Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands

Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands
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News Article | November 14, 2016
Site: www.eurekalert.org

BOSTON - A new study led by clinician-researchers at Beth Israel Deaconess Medical Center (BIDMC) testing the safety and effectiveness of anticoagulant strategies for patients with atrial fibrillation who undergo stenting procedures has shown that therapies combining the anticoagulant drug rivaroxaban with either single or dual anti-platelet therapy (DAPT) were more effective in preventing bleeding complications than the current standard of care. Principal Investigator C. Michael Gibson, MD, Chief of Clinical Research in the Division of Cardiovascular Medicine at BIDMC, reported the new research findings today online in The New England Journal of Medicine and simultaneously presented the findings at the American Heart Association's Scientific Sessions 2016 in New Orleans. The PIONEER AF-PCI randomized clinical trial involved more than 2,100 patients at 430 sites in 26 countries. Each year, nearly 1 million patients in the United States undergo percutaneous coronary intervention (PCI) and are implanted with stents positioned to treat narrowed coronary arteries. Following PCI, patients receive dual anti-platelet therapy - a combination of aspirin and a second blood-thinning medication - to prevent the formation of blood clots in the stent. Approximately 5 to 8 percent of patients undergoing PCI have atrial fibrillation, the most common type of cardiac arrhythmia and an important risk factor for stroke. These patients typically take a blood thinner, such as warfarin (Coumadin), to prevent stroke. "In managing the stented patient with atrial fibrillation, a pharmacologic strategy must carefully balance the risk of stent thrombosis, or blood clot, with the risk of bleeding complications," said Gibson, who is also Professor of Medicine at Harvard Medical School and chairman of the PERFUSE (Percutaneous/Pharmacologic Endoluminal Revascularization for Unstable Syndromes Evaluation) Study Group. "This trial, which tested two entirely new strategies, now provides us with randomized clinical trial data demonstrating that a combination of rivaroxaban with anti-platelet therapy is successful in minimizing bleeding while preventing clotting." Current guidelines call for combining three drugs - DAPT plus a vitamin K antagonist (VKA) anticoagulant - in a strategy known as "triple therapy." But as the authors note, this approach may result in excess major bleeding rates of 4 to 12 percent within the first year of treatment. The PIONEER AF-PCI trial studied men and women over age 18 with atrial fibrillation who had undergone a PCI procedure with stent placement. The study subjects were randomly assigned to one of three groups: Group 1 received reduced dose rivaroxaban plus a P2Y-12 inhibitor monotherapy; Group 2 received very low dose rivaroxaban plus DAPT; and Group 3 received VKA plus DAPT. The findings showed that among patients with atrial fibrillation who underwent intracoronary stent placement, the administration of rivaroxaban in one of two dose strategies reduced the risk of clinically significant bleeding in about one out of every 10 to 11 patients as compared with triple therapy including a vitamin K antagonist. The risks of rehospitalization and death from all causes were also reduced in about one out of every 10 to 15 cases. "This new treatment strategy benefits patient health as well as hospital finances," added Gibson. The PIONEER AF-PCI study is supported by Janssen Scientific Affairs LLC, and Bayer Health Care Pharmaceuticals. Study coauthors include BIDMC investigators Serge Korjian, MD and, Yazan Daaboul, MD,; Roxana Mehran, MD, and Jonathan Halperin, MD, of Mount Sinai Medical Center, New York; Christoph Bode, MD, of the University of Freiburg, Germany; Freek W.A. Verheugt, MD, of Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam; Peter Wildgoose, PhD, Mary Birmingham, PharmD, Juliana Ianus, PhD, and Paul Burton, MD, PhD, of Jansen Pharmaceuticals, Inc.; Martin van Eickels, MD, of Bayer Pharmaceuticals; Gregory Y.H. Lip, MD of The University of Birmingham Centre for Cardiovascular Services, Birmingham, UK; Marc Cohen, MD, of Newark Beth Israel Medical Center, Newark, NJ; Steen Husted, MD, of Aarhus University Hospital, Herning, Denmark; Eric D. Peterson, MD, MPH of Duke Clinical Research Institute, Durham, NC; and Keith AA Fox, MB, ChB, of the Royal Infirmary of Edinburgh, UK. Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, MetroWest Medical Center, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www. .

Van Der Molen A.J.,Leiden University | Hovius M.C.,Onze Lieve Vrouwe Gasthuis
American Journal of Roentgenology | Year: 2012

OBJECTIVE. To present a problem-based algorithm in the work-up of patients with Hematuria. Since the 2010 Dutch Guideline on Hematuria was problem-based, this served as an illustration for such an approach.. CONCLUSION. The work-up of hematuria should be individualized and risk-based. Given the a priori low likelihood of cancer in hematuria, risk categories should be established and imaging algorithms should be tailored to populations at low-risk, medium-risk and high-risk for developing urothelial cancer. © American Roentgen Ray Society.

Verheugt F.W.A.,Onze Lieve Vrouwe Gasthuis
American Journal of Cardiology | Year: 2013

After acute coronary syndrome (ACS), long-term dual antiplatelet therapy with acetylsalicylic acid and a P2Y12 platelet receptor antagonist is the standard of care for secondary prevention. Despite the introduction of more potent P2Y12 receptor antagonists, the risk of a recurrent vascular event within 12 months remains at approximately 10%, indicating a need for improved secondary prevention strategies. A recent phase III trial found that addition of a third antiplatelet agent, vorapaxar, in patients with atherosclerosis might benefit those who have previously experienced a myocardial infarction, although a trial in patients with ACS found this strategy led to increased bleeding without significant efficacy improvement. Previously, data from patients with ACS given vitamin K antagonists in addition to acetylsalicylic acid demonstrated significant reductions in vascular events, but this was associated with an unacceptable bleeding risk. As expected, phase II trials of newer oral anticoagulants in addition to dual antiplatelet therapy also found increased bleeding risk, with only the direct factor Xa inhibitors apixaban and rivaroxaban continuing to phase III. The phase III trial of full-dose apixaban was stopped early for safety concerns, because the major bleeding rates were significantly increased with minimal improvement in efficacy. However, the phase III trial of low-dose rivaroxaban demonstrated a significantly reduced incidence of recurrent vascular events without an increased risk of fatal bleeding. In conclusion, these trials underline the potential importance of optimal dose selection in phase III studies and suggest that the long-term use of low-dose anticoagulation, together with dual antiplatelet therapy, might have a role in secondary prevention after ACS. © 2013 Elsevier Inc. All rights reserved.

Amoroso G.,Onze Lieve Vrouwe Gasthuis | Kiemeneij F.,Onze Lieve Vrouwe Gasthuis
Heart | Year: 2010

Objective: Primary percutaneous coronary intervention (PPCI) has been acknowledged by the most recent European guidelines to be the preferred treatment for ST elevation myocardial infarction (STEMI). Patients undergoing PPCI are expected to receive a broad spectrum of anticoagulants and antiplatelet agents, which increases the risk of bleedings, in most cases, at the site of vascular access. The burden of bleeding complications after PPCI is as negative as that of ischemic complications not only on in-hospital morbidity, but also on mid- and long-term survival. Owing to the unique features of the radial artery, transradial approach (TRA) seems able to overcome most of the problems related to vascular access particularly in case of STEMI. In this short review we discuss the results of the latest studies and we highlight not only the safety and feasibility of TRA-PPCI, but also the advantages in terms of morbidity and mortality. We finally report on our experience at OLVG Amsterdam, and how TRA can also change the logistics in case of a PPCI programme (short stay).

Verheugt F.W.A.,Onze Lieve Vrouwe Gasthuis
Netherlands Heart Journal | Year: 2010

In patients with nonvalvular atrial fibrillation oral anticoagulation with the vitamin K antagonists acenocoumarol, phenprocoumon and warfarin reduces the risk of stroke by more than 60%, whereas single or double antiplatelet therapy is much less effective and sometimes associated with a similar bleeding risk as vitamin K antagonists. Besides bleeding, INR monitoring and high interindividual variability remain the largest drawbacks of vitamin K antagonists. In the last decade oral agents have been developed that directly block the activity of thrombin (factor IIa), as well as drugs that directly inhibit activated factor X (Xa), which is the first protein in the final common pathway to the activation of thrombin. These agents have huge advantages in that they do not need monitoring and have a fast onset and offset of action. This survey addresses the role of classical and modern anticoagulation in stroke prevention in atrial fibrillation.

Verheugt F.W.A.,Onze Lieve Vrouwe Gasthuis
Nature Reviews Cardiology | Year: 2010

Warfarin reduces the risk of stroke in atrial fibrillation by around 60%, while antiplatelet therapy is much less effective. Bleeding is, however, a notable adverse effect with warfarin. Another major drawback of warfarin is the need for frequent clotting assessment. Oral agents have been developed that directly inhibit the activity of thrombin (factor IIa), as well as drugs that directly block activated factor X (factor Xa), which is the first enzyme in the final common pathway to the activation of thrombin. These drugs have fast onset and offset of action and anticoagulation does not seem to need monitoring. These new agents for stroke prevention in atrial fibrillation are being investigated in ongoing phase III trials. In one of these trials an oral thrombin blocker has so far shown superiority to warfarin in efficacy and safety. In this Review, I address the potential of modern oral anticoagulants to improve stroke prevention in atrial fibrillation. © 2010 Macmillan Publishers Limited. All rights reserved.

Oudemans-van Straaten H.M.,Onze Lieve Vrouwe Gasthuis
Critical care (London, England) | Year: 2011

Heparin is the most commonly prescribed anticoagulant for continuous renal replacement therapy. There is, however, increasing evidence questioning its safety, particularly in the critically ill. Heparin mainly confers its anticoagulant effect by binding to antithrombin. Heparin binds to numerous other proteins and cells as well, however, compromising its efficacy and safety. Owing to antithrombin consumption and degradation, and to the binding of heparin to acute phase proteins, and to apoptotic and necrotic cells, critical illness confers heparin resistance. The nonspecific binding of heparin further leads to an unpredictable interference with inflammation pathways, microcirculation and phagocytotic clearance of dead cells, with possible deleterious consequences for patients with sepsis and systemic inflammation. Regional anticoagulation with citrate does not increase the patient's risk of bleeding. The benefits of citrate further include a longer or similar circuit life, and possibly better patient and kidney survival. This needs to be confirmed in larger randomized controlled multicenter trials. The use of citrate might be associated with less inflammation and has useful bio-energetic implications. Citrate can, however, with inadequate use cause metabolic derangements. Full advantages of citrate can only be realized if its risks are well controlled. These observations suggest a greater role for citrate. © 2011 BioMed Central Ltd

Verheugt F.W.A.,Onze Lieve Vrouwe Gasthuis | Granger C.B.,Duke University
The Lancet | Year: 2015

In patients with non-valvular atrial fibrillation, oral anticoagulation with vitamin K antagonists reduces the risk of stroke by more than 60%. But vitamin K antagonists have limitations, including causing serious bleeding such as intracranial haemorrhage and the need for anticoagulation monitoring. In part related to these limitations, they are used in only about half of patients who should be treated according to guideline recommendations. In the past decade, oral agents have been developed that directly block the activity of thrombin (factor IIa), as well as drugs that directly inhibit activated factor X (Xa), which is the first protein in the final common pathway to the activation of thrombin. These novel non-vitamin K antagonist oral anticoagulants (NOACs) have been shown to be at least as good as warfarin for stroke prevention in atrial fibrillation and they have proved to have better safety profiles. Their net advantage is underscored by significantly lower all-cause mortality compared with warfarin in large clinical trials. Because of these features and their ease of use, they are recommended for stroke prevention in atrial fibrillation. They have also a fast onset and offset of action, but they currently lack specific antidotes. This paper addresses the role of anticoagulation for stroke prevention in atrial fibrillation in the era of NOACs, with a focus on special situations including management in the event of bleeding and around the time of procedures including cardioversion, catheter ablation, and device implantation. Also their use in patients with concomitant coronary artery disease, with advanced age, with chronic kidney disease, or with valvular heart disease will be discussed as well as the interaction of NOACs with other cardiac medication, and switching between anticoagulants. © 2015 Elsevier Ltd.

Oudemans-Van Straaten H.M.,Onze Lieve Vrouwe Gasthuis
Blood Purification | Year: 2010

Background: Heparins are used for circuit anticoagulation during continuous renal replacement therapy (CRRT). Because heparins cause systemic anticoagulation, they increase the risk of bleeding. Citrate provides regional anticoagulation. Since citrate is a buffer as well, its use has metabolic consequences. The preferential use of citrate therefore remains controversial. Methods: A synthesis was performed of published studies comparing citrate to heparin for anticoagulation in CRRT with specific regard to feasibility, efficacy and safety. Search of the literature was made to explain the reported superiority of citrate. Results: Citrate provides good metabolic control if and when a well-designed protocol is strictly followed. Randomized studies report similar or longer circuit survival with citrate compared to heparin and less bleeding. The largest randomized trial up to now found that citrate was better tolerated than heparin and improved patient and kidney survival, especially in patients after surgery, with sepsis, a high degree of organ failure or younger age. Both citrate and heparin interfere with inflammation. Conclusion: During critical illness, regional anticoagulation with citrate for CRRT seems superior to heparin anticoagulation concerning tolerance and safety, mainly due to less bleeding. Whether circuit survival is better depends on the modality. In addition, citrate seems to improve patient and kidney survival. This finding needs to be confirmed. Citrate seems to confer a specific benefit in severe organ failure and sepsis. To what extent citrate protects or heparin does harm in the setting of multiple organ failure needs to be unraveled. © 2010 S. Karger AG, Basel.

Oudemans-van Straaten H.M.,Onze Lieve Vrouwe Gasthuis | Ostermann M.,King's College London
Critical Care | Year: 2012

To prevent clotting in the extracorporeal circuit during continuous renal replacement therapy (CRRT) anticoagulation is required. Heparin is still the most commonly used anticoagulant. However, heparins increase the risk of bleeding, especially in critically ill patients. Evidence has accumulated that regional anticoagulation of the CRRT circuit with citrate is feasible and safe. Compared to heparin, citrate anticoagulation reduces the risk of bleeding and requirement for blood products, not only in patients with coagulopathy, but also in those without. Metabolic complications are largely prevented by the use of a strict protocol, comprehensive training and integrated citrate software. Recent studies indicate that citrate can even be used in patients with significant liver disease provided that monitoring is intensified and the dose is carefully adjusted. Since the citric acid cycle is oxygen dependent, patients at greatest risk of accumulation seem to be those with persistent lactic acidosis due to poor tissue perfusion. The use of citrate may also be associated with less inflammation due to hypocalcemia-induced suppression of intracellular signaling at the membrane and avoidance of heparin, which may have proinflammatory properties. Whether these beneficial effects increase patient survival needs to be confirmed. However, other benefits are the reason that citrate should become the first choice anticoagulant for CRRT provided that its safe use can be guaranteed. © 2012 BioMed Central Ltd.

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