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E J Topol

Publications and source records attributed to E J Topol.

At least 73 records · Page 4Linked to original sources
PubMed2001

Outcome of acute ST-segment elevation myocardial infarction in patients with prior coronary artery bypass surgery receiving thrombolytic therapy.

BACKGROUND: Patients with prior coronary bypass surgery with acute ST-segment elevation myocardial infarction (MI) pose an increasingly common clinical problem. We assessed the characteristics and outcomes of such patients undergoing thrombolysis for acute MI. METHODS AND RESULTS: We compared the characteristics and outcomes of patients in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (GUSTO-I) who had had prior bypass (n = 1784, 4% of the population) with those without prior coronary artery bypass grafting (CABG), all of whom were randomized to receive one of four thrombolytic strategies. Patients with prior bypass were older with significantly more prior MI and angina. Overall, 30-day mortality was significantly higher in patients with prior bypass (10.7% vs 6.7% for no prior bypass, P <.001); these patients also had significantly more pulmonary edema, sustained hypotension, or cardiogenic shock. Patients with prior bypass showed a 12.5% relative reduction (95% confidence interval, 0% to 41.9%) in 30-day mortality with accelerated alteplase over the streptokinase monotherapies. In the 62% of patients with prior CABG who underwent coronary angiography, the infarct-related vessel was a native coronary artery in 61.9% and a bypass graft in 38.1% of cases. The Thrombolysis in Myocardial Infarction (TIMI) 3 flow rate was 30.5% for culprit native coronary arteries and 31.7% for culprit bypass grafts. Patients with prior bypass had more severe infarct-vessel stenoses (99% [90%, 100%] vs 90% [80%, 99%], P <.001). CONCLUSIONS: The 30-day mortality in patients with prior CABG was significantly higher than that for patients without prior CABG. As in the overall trial, these patients derived an incremental survival benefit from treatment with accelerated alteplase, but mortality remained high (16.7%) at 1 year. These results are at least partially explained by the higher baseline risk of these patients and by the lower rate of patency of the infarct-related artery.

Coronary Angiography↗
PubMed2001

Variation in patient management and outcomes for acute coronary syndromes in Latin America and North America: results from the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial.

BACKGROUND: Although more than 9500 patients have been enrolled in major clinical trials in Latin America, practice patterns in this region have rarely been examined. We sought to compare characteristics, resource utilization, and outcomes of patients treated for acute coronary syndromes in Latin America with those in North America. METHODS: The Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Theraphy Trial (PURSUIT) enrolled 10,948 patients with non-ST-segment elevation acute coronary syndromes, including 585 in Latin America and 4358 in North America. We analyzed regional differences in patient groups, treatment patterns, and outcomes and used logistic regression analysis to identify association of enrollment region and survival. RESULTS: For patients in Latin America, the length of hospital stay was significantly longer (10 [7, 15] days vs 6 [4, 9], P <.001). Angiograms, angioplasty, and bypass surgery were significantly less common in Latin America (46.2%, 17.6%, and 11.3% vs 79.4%, 33.6%, and 19.4%, P <.001). Thirty-day death/myocardial infarction was not significantly higher, although mortality alone was significantly higher (6.8% vs 3.1%, P <.001). After adjustment for baseline characteristics, enrollment in Latin America remained an independent predictor for death at 30 days (odds ratio [OR] [95% confidence interval (CI)] 2.42 [1.60-3.67]) and persisted at 6 months (OR [95% CI] 2.5 [1.8-3.4]). CONCLUSIONS: Latin American patients treated for acute coronary syndromes were managed less invasively and were twice as likely as their North American counterparts to die within 6 months. This mortality difference was not explained by imbalances in baseline risk.

Angina, Unstable↗
PubMed2001

Recurrent ischemia after thrombolysis for acute myocardial infarction.

BACKGROUND: Reliable predictors have yet to be found for recurrent ischemia after thrombolysis for acute myocardial infarction (AMI), nor do we know whether early angiography can herald recurrent ischemia. This study sought to investigate the relationship between recurrent ischemia and cardiac procedures after thrombolysis for AMI. METHODS: The Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial prospectively studied recurrent ischemia, which was defined as the presence of angina and changes in hemodynamics or the electrocardiogram. Cox regression analysis was used to identify predictors of recurrent ischemia. Other variables examined included time to coronary angiography and revascularization. RESULTS: Of 21,772 US GUSTO-I patients, 6313 (29%) had recurrent ischemia before discharge. Women (hazard ratio [HR] 1.25, 95% confidence interval [CI] 1.17-1.33) and patients with hypercholesterolemia (HR 1.14, 95% CI 1.07-1.22) or prior angina (HR 1.40, 95% CI 1.32-1.49) had a higher likelihood of recurrent ischemia. Current smoking and hours to thrombolysis were inversely related to recurrent ischemia (HR 0.86, 95% CI 0.81-0.92, HR 0.97, 95% CI 0.95- 0.99, respectively). Patients who underwent angiography before recurrent ischemia had a marginally increased risk of ischemia within 12 hours after angiography (HR 1.2, 95% CI 1.1-1.4); ultimately, they had a considerably lower risk 1 week after angiography than did patients without angiography (HR 0.57, 95% CI 0.45-0.72). CONCLUSIONS: Female sex, hypercholesterolemia, prior angina, and nonsmoking status weakly predict recurrent ischemia. Early coronary angiography reduces recurrent ischemia, probably because high-risk patients are identified and revascularized.

Cardiac Catheterization↗
PubMed2001

Effect of smoking status and abciximab use on outcome after percutaneous coronary revascularization: Pooled analysis from EPIC, EPILOG, and EPISTENT.

BACKGROUND: Tobacco use has been studied in relation to the development of atherosclerotic heart disease and outcome after acute coronary syndromes, though outcome data after percutaneous coronary intervention (PCI) are limited. Tobacco use has been associated with increased fibrinogen levels, thrombin generation, and increased platelet aggregation, and these factors may cause ischemic events after PCI. METHODS: We assessed whether smokers undergoing PCI have more ischemic events and if glycoprotein IIb/IIIa receptor blockade is particularly beneficial in preventing ischemic events in this cohort. We examined clinical outcomes for smokers and nonsmokers by using pooled analysis from 3 large, placebo-controlled trials of the glycoprotein IIb/IIIa antagonist abciximab during PCI. RESULTS: Among 6519 patients, 34% were smokers. The primary end point of death, myocardial infarction, or urgent revascularization within 30 days was reduced by abciximab from 12.3% to 6.4% (relative risk reduction, 48%; P <.001) in smokers and from 11.3% to 5.9% (relative risk reduction, 48%; P <.001) in nonsmokers treated with abciximab. At 6 months, death, myocardial infarction, or urgent revascularization was reduced from 14.4% to 8.5% (relative risk reduction, 41%; P <.001) in smokers and from 14.6% to 8.8% (relative risk reduction, 40%; P <.001) in nonsmokers. Adjusting for baseline differences, smoking was an independent predictor of poor outcome at 30 days (odds ratio, 1.22; 95% confidence interval, 1.02, 1.47; P =.03). CONCLUSIONS: This pooled analysis demonstrates that after PCI, smokers had worse 30-day outcomes than did nonsmokers. However, both groups had a comparable degree of benefit with platelet inhibition through the use of abciximab.

Abciximab↗
PubMed2001

Predictors of left ventricular function after acute myocardial infarction: effects of time to treatment, patency, and body mass index: the GUSTO-I angiographic experience.

BACKGROUND: Despite the significant survival benefit associated with successful reperfusion therapy for acute myocardial infarction, global indices of outcome left ventricular function, such as ejection fraction, have often demonstrated little or no improvement. Although these measurements are confounded by numerous clinical, physiologic, and angiographic variables, no comprehensive analysis of this issue in a large series of patients is available. We used the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) database to better understand this phenomenon by determining independent predictors of left ventricular function and their interplay with regard to outcome ventricular function and improvement in function during the initial postinfarction week. METHODS: Ninety-minute and 5- to 7-day posttreatment global and regional indices derived from left ventriculograms were analyzed from a population of 676 patients. These observations were combined with clinical data to describe independent determinants of ventricular function outcome. RESULTS: Clinical factors predictive of global and regional ventricular function as well as improvement in function between 90 minutes and 5 to 7 days included time to treatment, early infarct-related artery flow grade, and body mass index. These same factors contribute significantly to compensatory hyperkinesis of the noninfarct zone, which is critical to maintenance of global ventricular function during this time period. CONCLUSIONS: The ventricular function benefits of early complete reperfusion after myocardial infarction are readily demonstrable after adjustment for multiple covariables and include (1) maintenance of global ventricular function and (2) prevention or delay in ventricular dilatation.

Aged↗
PubMed2001

Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina: Final report reanalysis of the Bivalirudin Angioplasty Study.

BACKGROUND: This study was a reanalysis of the Bivalirudin Angioplasty Study, which compared bivalirudin with high-dose heparin during coronary angioplasty for unstable angina. METHODS: Differences in rates of death, myocardial infarction, or repeat revascularization were compared at 7, 90, and 180 days after angioplasty with intention-to-treat analysis. RESULTS: The combined end point occurred in 135 of 2161 patients (6.2%) in the bivalirudin group and in 169 of 2151 patients (7.9%) in the heparin group at 7 days (P =.039). Differences persisted between the groups at 90 days (P =.012) and 180 days (P =.153). Bleeding occurred in 76 patients (3.5%) in the bivalirudin group versus 199 (9.3%) in the heparin group (P <.001). CONCLUSIONS: This analysis supports the hypothesis that bivalirudin reduces ischemic complications and bleeding after angioplasty. Further trials are needed to evaluate bivalirudin versus heparin in conjunction with platelet-glycoprotein IIb/IIIa inhibitors and for coronary stenting.

Actuarial Analysis↗
PubMed2001

Common variations in platelet glycoproteins: pharmacogenomic implications.

Atherosclerosis and its complications are the result of complex interactions between the environment and genetic factors. Platelets play an important role in this disease process and antiplatelet agents are an essential part of its treatment. However, individual response to antiplatelet therapy is variable and agents that are safe and effective in one individual may be ineffective or harmful in another. It is likely that genetic factors are involved in this variance as platelet, and platelet-associated proteins are highly polymorphic. Up to 30% of natural variation in platelet reactivity is related to genetic inheritance. Rare inherited defects of platelet function due to the absence or reduced surface expression of platelet adhesion receptors have long been recognised. These cause minor bleeding defects and are usually clinically apparent. Antiplatelet agents should be avoided in these situations. The importance of the more common genetic variations or polymorphisms, which result in minor changes in the expressed protein and are often clinically silent, is unknown. Investigations are ongoing into the role of this variation in platelet physiology. A number of polymorphisms in platelet surface glycoproteins have received particular attention; the (A1/2) polymorphism resulting in conformational change at the amino terminus of the beta-3 chain of the platelet fibrinogen receptor glycoprotein (GP) IIb/IIIa and polymorphisms in the platelet collagen (GPIa/IIa and GPVI) and von Willebrand receptors (GPIb-IX). The (A2) allele has been associated with resistance to the antiplatelet agent aspirin and increased platelet responsiveness. The GPIa polymorphism has been associated with increased surface expression of GPIa and increased platelet adhesion to collagen. Recently, conflicting reports of the association of these polymorphisms with coronary artery disease (CAD) and its complications have been described. Mutations have also been identified in other platelet surface receptors including the recently identified G(i)-linked platelet adenosine diphosphate (ADP) receptor (P2Y(12)), targeted by the antiplatelet agents ticlopidine and clopidogrel. These discoveries have stimulated interest in the role of genetic factors in platelet physiology. In this article, the current knowledge of the influence of genetic make-up on antiplatelet therapy is discussed.

Animals↗
PubMed2001

Oral glycoprotein IIb/IIIa inhibitors: why don't they work?

Despite their promise as orally active potent inhibitors of platelet aggregation, the oral platelet glycoprotein IIb/IIIa inhibitors have failed to provide a reduction in late ischemic events. In fact, with five large-scale randomized trials now complete, including over 42 000 patients, these agents have been associated with a surprising, yet consistent, excess in mortality. Peculiarly, this fatality risk has occurred in the absence of a commensurate increase in other ischemic end-points. While these findings have curtailed the further clinical development of this class of potent platelet inhibitors, the obvious dissociation between platelet suppression and adverse outcome requires further clarification. Multiple putative explanations for this excess in ischemic events with oral glycoprotein IIb/IIIa inhibitors have been proposed, but definitive data implicating a specific mechanism are currently not available. While the lack of concurrent aspirin may account for some of this effect, it is unlikely to fully explain the mortality excess. Potential mechanisms include partial agonist activity leading to increased expression of platelet-leukocyte adhesion molecules, sub-optimal inhibition of platelet aggregation, genetic polymorphisms, especially phospholipase A(2) polymorphism, and promotion of cardiac myocyte apoptosis via activation of caspase 3. Definitive elucidation of these adverse mechanisms will be required if further clinical development of the oral platelet glycoprotein IIb/IIIa inhibitors is to be pursued.

Administration, Oral↗
PubMed2001

Introduction.

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Journal Article↗
PubMed2001

Dual antiplatelet therapy with clopidogrel and aspirin after carotid artery stenting.

BACKGROUND: Carotid artery stenting is being used as an alternative to carotid endarterectomy, both within the context of clinical trials and in non-surgical candidates. Though stenting is known to activate platelets, the role of antithrombotic therapy in carotid stenting has not been fully characterized. METHODS AND RESULTS: Consecutive patients (n = 162) were followed in a single-center carotid stent registry. The cumulative rate of 30-day death, stroke, transient ischemic attack and myocardial infarction in those patients receiving a thienopyridine was determined, as were rates of stent thrombosis and intracranial hemorrhage. The mean age of the patients was 70.3 years and there was an extremely high prevalence of cardiovascular comorbidities, including 40% with unstable angina. The carotid lesion was symptomatic in 59% of patients. The average pre-treatment stenosis was 83%. The cumulative 30-day rate of death, stroke, transient ischemic attack and myocardial infarction was 5.6%. Specifically, in the patients who received ticlopidine (n = 23), the rate was 13%, versus 4.3% in the patients who received clopidogrel (n = 139) (p = 0.01). In this series, there were no cases of stent thrombosis and 1 intracranial hemorrhage. CONCLUSION: Dual antiplatelet therapy with clopidogrel plus aspirin in patients receiving carotid artery stents is associated with a low rate of ischemic events. Furthermore, clopidogrel appears superior to ticlopidine. Thus, our findings lend support to the dual antiplatelet strategy of clopidogrel plus aspirin for patients undergoing carotid artery stenting.

Aged↗
PubMed2000

Economic assessment of platelet glycoprotein IIb/IIIa receptor blockade with abciximab and low-dose heparin during percutaneous coronary revascularization: results from the EPILOG randomized trial. Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade.

BACKGROUND: In the EPILOG trial (Evaluation in PTCA to Improve Long-term Outcome with abciximab GP IIb/IIIa blockade), abciximab administered with weight-adjusted heparin diminished the risk of ischemic complications within 30 days by 56% among patients undergoing percutaneous coronary revascularization, without increased bleeding complications. METHODS AND RESULTS: A prospective economic assessment was performed in the 2792 patients enrolled in EPILOG. Patients were randomized to receive placebo with standard-dose weight-adjusted heparin, abciximab with low-dose weight-adjusted heparin, or abciximab with standard-dose weight-adjusted heparin during percutaneous coronary intervention. Hospital billing data for the baseline hospitalization were collected for 2581 patients (92.4% of total) and imputed for the remainder, with physician fees estimated from the Medicare Fee Schedule. For the baseline hospitalization, medical costs (hospitalization and physician fees) averaged $9632 for the placebo arm compared with $8758 (P:=0.005) and $9092 (P:=0.176) for the abciximab with low-dose and standard-dose heparin arms, respectively. Inclusive of average drug cost ($1454 to $1457), the net incremental baseline cost of these 2 abciximab strategies was $583 with low-dose weight-adjusted heparin and $914 with standard-dose weight-adjusted heparin. During 6-month follow-up, average hospital costs were not significantly different in the 3 treatment groups; cumulative net incremental costs were $1236 and $1268 in the abciximab with low-dose and standard-dose heparin groups, respectively. CONCLUSIONS: Treatment with abciximab and low-dose, weight-adjusted heparin during percutaneous coronary revascularization reduces ischemic events and associated costs, thereby offsetting some of the cost of the drug. The suppression of bleeding complications associated with this agent by heparin dose reduction optimizes the economic attractiveness of this treatment strategy.

Abciximab↗
PubMed2000

Enhanced efficacy of eptifibatide administration in patients with acute coronary syndrome requiring in-hospital coronary artery bypass grafting. PURSUIT Investigators.

BACKGROUND: Patients with a recent episode of non-ST-segment elevation acute coronary syndrome before CABG have higher rates of operative morbidity and mortality than patients with stable coronary syndromes. The efficacy of administering eptifibatide to these patients undergoing in-hospital CABG is unknown. METHODS AND RESULTS: The Platelet Glycoprotein IIb-IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial randomized 10 948 patients to receive either eptifibatide or placebo. There were 1558 study participants who underwent in-hospital CABG: 692 received placebo, and 866 received eptifibatide. The main substudy analysis end point was death or myocardial infarction (MI) rates at the 6-month follow-up. The 30-day death or MI rates were 30. 8% and 26.1% for the placebo and eptifibatide groups, respectively (P:=0.041). The benefit of eptifibatide administration persisted through 6-months of follow-up (32.7% versus 27.6% for placebo versus eptifibatide, respectively; P:=0.029). There was a greater reduction in the 6-month death or MI rate for patients who received eptifibatide within 72 hours of CABG (33.6% versus 23.8%; P:=0.002) compared with the >72-hour group (31.6% versus 32%; P:=1.0). The incidence of major bleeding was 56.6% for placebo-treated patients versus 58.2% for eptifibatide-treated patients (P:=0.7). CONCLUSIONS: Eptifibatide administration in patients undergoing in-hospital CABG with a recent episode of a non-ST-segment elevation acute coronary syndrome results in a significant reduction in death or MI that is evident at 7 days and persists through the 6-month follow-up without a significant increase in perioperative bleeding rates.

Acute Disease↗
PubMed2000

Facilitation of early percutaneous coronary intervention after reteplase with or without abciximab in acute myocardial infarction: results from the SPEED (GUSTO-4 Pilot) Trial.

OBJECTIVES: We examined the utility of early percutaneous coronary intervention (PCI) in a trial that encouraged its use after thrombolysis and glycoprotein IIb/IIIa inhibition for acute myocardial infarction (MI). BACKGROUND: Early PCI has shown no benefit when performed early after thrombolysis alone. METHODS: We studied 323 patients (61%) who underwent PCI with planned initial angiography, at a median 63 min after reperfusion therapy began. A blinded core laboratory reviewed cineangiograms. Ischemic events, bleeding, angiographic results, and clinical outcomes were compared between early PCI and no-PCI patients (n = 162), between patients with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 or 1 before PCI versus flow grade 2 or 3, and among three treatment regimens. RESULTS: Early PCI patients showed a procedural success (<50% residual stenosis and TIMI flow grade 3) rate of 88% and a 30-day composite incidence of death, reinfarction, or urgent revascularization of 5.6%. These patients had fewer ischemic events and bleeding complications (15%) than did patients not undergoing early PCI (30%, p = 0.001). Early PCI was used more often in patients with initial TIMI flow grade 0 or 1 versus flow grade 2 or 3 (83% vs. 60%, p < 0.0001). Patients receiving abciximab with reduced-dose reteplase (5 U double bolus) showed an 86% incidence of TIMI grade 3 flow at approximately 90 min and a trend toward improved outcomes. CONCLUSIONS: In this analysis, early PCI facilitated by a combination of abciximab and reduced-dose reteplase was safe and effective. This approach has several advantages for acute MI patients, which should be confirmed in a dedicated, randomized trial.

Abciximab↗
PubMed2000

Survival outcomes 1 year after reperfusion therapy with either alteplase or reteplase for acute myocardial infarction: results from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) III Trial.

BACKGROUND: New recombinant plasminogen activators have been developed to simulate the fibrinolytic action of the physiological serine protease tissue plasminogen activator (alteplase, t-PA), and have prolonged half-life features permitting bolus administration. One such activator, reteplase (r-PA), was compared with t-PA in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO)-III Trial. METHODS AND RESULTS: At 1-year follow-up, survival status was ascertained in 97.4% of the 15 059 patients enrolled in the GUSTO-III trial. At 1 year, the mortality rate for the t-PA-assigned group was 11.06%, and for r-PA it was 11.20% (P:=0. 77). The absolute mortality difference of 0.14% has 95% CIs of -1. 21% to 0.93%. There were no significant differences in outcome by intention-to-treat for the 2 different plasminogen activators in the prespecified groups (age, infarct location, time-to-treatment). The absolute difference in mortality rates between t-PA and r-PA progressively narrowed over the predetermined observation times after random assignment; it was 0.31% at 24 hours, 0.26% at 7 days, 0.23% at 30 days, and 0.14% at 1 year. Of note, mortality rate in the trial between 30 days and 1 year in 13 883 patients was 4.02% and did not differ between the treatment groups. However, this mortality rate was substantially greater than in GUSTO-I, in which mortality rate for t-PA versus streptokinase between 30 days and 1-year was 2.97% (heart rate 1.36, 95% CI 1.23, 1.50, P:<0.001). CONCLUSIONS: The r-PA and t-PA strategies yielded similar survival outcomes after 30 days in this trial. The increase in mortality rate during extended follow-up compared with previous trials may reflect higher-risk patients and highlights the need for improved secondary prevention strategies.

Acute Disease↗
PubMed2000

Safety of femoral closure devices after percutaneous coronary interventions in the era of glycoprotein IIb/IIIa platelet blockade.

We compared in-hospital femoral complications of Angio-Seal, Perclose, and manual compression in consecutive patients who underwent percutaneous coronary interventions in the era of glycoprotein IIb/IIIa platelet inhibition. Femoral closure devices have a similar overall risk profile as manual compression, even in patients treated with glycoprotein IIb/IIIa platelet inhibition, although certain rare complications such as retroperitoneal hemorrhage and severe access-site infection may be more common with the use of these devices.

Angioplasty, Balloon, Coronary↗
PubMed2000

Evaluation of the effects of aspirin combined with angiotensin-converting enzyme inhibitors in patients with coronary artery disease.

BACKGROUND: Several studies have suggested that there may be an interaction between angiotensin-converting enzyme (ACE) inhibitors and aspirin in patients with congestive heart failure, such that their benefits are attenuated when used in combination. Whether this interaction exists in patients with coronary artery disease is not known. SUBJECTS AND METHODS: Patients enrolled in two large trials, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) and Evaluation in PTCA to Improve Long-Term Outcome with Abciximab GP IIb/IIIa Blockade (EPILOG), were stratified according to use of aspirin and ACE inhibitors on discharge from the hospital. In the EPILOG trial, left ventricular systolic function was assessed by contrast ventriculography. The primary endpoint was all-cause mortality at 1 year. EPILOG patients, all of whom were receiving aspirin, were also examined for the combined endpoint of death or nonfatal myocardial infarction. Stratified and multivariate analyses were used to adjust for baseline differences in patient characteristics. RESULTS: We studied 31,622 patients in the GUSTO-I trial and 2,619 patients in the EPILOG trial. There were 615 deaths among the GUSTO-I patients and 45 deaths among the EPILOG patients at 1 year. Unadjusted mortality was greater among patients treated with both ACE inhibitors and aspirin than among patients treated with aspirin alone (3.3% versus 1.6%, P <0.001 for GUSTO-I; and 3.7% versus 1.2%, P <0.001 for EPILOG). Similarly, the composite endpoint of death or nonfatal myocardial infarction was more frequent among EPILOG patients who were taking ACE inhibitors (6.3% versus 3.3%, P = 0. 001). After adjusting for confounders, combined use of aspirin and ACE inhibitors was associated with increased mortality in GUSTO-I patients (hazard ratio [HR] = 2.2, 95% confidence interval [CI]: 1.1 to 4.3, P = 0.03) compared with aspirin alone. In EPILOG patients, after adjusting for clinical factors and extent of left ventricular dysfunction, the combination of aspirin and ACE inhibitors was associated with an increased risk of death (HR = 2.1, 95% CI: 1.1 to 3.8, P = 0.02) and of death or nonfatal myocardial infarction (HR = 1.5, 95% CI: 1.1 to 2.5, P = 0.02) compared with aspirin alone. CONCLUSION: These observational findings suggest the possibility of an interaction between aspirin and ACE inhibitors among patients with ischemic heart disease. Further study of this issue is warranted.

Aged↗