Biomedical subjects

E J Topol

Publications and source records attributed to E J Topol.

At least 163 records · Page 9Linked to original sources

PubMed1999

Clinical significance of thrombocytopenia during a non-ST-elevation acute coronary syndrome. The platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial experience.

BACKGROUND: The significance of thrombocytopenia in patients experiencing an acute coronary syndrome (ACS) has not been examined systematically. We evaluated this condition in a large non-ST-elevation ACS clinical trial, with particular interest paid to its correlation with clinical outcomes. METHODS AND RESULTS: Patients presenting without persistent ST elevation during an ACS were randomized to receive a double-blind infusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor eptifibatide or placebo in addition to other standard therapies including heparin and aspirin. The primary end point was death/nonfatal myocardial infarction (MI) at 30 days, whereas bleeding and stroke were the main safety outcomes. Thrombocytopenia (nadir platelet count <100x10(9)/L or <50% of baseline) occurred in 7.0% of enrolled patients. The time to onset was a median of 4 days in both treatment arms. Patients with thrombocytopenia were older, weighed less, were more likely nonwhite, and had more cardiac risk factors. These patients experienced significantly more bleeding events: they were more than twice as likely to experience moderate/severe bleeding after adjustment for confounders. Univariably, ischemic events (stroke, MI, and death) occurred significantly (P<0.001) more frequently in patients with thrombocytopenia; multivariable regression modeling preserved this association with death/nonfatal MI at 30 days. Neither the use of heparin or eptifibatide was found to independently increase thrombocytopenic risk. CONCLUSIONS: Although causality between thrombocytopenia and adverse clinical events could not be established definitively, thrombocytopenia was highly correlated with both bleeding and ischemic events, and the presence of this condition identified a more-at-risk patient population.

Acute Disease↗

PubMed1999

Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators.

BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial. These strokes are, however, associated with substantial morbidity and mortality rates. The majority of strokes were of nonhemorrhagic causes. Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed. We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population.

Acute Disease↗

PubMed1999

Sustained suppression of ischemic complications of coronary intervention by platelet GP IIb/IIIa blockade with abciximab: one-year outcome in the EPILOG trial. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade.

BACKGROUND: Blockade of the platelet glycoprotein IIb/IIIa receptor with the monoclonal antibody fragment abciximab was shown in a placebo-controlled randomized trial to reduce the incidence of acute ischemic complications within 30 days among a broad spectrum of patients undergoing percutaneous coronary revascularization. The durability of clinical benefit in this setting has not been established. METHODS AND RESULTS: A total of 2792 patients enrolled in the Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade (EPILOG) trial were followed with maintenance of double-blinding for 1 year. Patients had been assigned at the time of their index coronary interventional procedure to receive placebo with standard-dose, weight-adjusted heparin (100 U/kg initial bolus), abciximab with standard-dose, weight-adjusted heparin, or abciximab with low-dose, weight-adjusted heparin (70 U/kg initial bolus). The primary outcome was the composite of death, myocardial infarction, or urgent repeat revascularization by 30 days; this composite end point and its individual components were also assessed at 6 months and 1 year. Rates of any repeat revascularization (urgent or elective), target vessel revascularization, and a composite of death, myocardial infarction, or any repeat revascularization were also reported. Follow-up at 1 year was 99% complete for survival status and 97% complete for other end points. By 1 year, the incidence of the primary composite end point was 16.1% in the placebo group, 9.6% in the abciximab with low-dose heparin group (P<0.001), and 9.5% in the abciximab with standard-dose heparin group (P<0.001). Each of the components of this composite end point was reduced to a similar extent. Nonurgent or target vessel repeat revascularization rates were not significantly decreased by abciximab therapy. Mortality rates over 1 year increased with increasing levels of periprocedural creatine kinase MB fraction elevation. CONCLUSIONS: Acute reductions in ischemic events after percutaneous coronary intervention by abciximab are sustained over follow-up to at least 1 year. Early periprocedural myocardial infarctions suppressed by this therapy are associated with long-term mortality rates.

Abciximab↗

PubMed1999

Prior aspirin use predicts worse outcomes in patients with non-ST-elevation acute coronary syndromes. PURSUIT Investigators. Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy.

Aspirin is beneficial in the prevention and treatment of cardiovascular events, but patients who have events while taking aspirin may have worse outcomes than those not on aspirin. We investigated the association between prior aspirin use and clinical outcomes in 9,461 patients with non-ST-elevation acute coronary syndromes enrolled in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, before and after adjustment for baseline factors. We also examined whether eptifibatide has a differential treatment effect in prior aspirin users. Prior aspirin users were less likely to have an enrollment myocardial infarction (MI) (vs unstable angina) (43.9% vs 48.8%, p = 0.001) but more likely to have death or MI at 30 days (16.1% vs 13.0%, p = 0.001) and at 6 months (19.9% vs 15.9%, p = 0.001). After adjustment, prior aspirin users remained less likely to have an enrollment MI (odds ratio 0.88, 95% confidence interval 0.79 to 0.97) and more likely to have death or MI at 30 days (odds ratio 1.16, 95% confidence interval 1.00 to 1.33) but not at 6 months (odds ratio 1.14, 95% confidence interval 0.98 to 1.33). In a multivariable model, eptifibatide did not have a different treatment effect in prior aspirin users compared with nonusers (p = 0.534). Prior aspirin users had fewer enrollment MIs but worse long-term outcomes than nonusers. We found no evidence for a different treatment effect of eptifibatide in prior aspirin users.

Acute Disease↗

PubMed1999

Reduction in myocardial infarct size by basic fibroblast growth factor following coronary occlusion in a canine model.

In a canine model of permanent coronary occlusion it has been shown that basic fibroblast growth factor (bFGF) reduced infarct size and this was associated with an increase in myocardial capillary density a week after infarction. In a preliminary work from our own laboratory using a model of occlusion followed by prolonged reperfusion we observed a similar reduction in infarct size without evidence of myocardial neovascularization. The aim of the present investigation was to evaluate the effects of bFGF on infarct size and blood flow to the infarct zone in an acute experiment in which myocardial neovascularization would be excluded as a mechanism by the short duration of the study. Seventeen mongrel dogs were anesthetized and the heart was exposed through a left thoracotomy. The left anterior descending (LAD) coronary artery was isolated and occluded for 3 h. Fifteen min after LAD occlusion dogs received bFGF 20 microg of bFGF (n=6) or placebo (n=11) by intracoronary injection infused over 5 min. We measured heart rate, aortic pressure, regional coronary blood flow (CBF), regional shortening fraction (SF) at 1, 30 and 180 min of occlusion, then the LAD was reperfused for 5 min then the dogs were euthanized and infarct size was measured. Regional CBF was similar between the two groups of dogs throughout all the study. The SF was similar between the two groups prior the onset of ischemia and at the beginning of the ischemic period. After 180 min of ischemia SF was 2.7+/-4.1% for bFGF and -3.1+/-4.7 for placebo (P=0.049), and during reperfusion SF was 3.4+/-4.6% for bFGF and 0.4+/-1.0% for placebo treated dogs (P=0.023). The infarct size, normalized for the area at risk was 14.2+/-5.2% in bFGF group vs 25.8+/-8.2% in placebo group (P=0.015). In summary we have demonstrated that bFGF significantly limits myocardial necrosis after acute coronary occlusion, and that this occurred without an increase in regional myocardial perfusion and within a period of time too brief for angiogenesis to have occurred. By exclusion, it appears that the salutary effect of bFGF is likely to be mediated by a cellular mechanism. The mechanism or mechanisms responsible for myocardial salvage by bFGF may have significant potential to be exploited in the clinical arena as the basis for therapies to protect the acutely ischemic myocardium.

Animals↗

PubMed1999

Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of Platelet IIb/IIIa Inhibitor for Stenting.

CONTEXT: Thrombotic thrombocytopenic purpura (TTP) is a rare and often fatal disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, mental status changes, and renal dysfunction. Ticlopidine hydrochloride is 1 of several drugs that have been associated with this disorder and is currently used routinely in the approximately 500000 patients per year in the United States who undergo a percutaneous coronary intervention involving a stent. OBJECTIVES: To determine the incidence and describe the clinical course of TTP due to ticlopidine therapy following stenting. DESIGN: Retrospective analysis of cohort of all patients undergoing coronary stenting at the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) study sites. SETTING: Sixty-three centers throughout the United States and Canada. PATIENTS: A total of 43322 patients who underwent a percutaneous coronary intervention and received a coronary stent during a 1-year period from 1996 to 1997. MAIN OUTCOME MEASURES: Cases of TTP following stenting during the 1-year period to determine the incidence of TTP due to ticlopidine therapy following coronary stenting. Additional cases were collected from these and other centers across North America to further describe the clinical presentation and course of TTP due to ticlopidine therapy following stenting. RESULTS: Nine cases of TTP following stenting were recognized at the 63 centers during the specified period, giving an incidence of 1 case per 4814 patients treated (0.02%; 95% confidence interval, 1 case per 2533 to 1 case per 10 541 patients treated). Ten additional cases of TTP related to ticlopidine therapy following stenting were identified from other centers, were identified from the primary centers outside the pre-defined period, or involved a noncoronary stent. Four patients (21%) received ticlopidine for 2 weeks or fewer, 14 patients (74%) for 2 to 4 weeks, and 1 patient (5%) for 8 weeks. The mean time of ticlopidine treatment prior to TTP diagnosis was 22 days (range, 5-60 days). The overall mortality rate was 21% (4/19), with all 4 deaths occurring in patients not treated with plasmapheresis, whereas there were no deaths among the 13 patients who received plasmapheresis. CONCLUSION: The findings of a TTP incidence of 0.02% in our cohort of ticlopidine-treated patients following coronary stenting suggests that TTP occurs much more commonly in this population than the estimated incidence of 0.0004% in the general population. The mortality rate for this rare complication exceeds 20%. Limiting ticlopidine therapy to 2 weeks after stenting does not prevent the development of TTP. Rapid diagnosis and treatment that includes plasmapheresis are critical for improved survival.

Aged↗

PubMed1999

Prognostic value of the admission electrocardiogram in acute coronary syndromes.

CONTEXT: The presence of ischemic changes on electrocardiogram (ECG) correlates with poorer outcomes in patients with acute chest pain. OBJECTIVE: To determine the prognostic value of various ECG presentations of acute myocardial ischemia. DESIGN: Retrospective analysis of the presenting ECGs of patients enrolled in Global Use of Strategies To Open Occluded Arteries in Acute Coronary Syndromes (GUSTO-IIb). SETTING: Three hundred seventy-three hospitals in 13 countries in North America, Europe, Australia, and New Zealand. PATIENTS: A total of 12142 patients who reported symptoms of cardiac ischemia at rest within 12 hours of admission and had signs of myocardial ischemia confirmed by ECG. On presenting ECG, 22% of patients had T-wave inversion, 28% had ST-segment elevation, 35% had ST-segment depression, and 15% had a combination of ST-segment elevation and depression. MAIN OUTCOME MEASURE: Ability of presenting ECG to predict death or myocardial reinfarction during the first 30 days of follow-up. RESULTS: The 30-day incidence of death or myocardial reinfarction was 5.5% in patients with T-wave inversion, 9.4% in those with ST-segment elevation, 10.5% in those with ST-segment depression, and 12.4% in those with ST-segment elevation and depression (P<.001). After adjusting for factors associated with an increased risk of 30-day death or reinfarction, compared with those who had T-wave inversion only, the odds of 30-day death or reinfarction were 1.68 (95% confidence interval [CI], 1.36-2.08) in those with ST-segment elevation, 1.62 (95% CI, 1.32-1.98) for those with ST-segment depression, and 2.27 (95% CI, 1.80-2.86) for those with combined elevation and depression. An elevated creatine kinase level at admission correlated with a higher risk of death (odds ratio [OR], 2.36; 95% CI, 1.92-2.91) and death or reinfarction (OR, 1.56; 95% CI, 1.32-1.85). The ECG category and creatine kinase level at admission remained highly predictive of death and myocardial infarction after multivariate adjustment for the significant baseline predictors of events. CONCLUSIONS: The ECG at presentation allows immediate risk stratification across the spectrum of acute coronary syndromes. An elevated creatine kinase level at admission is associated with worse outcomes.

Australia↗

PubMed1999

One-year survival among patients with acute myocardial infarction complicated by cardiogenic shock, and its relation to early revascularization: results from the GUSTO-I trial.

BACKGROUND: Although 30-day survival is increased in patients with acute myocardial infarction complicated by cardiogenic shock who undergo coronary revascularization, the longer-term outcome in such patients and the duration of benefit from revascularization are unknown. METHODS AND RESULTS: We analyzed 30-day survivors of acute myocardial infarction in the Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial and identified 36 333 who had not had cardiogenic shock (systolic blood pressure <90 mm Hg for >/=1 hour, group 1) and 1321 patients who had shock (group 2). Group 2 patients were older and sicker. At 1 year, 97.4% of group 1 patients were alive versus 88.0% of group 2 (P=0.0001). Among group 2 patients, 578 (44%) had undergone revascularization within 30 days (group 2A) and 728 (56%) had not (group 2B). Revascularization was not required by protocol but was selected by the attending physicians. At 1 year, 91.7% of group 2A patients were alive versus 85.3% of group 2B (P=0.0003). With the use of multivariable logistic regression analysis to adjust for differences in baseline characteristics of shock patients alive at 30 days, revascularization within 30 days was independently associated with reduced 1-year mortality (odds ratio 0.6, [95% confidence interval 0.4, 0.9], P=0.007). CONCLUSIONS: Most patients (88%) with acute myocardial infarction complicated by cardiogenic shock who are alive at 30 days survived at least 1 year. Shock patients who underwent revascularization within 30 days had improved survival at 1 year compared with shock patients who did not receive revascularization, even after adjustment for differences in baseline characteristics between the 2 groups.

Aged↗

PubMed1999

Support for the open-artery hypothesis in survivors of acute myocardial infarction: analysis of 11,228 patients treated with thrombolytic therapy.

We examined the possible benefits of achieving and maintaining infarct-related artery potency beyond the time when preservation of left ventricular function would be expected. The open-artery hypothesis suggests that a patent infarct-related artery confers a survival benefit greater than that expected from myocardial salvage alone, which extends beyond the time when preservation of left ventricular function is expected. We examined the survival experience of patients undergoing thrombolysis in the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-I) trial for whom data on the potency of the infarct artery were available. Univariable analysis was used to determine the unadjusted relations of angiographic variables and revascularization procedures to both 30-day and 1-year mortality in 30-day survivors. Multivariable analysis was used to test for interactions between patency and each characteristic and to adjust both for all other variables and for baseline characteristics known to predict mortality. In both univariable and multivariable analysis, patients with an open rather than a closed infarct-related artery had significantly lower 30-day mortality (p <0.001). This benefit cannot be accounted for by myocardial salvage alone, because it remained after adjustment for left ventricular ejection fraction. Patency was also associated with lower 1-year mortality in 30-day survivors, but not after adjustment for other variables affecting late mortality. Having an open infarct-related artery at the time of first catheterization confers a survival advantage that extends beyond the benefit of myocardial salvage from thrombolytic therapy, and is independent of ejection fraction.

Aged↗

PubMed1999

Effects of stroke on medical resource use and costs in acute myocardial infarction. GUSTO I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries Study.

BACKGROUND: Stroke occurs concurrently with myocardial infarction (MI) in approximately 30 000 US patients each year. This number is expected to rise with the increasing use of thrombolytic therapy for MI. However, no data exist for the economic effect of stroke in the setting of acute MI (AMI). The purpose of this prospective study was to assess the effect of stroke on medical resource use and costs in AMI patients in the United States. METHODS AND RESULTS: Medical resource use and cost data were prospectively collected for 2566 randomly selected US GUSTO I patients (from 23 105 patients) and for the 321 US GUSTO I patients who developed non-bypass surgery-related stroke during the baseline hospitalization. Follow-up was for 1 year. All costs are expressed in 1993 US dollars. During the baseline hospitalization, stroke was associated with a reduction in cardiac procedure rates and an increase in length of stay, despite a hospital mortality rate of 37%. Together with stroke-related procedural costs of $2220 per patient, the baseline medical costs increased by 44% ($29 242 versus $20 301, P<0.0001). Follow-up medical costs were substantially higher for stroke survivors ($22 400 versus $5282, P<0.0001), dominated by the cost of institutional care. The main determinant for institutional care was discharge disability status. The cumulative 1-year medical costs for stroke patients were $15 092 higher than for no-stroke patients. Hemorrhagic stroke patients had a much higher hospital mortality rate than non-hemorrhagic stroke patients (53% versus 15%, P<0.001), which was associated with approximately $7200 lower mean baseline hospitalization cost. At discharge, hemorrhagic stroke patients were more likely to be disabled (68% versus 46%, P=0.002). CONCLUSIONS: In this first large prospective economic study of stroke in AMI patients, we found that strokes were associated with a 60% ($15 092) increase in cumulative 1-year medical costs. Baseline hospitalization costs were 44% higher because of longer mean lengths of stay. Stroke type was a key determinant of baseline cost. Follow-up costs were more than quadrupled for stroke survivors because of the need for institutional care. Disability level was the main determinant of institutional care and thus of follow-up costs.

Activities of Daily Living↗

PubMed1999

Platelet GPIIb-IIIa blockers.

Regardless of the event that stimulates the aggregation of platelets, the receptor alpha(IIb)beta3--one of a family of adhesion receptors known as integrins--has a key role in the process. The past decade has seen the publication of 10 phase III (randomised) clinical trials of four members of a new class of antiplatelet drugs, the GPIIb-IIIa blockers, targeted at this important receptor. Three (abciximab, eptifibatide, and tirofiban) are licensed for human use. 10 other GbIIb-IIIa blockers are in phase II or III human studies. In all 10 placebo-controlled trials, done in the clinical settings of percutaneous coronary intervention or acute coronary syndrome in patients on aspirin, the endpoints favoured the active drug, with a risk reduction for death or non-fatal myocardial infarction of about 21% overall. With attention to heparin dose the risk of bleeding is not a major concern with these agents. The GPIIb-IIIa blockers are taking the clinician and patient out of the era of aspirin monotherapy when platelet inhibition is required.

Humans↗

PubMed1999

Reperfusion revisited: beyond TIMI 3 flow.

Therapy for acute myocardial infarction has advanced dramatically since the early 1980s with the use of early intravenous fibrinolytic therapy. Combining low-dose fibrinolysis and platelet lysis appears to provide an additional increase in infarct-related artery (IRA) patency, but the large-scale mortality reduction trials evaluating this strategy are just getting under way. Recently, considerable attention has shifted away from the epicardial arteries to the microvasculature. Contemporary evidence suggests that epicardial patency does not necessarily translate to actual perfusion at the myocardial level. Techniques to evaluate beyond thrombolysis in myocardial infarction (TIMI) epicardial flow are now available and validated. In addition, there are promising treatments for the prevention or alleviation of certain forms of microvascular obstruction. This review attempts to clarify the confusion surrounding epicardial flow and "myocardial malperfusion" and to provide some insight into the next direction in acute myocardial infarction therapeutics.

Animals↗

PubMed1999

Effect of institutional volume and academic status on outcomes of coronary interventions: the IMPACT-II experience.

BACKGROUND: Rates of morbidity and mortality after interventional procedures are reported to be inversely associated with institutional volume. METHODS: This study assessed both procedural volume and academic status at the 82 US centers that participated in the IMPACT-II trial. Interventional volumes at the sites ranged from 90 to 3300 cases per year. Patients were randomly assigned to a platelet glycoprotein IIb/IIIa inhibitor (eptifibatide) or placebo during procedures done by experienced operators. The primary end point was the composite of death, myocardial infarction, nonelective repeat coronary intervention, or nonelective coronary artery bypass surgery at 30 days, or placement of an intracoronary stent for abrupt closure during the initial procedure. RESULTS: Baseline patient characteristics and median length of stay were similar between the academic and nonacademic centers. In univariable analysis, volume as a continuous variable had a nonlinear relation with the incidence of the composite end point, with better outcomes noted at the highest volume institutions. Academic status did not predict outcome. When added to a predictive model that contained the variables unstable angina, weight, prior coronary artery bypass grafting, heart rate, and platelet count, procedural volume continued to be associated with the composite outcome (P =.04). CONCLUSIONS: We conclude that among hospitals participating in this trial, there is a nonlinear relation between annual interventional volume and outcomes. This relation is complex, involving variations in periprocedural infarction rates and additional, undefined institutional differences (other than academic status) that result in differences in procedural outcome.

Academic Medical Centers↗

PubMed1999

Insights into the pathophysiology of atherosclerosis and prognosis of black Americans with acute coronary syndromes.

BACKGROUND: Disparities in prognosis for black and white patients with coronary heart disease have been widely reported. For several reasons it is unclear to what extent biologic factors contribute to these differences. METHODS: The current medical literature regarding the pathophysiologic characteristics of cardiovascular disease is reviewed with emphasis on how racially mediated biologic differences may affect the manifestation, treatment, and prognosis of patients with coronary heart disease, particularly patients with acute coronary syndromes. RESULTS: Black patients with coronary heart disease have a higher prevalence of ischemic heart disease risk factors, including hypertension, left ventricular hypertrophy, diabetes, and tobacco use. Other factors related to atherosclerosis, vascular reactivity, and thrombolysis that quantitatively and functionally differ among racial groups are identified. Prospective, randomized trials comparing outcomes among patients with acute coronary syndromes have included only a fraction of the available black population, although they reveal a similar short-term mortality rate for black and white patients. Several factors, including enhanced fibrinolysis among black patients with acute myocardial infarction, may in part counterbalance better understood and more prevalent comorbidities to equalize short-term (30-day) survival. All-cause, long-term (1-year) mortality appears worse for black patients compared with white patients with similar cardiovascular risk profiles. CONCLUSION: As racially mediated biologic differences between black and white patients become better understood, targeted interventions to prevent coronary heart disease and treat acute coronary syndromes in black patients can be developed.

Acute Disease↗

PubMed1999

Neurosurgical evacuation of intracranial hemorrhage after thrombolytic therapy for acute myocardial infarction: experience from the GUSTO-I trial. Global Utilization of Streptokinase and tissue-plasminogen activator (tPA) for Occluded Coronary Arteries.

BACKGROUND: Intracranial hemorrhage is an uncommon but very dangerous complication in patients receiving thrombolytic therapy for acute myocardial infarction. Neurosurgical evacuation is often an available treatment option. However, the association between neurosurgical evacuation and clinical outcomes in these patients has yet to be determined. METHODS: The GUSTO-I trial randomly assigned 41,021 patients with acute myocardial infarction to 1 of 4 thrombolytic strategies in 1081 hospitals in 15 countries. A total of 268 patients (0.65%) had an intracranial hemorrhage. We assessed differences in clinical characteristics, neuroimaging features, Glasgow coma scale scores, functional status (disabled: moderate or severe deficit; not disabled: no or minor deficit) and 30-day mortality rate between the 46 patients who underwent neurosurgical evacuation and the 222 patients who did not. RESULTS: Mortality rate at 30 days for all patients with intracranial hemorrhage was 60%; an additional 27% were disabled. Evacuation was associated with significantly higher 30-day survival (65% versus 35%, P <.001) and a trend toward improved functional status (nondisabling stroke: 20% versus 12%, P =.15). CONCLUSIONS: Although intracranial hemorrhage is uncommon after thrombolysis for acute myocardial infarction, 87% of patients die or have disabling stroke. Although not definitive, these data indicate that neurosurgical evacuation may be associated with improved clinical outcomes. Physicians treating such patients should consider early neurosurgical consultation and intervention in these patients.

Aged↗

PubMed1999

Smoking status and outcome after primary coronary angioplasty for acute myocardial infarction.

BACKGROUND: Because of the increased propensity of intracoronary thrombi to form in cigarette smokers, percutaneous transluminal angioplasty (PTCA) for acute myocardial infarction (AMI) may be less effective in smokers. We sought to determine the impact of smoking status on outcome after PTCA for AMI. METHODS: Patients enrolled in the GUSTO IIb Angioplasty Substudy were randomly assigned to receive PTCA or tissue-plasminogen activator (tPA) for AMI. The interaction of smoking status (nonsmokers = 344, former smokers = 294, current smokers = 490) and treatment strategy with the occurrence of death, nonfatal reinfarction, or nonfatal, disabling stroke at 30 days was analyzed. Procedural success (residual stenosis <50% and Thrombolysis in Myocardial Infarction [TIMI] flow grade 3) was also analyzed for patients who underwent PTCA (n = 444). RESULTS: Among patients who underwent PTCA, nonsmokers had worse percent stenosis of the culprit lesion before reperfusion (P =.03) and more often had TIMI flow grade 0 (P <.05). Procedural success was more common in smokers (65.6%) than in former smokers (53.3%) and nonsmokers (52. 4%; P =.02), reflecting a higher rate of postprocedure TIMI 3 flow. PTCA was associated with a better 30-day outcome than tPA for current smokers (odds ratio [95% confidence interval] = 0.41 [0.19 to 0.88]), with a similar trend for former smokers (0.73 [0.34 to 1. 58]) and nonsmokers (0.77 [0.42 to 1.40]). At 6 months, smokers randomly assigned to PTCA also had fewer deaths and reinfarction (0. 58 [0.31 to 1.07]). CONCLUSIONS: Although smoking status affects angiographic variables before and after PTCA for AMI, PTCA is associated with a better 30-day outcome than tPA regardless of smoking status and should be considered when readily available.

Angioplasty, Balloon, Coronary↗

PubMed1999

Cardiogenic shock complicating acute myocardial infarction: predictors of death. GUSTO Investigators. Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries.

BACKGROUND: Current knowledge of predictors of death among patients with cardiogenic shock complicating myocardial infarction is limited. We aimed to develop a risk assessment prognostic algorithm of 30-day mortality, including clinical and hemodynamic data prospectively collected among patients with cardiogenic shock in the 41,021-patient Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial. METHODS: We used logistic regression modeling techniques to evaluate the relations between demographic, clinical, and hemodynamic characteristics and 30-day mortality rate for the entire shock population (n = 2968) and for patients who underwent right-heart catheterization (n = 995). RESULTS: The odds (95% confidence interval) of dying were 1.49 times higher (1.27-1.74) for patients 10 years older and 1.70 times higher (1.19-2.44) for patients with prior infarction. Findings derived from physical examination, such as altered sensorium and cold, clammy skin, were important independent predictors of prognosis (odds of dying 1.68 times higher for each [1.19-2.39 and 1.15-2.46]). The odds of dying were also 2.25 times higher (1.61-3.15) in patients with oliguria. Mortality rate was lowest for cardiac output and pulmonary capillary wedge measurements of 5.1 L/min and 20 mm Hg, respectively, and increased with either higher or lower values. Patients with shock had better outcomes than patients in whom shock developed later, although for the latter subgroup, prognosis was worse in patients who had heart failure (Killip class II to III). CONCLUSIONS: We devised a prognostic algorithm for patients with cardiogenic shock complicating acute myocardial infarction. In addition to demographic and easily derived physical examination features, data derived from right-heart catheterization added valuable information that increased the ability to predict outcome in this high-risk population.

Aged↗

PubMed1999

Prophylactic lidocaine use in acute myocardial infarction: incidence and outcomes from two international trials. The GUSTO-I and GUSTO-IIb Investigators.

BACKGROUND: Early meta-analyses suggested that prophylactic lidocaine use reduces ventricular fibrillation but increases mortality rates after acute myocardial infarction. We determined the frequency and effect on clinical outcomes with its use in the thrombolytic era. METHODS AND RESULTS: We studied 43,704 patients enrolled in GUSTO-I or GUSTO-IIb who had ST-segment elevation, underwent thrombolysis, and survived at least 1 hour after enrollment. Odds ratios (OR) and confidence intervals (CI) were calculated for the risk of asystole, atrioventricular block, ventricular fibrillation, and ventricular tachycardia during hospitalization; for 24-hour, in-hospital, and 30-day mortality rates; and for 24-hour and 30-day mortality rates after adjustment for baseline predictors of death. In GUSTO-I and GUSTO-IIb, 16% and 3.5% of patients, respectively, received prophylactic lidocaine. They had a lower risk of death at 24 hours (OR 0.81, 95% CI 0.67 to 0.97) and trends toward lower odds of in-hospital death (OR 0.90, 95% CI 0.81 to 1.01) and death at 30 days (OR 0.92, 95% CI 0.82 to 1. 02). After adjustment for baseline characteristics, however, the odds of death were similar with or without lidocaine (OR 0.90 and 0. 97, respectively). Outside the United States, lidocaine was associated with higher incidences of all serious arrhythmias, but in US patients it conferred a lower likelihood of ventricular fibrillation and no increase in asystole, atrioventricular block, or mortality rates. CONCLUSIONS: Prophylactic lidocaine use has decreased with the advent of thrombolysis, although its use may not be associated with increased mortality rates.

Aged↗