Standard therapy for the treatment of acute pulmonary embolism (PE) consists of regimes involving anticoagulation therapy alone. Thrombolytic therapy (TT) may provide a mechanism for more rapid thrombus resolution and improvement in pulmonary blood flow and may therefore offer benefit among certain patient groups, such as those presenting with features of cardiopulmonary compromise. However, previous studies have failed to demonstrate a clear mortality advantage for TT among patients presenting with acute PE, and as such inconsistent data exist regarding indications and benefit of TT in this setting. It remains unclear how these mixed reports have influenced the prevalence of TT in both academic and community hospital settings.
Consequently, in order to address this knowledge gap Ibrahim and co-workers analysed a statewide (Pennsylvania, US) database involving 15,116 patients who had a primary diagnosis of PE. Patients with a prior diagnosis of major bleeding were excluded. Specifically the prevalence of TT together with 30-day and in-hospital mortality, before and after propensity adjustment, were recorded.
Only 356 (2.4%) patients received TT. These patients were more likely to be younger (p<0.001), male (p =0.01) and covered by medical insurance (p<0.001). Patients who did not receive TT were more likely to have diagnoses of lung disease, heart failure, and/or cerebrovascular disease and less likely to have a history of ischaemic heart disease (p<0.02) and/or pulmonary vascular disease (p<0.02). Physical examination among patients receiving TT revealed a higher incidence of tachycardia (>110bpm), lower systolic blood pressure (<100mmHg), higher respiratory rate (<30/min), hypoxaemia (arterial oxygen saturation <90%), acidosis (pH<7.25), elevated levels of troponin (≥0.1ng/ml), and/or higher pulmonary arterial pressure (>40mmHg); p<0.01 for each.
Researchers found that the overall 30-day mortality rate for patients receiving TT was 17.4% versus 8.6% for those who did not (OR 2.2 [95% CI, 1.7-3.0]; p<0.001). However, when patients were divided into quintiles based on the predicted probability of receiving TT, which was calculated through propensity score analysis and therefore reflected high-risk features at presentation, the use of TT appeared to corresponded to an increased OR for 30-day mortality among patients from the lowest two quintiles (OR 2.8 [95% CI, 1.3-5.9], and 3.9 [95% CI, 2.2-7.1]; p<0.01 for each) which was absent among patients from the highest two quintiles (OR 1.0 [95%CI, 0.5-2.0], and 0.7 [95%CI, 0.3-1.4]; p>0.29 for each).
Although this study is limited to clinical practice within a single US state the results appear to suggest a potential harm of TT administered to patients who lack high-risk features at presentation, such as haemodynamic compromise. Although it is reassuring that TT appeared to do no harm among subjects with high-risk features at presentation, the numbers are small (143). Further large scale randomised controlled trials are required in order to fully understand the role and safety of TT in acute PE.
- Ibrahim SA, Stone RA, Obrosky DS et al. Thrombolytic therapy and mortality in patients with acute pulmonary embolism. Arch Intern Med. 2008;168:2183-2190.