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Biomedical subjects

Eric J Topol

Publications and source records attributed to Eric J Topol.

At least 199 records · Page 11Linked to original sources
PubMed2003

Mortality benefit of beta blockade in patients with acute coronary syndromes undergoing coronary intervention: pooled results from the Epic, Epilog, Epistent, Capture and Rapport Trials.

The effects of beta blocker therapy in the settings of heart failure and coronary artery disease have been well described, although little data exist in patients presenting with acute coronary syndromes undergoing percutaneous coronary intervention. The current study will attempt to evaluate the efficacy of beta blocker therapy in this setting. Pooled data from five randomized, controlled trials of abciximab during coronary intervention were used to analyze the clinical efficacy of beta blocker therapy. The pooled analysis evaluated the end points of all-cause mortality, myocardial infarction, repeat revascularization, and the combined endpoint of death and myocardial infarction in 2,894 patients. At 30 days, death occurred in 12 of 1,939 (0.6%) patients receiving beta blocker therapy and in 19 of 955 (2.0%) patients not receiving beta blocker therapy, (P < 0.001). At 6 months, death occurred in 33 of 1,939 (1.7%) patients receiving beta blocker therapy and 35 of 955 (3.7%) not receiving beta blocker therapy, (P < 0.001). After creating a propensity model and adjusting for variables predictive of mortality in the multivariable analysis, beta blocker therapy continued to be associated with a significant reduction in mortality. The findings were similar to those shown for the effects of beta blocker therapy in separate subgroups of patients with unstable angina and acute myocardial infarction. This analysis demonstrates a lower short-term mortality in patients receiving beta blocker therapy who undergo percutaneous coronary intervention for unstable angina or acute myocardial infarction.

Adrenergic beta-Antagonists↗
PubMed2003

Scientific and therapeutic advances in antiplatelet therapy.

Over the past decade, the platelet has emerged as a pivotal entity in cardiovascular diseases. Indeed, the 'preeminence of the platelet' has spawned a variety of drugs that have been shown in large-scale randomized trials to improve patient outcomes in acute coronary syndromes and percutaneous revascularization procedures. Although the platelet was initially viewed only as a bystander in haemostasis, it is now evident that the platelet is in fact a key mediator of thrombosis as well as of inflammation. New insights at the cellular and genomic levels will probably generate novel drugs to inhibit platelet function more effectively and safely than previously possible.

Adenosine Diphosphate↗
PubMed2003

Sustained ventricular arrhythmias and mortality among patients with acute myocardial infarction: results from the GUSTO-III trial.

BACKGROUND: In many patients, ventricular arrhythmias will develop early after acute myocardial infarction. We studied the incidence, timing, and outcomes of such arrhythmias in the international Global Utilization of Streptokinase and TPA (alteplase) for Occluded Coronary Arteries (GUSTO)-III trial. METHODS: We identified independent predictors of inhospital ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared 30-day and 1-year mortality rates of patients who did (n = 1121) and did not (n = 13,921) have these arrhythmias during the index hospitalization. RESULTS: Significant independent predictors of inhospital VF were higher Killip class, lower baseline systolic pressure, intravenous preenrollment lidocaine use, shorter time to thrombolysis, and beta-blocker use <2 weeks before enrollment; independent predictors of inhospital VT were lower baseline systolic pressure, intravenous lidocaine use before enrollment, higher Killip class, faster baseline heart rate, and advanced age. The 30-day mortality rate was 31% in patients with VF, 24% in those with VT, 44% in those with both, and 6% in those with neither (P =.001). The corresponding 1-year mortality rates were 34%, 29%, 49%, and 9% (P =.001). The 30-day and 1-year mortality rates were higher for patients with late (>48 hours after enrollment) versus early arrhythmias (< or =48 hours after enrollment). CONCLUSIONS: Despite thrombolysis, inhospital ventricular arrhythmias are associated with higher 30-day and 1-year mortality rates after acute myocardial infarction, particularly when occurring later during the initial hospitalization. Better therapies are needed to improve outcomes of these arrhythmias.

Acute Disease↗
PubMed2003

Frequency, patient characteristics, and outcomes of mild-to-moderate heart failure complicating ST-segment elevation acute myocardial infarction: lessons from 4 international fibrinolytic therapy trials.

BACKGROUND: There is a paucity of data on the incidence of mild-to-moderate heart failure (HF) complicating ST-segment elevation acute myocardial infarction (MI) and its impact on short-term outcomes. Our objective was to determine the incidence, timing, and consequences of mild-to-moderate HF complicating acute MI. METHODS: We examined the occurrence of death or death/recurrent MI (re-MI) in patients enrolled in the Global Utilization of Streptokinase and Tissue-Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I), the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO IIb), the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO-III), and Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-II) trials, which examined different fibrinolytic therapies for MI. We excluded patients who had cardiogenic shock (n = 2994) or unknown HF status at all time points (n = 13,716). Of the remaining 61,041 patients, 17,949 patients (29.4%) had HF, 1566 (8.7%) only at baseline, 10,339 (57.6%) only after admission, and 6044 (33.7%) at baseline and after. RESULTS: The incidence of HF was 32.5% in the United States and 26.9% elsewhere. At 30 days, death and death/re-MI occurred in 2% and 4% of patients without HF and 8% and 12% of patients with HF, respectively (2% and 4% of patients with HF only at baseline, 7% and 13% of patients with HF only after baseline, and 10% and 13% of patients with HF at baseline and later). By use of multivariable analyses, the presence of HF was associated with 1.55 times greater risk of dying at 30 days (95% CI 1.38-1.74) and 2.15 times greater risk of death/re-MI (95% CI 1.96-2.36). CONCLUSION: Mild-to-moderate HF is a frequent and ominous complication of MI, especially when it does not resolve or develops after admission.

Clinical Trials as Topic↗
PubMed2003

Thyrotoxicosis and the cardiovascular system: subtle but serious effects.

Thyrotoxicosis is associated with increased cardiovascular morbidity and mortality, primarily due to heart failure and thromboembolism. However, its signs and symptoms may be subtle and can easily be missed. Therefore, one should suspect thyrotoxicosis in patients with palpitations, exercise intolerance, dyspnea on exertion, and other cardiovascular signs.

Adrenergic beta-Antagonists↗
PubMed2003

Using C-reactive protein to assess cardiovascular disease risk.

C-reactive protein (CRP), a marker of inflammation, is directly involved in atherogenesis, and elevated CRP levels (as measured by highly sensitive assays) are associated with increased cardiovascular risk. We welcome the recent joint guidelines on CRP testing from the Centers for Disease Control and Prevention and the American Heart Association; however, whereas the guidelines suggest measuring the CRP level only in patients at intermediate risk, we advocate measuring it as well in patients at high risk.

Biomarkers↗
PubMed2003

Clopidogrel is associated with better in-hospital and 30-day outcomes than ticlopidine after coronary stenting.

BACKGROUND: Recent reports of fatal ticlopidine-induced blood dyscrasias have led many interventional cardiologists to administer clopidogrel instead of ticlopidine for coronary stenting. Most studies have demonstrated similar outcomes and a more favourable safety profile supporting this change in practice patterns. OBJECTIVES: To assess the clinical outcomes in patients who received clopidogrel rather than ticlopidine after coronary stenting. METHODS: Between June 1996 and December 1998, 652 patients received a clopidogrel-based periprocedural regimen (300 mg loading dose followed by 75 mg daily in addition to acetylsalicylic acid 325 mg daily) and 1717 patients received a ticlopidine-based regimen (500 mg loading dose followed by 250 mg bid in addition to acetylsalicylic acid 325 mg daily). In-hospital and 30-day outcomes were assessed in the two groups. RESULTS: At 30 days, unadjusted mortality was 0.3% in the clopidogrel group versus 1.5% in the ticlopidine group, and myocardial infarction (MI) was also reduced in the clopidogrel group (4.0% versus 6.5%). No difference was found in the rate of repeat revascularization (1.4% versus 1.2%). The combination of death/MI/repeat revascularization at 30 days was reduced by 32%, an absolute difference of 2.9% (6.2% versus 9.1%). On multivariate analysis, clopidogrel was found to be an independent predictor of freedom from nonfatal MI (odds ratio [OR] 0.64, 95% CI 0.41 to 0.99, P=0.04), the composite of death or MI (OR 0.62, 95% CI 0.40 to 0.95, P=0.03) and the composite of death/MI/revascularization (OR 0.69, 95% CI 0.48 to 1.00, P=0.05). CONCLUSION: After coronary stenting, in a large, nonrandomized, consecutive patient experience, clopidogrel appears to be associated with more favourable clinical outcomes than ticlopidine, without increasing the risk of bleeding or peripheral vascular complications.

Aged↗
PubMed2002

Lack of benefit from intravenous platelet glycoprotein IIb/IIIa receptor inhibition as adjunctive treatment for percutaneous interventions of aortocoronary bypass grafts: a pooled analysis of five randomized clinical trials.

BACKGROUND: Despite widespread use of platelet glycoprotein (GP) IIb/IIIa receptor inhibitors for percutaneous coronary interventions (PCI) of bypass grafts, data supporting this strategy are lacking. METHODS AND RESULTS: A pooled analysis of 5 randomized intravenous GP IIb/IIIa inhibitor trials (EPIC, EPILOG, EPISTENT, IMPACT II, and PURSUIT) was performed, and outcomes of graft interventions were assessed at 30 days and 6 months. Compared with PCI of native circulation (n=13 158), graft interventions (n=627) were associated with worse outcomes and in particular with a doubling of mortality at 30 days (2.1% versus 1.0%, P=0.006) and 6 months (4.7% versus 2.0%, P<0.001). Revascularization of a graft was identified as an independent predictor of death, myocardial infarction, or revascularization at 6 months (hazard ratio, 1.42; 95% CI, 1.24 to 1.63; P<0.001). Among patients undergoing graft PCI, the incidence of the triple end point at 30 days was 16.5% in the platelet GP IIb/IIIa inhibitor group and 12.6% in the placebo group (odds ratio, 1.38; 95% CI, 0.85 to 2.24; P=0.18). At 6 months, 39.4% of patients randomized to GP IIb/IIIa inhibitors and 32.7% of patients allocated to placebo had an ischemic event (hazard ratio, 1.29; 95% CI, 0.97 to 1.72; P=0.07). CONCLUSIONS: Intravenous platelet GP IIb/IIIa receptor inhibition does not improve outcomes after PCI of bypass grafts. In the absence of mechanical emboli protection, this procedure is associated with high incidence of death and nonfatal ischemic events.

Abciximab↗
PubMed2002

Association between CK-MB elevation after percutaneous or surgical revascularization and three-year mortality.

OBJECTIVES: The goal of this study was to assess the long-term impact of creatine kinase-MB isoform (CK-MB) elevation after percutaneous or surgical revascularization. BACKGROUND: The long-term impact of CK-MB elevation after coronary artery bypass grafting (CABG) is not as well characterized as that following percutaneous coronary intervention (PCI). METHODS: The three-year cumulative survival of consecutive patients who underwent their first percutaneous or surgical revascularization procedure between January 1, 1995 and August 31, 2000 and had CK-MB determination was assessed using the Social Security Death Index. RESULTS: The 3,812 patients undergoing CABG had a less favorable coronary risk profile than the 3,573 patients undergoing PCI. The incidence of CK-MB elevation above normal range was 90% and 38% for the CABG and PCI groups (p < 0.001). In 6% and 5%, respectively, the elevation surpassed 10x the upper limit of normal (ULN). At an average follow-up of three years, there were 712 deaths, 83 of which occurred within 30 days of procedure. The cumulative survival was 92% and 90% for CABG and PCI, respectively (p = 0.003). Chronic renal insufficiency (adjusted hazard ratio [HR] 3.8, [95% confidence interval 3.1 to 4.6]), age (HR 1.5 per decade [1.3 to 1.6]), ejection fraction <40% (HR 1.3 [1.1 to 1.5] and PCI (HR 1.6 [1.3 to 1.9]) were the main predictors of increased mortality. Creatine kinase-MB isoform elevation only above 10 x ULN was independently predictive of mortality in the CABG (HR 1.3 [1.1 to 1.5]) and PCI (HR 1.1 [1.0 to 1.2]) groups, p < 0.001. CONCLUSIONS: Creatine kinase MB isoform elevation after revascularization is very common, particularly in CABG patients. When extensive, it is independently correlated with increased mortality over a three-year period. Identification and aggressive management of patients with high levels of CK-MB after revascularization may improve their outcome.

Aged↗
PubMed2002

Outcome of acute myocardial infarction in patients with prior coronary artery bypass grafting treated with combination reduced fibrinolytic therapy and abciximab.

ST-segment elevation acute myocardial infarction (AMI) in patients who have undergone previous coronary artery bypass grafting (CABG) is associated with low reperfusion rates and poor outcome after fibrinolytic therapy. The efficacy of a combination strategy (reduced fibrinolytic plus platelet glycoprotein IIb/IIIa agent) in this setting is unknown. In the Global Use of Streptokinase and TPA for Occluded coronary arteries V (GUSTO V) trial, 553 patients with a history of CABG were treated with standard-dose reteplase (n = 273), or half-dose reteplase and full-dose abciximab (n = 280) in the first 6 hours of evolving ST-segment elevation MI. Mortality at 30 days was significantly higher in patients who underwent prior CABG compared with patients with no prior CABG (odds ratio [OR] 1.64, 95% confidence interval [CI] 1.21 to 2.24, p = 0.001). In patients who underwent prior CABG, mortality at 7 days was reduced 15% with combination therapy compared with reteplase alone, which was not statistically significant (OR 0.85, 95% CI 0.40 to 1.81, p = 0.66). Patients who underwent prior CABG treated with the combination therapy had fewer episodes of recurrent ischemia (OR 0.60, 95% CI 0.37 to 0.96, p = 0.02), high degree atrioventricular block (OR 0.17, 95% CI 0.02 to 0.82, p = 0.01), and ventricular tachycardia (OR 0.29, 95% CI 0.07 to 0.96, p = 0.04). There was a trend toward reduced urgent revascularization (OR 0.61, 95% CI 0.36 to 1.03, p = 0.06) but no significant difference in reinfarction (OR 0.61, 95% CI 0.31 to 1.52, p = 0.40). In the GUSTO V trial, patients who underwent prior CABG had significantly higher event rates compared with patients without CABG. As in the overall trial, combination therapy in patients who underwent prior CABG led to a consistent reduction in key secondary complications of AMI, including recurrent ischemia and a trend toward reduced urgent revascularization.

Abciximab↗
PubMed2002

Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial.

CONTEXT: Following percutaneous coronary intervention (PCI), short-term clopidogrel therapy in addition to aspirin leads to greater protection from thrombotic complications than aspirin alone. However, the optimal duration of combination oral antiplatelet therapy is unknown. Also, although current clinical data suggest a benefit for beginning therapy with a clopidogrel loading dose prior to PCI, the practical application of this therapy has not been prospectively studied. OBJECTIVES: To evaluate the benefit of long-term (12-month) treatment with clopidogrel after PCI and to determine the benefit of initiating clopidogrel with a preprocedure loading dose, both in addition to aspirin therapy. DESIGN, SETTING, AND PARTICIPANTS: The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, a randomized, double-blind, placebo-controlled trial conducted among 2116 patients who were to undergo elective PCI or were deemed at high likelihood of undergoing PCI, enrolled at 99 centers in North America from June 1999 through April 2001. INTERVENTIONS: Patients were randomly assigned to receive a 300-mg clopidogrel loading dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter, all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through 12 months, patients in the loading-dose group received clopidogrel, 75 mg/d, and those in the control group received placebo. Both groups received aspirin throughout the study. MAIN OUTCOME MEASURES: One-year incidence of the composite of death, myocardial infarction (MI), or stroke in the intent-to-treat population; 28-day incidence of the composite of death, MI, or urgent target vessel revascularization in the per-protocol population. RESULTS: At 1 year, long-term clopidogrel therapy was associated with a 26.9% relative reduction in the combined risk of death, MI, or stroke (95% confidence interval [CI], 3.9%-44.4%; P =.02; absolute reduction, 3%). Clopidogrel pretreatment did not significantly reduce the combined risk of death, MI, or urgent target vessel revascularization at 28 days (reduction, 18.5%; 95% CI, -14.2% to 41.8%; P =.23). However, in a prespecified subgroup analysis, patients who received clopidogrel at least 6 hours before PCI experienced a relative risk reduction of 38.6% (95% CI, -1.6% to 62.9%; P =.051) for this end point compared with no reduction with treatment less than 6 hours before PCI. Risk of major bleeding at 1 year increased, but not significantly (8.8% with clopidogrel vs 6.7% with placebo; P =.07). CONCLUSIONS: Following PCI, long-term (1-year) clopidogrel therapy significantly reduced the risk of adverse ischemic events. A loading dose of clopidogrel given at least 3 hours before the procedure did not reduce events at 28 days, but subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.

Administration, Oral↗
PubMed2002

Mortality at 1 year with combination platelet glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytic therapy vs conventional fibrinolytic therapy for acute myocardial infarction: GUSTO V randomized trial.

CONTEXT: Among patients with acute myocardial infarction, combination reperfusion therapy with a platelet glycoprotein IIb/IIIa receptor inhibitor (abciximab) and a half dose of a plasminogen activator (reteplase) did not significantly reduce mortality at 30 days compared with a full dose of reteplase. Rates of nonfatal ischemic complications were significantly diminished. OBJECTIVE: To determine if the beneficial effects of abciximab and reteplase (combination therapy) on early nonfatal complications would translate into a reduction in the risk of death by 1 year. DESIGN, SETTING, AND PATIENTS: One-year follow-up of a randomized controlled trial (Global Use of Strategies To Open Coronary Arteries [GUSTO] V). Of 16 588 patients who had been treated in 820 community and referral hospitals in 20 countries between July 1999 and February 2001, mortality data were available for 16 453 (99.2%). INTERVENTION: Patients were randomly assigned to receive (intravenously) a standard dose of reteplase (two 10-U boluses, 30 minutes apart) or the combination of a standard dose of abciximab (0.25 mg/kg bolus, 0.125 microg/kg per minute infusion [maximum 10 micro g/min for 12 hours]) and a half dose of reteplase (two 5-U boluses, 30 minutes apart). MAIN OUTCOME MEASURE: One-year all-cause mortality rates. RESULTS: All-cause mortality at 1 year occurred in 692 (8.38%) of 8260 patients in the reteplase group and 698 (8.38%) of the 8328 patients in the combination therapy group (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.90-1.11; P>.99). Reinfarction within the first 7 days occurred in 3.5% of patients in the reteplase group and 2.3% of patients in the combination therapy group, and was significantly associated with 1-year mortality (22.6% in patients with reinfarction vs 8.0% in patients without reinfarction; HR, 3.08; 95% CI, 2.53-3.75; P<.001). However, treatment assignment did not significantly influence time of mortality regardless of reinfarction status. CONCLUSION: Combination therapy (abciximab and reteplase) did not reduce mortality over 1 year compared with fibrinolytic therapy with reteplase alone.

Abciximab↗
PubMed2002

Effect of abciximab on angiographic complications during percutaneous coronary stenting in the Evaluation of Platelet IIb/IIIa Inhibition in Stenting Trial (EPISTENT).

In the Evaluation of Platelet IIb/IIIa Inhibition in Stenting Trial (EPISTENT), abciximab reduced ischemic complications of stent implantation at 30 days and 6 months. The responsible mechanisms remain unclear. We sought to determine if abciximab decreases ischemic complications by decreasing the incidence of angiographic complications during coronary stenting. In EPISTENT, patients were randomized to stenting with abciximab (abciximab group), stenting with placebo (placebo group), or balloon angioplasty with abciximab. Angiographic complications (including major or minor dissection, distal embolization, thrombus postprocedure, side branch or other vessel occlusion, residual stenosis >50%, transient coronary occlusion, and Thrombolysis In Myocardial Infarction final flow <3) were recorded prospectively. Creatine kinase (CK)-MB enzyme levels after intervention were measured at 6-hour intervals. We analyzed angiographic complications and CK-MB elevations in the abciximab group (n = 784) and the placebo group (n = 803). Angiographic complications were 29% less frequent in the abciximab group compared with the placebo group (17.0% vs 23.8%; p = 0.001). In patients with angiographic complications, there was a nonsignificant reduction in the incidence of CK-MB elevation >3 times normal with abciximab therapy (19.7% vs 24.5% in placebo group; p = 0.314). Abciximab (compared with placebo) significantly reduced the incidence of CK-MB elevation >3 times normal in those without any angiographic complications (6.5% vs 10.7%; p = 0.007). In summary, abciximab (compared with placebo) significantly reduced angiographic complications during coronary stenting. Abciximab also prevented CK-MB elevations in patients without angiographic complications.

Abciximab↗
PubMed2002

Cox-2: where are we in 2003? - Cardiovascular risk and Cox-2 inhibitors.

Selective cyclooxygenase-2 (COX-2) inhibitors were developed to reduce the gastrointestinal toxicity of conventional nonsteroidal anti-inflammatory agents. However, COX-2 inhibitors decrease prostacyclin production and may disrupt the normal homeostatic balance, leading to a prothrombotic state and offsetting the potential gastrointestinal benefits. Available clinical data and basic biological studies raise significant concern about the potential prothrombotic effect of this class of drugs. Two recent studies with a newer, more selective COX-2 inhibitor have added to the already existing concern about the cardiovascular safety of these agents. The widespread use of these agents mandates prospective, randomized evaluation of the cardiovascular safety of COX-2 inhibitors.

Animals↗
PubMed2002

Administration of recombinant P-selectin glycoprotein ligand Fc fusion protein suppresses inflammation and neointimal formation in Zucker diabetic rat model.

OBJECTIVE: P-selectin-mediated leukocyte-endothelium and leukocyte-platelet interaction has been reported after vascular injury and has been correlated with neointimal hyperplasia, but its role in neointimal formation after arterial injury in diabetes has not been described. METHODS AND RESULTS: Using a Zucker diabetic rat balloon injury model, we examined the role of P-selectin in the vascular inflammatory process and neointimal formation after balloon injury. Immunohistochemistry revealed that P-selectin was intensely expressed and that CD45-positive leukocyte infiltration was significantly increased after arterial injury. A single preprocedural intravenous administration of a recombinant P-selectin-soluble glycoprotein ligand-Ig inhibited CD45-positive leukocyte accumulation and suppressed neointimal formation in the Zucker diabetic rat model. CONCLUSIONS: These results suggest that reduction of P-selectin-mediated leukocyte activation with the use of recombinant P-selectin-soluble glycoprotein ligand-Ig decreases the inflammatory response and limits neointimal formation after balloon injury in diabetes.

Animals↗