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Amsterdam-Zuidoost, Netherlands

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.


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.


Physicians are not always aware that locally administered glucocorticoids can cause systemic toxicity. This risk is greatly enhanced in the case of pharmacological interactions. We present two cases of HIV-infected patients who developed Cushing-like symptoms as a result of a pharmacological interaction. Their antiretroviral treatment regimen consisted of atazanavir, ritonavir, tenofovir and emtricitabine. One patient received salmeterol/fluticasone inhalations for asthmatic bronchitis. The other was treated with intra-articular triamcinolonacetonide injections for ongoing shoulder complaints. Ritonavir exhibits strong inhibition of hepatic enzyme CYP 3A4, which is part of the major metabolic pathway of most glucocorticoids. As a result of this interaction even locally administered glucocorticoids can cause symptoms of overdose, e.g. Cushing-like symptoms. Beclomethasone is a safe alternative for inhaled glucocorticoids as it is not metabolized by CYP 3A4. There is no substitute for intra-articular administration of triamcinolonacetonide. Depending on necessity of the administration of the drug, changing ritonavir-containing antiretroviral therapy to a non-interacting compound, e.g., an integrase inhibitor, is an option.


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.


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

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