Out of hospital treatment of pulmonary embolism: guidance through risk assessment

The implementation of low-molecular-weight-heparine (LMWH) bridging therapy in the standard treatment of patients with nonmassive pulmonary embolism (PE), has led to high interests in the treatment of patients with PE on an outpatient basis. To enable outpatient treatment of these patients, it is of utmost importance to identify patients at low risk for adverse clinical outcome. Therefore, insights in risk stratification were the initial focus of this thesis. We identified risk factors for serious adverse events during the first 10 days of treatment and developed a prognostic model for short term adverse events in patients with PE. We describe a prospective, multicenter management study of 152 low risk patients with acute PE, who were treated as outpatients. Low risk was defined as being hemodynamic stable and having a low N-terminal-pro-Brain Natriuretic Peptide (NT-proBNP level) (<500 pg/ml). No deaths, major bleedings or recurrent venous thromboembolism occurred in the first 10 days of treatment or in the follow-up period of 3 months in these patients. We concluded that outpatient treatment of a selected group of low risk patients with non-massive acute PE and a NT-proBNP level <500 pg/ml appears to be safe. Approximately 45% of the patients with acute PE are candidates for home treatment. Out of hospital therapy is considered to be convenient by the vast majority of the patients and it can contribute to the reduction of health care costs. Next to outpatient treatment early discharge is also conceivable, for example after normalization of the NT-proBNP level during hospitalization. We investigated if early discharge before reaching an adequate international normalized ratio (INR), results in the same quality of treatment compared to patients who are hospitalized until reaching an adequate INR. Our study showed that the development of guidelines for early discharge of a selected group of low risk PE patients is warranted, with focus on intensification of monitoring of INR values to shorten the period of the combination of LMWH and oral anticoagulation therapy. Continuation of the LMWH for at least 5 days after diagnosis of PE remains important as well. In case that the INR drops below the therapeutic range (“under-anticoagulation”), LMWH should be restarted. Finally, outpatient treatment is convenient and will reduce costs of medical care. However, the main focus of the outpatient treatment should remain patient’s safety. This thesis gives more insights in the risk stratification in PE-patients and contributes to the implementation of guidelines for outpatient treatment of low risk patients. However, before we are that far, further validation of the results is warranted.