| 11. |
- Bowman, Louise, et al.
(författare)
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Understanding the use of observational and randomized data in cardiovascular medicine
- 2020
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 41:27, s. 2571-2578
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Tidskriftsartikel (refereegranskat)abstract
- The availability of large datasets from multiple sources [e.g. registries, biobanks, electronic health records (EHRs), claims or billing databases, implantable devices, wearable sensors, and mobile apps], coupled with advances in computing and analytic technologies, have provided new opportunities for conducting innovative health research. Equally, improved digital access to health information has facilitated the conduct of efficient randomized controlled trials (RCTs) upon which clinical management decisions can be based, for instance, by permitting the identification of eligible patients for recruitment and/or linkage for follow-up via their EHRs. Given these advances in cardiovascular data science and the complexities they behold, it is important that health professionals have clarity on the appropriate use and interpretation of observational, so-called 'real-world', and randomized data in cardiovascular medicine. The Cardiovascular Roundtable of the European Society of Cardiology (ESC) held a workshop to explore the future of RCTs and the current and emerging opportunities for gathering and exploiting complex observational datasets in cardiovascular research. The aim of this article is to provide a perspective on the appropriate use of randomized and observational data and to outline the ESC plans for supporting the collection and availability of clinical data to monitor and improve the quality of care of patients with cardiovascular disease in Europe and provide an infrastructure for undertaking pragmatic RCTs. Moreover, the ESC continues to campaign for greater engagement amongst regulators, industry, patients, and health professionals in the development and application of a more efficient regulatory framework that is able to take maximal advantage of new opportunities for improving the design and efficiency of observational studies and RCT in patients with cardiovascular disease.
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| 12. |
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| 13. |
- Eggers, Kai M., et al.
(författare)
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Clinical and prognostic implications of circulating pentraxin 3 levels in non ST-elevation acute coronary syndrome
- 2013
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 46:16-17, s. 1655-1659
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Pentraxin 3 (PTX3) is the prototype of the long pentraxin family. PTX3 is involved in inflammatory processes affecting the cardiovascular system, and PTX3 levels have been shown to be elevated and independently prognostic in ST-elevation myocardial infarction. Data on PTX3 levels in non-ST-elevation acute coronary syndrome (NSTE-ACS), in contrast, are limited. The aim of the present analysis was to investigate the implications of PTX3 levels in a fairly large sample of NSTE-ACS patients and in comparison to levels of C-reactive protein (CRP). Design and methods: We measured levels of PTX3 and CRP in both 82 healthy controls and 401 NSTE-ACS patients from the GUSTO IV study, and studied the associations of these biomarkers to clinical data and 1-year mortality. Results: NSTE-ACS patients had significantly higher median PTX3 levels compared to healthy controls (3.8 vs. 1.9 mu g/L; p < 0.001). PTX3 levels in patients with NSTE-ACS were independently related to female sex and cardiac troponin T levels, but not to age or cardiovascular risk factors. PTX3 levels were higher in patients who died within 1 year but did not emerge as an independent predictor of 1-year mortality (adjusted OR 1,2 [95% Cl 0.6-2.31). This was in contrast to CRP (adjusted OR 1.5 [95% Cl 1.1-2.3]). Neither PTX3 nor CRP yielded significant discriminative value regarding mortality prediction. Conclusions: PTX3 levels are elevated in NSTE-ACS. However, the prognostic information provided by PTX3 levels is limited and inferior compared to CRP. Our data, thus, do not support the measurement of PTX3 in patients with NSTE-ACS.
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| 14. |
- Eggers, Kai M., 1962-, et al.
(författare)
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ST2 and mortality in non-ST-segment elevation acute coronary syndrome
- 2010
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 159:5, s. 788-794
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: ST2 is a member of the interleukin-1 receptor family that is up-regulated in conditions associated with increased myocardial strain. ST2 has been shown to be independently predictive of adverse outcome in heart failure and ST-segment elevation myocardial infarction, but its prognostic value in non-ST-elevation acute coronary syndrome (NSTE-ACS) has not been established. METHODS: We measured ST2 at randomization and after 24, 48, and 72 hours in 403 NSTE-ACS patients from the GUSTO IV study, and studied its kinetics and its associations to clinical baseline factors and 1-year mortality. RESULTS: Median ST2 levels decreased from 28.4 U/mL at randomization to 21.8 U/mL at 72 hours (P < .001). Peak levels were noted 6 to 17 hours after symptom onset. Randomization ST2 levels were independently associated to N-terminal pro-B-type natriuretic peptide but otherwise exhibited only weak relations to cardiovascular risk factors and comorbidities, and biomarkers of myocardial necrosis or inflammation. ST2 was related to 1-year mortality independently of clinical risk indicators (odds ratio 2.3 [95% CI 1.1-4.6], P = .03) but lost its predictive value after additional adjustment for prognostic biomarkers, in particular N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: ST2 levels are elevated early in NSTE-ACS and predict 1-year mortality. Our data indicate that ST2 represents an interesting novel pathophysiologic pathway in the setting of ischemia-related myocardial dysfunction. However, future prospective evaluations in larger populations are needed before the clinical utility of ST2 can be determined.
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| 15. |
- 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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| 16. |
- 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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| 17. |
- Westerhout, Cynthia M., et al.
(författare)
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Dynamic modeling of 90-day mortality in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention
- 2013
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 165:3, s. 354-
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Tidskriftsartikel (refereegranskat)abstract
- Aims Dynamic risk models update the risk profile of ST-elevation myocardial infarction (STEMI) patients over the acute period following the event and have implications to clinical practice and research. Methods and Results Multivariable survival models were developed in 5,745 STEMI patients undergoing primary percutaneous coronary intervention (PCI) enrolled in the APEX-AMI trial to predict 90-day mortality from 4 clinically relevant times: baseline, 2 hours, 24 hours, and 96 hours. Culprit coronary thrombolysis in myocardial infarction flow grade, 30-minute post-PCI worst-lead ST-elevation residual, and in-hospital clinical events were considered in the models. The 90-day mortality was 4.7%; the cumulative proportion of mortality occurring within 2, 24, and 96 hours was 8%, 22%, and 40% respectively. Relative to the baseline risk factors, age and systolic blood pressure remained highly ranked in the post-baseline models. However, the relative importance of heart rate, Killip class, and creatinine declined, whereas markers of coronary reperfusion and in-hospital events (shock, congestive heart failure) became increasingly influential. The c-index increased from 0.819 at baseline to 0.847 at 96 hours. Over the forecasting periods, the proportion of "low-risk" (<1.1% 90-day mortality) patients increased from 20% to 49%. This approach derived from an unfolding series of models reveals the shifting levels of mortality risk from baseline to 96 hours. Conclusion This novel approach in STEMI patients undergoing primary PCI demonstrates the dynamic nature of risk over time and may prove useful in understanding risk and in clinical decision making.
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| 18. |
- Westerhout, Cynthia M., et al.
(författare)
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No prognostic significance of chronic infection with Chlamydia pneumoniae in acute coronary syndromes : insights from the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial
- 2007
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 154:2, s. 306-312
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although relationships between chronic Chlamydia pneumoniae (Cpn) infection and the risk of coronary events in stable coronary artery disease patients have been reported, a similar link in acute coronary syndrome (ACS) patients has not been consistently observed. METHODS: In a nested case-control substudy of the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial, 295 cases (30-day death/myocardial infarction [MI]) were matched by age, sex, baseline creatine kinase-myocardial kinase, and smoking status with 295 control subjects. To test the hypothesis on 1-year mortality, another subset (n = 276) was drawn from the 590-patient cohort; 138 patients who died at 1 year plus the matching controls who survived at 1 year. We measured Cpn IgG and IgA antibody titers in baseline serum with microimmunofluorescence. Conditional logistic regression was used to quantify the prognostic relevance seropositivity (IgG > or = 1:32; IgA > or = 1:16) and elevated titer levels. RESULTS: The prevalence of Cpn IgG and IgA was similar between cases and controls (30-day death/MI: IgG, 80% vs 85%, P = .126; IgA, 45% vs 37%, P = .079), and were not statistically significant predictors of 30-day death/MI after baseline adjustment. Likewise, the 1-year death cohort had comparable proportions of Cpn IgG and IgA among cases and controls (86% vs 91% [P = .265] and 49% vs 43% [P = .334], respectively), and did not add prognostic value. CONCLUSIONS: These findings are in concert with study results suggesting that chronic Cpn infection is not associated with 30-day death/MI or 1-year mortality in non-ST elevation ACS.
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| 19. |
- Westerhout, Cynthia M., et al.
(författare)
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Predictors of stroke within 30 days in patients with non-ST-segment elevation acute coronary syndromes
- 2006
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:24, s. 2956-2961
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We aimed to identify predictors of stroke within 30 days in patients who suffered NSTE-ACS. METHODS AND RESULTS: We pooled data from six trials (n=31 402) that randomized NSTE-ACS patients either to platelet glycoprotein (GP) IIb/IIIa receptor blockers or to placebo/control therapy. Potential predictors of stroke included treatment, demographic, and clinical characteristics. We identified predictors using univariable and multivariable logistic models, and their performance was evaluated with calibration (Hosmer-Lemeshow test) and discrimination (c-statistic). We found 228 (0.7%) all-cause strokes: 155 (0.5%) non-haemorrhagic, 20 (0.06%) haemorrhagic, and 53 without computed tomography (CT) confirmation. Patients with any type of stroke had a 30-day mortality of 25%. Randomization to GP IIb/IIIa receptor blockers was not significantly associated with all-cause stroke [OR (95% CI) 1.08 (0.83-1.41)]. Older age [OR per 10-year increase 1.5 (1.3-1.7)], prior stroke [2.1 (1.4-3.1)], and elevated heart rate [per 10-beat increase 1.1 (1.0-1.2)] were the strongest predictors of 30-day all-cause stroke. Similar predictors were found for non-haemorrhagic and haemorrhagic strokes. Smoking, previous myocardial infarction, diabetes, and hypertension were not independent predictors of all-cause stroke. The multivariable model to predict all-cause stroke was well calibrated, but its discrimination was only moderate [c-statistic 0.69 (0.65-0.72)]. CONCLUSION: Stroke is a rare complication occurring early after NSTE-ACS, but is associated with high mortality. We found no evidence that GP IIb/IIIa receptor blockers increase stroke risks. A few clinical characteristics predicted higher stroke risks. Thus, incident strokes in NSTE-ACS patients remain largely unexplained.
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| 20. |
- Westerhout, Cynthia M., et al.
(författare)
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Short- and long-term risk stratification in acute coronary syndromes : the added value of quantitative ST-segment depression and multiple biomarkers
- 2006
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 48:5, s. 939-947
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The purpose of this study was to develop 30-day and 1-year risk stratification models for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients that incorporate quantitative ST-segment depression and novel biomarkers. BACKGROUND: Several novel biomarkers have changed the risk profile of ACS; thus, the reassessment of traditional indicators such as ST-segment depression in this new context is warranted. METHODS: Multivariable logistic regression was used to identify significant predictors of 30-day death and death/myocardial infarction (MI) and 1-year mortality in 7,800 NSTE-ACS patients enrolled in the GUSTO-IV (Global Utilization of Strategies to Open Occluded Arteries-IV ACS) trial between 1998 and 2000. RESULTS: Among all other predictors, the degree of ST-segment depression had the highest prognostic value for 30-day death, 30-day death/MI, and 1-year death. Troponin T (TnT), creatinine clearance, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart rate, and age were also highly influential on adverse outcomes. Unlike TnT and NT-proBNP, C-reactive protein was only predictive of long-term death. In contrast to mortality, the contribution of TnT to predicting 30-day death/MI increased, whereas NT-proBNP's role was attenuated. The discriminatory power was excellent (c-index [adjusted for over-optimism]: 0.82 [30-day death]; 0.72 [30-day death/MI]; 0.81 [1-year]). CONCLUSIONS: In this large contemporary study of NSTE-ACS patients, novel insights into risk stratification were observed-in particular, the utility of quantitative ST-segment depression and multiple biomarkers. Collection of these indicators in future NSTE-ACS populations is recommended to evaluate generalizability and clinical application of these findings.
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