Abstract
Objetivos
Estimar la prevalencia de fármacos que interaccionan con los anticoagulantes orales y establecer asociaciones entre variables y complicaciones hemorrágicas.
Diseño
Estudio longitudinal, retrospectivo.
Emplazamiento
Zona básica de salud de Colmenar, Málaga.
Participantes
Pacientes anticoagulados seguidos en atención primaria.
Mediciones principales
Indicaciones, tiempo de seguimiento, valor del último INR, complicaciones y grupos terapéuticos de mayor uso.
Resultados
El 74,2% de los pacientes tiene un tiempo de protrombina (INR) en el rango terapéutico. El 16,14% presenta complicaciones menores. El 60,2% de pacientes cumple criterios de polimedicación. El 88,2% cumple criterios de polimedicación en los últimos 6 meses. Los fármacos usados con mayor capacidad de interacción son: antiulcerosos (26,9%), del aparato locomotor (10,7%), fármacos cardiovasculares (2,2%), hipolipidemiantes (8,6%) y antidiabéticos (17,2%). El número de fármacos usados en los últimos 6 meses se relaciona con presencia de complicaciones hemorrágicas (odds ratio [OR] = 1,10). El alopurinol y el pantoprazol tienen una relación significativa con la presencia de hemorragias menores (OR = 19,25 y 7,37, respectivamente). Las variables relacionadas con la presencia de hemorragia fueron: alopurinol (OR = 25,84), número de controles con una INR fuera de rango en los últimos 6 meses (OR = 1,31) y tiempo de tratamiento (OR = 1,07).
Conclusiones
El porcentaje de pacientes en rango terapéutico en la última determinación de INR indica una buena calidad. El número de complicaciones hemorrágicas menores supera el estándar del consenso para el control de los enfermos anticoagulados. El uso de fármacos con mayor capacidad de interacción con los anticoagulantes orales presenta valores muy altos en los grupos antiulcerosos y antidiabéticos. Es necesario realizar un control farmacológico en los pacientes anticoagulados y evitar la polimedicación.
Palabras clave: Anticoagulación oral, Interacciones farmacológicas, Polimedicación
Abstract
Objectives
To estimate the prevalence of drugs that interact with oral anticoagulants and establish relationships between variables and haemorrhagic complications.
Design
Longitudinal, retrospective study of patient anticoagulant.
Setting
Colmenar basic health area, Malaga, Spain.
Participants
Patients on anticoagulants followed up in primary care.
Main measurements
Indications, time of follow-up, value of last prothrombin time (INR), complications and therapeutic groups of major use.
Results
The 74.2% of the patients had a prothrombin time (INR) in the therapeutic range; 16.14% had minor complications; 60.2% of the patients complied with the criteria of multiple medication and 88.2% complied with the criteria of multiple medication in the last 6 months. The drugs used with a higher capacity to interact are: anti-ulcer (26.9%), locomotor system (10.7%), cardiovascular drugs (2.2%), lipid lowering drugs (8.6%), and antidiabetics (17.2%). The number of drugs used in the last 6 months is associated with the presence of haemorrhagic complications (odds ratio [OR], 1.10). Allopurinol and pantoprazole had a significant relationship with the presence of minor haemorrhages (OR, 19.25 and 7.37, respectively). The variables associated with the presence of a haemorrhage were: allopurinol (OR, 25.84), number of controls with an INR outside the therapeutic range in the last 6 months (OR, 1.31) and time on treatment (OR, 1.07).
Conclusions
The percentage of patients within the therapeutic range in the last determination of INR indicates good quality. The number of minor complications exceeded the consensus standard for the control of patients on anticoagulants. The use of drugs with a higher capacity for interacting with oral anticoagulants was very high in the anti-ulcer and antidiabetic groups. Pharmacological control of patients on anticoagulants is necessary and multiple medications should be avoided.
Key words: Oral anticoagulation, Pharmacological interactions, Multiple medication
Bibliografía
- 1.Hirsch J. Drug therapy: oral anticoagulant drugs. N Engl J Med. 1991;324:1865–1875. doi: 10.1056/NEJM199106273242606. [DOI] [PubMed] [Google Scholar]
- 2.Hirsch J., Fuster V., Ansell J., Halperia Jl. American Hearth Association/American College of Cardiology. Foundation Guide to Warfarin Therapy. Circulation. 2003;107:1692–1711. doi: 10.1161/01.CIR.0000063575.17904.4E. [DOI] [PubMed] [Google Scholar]
- 3.Ansel J. Oral anticoagulant therapy: fifty years later. Arch Intern Med. 1993;153:586–596. [PubMed] [Google Scholar]
- 4.Mediplus analysis of oral anticoagulant therapy (OAT). London: IMS Health; 1999 (study number MP990207).
- 5.Higashi M., Veenstra D.L., Wittkosky A.K. Association between CYP2C9 genetic variants and anticoagulation related outcomes during warfarin therapy. JAMA. 2002;287:1690–1698. doi: 10.1001/jama.287.13.1690. [DOI] [PubMed] [Google Scholar]
- 6.Alving B.M., Strickler M.P., Knight R.D. Hereditery warfarin resistence: investigation of a rare phenomenon. Arch Intern Med. 1985;145:499–501. [PubMed] [Google Scholar]
- 7.Mannuci P.M. Genetic control of anticoagulation. Lancet. 1999;353:688–689. doi: 10.1016/S0140-6736(98)00326-2. [DOI] [PubMed] [Google Scholar]
- 8.Wells P.S., Hoolbrook A.M., Crowter N.R. The interaction of warfarin with drugs and food: a critical review of the literature. Ann Intern Med. 1994;121:676–683. doi: 10.7326/0003-4819-121-9-199411010-00009. [DOI] [PubMed] [Google Scholar]
- 9.Rose P. Audit of anticoagulant therapy. J Clin Pathol. 1996;49:5–9. doi: 10.1136/jcp.49.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.De las Nieves M.A. Hospital Costa del Sol, Junta de Andalucía; Marbella: 2001. Guía clínica para la anticoagulación oral. [Google Scholar]
- 11.Hirsh J., Dalen J.E., Deykin D., Poller L., Bussey H. ACCP consensus: oral anticoagulants, mechanism of action, clinical effectiveness and optimal therapeutic range. Chest. 1995;108:231–246. doi: 10.1378/chest.108.4_supplement.231s. [DOI] [PubMed] [Google Scholar]
- 12.Neselstuen G.L., Zytkovicz T.H., Howard J.B. The mode of action of vitamin K. identification of carboxyglutamic acid as a component of prothrombine. J Biol Chem. 1974;249:6347–6350. [PubMed] [Google Scholar]
- 13.Price P.A. Role of vitamin K dependent proteins in bone metabolism. Annu Rev Nutr. 1988;8:565–583. doi: 10.1146/annurev.nu.08.070188.003025. [DOI] [PubMed] [Google Scholar]
- 14.Maillard C., Berruyer M., Serre C.M. Protein S, a vitamin K dependent protein is a bone matrix component synthesized and secreted by osteoblast. Endocrinology. 1992;130:1599–1604. doi: 10.1210/endo.130.3.1531628. [DOI] [PubMed] [Google Scholar]
- 15.Standing Advisory Committee for Haematology of the Royal College of Pathologists Drug interactions with coumarin derivate anticoagulants. BMJ. 1982;285:274–275. doi: 10.1136/bmj.285.6337.274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.San José J., Sánchez C. Guía de actuación en atención primaria. 2.ª ed. semFYC; Barcelona: 2003. Interacciones medicamentosas en atención primaria de salud. [Google Scholar]
- 17.Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation Stroke Prevention in Atrial Fibrillation II Study. Lancet. 1994;343:687–691. [PubMed] [Google Scholar]
- 18.Hart R.G., Benavente O., Pearce L.A. Increased risk of intracranial haemorrhage when aspirin is combined with warfarin: a metaanalysis and hypothesis. Cerebrovasc Dis. 1999;9:215–217. doi: 10.1159/000015958. [DOI] [PubMed] [Google Scholar]
- 19.Paterson C.E., Kwaan H.C. Current concepts of warfarin therapy. Arch Intern Med. 1986;146:581–584. [PubMed] [Google Scholar]
- 20.Poller L., Shiach C.R., MacCallum K. Multicentre randomised study of computerised anticoagulant dosage: European Concerted Action on Anticoagulation. Lancet. 1998;352:1505–1509. doi: 10.1016/s0140-6736(98)04147-6. [DOI] [PubMed] [Google Scholar]
- 21.Pea F. Pharmacology of drugs for hyperuricemia. Mechanisms, kinetic and interactions. Contrib Nephrol. 2005;147:35–46. doi: 10.1159/000082540. [DOI] [PubMed] [Google Scholar]
- 22.Mungall D., White R. Aging and warfarin therapy. Ann Intern Med. 1992;117:878–879. doi: 10.7326/0003-4819-117-10-878. [DOI] [PubMed] [Google Scholar]
- 23.Redwood M., Taylor C., Bain B.J. The association of age with dosage requirement for warfarin. Age Ageing. 1991;20:217–220. doi: 10.1093/ageing/20.3.217. [DOI] [PubMed] [Google Scholar]
- 24.Blann A., Fitzmaurice D.A., Lip G. Anticoagulation in hospitals and general practice. BMJ. 2003;326:153–156. doi: 10.1136/bmj.326.7381.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Movahed A., Nair K.G., Ashavaid T.F., Kumar P. Free radical generation and the role of allopurinol as a cardioprotective agent during coronary artery bypass grafting surgery. Cardiovasc Med. 1996;12:138–144. [PubMed] [Google Scholar]