The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform
Kristin L Newby - One of the best experts on this subject based on the ideXlab platform.
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use of evidence based medicine for acute coronary syndromes in the elderly and very elderly insights from the Sibrafiban vs aspirin to yield maximum protection from ischemic heart events postacute coronary syndromes trials
2007Co-Authors: Cheukkit Wong, Kristin L Newby, Paul W Armstrong, Manju V Bhapker, Phil Aylward, Matthias Pfisterer, Karen P Alexander, Judith S Hochman, Frans Van De Werf, Robert M CaliffAbstract:Background Evidence-based medications (EBM) are underused in older patients despite potentially larger absolute benefits. Little is known about factors influencing prescribing in the elderly with acute coronary syndromes. Methods Among the 15 904 patients from the Sibrafiban vs aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes (SYMPHONY) and second SYMPHONY trials, we examined the rates of use of EBM according to age ( Results Ninety-day mortality increased with age ( Conclusions Despite higher mortality risk, EBM use was lower among older patients even considering eligibility. Among those aged ≥75 years, age was no longer the major factor predicting EBM use. The modest C indices suggest other factors are associated with prescribing, underscoring the need for treatment algorithms and quality assurance measures in older patients.
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prognostic significance of elevated troponin i after percutaneous coronary intervention
2002Co-Authors: Warren J Cantor, Kristin L Newby, Robert H Christenson, Robert H Tuttle, Vic Hasselblad, Paul W Armstrong, David J Moliterno, Robert M Califf, Eric J Topol, Magnus E OhmanAbstract:Abstract 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, ≥1.5 ng/ml) and CK-MB (positive, ≥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.
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long term oral platelet glycoprotein iib iiia receptor antagonism with Sibrafiban after acute coronary syndromes study design of the Sibrafiban versus aspirin to yield maximum protection from ischemic heart events post acute coronary syndromes symphony trial
1999Co-Authors: Kristin L NewbyAbstract:Abstract Background Despite progress, atherosclerotic vascular disease remains a major cause of morbidity and mortality. Intravenous therapy with platelet glycoprotein (GP) IIb/IIIa receptor antagonists improves outcome in patients with acute coronary syndromes (ACS). Whether potent long-term antiplatelet therapy with oral GP IIb/IIIa antagonists will further improve outcome at a dose that is tolerable in long-term treatment is unknown. Trial Design SYMPHONY (Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events post-acute cOroNary syndromes) was a randomized, double-blind, aspirin-controlled trial with 2 concentration regimens of Sibrafiban, an oral peptidomimetic GP IIb/IIIa antagonist, for long-term treatment instead of aspirin in patients after an ACS. Patients were eligible for SYMPHONY if they presented within 7 days of an ACS (≥20 minutes of ischemic symptoms), had been clinically stable for at least 12 hours, and met one of the following inclusion criteria: ST-segment depression or elevation of at least 0.5 mm or new left bundle branch block with the ACS or elevated creatinine kinase MB more than the upper limit of normal and >3% of total creatine kinase or, if creatine kinase MB was not measured, an elevated level of troponin T or I. Approximately 9000 patients post ACS were randomized 1:1:1 to treatment with either aspirin (80 mg every 12 hours) or high-dose or low-dose Sibrafiban every 12 hours. Assignment of tablet strength (3, 4.5, or 6 mg) within the Sibrafiban arms was based on body weight and renal function to achieve a target steady-state plasma concentration. The duration of study drug therapy was 90 days. Patients who had intracoronary stenting during the course of the study initially received a blinded stent medication assignment for 2 to 4 weeks based on their initial randomization as follows: aspirin/ticlopidine 250 mg twice daily, low-dose Sibrafiban/ticlopidine placebo twice daily, and high-dose Sibrafiban/ticlopidine placebo twice daily. After the second interim safety assessment by the Data and Safety Monitoring Board the stent regimen for the low-dose group was modified to include ticlopidine 250 mg twice daily. End Points The primary efficacy end point of SYMPHONY was the 90-day incidence of a composite of all-cause mortality, myocardial infarction or reinfarction, and severe recurrent ischemia. A clinical events classification committee was established to determine the end points of reinfarction and severe recurrent ischemia. The primary safety end points were the incidence of major bleeding or minor bleeding and the combined incidence of major and minor bleeding. Bleeding classification was done by computer algorithm. Tolerability was assessed by the rate of study drug discontinuation from bleeding. (Am Heart J 1999;138:210-8.)
Robert M Califf - One of the best experts on this subject based on the ideXlab platform.
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use of evidence based medicine for acute coronary syndromes in the elderly and very elderly insights from the Sibrafiban vs aspirin to yield maximum protection from ischemic heart events postacute coronary syndromes trials
2007Co-Authors: Cheukkit Wong, Kristin L Newby, Paul W Armstrong, Manju V Bhapker, Phil Aylward, Matthias Pfisterer, Karen P Alexander, Judith S Hochman, Frans Van De Werf, Robert M CaliffAbstract:Background Evidence-based medications (EBM) are underused in older patients despite potentially larger absolute benefits. Little is known about factors influencing prescribing in the elderly with acute coronary syndromes. Methods Among the 15 904 patients from the Sibrafiban vs aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes (SYMPHONY) and second SYMPHONY trials, we examined the rates of use of EBM according to age ( Results Ninety-day mortality increased with age ( Conclusions Despite higher mortality risk, EBM use was lower among older patients even considering eligibility. Among those aged ≥75 years, age was no longer the major factor predicting EBM use. The modest C indices suggest other factors are associated with prescribing, underscoring the need for treatment algorithms and quality assurance measures in older patients.
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prognostic significance of elevated troponin i after percutaneous coronary intervention
2002Co-Authors: Warren J Cantor, Kristin L Newby, Robert H Christenson, Robert H Tuttle, Vic Hasselblad, Paul W Armstrong, David J Moliterno, Robert M Califf, Eric J Topol, Magnus E OhmanAbstract:Abstract 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, ≥1.5 ng/ml) and CK-MB (positive, ≥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.
Paul W Armstrong - One of the best experts on this subject based on the ideXlab platform.
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use of evidence based medicine for acute coronary syndromes in the elderly and very elderly insights from the Sibrafiban vs aspirin to yield maximum protection from ischemic heart events postacute coronary syndromes trials
2007Co-Authors: Cheukkit Wong, Kristin L Newby, Paul W Armstrong, Manju V Bhapker, Phil Aylward, Matthias Pfisterer, Karen P Alexander, Judith S Hochman, Frans Van De Werf, Robert M CaliffAbstract:Background Evidence-based medications (EBM) are underused in older patients despite potentially larger absolute benefits. Little is known about factors influencing prescribing in the elderly with acute coronary syndromes. Methods Among the 15 904 patients from the Sibrafiban vs aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes (SYMPHONY) and second SYMPHONY trials, we examined the rates of use of EBM according to age ( Results Ninety-day mortality increased with age ( Conclusions Despite higher mortality risk, EBM use was lower among older patients even considering eligibility. Among those aged ≥75 years, age was no longer the major factor predicting EBM use. The modest C indices suggest other factors are associated with prescribing, underscoring the need for treatment algorithms and quality assurance measures in older patients.
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prevalence and management of hypertension in acute coronary syndrome patients varies by sex observations from the Sibrafiban versus aspirin to yield maximum protection from ischemic heart events postacute coronary syndromes symphony randomized clinical trials
2005Co-Authors: Camille G Frazier, Paul W Armstrong, Svati H Shah, Manjushri Bhapkar, Darren K Mcguire, Zygmunt Sadowski, A Kristinsson, Philip E Aylward, W Klein, Douglas W WeaverAbstract:Background Hypertension affects 1 billion individuals worldwide and is an independent risk factor for death after acute coronary syndromes (ACS). Methods We examined the prevalence and medical treatment of hypertension among 15 904 ACS patients randomized in the SYMPHONY and 2nd SYMPHONY trials. Analyses were performed overall and according to sex for the United States and across international practice. Multivariable models identified factors associated with use of antihypertensive medication classes and examined the association of hypertension and sex with mortality. Results In the United States, hypertension was more prevalent in women than in men, overall (63% vs 50%) and within every decile of age. Hypertensive women more often received calcium-channel blockers (35% vs 30%) and diuretics (33% vs 19%) and less often received β-blockers (51% vs 57%). Angiotensin-converting enzyme inhibitor use was similar (35% vs 34%). Women received multiple agents more frequently than did men: 2 agents, 35% vs 30%; ≥3 agents, 16% vs 13%. Female sex independently predicted drug-class use only for diuretics. Mortality was higher in hypertensive women than in hypertensive men; after multivariable adjustment, mortality was similar without evidence of a differential association between hypertension and mortality according to sex. Although there was international variation in the use of individual classes of agents, the overall findings by sex were similar across regions. Conclusion Hypertension is more prevalent in women than in men with ACS, and its medical management varies by sex, but its association with mortality is similar. Opportunities exist to improve medical therapy and outcomes in women with hypertension.
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prognostic significance of elevated troponin i after percutaneous coronary intervention
2002Co-Authors: Warren J Cantor, Kristin L Newby, Robert H Christenson, Robert H Tuttle, Vic Hasselblad, Paul W Armstrong, David J Moliterno, Robert M Califf, Eric J Topol, Magnus E OhmanAbstract:Abstract 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, ≥1.5 ng/ml) and CK-MB (positive, ≥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.
Christopher P Cannon - One of the best experts on this subject based on the ideXlab platform.
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pharmacokinetics and pharmacodynamics of Sibrafiban an orally administered iib iiia antagonist in patients with acute coronary syndrome
1999Co-Authors: Nishit B Modi, Christopher P Cannon, William Novotny, James D Reimann, Eugene BraunwauldAbstract:Sibrafiban is a double prodrug that is converted to the inactive single prodrug and to the active IIb/IIIa antagonist following oral administration. Pharmacokinetics (PK) and pharmacodynamics (PD) of oral Sibrafiban and its metabolites were evaluated in patients postacute coronary syndrome receiving once- or twice-daily Sibrafiban for up to 28 days at several dose levels. Mean peak concentrations of Sibrafiban were < 5 ng/mL. Peak single prodrug concentrations occurred 1.7 +/- 1.0 (mean +/- SD) hours after Sibrafiban dosing. Total apparent plasma clearance of the single prodrug was 40 +/- 15 L/h, and the elimination half-life was 2.3 +/- 0.8 hours. Mean values of the steady-state pharmacokinetics for total concentrations of the active drug over all doses were: time to peak plasma concentration, 5.0 +/- 1.7 hours; apparent clearance, 13.9 +/- 3.9 L/h; and half-life, 11.0 +/- 2.8 hours. Once-daily dosing resulted in high peak-trough excursions in active drug concentrations: trough concentrations were 21% +/- 6% of peak. Twice-daily dosing resulted in an AUC for the active drug on Day 28 that was 168% +/- 36% of that on Day 1, and steady-state trough concentrations were 54% +/- 10% of peak with sustained inhibition of platelet aggregation. Dose-adjusted steady-state active drug concentrations increased with increasing age and with decreasing renal function and body weight.
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platelet activation in patients after an acute coronary syndrome results from the timi 12 trial
1999Co-Authors: Kenneth A Ault, Christopher P Cannon, Jane Mitchell, John Mccahan, William Novotny, James D Reimann, Russell P Tracy, Eugene BraunwaldAbstract:Abstract OBJECTIVES This study was designed to determine the magnitude and time course of platelet activation during therapy of acute coronary syndromes with an oral platelet antagonist. BACKGROUND Platelet activation and aggregation are central to the pathogenesis of the acute coronary syndromes (ACS). However, few data are available on levels of platelet activation over time in patients with ACS, especially in the setting of chronic glycoprotein (GP) IIb/IIIa inhibition. METHODS The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind trial evaluating the effects of Sibrafiban, an oral, selective antagonist of the platelet glycoprotein IIb/IIIa receptor in patients stabilized after an ACS. A subset of 90 of the 329 patients in the study had measurement of platelet activation as assessed by the expression of platelet associated P-Selectin on days 0, 7 and 28. Platelet activation was measured in blood samples that were fixed either immediately (spontaneous activation) or after 5 minute incubation with 0, 1 μM or 5 μM ADP in order to assess platelet responsiveness to very low or moderate stimulation. RESULTS At baseline there was a significant elevation of spontaneous platelet activation as compared to samples obtained from normal donors or from patients who did not have acute coronary syndromes (ACS patients 27.6 ± 18.7%, Normal controls 8.5 ± 4.4%, Patient controls 10.9 ± 7.1%, p CONCLUSIONS These results suggest that platelets remain activated long after clinical stabilization post ACS. Although platelet activation decreased after one month of oral GPIIb/IIIa inhibition, levels remained higher than normal, suggesting the need for long-term antiplatelet therapy following ACS.
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Sibrafiban point of view
1999Co-Authors: M Dooley, K L Goa, F J Van De Werf, Christopher P CannonAbstract:Sibrafiban is the orally administered, nonpeptide. double-prodrug of Ro 44-3888 which is a selective glycoprotein IIb/IIIa receptor antagonist. It is currently undergoing clinical trials for secondary prevention of cardiac events in patients stabilised after acute coronary syndromes. In a phase II dose-finding study (TIMI 12) in patients stabilised after a myocardial infarction (MI) or an episode of unstable angina, there was a dose-dependent inhibition of platelet aggregation which correlated closely with the plasma concentration of the total active drug. An ongoing phase III study (SYMPHONY) compares the effects of Sibrafiban on cardiac events with that of aspirin in patients stabilised after a Q wave Ml or an episode of unstable angina. This large trial uses twice daily dosage regimens to produce the plasma concentrations which were associated with less bleeding in the earlier dose-ranging trial. A long term (minimum duration 12 months) phase III study (2nd SYMPHONY) is under way to compare the effects of Sibrafiban on cardiac events with those of aspirin in patients stabilised after an MI or an episode of unstable angina. The most common adverse events associated with Sibrafiban include bleeding. with minor haemorrhages occurring more often than with aspirin.
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randomized trial of an oral platelet glycoprotein iib iiia antagonist Sibrafiban in patients after an acute coronary syndrome results of the timi 12 trial
1998Co-Authors: Christopher P Cannon, Kenneth A Ault, Carolyn H Mccabe, Steven Borzak, Timothy D Henry, Marc D Tischler, Hiltrud S Mueller, Robert L Feldman, Sebastian T Palmeri, Scott HamiltonAbstract:Background—Inhibitors of the platelet glycoprotein IIb/IIIa receptor given intravenously have been shown to be effective in reducing ischemic complications after coronary angioplasty and in unstable angina, making this a promising new class of agents for the treatment and prevention of ischemic events in patients with acute coronary syndromes. Sibrafiban (Ro 48–3657) is an oral, peptidomimetic, selective antagonist of the glycoprotein IIb/IIIa receptor. Methods and Results—The Thrombolysis in Myocardial Infarction (TIMI) 12 trial was a phase II, double-blind, dose-ranging trial designed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of Sibrafiban in 329 patients after acute coronary syndromes. In the PK/PD cohort of TIMI 12, 106 patients were randomized to receive one of seven dosing regimens of Sibrafiban, ranging from 5 mg daily to 10 mg twice daily for 28 days. In the safety cohort, 223 patients were randomized to one of four dose regimens of Sibrafiban (ranging ...
Douglas W Weaver - One of the best experts on this subject based on the ideXlab platform.
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prevalence and management of hypertension in acute coronary syndrome patients varies by sex observations from the Sibrafiban versus aspirin to yield maximum protection from ischemic heart events postacute coronary syndromes symphony randomized clinical trials
2005Co-Authors: Camille G Frazier, Paul W Armstrong, Svati H Shah, Manjushri Bhapkar, Darren K Mcguire, Zygmunt Sadowski, A Kristinsson, Philip E Aylward, W Klein, Douglas W WeaverAbstract:Background Hypertension affects 1 billion individuals worldwide and is an independent risk factor for death after acute coronary syndromes (ACS). Methods We examined the prevalence and medical treatment of hypertension among 15 904 ACS patients randomized in the SYMPHONY and 2nd SYMPHONY trials. Analyses were performed overall and according to sex for the United States and across international practice. Multivariable models identified factors associated with use of antihypertensive medication classes and examined the association of hypertension and sex with mortality. Results In the United States, hypertension was more prevalent in women than in men, overall (63% vs 50%) and within every decile of age. Hypertensive women more often received calcium-channel blockers (35% vs 30%) and diuretics (33% vs 19%) and less often received β-blockers (51% vs 57%). Angiotensin-converting enzyme inhibitor use was similar (35% vs 34%). Women received multiple agents more frequently than did men: 2 agents, 35% vs 30%; ≥3 agents, 16% vs 13%. Female sex independently predicted drug-class use only for diuretics. Mortality was higher in hypertensive women than in hypertensive men; after multivariable adjustment, mortality was similar without evidence of a differential association between hypertension and mortality according to sex. Although there was international variation in the use of individual classes of agents, the overall findings by sex were similar across regions. Conclusion Hypertension is more prevalent in women than in men with ACS, and its medical management varies by sex, but its association with mortality is similar. Opportunities exist to improve medical therapy and outcomes in women with hypertension.