Thrombolysis for pulmonary embolism may benefit younger patients, harm older patients

Thrombolysis for pulmonary embolism may benefit younger patients, harm older patients

1. Thrombolysis for pulmonary embolism (PE) in intermediate-risk patients decreased mortality in patients younger than 65 years but not in older patients when compared with anticoagulation. 

2. Thrombolysis increased risk of major bleeding in intermediate-risk patients older than 65 years but not in younger patients. 

Evidence Rating Level: 1 (Excellent)       

Study Rundown: Pulmonary embolism (PE) can be treated with thrombolysis or anticoagulation. Currently, there is no consensus regarding the risks and benefits of thrombolysis relative to anticoagulation. This study evaluated efficacy and safety of thrombolytic use based on a meta-analysis of randomized control trials (RCTs), predominantly patients who were hemodynamically stable with right ventricular (RV) dysfunction (intermediate risk of PE). This study found that in patients older than 65 years, thrombolysis does not improve survival and increases risk of major bleeding. For younger patients there is a survival benefit and no association with increased risk of bleeding. In the complete cohort of patients, thrombolysis decreased the risk of recurrence but increased the risk of intracranial hemorrhage (ICH).

This study has significant limitations. Only mean ages were reported in the RCTs, thereby limiting the reliability of the age-based subgroup analysis. The results cannot be reliably associated with patients with lower and higher risks of PE because of the small sample sizes for these patients. The definition of ‘major bleeding” and doses of thrombolytics vary amongst RCTs included in the study and mortality was evaluated at different end-points. While this study suggested that thrombolysis have a net benefit for younger patients and net harm for older patients, further research is required before incorporating these results at the bedside.

Click to read the study, published today in JAMA

Relevant Reading: Systemic thrombolytic therapy for acute pulmonary embolism: a systematic review and meta-analysis

In-Depth [systematic review and meta-analysis]: This study included 16 RCTs through April 2014 that compared the use of thrombolysis with the use of traditional anticoagulants (n = 2115) including 8 trials that only enrolled intermediate-risk patients (n = 1775). Primary outcomes were all-cause mortality and risk of major bleeding. Mean follow-up period was 81.7 days. Thrombolytic therapy was associated with significantly lower all-cause mortality (OR, 0.53; 95% CI, 0.32-0.88) but increased risk of major bleeding (OR, 2.73; 95% CI, 1.91-3.91) relative to anticoagulative therapy. This was also noted in the trials with only intermediate-risk patients including the post-2009 analysis. In patients older than 65 years there was no difference in all-cause mortality but they did have a greater risk of major bleeding (OR, 3.10; 95% CI, 2.10-4.56) compared to younger patients who showed no significant increase in risk of bleeding (P= 0.89). All patients who received thrombolysis had decreased the risk of recurrent pulmonary embolism (PE) (P= 0.003) but increased risk of intracranial hemorrhage (ICH) (P= 0.002).

Image: CC/Heilman 

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