopardy score, lower left ventricular ejection fraction, lesion eccentricity, and thrombus. With use of receiver operating characteristic methodology, the c statistic improved for the predictive model by adding angiographic to clinical parameters for the 30-day composite ischemia (from 0.62 to 0.68) and myocardial infarction (from 0.64 to 0.71) and 1-year composite ischemia (from 0.61 to 0.65) and myocardial infarction (from 0.63 to 0.69) end points. Conclusions— Among ACS patients managed with an early invasive strategy, baseline angiographic markers of disease burden, calcification, lesion severity, lower left ventricular ejection fraction, and morphological characteristics provided important added independent predictive value for 30-day and 1-year ischemic outcomes, beyond the well-recognized clinical risk factors. These findings emphasize the prognostic importance of the diagnostic angiogram in the risk stratification of patients presenting with ACSs. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00093158.

Reducing Cardiac Ischemic Events in Patients with ACS: Prasugrel versus Clopidogrel

Practice PearlPrasugrel significantly reduced cardiac ischemic events in patients with acute coronary syndrome who underwent percutaneous coronary intervention.

Relation of Dyspnea in Patients Unable to Perform Exercise Stress Testing to Outcome and Myocardial Ischemia

Limited information exists regarding the significance of dyspnea in patients who are unable to exercise and the contribution of myocardial ischemia to this symptom. To assess this, we evaluated results of dobutamine stress echocardiography (DSE) and long-term outcome of patients with dyspnea referred for DSE. We studied 6,376 consecutive patients who were unable to perform an exercise test and were referred for DSE. Patients were classified according to presenting symptoms and followed for 5.5 +/- 2.8 years. End points were cardiac ischemic events (myocardial infarction or revascularization), hospitalization for heart failure (HF), and death. Dobutamine stress echocardiogram was positive for ischemia in 19% of patients with dyspnea versus 24% (p = 0.002) of those with typical angina and 17% (p = 0.2) of asymptomatic patients. In multivariate analysis, risk of death was increased in dyspneic patients versus asymptomatic patients (hazard ratio [HR] 1.14, p = 0.02) and patients with chest pain (HR 1.20, p <0.001). Hospitalization for HF occurred more often in patients with dyspnea (HR 1.26, p = 0.05 vs asymptomatic; HR 1.24, p = 0.06 vs chest pain), especially in the subset without previous HF (HR 1.45, p = 0.006 vs chest pain). Risk of cardiac ischemic events in patients with dyspnea was similar versus asymptomatic patients (HR 0.92, p = 0.39) and decreased versus patients with chest pain (HR 0.70, p <0.001). In conclusion, in patients referred for DSE, dyspnea was associated with a poor outcome. This increased hazard seems not to be linked to myocardial ischemia, but instead to HF and death.

Treatment of atherosclerotic intracranial arterial stenosis.

David Pelz MD L. Nelson Hopkins MD Elad Levy MD Section Editors: Atherosclerotic stenosis of the major intracranial arteries (intracranial internal carotid artery, middle cerebral artery, vertebral artery, basilar artery) is probably the most common cause of stroke worldwide.1 Intracranial atherosclerosis causes 30% to 50% of strokes in Asia2 and 8% to 10% of strokes in North America.3 This review focuses on the medical and endovascular treatment of atherosclerotic intracranial arterial stenosis. Initially, a retrospective study suggested that warfarin was superior to aspirin for stroke prevention in patients with symptomatic intracranial arterial stenosis.4 This retrospective data combined with a proposed pathophysiological rationale for anticoagulation5 made warfarin a common treatment choice for symptomatic intracranial stenosis.6 However, the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial showed that aspirin was safer and as effective as warfarin for stroke prevention in patients with symptomatic intracranial stenosis. WASID was stopped early after a mean follow-up of 1.8 years because of higher rates of death and major hemorrhage in the warfarin arm. The primary end point of ischemic stroke, brain hemorrhage or vascular death, occurred in 22.1% of patients assigned aspirin and 21.8% of those in the warfarin group.7 The rates of myocardial infarction or sudden death were also higher in the warfarin arm. Certain high-risk subgroups of patients with intracranial stenosis were previously thought to benefit from anticoagulation, such as those with severe stenosis,4 vertebrobasilar disease,4 and those who have failed antithrombotic therapy.8 In WASID, however, patients with severe stenosis9 or those previously on antithrombotic therapy9,10 did not benefit from warfarin. Patients with basilar artery stenosis in WASID did appear to have a lower rate of the primary end point on warfarin, but there was no difference in the rate of stroke in the …

Abstract 6088: Clinical and Angiographic Predictors of 30-Day and One-Year Cardiac Ischemic Events in Patients with Non-ST Elevation Acute Coronary Syndromes: Results from the ACUITY (Acute Catheterization and Urgent Intervention Triage strategY) Trial

An early invasive strategy is of clinical benefit in moderate and high-risk acute coronary syndromes (ACS). Clinical predictors of short and long-term ischemic outcomes in pts with ACS have been well studied, whereas the extent, location and characteristics of angiographic coronary disease in predicting outcome is not well defined. The ACUITY trial randomized 13,819 pts with moderate and high risk ACS to unfractionated heparin or enoxaparin + GP IIb/IIIa inhibitors (GPI), versus bivalirudin + GPI, vs. bivalirudin alone. The angiographic substudy of ACUITY included the first 7000 consecutive randomized US patients. All angiograms were reviewed by an independent core laboratory for complete 3 vessel assessment of CAD extent and burden (total mm length of lesions&gt;30%DS), as well as baseline and final lesion and flow characteristics. Clinical and angiographic predictors of ischemic outcomes at 30 days and 1 year (death, MI, or ischemic target vessel revascularization) were identified by univariate and multivariable analysis using logistic regression analysis. Of 6921 pts with interpretable angiograms, 3826 pts (55.3%) were treated with PCI, 755 (10.9%) with CABG, and 2340 (33.8%) with medical therapy. Composite ischemia occurred in 595 (8.6%) pts at 30 days and 1153 (17.4%) pts at one year. Independent predictors of 30 day and 1 year ischemic cardiac events by multivariable analysis are shown in the table . Among moderate- to high-risk ACS patients, beyond the well recognized clinical risk factors of renal insufficiency and diabetes mellitus, angiographic manifestations of coronary atherosclerosis including greater burden and severity of disease, and presence of calcified lesions, are important independent predictors of 30 day and 1 year adverse outcomes. Table. Multivariate Predictors of Composite Ischemia

Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin: The ACUTE II study

Background In comparison with treatment with unfractionated heparin (UFH) and aspirin (ASA), both tirofiban administered with UFH and ASA, and enoxaparin plus ASA have shown superiority in reducing cardiac ischemic events in patients with unstable angina and non-ST-segment elevation myocardial infarction. Replacing UFH with enoxaparin when tirofiban is administered to patients may offer further therapeutic benefit, but could also increase bleeding. Objective Our objective was to provide estimates of the frequency of bleeding complications, as defined by means of the Thrombolysis In Myocardial Infarction(TIMI) group, and collect data on clinical efficacy of the combination of tirofiban with enoxaparin plus ASA. Methods Five hundred twenty-five patients with UA/NSTEMI were treated with tirofiban coadministered with ASA and randomized to receive either UFH (n = 210) or enoxaparin (n = 315). Therapy was administered for 24 to 96 hours. Bleeding incidences were assessed until 24 hours after trial therapy was discontinued; other clinical outcomes were assessed for as long as 30 days. Results The total bleeding rate (TIMI major + minor + loss-no-site) for the UFH group versus the enoxaparin group was 4.8% vs 3.5% (odds ratio [OR] 1.4, CI 0.6-3.4). The TIMI major and minor bleeding rates for the UFH versus the enoxaparin groups were 1.0% versus 0.3% (OR 3.0, CI 0.3-33.8) and 4.3% versus 2.5% (OR 1.7, CI 0.7-4.6). There was an increase in nuisance cutaneous and oral bleeds (<50 mL of blood loss) in the enoxaparin group. Death or myocardial infarction occurred with similar frequency in the 2 groups (9.0% vs 9.2%). However, refractory ischemia requiring urgent revascularization and rehospitalization because of unstable angina occurred more frequently in the UFH group (4.3% vs 0.6% and 7.1% vs 1.6%, respectively). Conclusions Combination therapy with tirofiban plus enoxaparin appears safe, relative to therapy with tirofiban plus UFH. (Am Heart J 2002;144:470-7.)

Enoxaparin was superior to heparin in preventing serious cardiac ischemic events in patients with unstable angina/non-Q-wave MI

Enoxaparin was superior to heparin in preventing serious cardiac ischemic events in patients with unstable angina/non-Q-wave MI

Angiotensin converting enzyme inhibition and coronary artery disease

To review the evidence on the effects of angiotensin converting enzyme (ACE) inhibitors in coronary artery disease. In studies of experimental atherosclerosis involving hypertensive and normotensive hyperlipidemic animals, ACE inhibitors have had potent anti-atherogenic effects, reducing the total aortic intimal surface involved and the aortic cholesterol content. In balloon-injured animals, ACE inhibitors have suppressed the myointimal proliferative response in rats and rabbits, but not in higher species such as pigs and baboons, indicating possible species-specific effects. In spontaneously hypertensive rats, ACE inhibitors have modulated alterations in endothelium-related vasodilation, although similar effects have not been observed in human hypertension. ACE inhibition has not been shown to prevent restenosis after percutaneous transluminal coronary angioplasty. However, cardiac ischemic events have been prevented by ACE inhibition in patients with coronary artery disease and left ventricular dysfunction in a number of studies, including the Studies of Left Ventricular Dysfunction (SOLVD), Survival and Ventricular Enlargement (SAVE) study, Acute Infarction and Ramipril Efficacy (AIRE) study and the Gruppo Italiano per lo Studio della Streptochinesi dell'Infarto Micardico 3 (GISSI-3) trial. Other ongoing studies such as the QUinapril Ischemic Event Trial (QUIET) are assessing ACE inhibitor effects in patients with coronary artery disease and a normal left ventricular function. ACE inhibitors prevent the development of atherosclerosis in hyperlipidemic animal models. They also prevent the myointimal proliferative response to injury in some animal models, but not in higher animal species or in humans. They can reduce the number of cardiac ischemic events in patients with coronary artery disease and left ventricular dysfunction; their effects in those patients with a normal left ventricular function are now being assessed.