We thank our correspondents and other colleagues for their feedback on their analysis of phenprocoumon related bleeding complications and liver injuries (1).
Dr Sroka reports on patients with atrial fibrillation who developed bleeding complications while taking guideline-conform prophylactic phenprocoumon or new oral anticoagulants (NOACs). At the same time he expresses hope that current guidelines will be rethought and assessed in the near future. As a matter of fact, in the scenario of guideline-conform therapy, it is primarily older patients who are given a multitude of medications for existing comorbidities, which may trigger interactions and adverse effects (2). The fundamental problem is that guidelines are based on randomized controlled studies that are more likely to include younger, less multimorbid patients who take far fewer additional medications (3). This does not do justice to the age-related higher risks associated with anticoagulant therapy (for example, after a fall), nor the potential interactions, for example, with phenprocoumon. Our analysis of the risk of bleeding complications associated with phenprocoumon treatment and practice conditions also showed a notable increase with older age. Especially the combination with analgesics, which is common in older age, represents a substantial risk factor for gastrointestinal bleeding complications. We have to concede, however, that, although we were able to quantify the risks of bleeding complications in detail, we were not able to calculate the benefit of anticoagulation—that is, the number of prevented thromboembolic complications in the studied population.
Dr Fischer in his reader’s letter emphasizes the importance of educational training programs for patients taking anticoagulants. In the context of our study, participation in and, where applicable, the intensity of, training programs were regrettably not documented. However, our results also show that the international normalized ratio (INR) was too high in about two-thirds of patients with bleeding complications. Routine clinical practice will show the extent to which exactly these patients benefit from NOACs (4). The product information for the three currently available NOACs includes dosage reductions and contraindications taking into consideration renal function—but the question remains about whether such dosage adjustments or stopping/switching medications are even feasible in routine clinical practice in older patients and in case of fluctuating renal function (5).
Prof. Dr. med. Petra Thürmann
Philipp Klee-Institut für Klinische Pharmakologie, Helios Klinikum Wuppertal
Lehrstuhl für Klinische Pharmakologie, Universität Witten/Herdecke
Conflict of interest statement
Professor Thürmann has received consulting fees from Biotest Pharma AG, Fresenius Kabi, and MYR GmbH and lecture fees from BayerVital, Biotest Pharma AG, Rottapharm Madaus GmbH, and from the German Institute for Quality and Efficiency in Health Care (IQWiG). Third-party funding was provided to her by Biotest Pharma AG, Stada GmbH, and Bayer Schering Pharma AG.
|1.||Schmiedl S, Rottenkolber M, Szymanski J, Siegmund W, Hippius M, Farker K, Drewelow B, Hasford J, Thürmann P: Bleeding complications and liver injuries during phenprocoumon treatment—a multicentre prospective observational study in internal medicine departments. Dtsch Arztebl Int 2013; 110(14): 244–52.|
|2.||Boyd CM, Darer J, Boult C, Fried LP, Boult L, Wu AW: Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases. JAMA 2005; 294: 716–24. CrossRef MEDLINE|
|3.||Thürmann PA: Weniger wäre tatsächlich mehr – die Arzneimittelversorgung alter Menschen. Z Evid Fortbild Qual Gesundhwes 2013; 107: 148–52. CrossRef MEDLINE|
|4.||Schott G, Bräutigam K, Ludwig WD: Orale Antikoagulation bei nicht valvulärem Vorhofflimmern. Empfehlungen zum Einsatz der neuen Antikoagulation Dabigatran (Pradaxa®) und Rivaroxaban (Xarelto®). Arzneimittelkommission der deutschen Ärzteschaft. Version1.0. September 2012.|
|5.||Helldén A, Odar-Cederlöf I, Nilsson G, Sjöviker S, Söderström A, von Euler A, Öhlén G, Bergman U: Renal function estimations and dose recommendations for dabigatran, gabapentin and valaciclovir: a data simulation study focused on the elderly. BMJ Open 2013; 3: e002686. doi:10.1136/bmjopen-2013–002686. CrossRef|