Although anticoagulant therapy has proven benefits, it frequently causes serious bleeding--especially in older patients. The main goal of this study is to improve the use of anticoagulant therapy in older persons by preventing bleeding complications and by seeking better laboratory predictors of complications. The study is also concerned with comprehensive health-related outcomes. Most importantly, bleeding during anticoagulant therapy is viewed as a paradigm for drug-induced illness in older persons. The proposed scientific methods and clinical strategies are expected to be valuable prototypes for future programs. Preliminary studies work and by others have (1) established predictors of anticoagulant-related bleeding (including older age), (2) shown that increased patient participation in care and physician consultation may prevent complications and improve health-related outcomes, and (3) found that new ways of monitoring warfarin may improve therapy. In the proposed project, it is hypothesized that a specific intervention prevents major bleeding during long-term anticoagulant therapy in patients greater than 65 years. The intervention is the """"""""Patient Participation Program"""""""" (PPP), which includes prothrombin time (PT) self-monitoring, patient training and education, and physician consultation from a specialized anticoagulant service. Testing the PPP involves a randomized clinical trial, which provides an opportunity to seek better pharmacological predictors of bleeding and thromboembolism. An incremental research plan has been designed with three specific aims. First, the patient-focused components of the PPP (PT self-monitoring, training in information-seeking, and education) will be piloted in 25 patients. Second, to determine the efficacy of the PPP, 325 patients greater than 65 years starting long-term anticoagulant therapy in two hospitals will be randomly assigned to receive usual care or the PPP plus usual care. The study has 80% power of detecting the expected 50% reduction in the cumulative frequency of major bleeding, which is the main outcome. Effects on health-related quality of life, frequency of thromboembolism, and mortality rates will also be measured. Third, the study will determine whether recently defined and more specific pharmacologic indices of anticoagulation--concentrations of specific prothrombin isomers, R(+)- and S(-)-warfarin, and vitamin K1--provide better prediction of bleeding and thromboembolism in the study population. The proposed project will test a novel approach to the prevention of serious complications of anticoagulant therapy in older persons and will assess the value of new pharmacologic methods for monitoring warfarin therapy. The findings will provide valuable insights into--and a prototype for--the prevention of drug-induced illness in older persons.
