| 31. |
- Fox, Keith A., et al.
(författare)
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Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non-ST-segment elevation acute coronary syndromes
- 2007
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Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 147:5, s. 304-310
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A recent randomized, controlled trial, the Fifth Organization to Assess Strategies in Acute Ischemic Syndromes (OASIS 5) trial, reported that major bleeding was 2-fold less frequent with fondaparinux than with enoxaparin in acute coronary syndromes (ACS). Renal dysfunction increases the risk for major bleeding. OBJECTIVE: To compare the efficacy and safety of fondaparinux and enoxaparin over the spectrum of renal dysfunction observed in the OASIS 5 trial. DESIGN: Subgroup analysis of a randomized, controlled trial. SETTING: Patients presenting to the hospital with non-ST-segment elevation ACS. PATIENTS: 19,979 of the 20,078 patients in the OASIS 5 trial in whom creatinine was measured at baseline. MEASUREMENTS: Death, myocardial infarction, refractory ischemia, and major bleeding were evaluated separately and as a composite end point at 9, 30, and 180 days. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease formula. RESULTS: The absolute differences in favor of fondaparinux (efficacy and safety) were most marked in patients with a GFR less than 58 mL/min per 1.73 m2; the largest differences occurred in major bleeding events. At 9 days, death, myocardial infarction, or refractory ischemia occurred in 6.7% of patients receiving fondaparinux and 7.4% of those receiving enoxaparin (hazard ratio, 0.90 [95% CI, 0.73 to 1.11]); major bleeding occurred in 2.8% and 6.4%, respectively (hazard ratio, 0.42 [CI, 0.32 to 0.56]). Statistically significant differences in major bleeding persisted at 30 and 180 days. The rates of the composite end point were lower with fondaparinux than with enoxaparin in all quartiles of GFR, but the differences were statistically significant only among patients with a GFR less than 58 mL/min per 1.73 m2. Limitations: Subgroup analyses warrant caution; the study was powered to detect noninferiority at 9 days. Fondaparinux is not approved for use in patients with ACS in the United States. CONCLUSIONS: The benefits of fondaparinux over enoxaparin when administered for non-ST-segment elevation ACS are most marked among patients with renal dysfunction and are largely explained by lower rates of major bleeding with fondaparinux.
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| 32. |
- Hernández, Adrián V., et al.
(författare)
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Effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST segment elevation acute coronary syndromes : benefit and harm in different age subgroups
- 2007
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 93:4, s. 450-455
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether the beneficial and harmful effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST elevation acute coronary syndromes (NSTE-ACS) depend on age. METHODS: A meta-analysis of six trials of platelet glycoprotein IIb/IIIa receptor blockers in patients with NSTE-ACS (PRISM, PRISM-PLUS, PARAGON-A, PURSUIT, PARAGON-B, GUSTO IV-ACS; n = 31 402) was performed. We applied multivariable logistic regression analyses to evaluate the drug effects on death or non-fatal myocardial infarction at 30 days, and on major bleeding, by age subgroups (<60, 60-69, 70-79, > or =80 years). We quantified the reduction of death or myocardial infarction as the number needed to treat (NNT), and the increase of major bleeding as the number needed to harm (NNH). RESULTS: Subgroups had 11 155 (35%), 9727 (31%), 8468 (27%) and 2049 (7%) patients, respectively. The relative benefit of platelet glycoprotein IIb/IIIa receptor blockers did not differ significantly (p = 0.5) between age subgroups (OR (95% CI) for death or myocardial infarction: 0.86 (0.74 to 0.99), 0.90 (0.80 to 1.02), 0.97 (0.86 to 1.10), 0.90 (0.73 to 1.16); overall 0.91 (0.86 to 0.99). ORs for major bleeding were 1.9 (1.3 to 2.8), 1.9 (1.4 to 2.7), 1.6 (1.2 to 2.1) and 2.5 (1.5-4.1). Overall NNT was 105, and overall NNH was 90. The oldest patients had larger absolute increases in major bleeding, but also had the largest absolute reductions of death or myocardial infarction. Patients > or =80 years had half of the NNT and a third of the NNH of patients <60 years. CONCLUSIONS: In patients with NSTE-ACS, the relative reduction of death or non-fatal myocardial infarction with platelet glycoprotein IIb/IIIa receptor blockers was independent of patient age. Larger absolute outcome reductions were seen in older patients, but with a higher risk of major bleeding. Close monitoring of these patients is warranted.
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| 33. |
- Hess, Otto M., et al.
(författare)
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Why don't we return to bare metal stents?
- 2008
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Ingår i: EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. - 1774-024X. ; 4:1, s. 36-41
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Tidskriftsartikel (refereegranskat)
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| 34. |
- Jackson, Kevin, et al.
(författare)
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Antithrombotic drug development for atrial fibrillation : proceedings, Washington, DC, July 25-27, 2005
- 2008
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 155:5, s. 829-40
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Tidskriftsartikel (refereegranskat)abstract
- In July 2005, leaders from academia, government, and industry convened in Washington, DC, to discuss key issues in the development of antithrombotic treatments for atrial fibrillation (AF). In addition to summarizing available data on the relative benefits and risks of currently available therapies in diverse clinical practice settings, we reviewed designs of ongoing trials and registries, focusing on areas of methodological controversy and uncertainty. Participants in this meeting described the growing burden of AF, summarized the data showing effectiveness of warfarin for prevention of stroke in AF, and noted that warfarin is both underused and poorly monitored and adjusted in general practice. There was consensus that there is an important unmet clinical need for better treatment of patients with AF at risk of stroke, including alternatives to warfarin that address its limitations. Comparative noninferiority trials to develop alternatives to warfarin must include warfarin management that is at least as good as that provided in historical trials. There was agreement that noninferiority trials can be done based on historical warfarin trials, and that placebo-controlled trials focused on patients not receiving warfarin in general practice can provide important information as well. Statistical principles for noninferiority in this setting were discussed, and a standard approach was proposed. A majority of clinical trial representatives suggested that large, simple, open-label trials would provide the most meaningful information relevant to future practice, but regulators cautioned that, in such a simple trial, one needs to ensure that the control group does at least as well as the historical controls for the noninferiority design to be interpretable. With this summary document, we hope to provide a helpful resource for future drug development for AF.
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| 35. |
- James, Stefan, 1964-, et al.
(författare)
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Comparison of ticagrelor, the first reversible oral P2Y(12) receptor antagonist, with clopidogrel in patients with acute coronary syndromes : Rationale, design, and baseline characteristics of the PLATelet inhibition and patient Outcomes (PLATO) trial
- 2009
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 157:4, s. 599-605
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antiplatelet therapy is essential treatment for acute coronary syndromes (ACS). Current therapies, however, have important limitations affecting their clinical success. Ticagrelor, the first reversible oral P2Y(12) receptor antagonist, provides faster, greater, and more consistent adenosine diphosphate-receptor inhibition than clopidogrel. The phase III PLATelet inhibition and patient Outcomes (PLATO) trial is designed to test the hypothesis that ticagrelor compared with clopidogrel will result in a lower risk of recurrent thrombotic events in a broad patient population with ACS. METHODS: PLATO is an international, randomized, double-blind, event-driven trial involving >18,000 patients hospitalized for ST-elevation ACS with scheduled primary percutaneous coronary intervention or for non-ST-elevation ACS. After loading doses of ticagrelor 180 mg or clopidogrel 300 mg in a double-blind, double-dummy fashion (with provision for additional 300 mg clopidogrel at percutaneous coronary intervention), patients will receive ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 6 to 12 months on top of acetylsalicylic acid. The primary efficacy end point is time to first occurrence of death from vascular causes, myocardial infarction, or stroke. The primary safety variable is PLATO-defined major bleeding. An extensive substudy program will explore the pathophysiology of ACS, indicators of prognosis and response to treatment, mechanisms of effect and safety of the study medications, health economics, and quality of life. CONCLUSION: The PLATO study will provide a pivotal comparison of the efficacy and safety of ticagrelor with those of clopidogrel in ACS patients, together with extensive information on treatment outcomes in different subsets of ACS in a broad patient population.
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| 36. |
- James, Stefan K., 1964-, et al.
(författare)
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Long-term safety and efficacy of drug-eluting versus bare-metal stents in Sweden
- 2009
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 360:19, s. 1933-1945
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The long-term safety and efficacy of drug-eluting coronary stents have been questioned. METHODS: We evaluated 47,967 patients in Sweden who received a coronary stent and were entered into the Swedish Coronary Angiography and Angioplasty Registry between 2003 and 2006 and for whom complete follow-up data were available for 1 to 5 years (mean, 2.7). In the primary analysis, we compared patients who received one drug-eluting coronary stent (10,294 patients) with those who received one bare-metal stent (18,659), after adjustment for differences in clinical characteristics of the patients and characteristics of the vessels and lesions. RESULTS: Analyses of outcome were based on 2380 deaths and 3198 myocardial infarctions. There was no overall difference between the group that received drug-eluting stents and the group that received bare-metal stents in the combined end point of death or myocardial infarction (relative risk with drug-eluting stents, 0.96; 95% confidence interval [CI], 0.89 to 1.03) or the individual end points of death (relative risk, 0.94; 95% CI, 0.85 to 1.05) and myocardial infarction (relative risk, 0.97; 95% CI, 0.88 to 1.06), and there was no significant difference in outcome among subgroups stratified according to the indication for stent implantation. Patients who received drug-eluting stents in 2003 had a significantly higher rate of late events than patients who received bare-metal stents in the same year, but we did not observe any difference in outcome among patients treated in later years. The average rate of restenosis during the first year was 3.0 events per 100 patient-years with drug-eluting stents versus 4.7 with bare-metal stents (adjusted relative risk, 0.43; 95% CI, 0.36 to 0.52); 39 patients would need to be treated with drug-eluting stents to prevent one case of restenosis. Among high-risk patients, the adjusted risk of restenosis was 74% lower with drug-eluting stents than with bare-metal stents, and only 10 lesions would need to be treated to prevent one case of restenosis. CONCLUSIONS: As compared with bare-metal stents, drug-eluting stents are associated with a similar long-term incidence of death or myocardial infarction and provide a clinically important decrease in the rate of restenosis among high-risk patients.
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| 37. |
- James, Stefan K., 1964-, et al.
(författare)
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The SCAAR-scare in perspective
- 2009
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Ingår i: EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology. - 1774-024X. ; 5:4, s. 501-504
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Tidskriftsartikel (refereegranskat)
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| 38. |
- James, Stefan K., 1964-, et al.
(författare)
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Troponin-T and N-terminal pro-B-type natriuretic peptide predict mortality benefit from coronary revascularization in acute coronary syndromes : a GUSTO-IV substudy
- 2006
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 48:6, s. 1146-1154
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study was designed to evaluate biomarkers for selection of patients with non-ST-segment elevation acute coronary syndromes (ACS) that derive mortality benefit from revascularization. BACKGROUND: Biomarkers are essential for identification of patients at increased risk, which may be reduced by revascularization. METHODS: During the initial 30 days, 2,340 patients of 7,800 (30%) with non-ST-segment elevation ACS in the GUSTO (Global Utilization of Strategies To open Occluded arteries)-IV trial underwent coronary revascularization. The 1-year mortality was calculated in 30-day survivors stratified by status of revascularization and levels of biomarkers. A propensity score for receiving revascularization was constructed and included in a survival analysis that also included the time point of revascularization as a time-dependent covariate. RESULTS: Elevation of troponin-T or N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with a high mortality. In patients with either or both of these markers elevated, a lower mortality following revascularization was observed. In contrast, patients without elevation of these markers had low 1-year mortality without any reduction in mortality following revascularization. In fact, in patients with normal levels of both troponin-T and NT-proBNP, a significant increase in 1-year mortality after revascularization was observed. Elevation of C-reactive protein, interleukin-6, creatinine clearance, and ST-segment depression was also related to a higher mortality. However, independent of these markers, mortality was lower after revascularization. CONCLUSIONS: Markers of troponin-T and NT-proBNP not only assist in risk stratification of patients with non-ST-segment elevation ACS but also appear to identify patients who have a reduced mortality associated with early coronary revascularization.
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| 39. |
- James, Stefan K., 1964-, et al.
(författare)
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Usefulness of biomarkers for predicting long-term mortality in patients with diabetes mellitus and non-ST-elevation acute coronary syndromes (A GUSTO IV substudy)
- 2006
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 97:2, s. 167-172
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Tidskriftsartikel (refereegranskat)abstract
- The present study evaluated whether biomarkers of ischemia, inflammation, myocardial damage, and dysfunction are equally useful in patients who have diabetes mellitus (DM) for prediction of cardiac events in non-ST-elevation acute coronary syndrome (ACS). DM was present in 1,677 of 7,800 patients (21.5%) who had non-ST-elevation ACS and were included in the Fourth Global Utilization of Strategies To Open Occluded Arteries (GUSTO IV) trial. Creatinine, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin T, C-reactive protein, and interleukin-6 were analyzed in serum samples that were obtained at a median of 9.5 hours from symptom onset. One-year mortality rates were 13.5% among patients who had DM (n = 227) and 6.9% among those who did not (n = 418, p < 0.001). The median level of NT-pro-BNP was 2 times as high in patients who had DM, whereas troponin T levels did not differ by DM status. Mortality increased with ascending quartiles of NT-pro-BNP, with 1-year mortality rates of 3.9% (n = 11) in the bottom quartile and 29% (n = 103) in the top quartile. In multivariable analyses, factors that were predictive of 1-year mortality in patients who did not have DM were also significant for those who did. Presence of ST depression > 0.5 mm had the highest odds ratio of 2.3 (95% confidence interval 1.2 to 4.6). NT-pro-BNP levels > 669 ng/L (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) and interleukin-6 levels > 10 ng/L (odds ratio 1.9, 95% confidence interval 1.2 to 3.0) were significant biomarker predictors. In conclusion, DM confers a high long-term mortality in non-ST-elevation ACS. Despite a larger proportion of ST depression and increased levels of NT-pro-BNP and interleukin-6 at admission, these factors provide independent prognostic information that may improve risk stratification and guidance of treatment.
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| 40. |
- Jernberg, Tomas, et al.
(författare)
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Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease
- 2006
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:10, s. 1166-1173
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: This study was designed to compare the degree of inhibition of platelet aggregation (IPA) of prasugrel with that of clopidogrel in stable aspirin-treated patients with coronary artery disease (CAD). METHODS AND RESULTS: Subjects (n=101) were randomly assigned to the following loading dose (LD) (day 1)/maintenance dose (MD) (days 2-28) combinations: prasugrel, 40 mg/5 mg; 40 mg/7.5 mg; 60 mg/10 mg; 60 mg/15 mg; or clopidogrel, 300 mg/75 mg. Turbidometric platelet aggregation was measured at multiple timepoints during the study. At 4 h after dosing, with 20 microM ADP, both prasugrel LDs achieved significantly higher mean IPA levels (60.6% and 68.4 vs. 30.0%, respectively; all P<0.0001) and lower percentage (3 vs. 52%, P<0.0001) of pharmacodynamic non-responders (defined as IPA <20%) than clopidogrel. Prasugrel 10 and 15 mg MDs achieved consistently higher mean IPA than clopidogrel 75 mg at day 28 (all P<0.0001). At pre-MD on day 28, there were no non-responders in the 10 and 15 mg prasugrel group, compared with 45% in the clopidogrel group (P=0.0007). CONCLUSION: In this population, prasugrel (40-60 mg LD and 10-15 mg MD) achieves greater IPA and a lower proportion of pharmacodynamic non-responders compared with the approved clopidogrel dosing.
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