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Biomedical subjects

Eric J Topol

Publications and source records attributed to Eric J Topol.

At least 217 records · Page 12Linked to original sources
PubMed2002

Patient outcomes after fibrinolytic therapy for acute myocardial infarction at hospitals with and without coronary revascularization capability.

OBJECTIVES: This study evaluated clinical outcomes in patients with acute myocardial infarction (MI) treated with fibrinolytic therapy in hospitals with and without coronary revascularization capability. BACKGROUND: Patients with MI may have better outcomes when admitted to certain hospitals with coronary revascularization capability. Development of regional heart care centers for the treatment of MI has been proposed. METHOD: We performed a retrospective analysis of 25,515 U.S. patients enrolled in the Global Use of Streptokinase and TPA (alteplase) for Occluded Coronary arteries (GUSTO)-I trial. Outcomes of patients admitted to hospitals with and without coronary revascularization capability were analyzed. We also analyzed patients who remained in hospitals without coronary revascularization capability compared with those transferred to hospitals with revascularization capability. RESULTS: Baseline characteristics and complications were similar between patients in the two hospital types. Patients in hospitals with coronary revascularization capability more often underwent cardiac catheterization (78.1% vs. 59.2%; p < 0.001), angioplasty (34.6% vs. 22.6%; p < 0.001), or bypass surgery (14.1% vs. 10.4%; p < 0.001) but had a similar adjusted 30-day (odds ratio [OR] 0.91, 95% confidence interval [CI] 82 to 1.02) and one-year (OR 0.98, 95% CI 0.90 to 1.07) mortality. Forty percent of patients admitted to hospitals without revascularization capability were transferred, with 94% of transfer patients undergoing angiography. Almost 80% of transfers occurred >48 h after hospital admission. CONCLUSION: Patients receiving fibrinolytic therapy for acute MI admitted to hospitals without coronary revascularization capability appear to have outcomes similar to those of patients admitted to hospitals with such capability when aspirin and beta-adrenergic blocking agents are given appropriately and transfer is available for angiography and angioplasty as needed.

Aged↗
PubMed2002

Death following creatine kinase-MB elevation after coronary intervention: identification of an early risk period: importance of creatine kinase-MB level, completeness of revascularization, ventricular function, and probable benefit of statin therapy.

BACKGROUND: Creatine kinase (CK)-MB elevation after percutaneous coronary intervention (PCI) has been associated with subsequent cardiac death. The patients at risk, the timing of risk, and potential treatment implications are uncertain. METHODS AND RESULTS: Eight thousand, four hundred nine consecutive non- acute myocardial infarction patients with successful PCI and no emergency surgery or Q-wave myocardial infarction were followed for 38+/-25 months; 1446 (17.2%) had post-PCI CK-MB above normal on routine ascertainment. Patients were prospectively stratified into those with CK-MB 1 to 5x or CK-MB >5x normal. No patient with CK-MB 1 to 5x normal died during the first week after PCI, and excess risk of early death for patients with CK-MB elevation occurred primarily in the first 3 to 4 months. The actuarial 4-month risk of death was 8.9%, 1.9%, and 1.2% for patients with CK-MB >5x, CK-MB 1 to 5x, and CK-MB < or =1x normal (P<0.001). Death within 4 months was independently correlated with the degree of CK-MB elevation, creatinine > or =2 mg%, post-PCI C-reactive protein, low ejection fraction, age, and congestive heart failure class (P<0.01 for all). In a matched subset analysis, incomplete revascularization (P<0.001), congestive heart failure class (P=0.005), and no statin treatment at hospital discharge (P=0.009) were associated with death. CONCLUSIONS: Patients with CK-MB elevation after PCI are at excess risk of death for 3 to 4 months, although prolonging hospitalization for CK-MB 1 to 5x is unlikely to modify risk. CK-MB >5x normal, incomplete revascularization, elevated C-reactive protein, heart failure, the elderly, and hospital discharge without on statin therapy increases risk. Several of these factors suggest that inflammation may play a part in the excess risk of death.

Aged↗
PubMed2002

Mortality benefit of beta-blockade after successful elective percutaneous coronary intervention.

OBJECTIVES: The goal of this study was to evaluate the mortality benefit of beta-blockers after successful percutaneous coronary intervention (PCI). BACKGROUND: Beta-blockers reduce mortality after myocardial infarction (MI), though limited data are available regarding their role after successful PCI. METHODS: Each year from 1993 through 1999, the first 1,000 consecutive patients undergoing PCI were systematically followed up. Patients presenting with acute or recent MI, shock, or unsuccessful revascularization procedures were excluded from the analysis. Clinical, procedural, and follow-up data of beta-blocker-treated and non-beta-blocker-treated patients were compared. A multivariate survival analysis model using propensity analysis was used to adjust for heterogeneity between the two groups. RESULTS: Of the 4,553 patients, 2,056 (45%) were treated with beta-blockers at the time of the procedure. Beta-blocker therapy was associated with a mortality reduction from 1.3% to 0.8% at 30 days (p = 0.13) and a reduction from 6.0% to 3.9% at one year (p = 0.0014). This survival benefit of beta-blockers was independent of left ventricular function, diabetic status, history of hypertension, or history of MI. Using propensity analysis, beta-blocker therapy remained an independent predictor for one-year survival after PCI (hazard ratio, 0.63; 95% confidence interval, 0.46 to 0.87; p = 0.0054). CONCLUSIONS: Within this large prospective registry, beta-blocker use was associated with a marked long-term survival benefit among patients undergoing successful elective percutaneous coronary revascularization.

Adrenergic beta-Antagonists↗
PubMed2002

Outcomes at 6 months for the direct comparison of tirofiban and abciximab during percutaneous coronary revascularisation with stent placement: the TARGET follow-up study.

BACKGROUND: Two placebo-controlled trials testing intravenous platelet glycoprotein IIb/IIIa antagonists in the setting of percutaneous coronary revascularisation with intracoronary stents have shown a durable reduction in ischaemic events to 6 months. These trials differed regarding their patient population, IIb/IIIa inhibitor, and reported extent of benefit. Whether a small-molecule agent affecting only the IIb/IIIa receptor would provide a similar outcome for ischaemic events and clinical restenosis at 6 months when directly compared with a monoclonal antibody known to affect several integrin receptors is unknown. METHODS: In 18 countries at 149 hospitals, 4809 patients undergoing elective or urgent stent implantation were randomly assigned a bolus and infusion of tirofiban or abciximab. Patients were followed for 6 months for the occurrence of death, myocardial infarction, and any target-vessel revascularisation. The results at 30 days have been reported previously. FINDINGS: At 6 months the composite endpoint of death, myocardial infarction, and target-vessel revascularisation occurred in 356 (14.8%) patients who received tirofiban and 345 (14.3%) patients who received abciximab (hazard ratio 1.04, 95% CI 0.90-1.21; p=0.591). The rates for the individual endpoints were 191 (8.0%) versus 159 (6.6%) for myocardial infarction (hazard ratio 1.21, 95% CI 0.98-1.50; p=0.074), 26 (1.1%) versus 25 (1.0%) for death (1.04, 0.60-1.80; p=0.893), and 194 (8.1%) versus 208 (8.6%) for target-vessel revascularisation (0.93, 0.77-1.14; p=0.495). INTERPRETATION: At 6 months, tirofiban provided a similar level of overall protection to abciximab against the composite of death, myocardial infarction, and any target-vessel revascularisation.

Abciximab↗
PubMed2002

Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation: incidence, predictors, and outcomes.

BACKGROUND: The prognosis of ventricular arrhythmias among patients with non-ST-elevation acute coronary syndromes is unknown. We studied the incidence, predictors, and outcomes of sustained ventricular arrhythmias in 4 large randomized trials of such patients. METHODS AND RESULTS: We pooled the datasets of the Global Use of Streptokinase and tPA for Occluded Arteries (GUSTO)-IIb, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON)-A, and PARAGON-B trials (n=26 416). We identified independent predictors of ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared the 30-day and 6-month mortality rates of patients who did (n=552) and did not (n=25 864) develop these arrhythmias during the index hospitalization. Independent predictors of in-hospital VF included prior hypertension, chronic obstructive pulmonary disease, prior myocardial infarction, and ST-segment changes at presentation. Except for hypertension, these variables also independently predicted in-hospital VT. In Cox proportional-hazards modeling, in-hospital VF and VT were independently associated with 30-day mortality (hazard ratio [HR], 23.2 [95% CI, 18.1 to 29.8] for VF and HR, 7.6 [95% CI, 5.5 to 10.4] for VT) and 6-month mortality (HR, 14.8 [95% CI, 12.1 to 18.3] for VF and HR, 5.0 [95% CI, 3.8 to 6.5] for VT). These differences remained significant after excluding patients with heart failure or cardiogenic shock and those who died <24 hours after enrollment. CONCLUSIONS: Despite the use of effective therapies for non-ST-elevation acute coronary syndromes, ventricular arrhythmias in this setting are associated with increased 30-day and 6-month mortality. More effective therapies are needed to improve the survival of patients with these arrhythmias.

Acute Disease↗
PubMed2002

Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction.

BACKGROUND: Among patients with suspected acute coronary syndromes, cardiac troponin T levels have prognostic value. However, there is concern that renal dysfunction may impair the prognostic value, because cardiac troponin T may be cleared by the kidney. METHODS: We analyzed the outcomes in 7033 patients enrolled in the Global Use of Strategies to Open Occluded Coronary Arteries IV trial who had complete base-line data on troponin T levels and creatinine clearance rates. The troponin T level was considered abnormal if it was 0.1 ng per milliliter or higher, and creatinine clearance was assessed in quartiles. The primary end point was a composite of death or myocardial infarction within 30 days. RESULTS: Death or myocardial infarction occurred in 581 patients. Among patients with a creatinine clearance above the 25th percentile value of 58.4 ml per minute, an abnormally elevated troponin T level was predictive of an increased risk of myocardial infarction or death (7 percent vs. 5 percent; adjusted odds ratio, 1.7; 95 percent confidence interval, 1.3 to 2.2; P<0.001). Among patients with a creatinine clearance in the lowest quartile, an elevated troponin T level was similarly predictive of increased risk (20 percent vs. 9 percent; adjusted odds ratio, 2.5; 95 percent confidence interval, 1.8 to 3.3; P<0.001). When the creatinine clearance rate was considered as a continuous variable and age, sex, ST-segment depression, heart failure, previous revascularization, diabetes mellitus, and other confounders had been accounted for, elevation of the troponin T level was independently predictive of risk across the entire spectrum of renal function. CONCLUSIONS: Cardiac troponin T levels predict short-term prognosis in patients with acute coronary syndromes regardless of their level of creatinine clearance.

Abciximab↗
PubMed2002

Early angioplasty in acute coronary syndromes without persistent ST-segment elevation improves outcome but increases the need for six-month repeat revascularization: an analysis of the PURSUIT Trial. Platelet glycoprotein IIB/IIIA in Unstable angina: Receptor Suppression Using Integrilin Therapy.

OBJECTIVES: We explored the effect of timing of percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS) without persistent ST-segment elevation on the need for repeat revascularization, and we related this effect to other events. BACKGROUND: Percutaneous coronary intervention is widely used to treat ACS without persistent ST-segment elevation. Moreover, restenosis and subsequent revascularization after PCI are more frequent in ACS than in stable angina. The optimal timing of PCI in ACS without persistent ST-segment elevation is unknown. METHODS: In the Platelet glycoprotein IIB/IIIA in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) database, patients were stratified by the time of PCI. In the PURSUIT trial, 9,461 patients received a platelet glycoprotein IIb/IIIa inhibitor, eptifibatide or placebo for 72 h. The investigators decided on other treatments. RESULTS: A total of 2,430 patients underwent PCI within 30 days. Repeat revascularization (during 165 days) was notably higher for PCI within 24 h of enrollment (n = 620 [19%]) than for PCI at 24 to 72 h (n = 624 [16.7%]), 3 to 7 days (n = 614 [13.2%]), or 8 to 30 days (n = 561 [7.7%]; p < 0.001), regardless of eptifibatide use. This gradual reduction in the revascularization rate for later PCI was also observed after multivariate analysis correcting for baseline characteristics and with time as a continuous variable. CONCLUSIONS: Percutaneous coronary intervention within 24 is associated with improved outcome (other analysis) but more repeat revascularization. Prospective analyses are needed to test the hypothesis that rapid PCI in ACS with a platelet glycoprotein IIb/IIIa receptor antagonist reduces myocardial infarction (and possibly death) and is therefore most suited for patients at highest risk of infarction, despite a higher need for repeat revascularization.

Aged↗
PubMed2002

Impact of different platelet glycoprotein IIb/IIIa receptor inhibitors among diabetic patients undergoing percutaneous coronary intervention: : Do Tirofiban and ReoPro Give Similar Efficacy Outcomes Trial (TARGET) 1-year follow-up.

BACKGROUND: The platelet glycoprotein IIb/IIIa receptor inhibitor abciximab, a monoclonal antibody, has been shown to improve early and late outcomes among diabetic patients undergoing percutaneous coronary intervention (PCI). It is unknown whether small-molecule agents confer similar benefits. METHODS AND RESULTS: In 18 countries, 4809 patients undergoing PCI with stent implantation were randomized to tirofiban or abciximab. At the time of enrollment, patients were stratified according to diabetes status. As compared with non-diabetic patients, patients with diabetes (n=1117) showed similar 30-day ischemic outcomes, an increased incidence of any target vessel revascularization (TVR) at 6 months (10.3% versus 7.8%; P= 0.008), and a trend toward higher 1-year mortality (2.5% versus 1.6%; P=0.056). Among diabetic patients randomized to tirofiban (n=560), the incidence of death, myocardial infarction (MI), or urgent TVR at 30 days was 6.2%, and among those randomized to abciximab (n=557) it was 5.4% (hazard ratio [HR] 1.16; P=0.540). At 6 months, the composite of death, MI, or any TVR occurred in 15.7% and in 16.9% of tirofiban and abciximab patients, respectively (HR 0.93; P=0.610). Any TVR occurred in 9.5% and 11.1%, respectively (HR 0.84; P= 0.366). The 1-year mortality was 2.1% in the tirofiban group and 2.9% in the abciximab group (HR 0.74; P= 0.436). CONCLUSIONS: Among diabetic patients undergoing PCI, tirofiban and abciximab were associated with comparable event rates, including similar rates of 6-month TVR and 1-year mortality. These findings suggest that the non-glycoprotein IIb/IIIa properties of abciximab do not translate into a discernible long-term clinical benefit among diabetic patients.

Abciximab↗
PubMed2002

Prognostic significance of elevated troponin I after percutaneous coronary intervention.

OBJECTIVES: We sought to assess the incidence and clinical significance of elevated cardiac troponin I (cTnI) after percutaneous coronary intervention (PCI). BACKGROUND: Elevated creatine kinase-MB (CK-MB) is prognostically important after PCI, but the prognostic significance of elevated cTnI after PCI is uncertain. METHODS: In a prospective substudy of the Sibrafiban Versus Aspirin to Yield Maximum Protection From Ischemic Heart Events Post-acute Coronary Syndromes (SYMPHONY) trials, which randomized patients with acute coronary syndromes (ACS) to receive aspirin or sibrafiban, we measured cTnI (positive, > or =1.5 ng/ml) and CK-MB (positive, > or =7 ng/ml) in 481 patients with PCI. Samples were collected immediately before and at 0, 8 and 16 h after PCI and analyzed by a core laboratory. The primary end point was the Kaplan-Meier estimate of death, myocardial infarction or severe, recurrent ischemia at 90 days. RESULTS: Overall, 230 patients (48%) had elevated cTnI after PCI. Such patients underwent PCI sooner and were more likely to have coronary stenting. Elevated cTnI was associated with nonsignificantly higher risks of the primary end point (11.5% vs. 8.7%; p = 0.15) and of death (1.8% vs. 0.4%; p = 0.4) and a significantly higher risk of death or infarction (10.6% vs. 4.2%; p = 0.005). This pattern was more pronounced for patients who became positive only after PCI: primary end point, 20.7% vs. 10.1% for patients who remained negative after PCI (p = 0.05); death, 5.2% vs. 0% (p = 0.02); death or infarction, 18.1% vs. 4.1% (p = 0.007). CONCLUSIONS: Elevated cTnI, often observed after PCI in patients with ACS, is associated with worse 90-day clinical outcomes. This marker, therefore, is a useful prognostic indicator in such patients.

Angina, Unstable↗
PubMed2002

Impact of clinical syndrome acuity on the differential response to 2 glycoprotein IIb/IIIa inhibitors in patients undergoing coronary stenting: the TARGET Trial.

BACKGROUND: Although glycoprotein IIb/IIIa inhibitors have been shown to reduce periprocedural and late ischemic events in patients undergoing stent implantation, the relative safety and efficacy of different agents in this class is less established. Also unknown is whether the acuity of the presenting clinical syndrome, which may affect the degree of platelet inhibition required or achieved, influences the response to different antiplatelet agents. METHODS AND RESULTS: A prospective, multicenter, double-blind, randomized trial was performed in which 4809 patients undergoing planned stenting were randomized to receive abciximab or tirofiban. In patients with acute coronary syndromes (ACS; n=3025), abciximab resulted in lower rates of myocardial infarction at 30 days (5.8% versus 8.5%; P=0.004) and 6 months (7.2% versus 9.8%; P=0.013), although 6-month mortality rates were identical (1.39% in both groups; P=0.99). Conversely, in patients without ACS (n=1784), myocardial infarction rates were not significantly lower with tirofiban, survival was similar, and target vessel revascularization was reduced, which translated into a trend toward enhanced 6-month event-free survival with tirofiban (89.7% versus 86.6%; P=0.056). CONCLUSIONS: In patients with ACS undergoing stent implantation, abciximab use compared with tirofiban results in greater suppression of periprocedural myonecrosis, although a survival benefit has not been demonstrated. Patients with stable coronary syndromes may have equivalent or better outcomes with tirofiban relative to abciximab, with fewer adverse hematologic and hemorrhagic events. These data raise important issues regarding the relative pharmacodynamic inhibition of platelet function required in varying clinical scenarios and have important implications for the cost-effective utilization of glycoprotein IIb/IIIa inhibitors.

Abciximab↗
PubMed2002

Practice patterns and outcomes of percutaneous coronary interventions in the United States: 1995 to 1997.

Randomized trials have demonstrated the superiority of coronary stents in combination with a platelet-focused pharmacologic approach in percutaneous coronary intervention (PCI). However, nationally representative data examining the impact of these technologies on patient outcomes and costs remain scarce. This study sought to determine the real-world impact of changes in the use of stents and anticoagulant agents in PCI on outcomes and costs. A nationally representative sample of 37,088 patients who underwent PCI from October 1995 to October 1997 was identified from in-patient hospital claims data acquired from HCIASachs. Utilization of coronary stents, antiplatelet and anticoagulant agents, and outcome measurements of in-hospital death, coronary artery bypass grafting (CABG), repeat PCI, bleeding, and costs were analyzed in 6-month intervals. Acute events (death, urgent CABG, or PCI) decreased (p <0.001), whereas use of stents, abciximab, or both, increased (p <0.001). Dosages of heparin and bleeding complications declined significantly (p <0.001) over the 2-year period. Heparin dosages were higher in patients who experienced bleeding or death than in those who did not (p <0.001). The average hospital length of stay decreased significantly (p <0.001), largely driven by a reduction in time between the procedure and hospital discharge. By the end of the study period, bleeding was the most frequent (5.5%) complication of PCI and was associated with considerable costs, adding $10,225 to baseline costs.

Anticoagulants↗