| 1. |
- Bhatt, Deepak L., et al.
(författare)
-
Rationale, design and baseline characteristics of the effect of ticagrelor on health outcomes in diabetes mellitus patients Intervention study
- 2019
-
Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:5, s. 498-505
-
Tidskriftsartikel (refereegranskat)abstract
- In the setting of prior myocardial infarction, the oral antiplatelet ticagrelor added to aspirin reduced the risk of recurrent ischemic events, especially, in those with diabetes mellitus. Patients with stable coronary disease and diabetes are also at elevated risk and might benefit from dual antiplatelet therapy. The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS, NCT01991795) is a Phase 3b randomized, double-blinded, placebo-controlled trial of ticagrelor vs placebo, on top of low dose aspirin. Patients >= 50 years with type 2 diabetes receiving anti-diabetic medications for at least 6 months with stable coronary artery disease as determined by a history of previous percutaneous coronary intervention, bypass grafting, or angiographic stenosis of >= 50% of at least one coronary artery were enrolled. Patients with known prior myocardial infarction (MI) or stroke were excluded. The primary efficacy endpoint is a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety endpoint is Thrombolysis in Myocardial Infarction major bleeding. A total of 19 220 patients worldwide have been randomized and at least 1385 adjudicated primary efficacy endpoint events are expected to be available for analysis, with an expected average follow-up of 40 months (maximum 58 months). Most of the exposure is on a 60 mg twice daily dose, as the dose was lowered from 90 mg twice daily partway into the study. The results may revise the boundaries of efficacy for dual antiplatelet therapy and whether it has a role outside acute coronary syndromes, prior myocardial infarction, or percutaneous coronary intervention.
|
|
| 2. |
- De Caterina, Raffaele, et al.
(författare)
-
New Oral Anticoagulants in Atrial Fibrillation and Acute Coronary Syndromes : ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease Position Paper
- 2012
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 59:16, s. 1413-1425
-
Forskningsöversikt (refereegranskat)abstract
- Until recently, vitamin K antagonists were the only available oral anticoagulants, but with numerous limitations that prompted the introduction of new oral anticoagulants targeting the single coagulation enzymes thrombin (dabigatran) or factor Xa (apixaban, rivaroxaban, and edoxaban) and given in fixed doses without coagulation monitoring. Here we review the pharmacology and the results of clinical trials with these new agents in stroke prevention in atrial fibrillation and secondary prevention after acute coronary syndromes, providing perspectives on their future incorporation into clinical practice. In phase III trials in atrial fibrillation, compared with warfarin, dabigatran etexilate 150 mg B.I.D. reduced the rates of stroke/systemic embolism without any difference in major bleeding; dabigatran etexilate 110 mg B.I.D. had similar efficacy with decreased bleeding; apixaban 5 mg B.I.D. reduced stroke, systemic embolism, and mortality as well as major bleeding; and rivaroxaban 20 mg Q.D. was noninferior to warfarin for stroke and systemic embolism without a difference in major bleeding. All these agents reduced intracranial hemorrhage. Edoxaban is currently being evaluated in a further large phase III trial. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischemia in patients with acute coronary syndromes who were mostly receiving dual antiplatelet therapy, with conflicting results on efficacy but consistent results for increased major bleeding. Overall, the new oral anticoagulants are poised to replace vitamin K antagonists for many patients with atrial fibrillation and may have a role after acute coronary syndromes. Although convenient to administer and manage, they present challenges that need to be addressed.
|
|
| 3. |
- De Caterina, Raffaele, et al.
(författare)
-
Oral anticoagulants in coronary heart disease (Section IV) Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2016
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 115:4, s. 685-711
-
Tidskriftsartikel (refereegranskat)abstract
- Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.
|
|
| 4. |
- De Caterina, Raffaele, et al.
(författare)
-
Parenteral anticoagulants in heart disease : Current status and perspectives (Section II) Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease
- 2013
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 109:5, s. 769-786
-
Tidskriftsartikel (refereegranskat)abstract
- Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.
|
|
| 5. |
- De Caterina, Raffaele, et al.
(författare)
-
Vitamin K antagonists in heart disease : Current status and perspectives (Section III)
- 2013
-
Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 110:6, s. 1087-1107
-
Tidskriftsartikel (refereegranskat)abstract
- Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting gamma-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.
|
|
| 6. |
- Vester, Mazen, et al.
(författare)
-
Myocardial perfusion imaging by 15O-H2O positron emission tomography predicts clinical revascularization procedures in symptomatic patients with previous coronary artery bypass graft.
- 2023
-
Ingår i: European Heart Journal Open. - 2752-4191. ; 3:3, s. oead044-
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: We wanted to assess if 15O-H2O myocardial perfusion imaging (MPI) in a clinical setting can predict referral to coronary artery catheterization [coronary angiography (CAG)], execution of percutaneous coronary intervention (PCI), and post-PCI angina relief for patients with angina and previous coronary artery bypass graft (CABG).METHODS AND RESULTS: We analysed 172 symptomatic CABG patients referred for 15O-H2O positron emission tomography (PET) MPI at Aarhus University Hospital Department of Nuclear Medicine & PET Centre, of which five did not complete the scan. In total, 145 (87%) enrolled patients had an abnormal MPI. Of these, 86/145 (59%) underwent CAG within 3 months; however, no PET parameters predicted referral to CAG. During the CAG, 25/86 (29%) patients were revascularized by PCI. Relative flow reserve (RFR) (0.49 vs. 0.54 P = 0.03), vessel-specific myocardial blood flow (MBF) (1.53 vs. 1.88 mL/g/min, P < 0.01), and vessel-specific myocardial flow reserve (MFR) (1.73 vs. 2.13, P < 0.01) were significantly lower in patients revascularized by PCI. Receiver operating characteristic analysis of the vessel-specific parameters yielded optimal cutoffs of 1.36 mL/g/min (MBF) and 1.28 (MFR) to predict PCI. Angina relief was experienced by 18/24 (75%) of the patients who underwent PCI. Myocardial blood flow was an excellent predictor of angina relief on both a global [area under the curve (AUC) = 0.85, P < 0.01] and vessel-specific (AUC = 0.90, P < 0.01) level with optimal cutoff levels of 1.99 mL/g/min and 1.85 mL/g/min, respectively.CONCLUSION: For CABG patients, RFR, vessel-specific MBF, and vessel-specific MFR measured by 15O-H2O PET MPI predict whether subsequent CAG will result in PCI. Additionally, global and vessel-specific MBF values predict post-PCI angina relief.
|
|
| 7. |
- Dalby, Lars, et al.
(författare)
-
The status of the Nordic populations of the Mallard (Anas platyrhynchos) in a changing world
- 2013
-
Ingår i: Ornis Fennica. - : Finnish Omithological Soc. - 0030-5685. ; 90:1, s. 2-15
-
Tidskriftsartikel (refereegranskat)abstract
- Dabbling ducks (Anas spp.) are importantmigratory quarry species, protected as a shared resource under international legislation. However, there is a lack of sufficient high-quality data on vital demographic rates and long-term trends in numbers to judge the conservation status of many duck populations at the flyway level. In response to reported declines in the North-West European flyway population of theMallard, we compiled available data on this species in the Nordic countries up to 2010. Generally, national breeding numbers showed increasing trends, wintering abundance showed variable trends, and productivitymeasures indicated stable or increasing trends.Major knowledge gaps were identified, namely the size of hunting bags, the influence of the released Mallards and the role of short-stopping in explaining changing patterns of wintering abundance across the North-West European flyway. Numerically the Nordic breeding population appears in “good condition”, and the wintering numbers have been either stable or increasing in the last two decades. The annual number of releases needs to be determined in order to judge the sustainability of the current levels of exploitation. Overall, none of the indicators showed alarming signs for the Mallard population in the Nordic countries when considered in isolation. However, the widespread decline in wintering numbers elsewhere across North-western Europe requires urgent pan-European action.
|
|
| 8. |
- Dalby, Lars, et al.
(författare)
-
The status of the Nordic populations of the Mallard (Anas platyrhynchos) in a changing world
- 2013
-
Ingår i: Ornis Fennica. - : University of Helsinki. - 0030-5685. ; 90:1, s. 2-15
-
Tidskriftsartikel (refereegranskat)abstract
- Dabbling ducks (Anas spp.) are important migratory quarry species, protected as a shared resource under international legislation. However, there is a lack of sufficient high-quality data on vital demographic rates and long-term trends in numbers to judge the conservation status of many duck populations at the flyway level. In response to reported declines in the North-West European flyway population of the Mallard, we compiled available data on this species in the Nordic countries up to 2010. Generally, national breeding numbers showed increasing trends, wintering abundance showed variable trends, and productivity measures indicated stable or increasing trends. Major knowledge gaps were identified, namely the size of hunting bags, the influence of the released Mallards and the role of short-stopping in explaining changing patterns of wintering abundance across the North-West European flyway. Numerically the Nordic breeding population appears in "good condition", and the wintering numbers have been either stable or increasing in the last two decades. The annual number of releases needs to be determined in order to judge the sustainability of the current levels of exploitation. Overall, none of the indicators showed alarming signs for the Mallard population in the Nordic countries when considered in isolation. However, the widespread decline in wintering numbers elsewhere across North-western Europe requires urgent pan-European action.
|
|
| 9. |
|
|
| 10. |
- Elmberg, Johan, 1960-, et al.
(författare)
-
Interpreting seasonal range shifts in migratory birds : a critical assessment of 'short-stopping' and a suggested terminology
- 2014
-
Ingår i: Journal of Ornithology = Journal fur Ornithologie. - 0021-8375 .- 1439-0361. ; 155:3, s. 571-579
-
Forskningsöversikt (refereegranskat)abstract
- The term 'short-stopping' is increasingly used in ecology to describe spatio-temporal changes in occurrence of migratory species. Spurred by the insight that it has been used in a variety of contexts, we reviewed its use in avian ecology. A literature search yielded 59 papers explicitly treating short-stopping in birds, most of them in peer-reviewed journals. The term was first used in 1967 to describe a northward shift in wintering Canada Geese in North America and has been used with increasing frequency to the present day. Geese dominate the short-stopping literature, which is confined to the northern hemisphere. Short-stopping has been used to describe (1) a shortened autumn migration that results in a wintering distribution closer to breeding areas, (2) a shortened spring migration that results in a breeding distribution closer to wintering areas, and (3) a delay in autumn migration that leads to a perceived reduced abundance in some part of the winter range. We advocate that short-stopping should be used only to describe (1) range shifts that involve shortening of the migratory corridor, and that they are qualified explicitly by season (i.e. breeding/winter) and degree (i.e. full or partial range shift). In other cases of breeding, wintering or entire range shifts where the migratory corridor is elongated or remains the same, we recommend using the term 'range shift', qualified by season, geography and orientation (i.e. the direction of the range shift). We also discuss the need for spatially explicit avian count monitoring mechanisms (rather than capture-recapture or hunting bag data) designed specifically to track such changes in distribution in the future.
|
|
| 11. |
- Elmberg, Johan, et al.
(författare)
-
Interpreting seasonal range shifts in migratory birds : a critical assessment of 'short-stopping' and a suggested terminology
- 2014
-
Ingår i: Journal of Ornithology = Journal fur Ornithologie. - : Springer Science and Business Media LLC. - 0021-8375. ; 155:3, s. 571-579
-
Forskningsöversikt (refereegranskat)abstract
- The term 'short-stopping' is increasingly used in ecology to describe spatio-temporal changes in occurrence of migratory species. Spurred by the insight that it has been used in a variety of contexts, we reviewed its use in avian ecology. A literature search yielded 59 papers explicitly treating short-stopping in birds, most of them in peer-reviewed journals. The term was first used in 1967 to describe a northward shift in wintering Canada Geese in North America and has been used with increasing frequency to the present day. Geese dominate the short-stopping literature, which is confined to the northern hemisphere. Short-stopping has been used to describe (1) a shortened autumn migration that results in a wintering distribution closer to breeding areas, (2) a shortened spring migration that results in a breeding distribution closer to wintering areas, and (3) a delay in autumn migration that leads to a perceived reduced abundance in some part of the winter range. We advocate that short-stopping should be usedonly to describe (1) range shifts that involve shortening of the migratory corridor, and that they are qualified explicitly by season (i.e. breeding/winter) and degree (i.e. full or partial range shift). In other cases of breeding, wintering or entire range shifts where the migratory corridor is elongated or remains the same, we recommend using the term 'range shift', qualified by season, geography and orientation (i.e. the direction of the range shift). We also discuss the need for spatially explicit avian count monitoring mechanisms (rather than capture-recapture or hunting bag data) designed specifically to track such changes in distribution in the future.
|
|
| 12. |
- Fox, Anthony D., et al.
(författare)
-
Current and potential threats to Nordic duck populations - a horizon scanning exercise
- 2015
-
Ingår i: Annales Zoologici Fennici. - 0003-455X .- 1797-2450. ; 52:4, s. 193-220
-
Tidskriftsartikel (refereegranskat)abstract
- We review the current and future threats to duck populations that breed, stage, moult and/or winter in the Nordic countries. Migratory duck species are sensitive indicators of their changing environment, and their societal value confirms the need to translate signals from changes in their distribution, status and abundance into a better understanding of changes occurring in their wetland environments. We used expert opinion to highlight 25 major areas of anthropogenic change (and touch briefly on potential mitigation measures through nature restoration and reserve management projects) that we consider key issues likely to influence Nordic duck populations now and in the near future to stimulate debate, discussion and further research. We believe such reviews are essential in contributing to development of successful management policy as well as stimulating specific research to support the maintenance of duck species in favourable future conservation status in the face of multiple population pressures and drivers.
|
|
| 13. |
- Fox, Anthony D., et al.
(författare)
-
Current and potential threats to Nordic duck populations - a horizon scanning exercise
- 2015
-
Ingår i: Annales Zoologici Fennici. - : Finnish Zoological and Botanical Publishing Board. - 0003-455X. ; 52:4, s. 193-220
-
Tidskriftsartikel (refereegranskat)abstract
- We review the current and future threats to duck populations that breed, stage, moult and/or winter in the Nordic countries. Migratory duck species are sensitive indicators of their changing environment, and their societal value confirms the need to translate signals from changes in their distribution, status and abundance into a better understanding of changes occurring in their wetland environments. We used expert opinion to highlight 25 major areas of anthropogenic change (and touch briefly on potential mitigation measures through nature restoration and reserve management projects) that we consider key issues likely to influence Nordic duck populations now and in the near future to stimulate debate, discussion and further research. We believe such reviews are essential in contributing to development of successful management policy as well as stimulating specific research to support the maintenance of duck species in favourable future conservation status in the face of multiple population pressures and drivers.
|
|
| 14. |
- Fox, Anthony D., et al.
(författare)
-
Seeking explanations for recent changes in abundance of wintering Eurasian Wigeon (Anas penelope) in northwest Europe
- 2016
-
Ingår i: Ornis Fennica. - 0030-5685. ; 93:1, s. 12-25
-
Tidskriftsartikel (refereegranskat)abstract
- We analysed annual changes in abundance of Eurasian Wigeon (Anas penelope) derived from mid-winter International Waterbird Census data throughout its northwest European flyway since 1988 using log-linear Poisson regression modelling. Increases in abundance in the north and east of the wintering range (Norway, Sweden, Denmark, Germany, Switzerland), stable numbers in the central range (Belgium, Netherlands, UK and France) and declining abundance in the west and south of the wintering range (Spain and Ireland) suggest a shift in wintering distribution consistent with milder winters throughout the range. However, because over 75% of the population of over 1 million individuals winters in Belgium, the Netherlands, UK and France, there was no evidence for a major movement in the centre of gravity of the wintering distribution. Between-winter changes in overall flyway abundance were highly significantly positively correlated (P = 0.003) with reproductive success measured by age ratios in Danish hunter wing surveys and less strongly and inversely correlated (P = 0.05) with mean January temperatures in the centre of the wintering range, suggesting that winter severity may also contribute to influence survival. However, adding winter severity to a model predicting population size based on annual reproductive success alone did not contribute to more effectively modelling the observed changes in population size. Patterns in annual reproductive success seem therefore to largely explain the recent dynamics in population size of northwest European Wigeon. Summer NAO significantly and positively explained 27% of variance in annual breeding success. Other local factors such as eutrophication of breeding sites and changes in predation pressure undoubtedly contribute to changes in the annual production of young and differences in hunting pressure as well as winter severity affect annual survival rates. However, it seems likely that the observed flyway population trend since 1988 has been mostly influenced by climate effects on the breeding grounds affecting reproductive success and marginally on the winter quarters affecting survival. We urge improved demographic monitoring of the population to better assess annual survival and reproductive success. We also recommend development of an adaptive management framework to remove uncertainties in our knowledge of Wigeon population dynamics as information is forthcoming to better inform management, especially to attempt to harmonise the harvest with annual changes in demography to ensure sustainable exploitation of this important quarry species now and in the future.
|
|
| 15. |
|
|
| 16. |
- Graham, Ian, et al.
(författare)
-
European guidelines on cardiovascular disease prevention in clinical practice: full text. Fourth Joint Task Force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts).
- 2007
-
Ingår i: European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. - : Oxford University Press (OUP). - 1741-8267. ; 14 Suppl 2
-
Tidskriftsartikel (refereegranskat)abstract
- Other experts who contributed to parts of the guidelines: Edmond Walma, Tony Fitzgerald, Marie Therese Cooney, Alexandra Dudina European Society of Cardiology (ESC) Committee for Practice Guidelines (CPG): Alec Vahanian (Chairperson), John Camm, Raffaele De Caterina, Veronica Dean, Kenneth Dickstein, Christian Funck-Brentano, Gerasimos Filippatos, Irene Hellemans, Steen Dalby Kristensen, Keith McGregor, Udo Sechtem, Sigmund Silber, Michal Tendera, Petr Widimsky, Jose Luis Zamorano Document reviewers: Irene Hellemans (CPG Review Co-ordinator), Attila Altiner, Enzo Bonora, Paul N. Durrington, Robert Fagard, Simona Giampaoli, Harry Hemingway, Jan Hakansson, Sverre Erik Kjeldsen, Mogens Lytken Larsen, Giuseppe Mancia, Athanasios J. Manolis, Kristina Orth-Gomer, Terje Pedersen, Mike Rayner, Lars Ryden, Mario Sammut, Neil Schneiderman, Anton F. Stalenhoef, Lale Tokgözoglu, Olov Wiklund, Antonis Zampelas
|
|
| 17. |
- Harrington, Robert A., et al.
(författare)
-
The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial : study design and rationale
- 2009
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 158:3, s. 327-334
-
Tidskriftsartikel (refereegranskat)abstract
- Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies.
|
|
| 18. |
- Huber, Kurt, et al.
(författare)
-
Antiplatelet and anticoagulation agents in acute coronary syndromes : What is the current status and what does the future hold?
- 2014
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 168:5, s. 611-621
-
Tidskriftsartikel (refereegranskat)abstract
- Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y(12) receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Patrono, Carlo, et al.
(författare)
-
Antiplatelet agents for the treatment and prevention of atherothrombosis
- 2011
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 32:23, s. 2922-32
-
Forskningsöversikt (refereegranskat)abstract
- The clinical pharmacology of antiplatelet drugs has been reviewed previously by the European Society of Cardiology (ESC) Task force and by the 8th American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. Moreover, information on the efficacy and safety of antiplatelet drugs in the treatment and prevention of atherothrombosis is provided by collaborative meta-analyses of 287 secondary prevention trials and 6 primary prevention trials. The present document intends to provide practicing physicians with an updated instrument to guide their choice of the most suitable antiplatelet strategy for the individual patient at risk, or with different clinical manifestations, of atherothrombosis.
|
|
| 24. |
- Sejr-Hansen, Martin, et al.
(författare)
-
Comparison of Quantitative Flow Ratio and Instantaneous Wave-Free Ratio for Immediate Assessment of Non-Culprit Lesions in Patients With ST-Segment Elevation Myocardial Infarction An iSTEMI Substudy
- 2018
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 72:13, s. B248-B249
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Quantitative flow ratio (QFR) is an angiography-based approach for in-procedure functional evaluation of coronary artery lesions. We evaluated the diagnostic performance of QFR with instantaneous wave-free ratio (iFR) in non-culprit lesions (NCLs) in patients with ST-segment elevation myocardial infarction (STEMI) and with staged fractional flow reserve (FFR) as reference standard.METHODS: This is a post-hoc analysis of the iSTEMI study. All NCLs were assessed with iFR in the acute setting and with iFR and FFR at staged (median 19 days) follow-up. QFR (Medis Medical Imaging bv., The Netherlands) was computed for all analyzable NCLs in a core lab by an investigator blinded to iFR and FFR results. Diagnostic cut-off values were 0.80 for QFR, 0.89 for iFR, and 0.80 for FFR.RESULTS: A total of 156 NCLs in 120 patients were included in the iSTEMI study. Paired iFR and FFR data were available for 146 NCls in 112 patients. Of these, QFR analysis was feasible in 103 (71 %) lesions assessed in the acute setting. Mean acute QFR was 0.800.13, acute iFR was 0.860.12, and staged FFR was 0.800.11. With staged FFR as reference standard, diagnostic accuracy was 84% (95%CI: 76-90) for acute QFR and 73% (95%CI: 66-83) for acute iFR (p¼0.09), area under the receiver operating curve (AUC) was 0.89 (95%CI: 0.82-0.95) vs. 0.77 (95%CI: 0.68-0.87) (p¼0.02), sensitivity was 83% (95%CI: 69-92) vs. 85% (95%CI: 73-92) (p¼0.79), specificity was 84% (95%CI: 72-92) vs. 64% (95%CI: 53-75) (p¼0.11), positive predictive value was 81% (95%CI: 57-82) vs. 70% (95%CI: 57-82)(p¼0.06), and negative predictive value was 86% (95%CI: 76-95) vs. 84% (95%CI: 69-91)(p¼0.37), for acute QFR and acute iFR, respectively.CONCLUSION: The diagnostic performance of acute QFR in post hocevaluation of NCLs in STEMI patients was at least similar to acuteassessment by iFR with staged procedure FFR as reference. QFR couldprovide an easy, safe and cost-effective solution to evaluate NCLs inthe acute phase, thus potentially reducing the number of unnecessaryfollow-up procedures.CATEGORIES IMAGING: Physiologic Lesion Assessment.
|
|
| 25. |
- Sejr-Hansen, Martin, et al.
(författare)
-
Quantitative flow ratio for immediate assessment of nonculprit lesions in patients with ST-segment elevation myocardial infarction—An iSTEMI substudy
- 2019
-
Ingår i: Catheterization and Cardiovascular Interventions. - : Wiley. - 1522-1946 .- 1522-726X. ; 94:5, s. 686-692
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: We evaluated the diagnostic performance of quantitative flow ratio (QFR) assessment of nonculprit lesions (NCLs) based on acute setting angiograms obtained in patients with ST-segment elevation myocardial infarction (STEMI) with QFR, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR) in the staged setting as reference. Background: QFR is an angiography-based approach for the functional evaluation of coronary artery lesions. Methods: This was a post-hoc analysis of the iSTEMI study. NCLs were assessed with iFR in the acute setting and with iFR and FFR at staged (median 13 days) follow-up. Acute and staged QFR values were computed in a core laboratory based on the coronary angiography recordings. Diagnostic cut-off values were ≤0.80 for QFR and FFR, and ≤0.89 for iFR. Results: Staged iFR and FFR data were available for 146 NCLs in 112 patients in the iSTEMI study. Among these, QFR analysis was feasible in 103 (71%) lesions assessed in the acute setting with a mean QFR value of 0.82 (IQR: 0.73–0.91). Staged QFR, FFR, and iFR were 0.80 (IQR: 0.70–0.90), 0.81 (IQR: 0.71–0.88), and 0.91 (IQR: 0.87–0.96), respectively. Classification agreement of acute and staged QFR was 93% (95%Cl: 87–99). The classification agreement of acute QFR was 84% (95%CI: 76–90) using staged FFR as reference and 74% (95%CI: 65–83) using staged iFR as reference. Conclusions: Acute QFR showed a very good diagnostic performance with staged QFR as reference, a good diagnostic performance with staged FFR as reference, and a moderate diagnostic performance with staged iFR as reference.
|
|
| 26. |
- Thim, Troels, et al.
(författare)
-
Agreement between iFR and FFR in staged follow-up evaluation of non-culprit stenoses after ST-segment elevation myocardial infarction (iSTEMI substudy)
- 2017
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 70:18, s. B91-B91
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND: Classification agreement between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) is approximately 80% in stable patients. It was recently shown that FFR guidance, as compared to iFR guidance, was associated with a higher risk of subsequent revascularization among patients with non- ST-segment elevation myocardial infarction. The classification agreement, and the impact of time interval, between iFR and FFR in the assessment of non-culprit lesions after recent ST-segment elevation myocardial infarction (STEMI) has not been described.METHODS: The iSTEMI study assessed agreement between iFR across non-culprit stenoses at the index procedure in patients with STEMI versus iFR and FFR at a follow-up angiography. The interval between STEMI and follow-up evaluation was at the discretion of the treating physicians. In this substudy, classification agreement between follow-up iFR and follow-up FFR was evaluated within groups defined according to follow-up time point after STEMI, i.e., <5days, 5-15days, and16 days. iFR<0.90 and FFR0.80 were considered hemodynamically significant.RESULTS: Among 120 patients with 157 non-culprit stenoses, follow-up iFR and FFR was available in 112 patients with 146 non-culprit stenoses. Median follow-up interval was 16 days (IQR 5-32 days). The overall classification agreement was 84%. With follow-up<5days after STEMI, there was classification agreement between iFR and FFR was in 27 of 35 (77%) non-culprit stenoses. With follow-up 5-15 after STEMI, there was classification agreement in 33 of 38 (86%) non-culprit stenoses. With follow-up 16 days after STEMI, there was classification agreement in 63 of 73 (86%) non-culprit stenoses. The observed differences in these proportions over time after STEMI were not statistically significant (<5versus5days, p¼0.19).CONCLUSION: Overall, classification agreement between iFR and FFR in the assessment of non-culprit lesions after STEMI was comparable to that observed in stable patients. Time interval between STEMI and follow-up evaluation may impact agreement between follow-up iFR and follow-up FFR, although the observed differences were not statistically significant.
|
|
| 27. |
- Thim, Troels, et al.
(författare)
-
Agreement between nonculprit stenosis follow-up iFR and FFR after STEMI (iSTEMI substudy)
- 2020
-
Ingår i: BMC Research Notes. - : BioMed Central. - 1756-0500. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate agreement between instantaneous wave free ratio (iFR) and fractional flow reserve (FFR) for the functional assessment of nonculprit coronary stenoses at staged follow-up after ST-segment elevation myocardial infarction (STEMI).RESULTS: We measured iFR and FFR at staged follow-up in 112 STEMI patients with 146 nonculprit stenoses. Median interval between STEMI and follow-up was 16 (interquartile range 5-32) days. Agreement between iFR and FFR was 77% < 5 days after STEMI and 86% after ≥ 5 days (p = 0.19). Among cases with disagreement, the proportion of cases with hemodynamically significant iFR and non-significant FFR were different when assessed < 5 days (5 in 8, 63%) versus ≥ 5 days (3 in 15, 20%) after STEMI (p = 0.04). Overall classification agreement between iFR and FFR was comparable to that observed in stable patients. Time interval between STEMI and follow-up evaluation may impact agreement between iFR and FFR.
|
|
| 28. |
- Thim, Troels, et al.
(författare)
-
Instantaneous wave-free ratio cutoff values for nonculprit stenosis classification in patients with ST-segment elevation myocardial infarction (an iSTEMI substudy)
- 2020
-
Ingår i: Coronary Artery Disease. - : Lippincott Williams & Wilkins. - 0954-6928 .- 1473-5830. ; 31:5, s. 411-416
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: The instantaneous wave-free ratio cutoff value of <0.90 for hemodynamic significance of coronary stenoses has been validated in stable patients. We examined different cutoff values in the evaluation of nonculprit stenoses in patients with ST-segment elevation myocardial infarction.Methods: We measured instantaneous wave-free ratio across nonculprit stenoses in the acute setting and at follow-up in 120 patients with ST-segment elevation myocardial infarction and 157 nonculprit stenoses, of which, 113 patients with 147 nonculprit stenoses completed follow-up.Results: The prevalence of nonculprit stenosis hemodynamic significance was 52% in the acute setting and 41% at follow-up. With follow-up, instantaneous wave-free ratio as reference, acute instantaneous wave-free ratio >0.90 had a negative predictive value of 89%. Acute instantaneous wave-free ratio <0.90 had a positive predictive value of 68%. Acute instantaneous wave-free ratio >0.93 had a negative predictive value of 100%. Acute instantaneous wave-free ratio <0.86 and <0.83 had positive predictive values of 71 and 77%. Using acute instantaneous wave-free ratio <0.90 as cutoff for hemodynamic significance yielded the highest degree of classification agreement between acute and follow-up instantaneous wave-free ratio.Conclusions: In patients with ST-segment elevation myocardial infarction, acute instantaneous wave-free ratio with the cutoff values <0.90 for hemodynamic significance appears optimal in the evaluation of nonculprit stenoses and has a high negative predictive value and a moderate positive predictive value.
|
|
| 29. |
- Thim, Troels, et al.
(författare)
-
Nonculprit Stenosis Evaluation Using Instantaneous Wave-Free Ratio in Patients With ST-Segment Elevation Myocardial Infarction
- 2017
-
Ingår i: JACC. - New York, USA : Elsevier. - 1936-8798 .- 1876-7605. ; 10:24, s. 2528-2535
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to examine the level of agreement between acute instantaneous wave-free ratio (iFR) measured across nonculprit stenoses in patients with ST-segment elevation myocardial infarction (STEMI) and iFR measured at a staged follow-up procedure.BACKGROUND: Acute full revascularization of nonculprit stenoses in STEMI is debated and currently guided by angiography. Acute functional assessment of nonculprit stenoses may be considered.METHODS: Immediately after successful primary culprit intervention for STEMI, nonculprit coronary stenoses were evaluated with iFR and left untreated. Follow-up evaluation with iFR was performed at a later stage. iFR <0.90 was considered hemodynamically significant.RESULTS: One hundred twenty patients with 157 nonculprit lesions were included. Median acute iFR was 0.89 (interquartile range: 0.82 to 0.94; n = 156), and median follow-up iFR was 0.91 (interquartile range [IQR]: 0.86 to 0.96; n = 147). Classification agreement was 78% between acute and follow-up iFR. The negative predictive value of acute iFR was 89%. Median time from acute to follow-up evaluation was 16 days (IQR: 5 to 32 days). With follow-up within 5 days after STEMI, no difference was observed between acute and follow-up iFR, and classification agreement was 89%. With follow-up ≥16 days after STEMI, acute iFR was lower than follow-up iFR, and classification agreement was 70%.CONCLUSIONS: Acute iFR evaluation appeared valid for ruling out significant nonculprit stenoses in patients with STEMI undergoing primary percutaneous coronary intervention. The time interval from acute to follow-up iFR influenced classification agreement, suggesting that inherent physiological disarrangements during STEMI may contribute to classification disagreement.
|
|
| 30. |
|
|
| 31. |
- Varenhorst, Christoph, 1977-
(författare)
-
Platelet Inhibition in Coronary Artery Disease – Mechanisms and Clinical Importance : Studies with Focus on P2Y12 Inhibition
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Despite the currently recommended dual antiplatelet treatment (DAT) with aspirin and P2Y12 inhibition in patients with coronary artery disease (CAD) there is a risk of adverse clinical outcome. Pharmacodynamic (PD) poor response to clopidogrel occurs in ~ 30% of clopidogrel-treated patients and is associated with an increased risk of recurrent thrombotic events. The aims of this thesis were to compare the PD and pharmacokinetic effects of clopidogrel 600 mg loading dose (LD)/ 75 mg standard maintenance dose (MD) with the novel P2Y12 inhibitor prasugrel 60 mg LD/10 mg MD, in 110 patients with CAD. The mechanisms behind clopidogrel poor response were investigated by assessing the pharmacodynamics after adding clopidogrel active metabolite (AM) and genotyping for variation in CYP-genes involved in thienopyridine metabolism. In another study, we compared the on-clopidogrel platelet reactivity of patients with stent thrombosis (ST) (n=48) or myocardial infarction (MI) (n=30) while on DAT and their matched controls (n=50 + 28). Prasugrel achieved a faster and greater P2Y12-mediated platelet inhibition than clopidogrel measured with light transmission aggregometry, VASP and VerifyNow® P2Y12. Prasugrel’s greater platelet inhibition was associated with higher exposure of AM. The addition of clopidogrel AM led to maximal platelet inhibition in all subjects, suggesting that prasugrel’s greater antiplatelet effect was related to more efficient AM generation compared to that of clopidogrel. Lower levels of AM as well as less platelet inhibition were seen in clopidogrel-treated patients with reduced-metabolizer genotype CYP2C19 compared to those with normal genotype. Patients with ST while on DAT showed higher on-clopidogrel platelet reactivity compared to matched stented controls. Patients with spontaneous MI after stenting did not. In conclusion, these results showed a high rate PD poor response to a high bolus dose of clopidogrel because of a partly genetically caused lower generation of AM which could be overcome by prasugrel treatment. In patients after coronary stenting, clopidogrel poor response was related to ST but not to spontaneous MI, illustrating difficulties in optimizing treatment with clopidogrel based on platelet function or genetic testing in individual patients.
|
|
| 32. |
- Wallentin, Lars, et al.
(författare)
-
How can we optimize the processes of care for acute coronary syndromes to improve outcomes?
- 2014
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 168:5, s. 622-631
-
Tidskriftsartikel (refereegranskat)abstract
- Acute coronary syndromes (ACS), either ST-elevation myocardial infarction or non ST-elevation ACS, are still one of the most common cardiac emergencies with substantial morbidity and mortality. The availability of evidence-based treatments, such as early and intense platelet inhibition and anticoagulation, and timely reperfusion and revascularization, has substantially improved outcomes in patients with ACS. The implementation of streamlined processes of care for patients with ST-elevation myocardial infarction and non ST-elevation ACS over the last decade including both appropriate tools, especially cardiac troponin, for rapid diagnosis and risk stratification and for decision support, and the widespread availability of modern antithrombotic and interventional treatments, have reduced morbidity and mortality to unprecedented low levels. These changes in the process of care require a synchronized approach, and research using a team-based strategy and effective regional networks has allowed healthcare systems to provide modern treatments for most patients with ACS. There are still areas needing improvement, such as the delivery of care to people in rural areas or with delayed time to treatment.
|
|
| 33. |
- White, Harvey D, et al.
(författare)
-
Darapladib for preventing ischemic events in stable coronary heart disease
- 2014
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 370:18, s. 1702-1711
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2.METHODS:In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization).RESULTS:During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02).CONCLUSIONS:In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).
|
|
| 34. |
- White, Harvey D., et al.
(författare)
-
Survival with Cardiac-Resynchronization Therapy in Mild Heart Failure
- 2014
-
Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 370:18, s. 1702-1711
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated lipoprotein-associated phospholipase A(2) activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A(2). Methods: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). Results: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). ConclusionsIn patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.)
|
|
