Systemic thrombolysis for acute pulmonary embolism increases stroke risk compared with catheter-directed intervention

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Although systemic thrombolysis achieves similar rates of mortality as catheter-directed intervention for the treatment of acute pulmonary embolism, it also carries “significantly increased odds of intracranial haemorrhagic complications,” according to data presented at the American Venous Forum (AVF; 24–26 February, Orlando, USA).

Nathan Liang, University of Pittsburgh Medical Center, Pittsburgh, USA, told the audience that acute pulmonary embolism is the third leading cause of cardiovascular mortality, accounting for 5–10% of all in-hospital deaths. Current treatment strategies include anticoagulation, surgical thrombectomy, systemic thrombolytics and catheter-directed interventions.

Catheter-directed interventions, Liang explained, are a relatively recent treatment alternative. Bleeding risk rates as low as 2.5% have been reported with this approach, as has significant postoperative echocardiographic right ventricular improvement. However, there are “limited or conflicting” data for mortality or clinical benefits, bleeding complications or cost of catheter-directed interventions, Liang said, with no head-to-head comparisons with systemic thrombolysis. This study was a short-term exploratory comparative analysis comparing the two methods.

Liang and colleagues identified patients presenting with acute pulmonary embolism in the National Inpatient Sample from 2009–2012 (n=263,955). Comorbidities, clinical characteristics, and invasive procedures were identified using International Classification of Diseases version 9 (ICD-9) codes and the Elixhauser comorbidity index. To adjust for anticipated baseline differences between the two treatment groups, propensity score matching was used to create a matched systemic thrombolysis cohort with clinical and comorbid characteristics similar to the catheter-directed intervention cohort. Subgroups of patients with and without haemodynamic shock were analysed separately. Primary outcomes were in-hospital mortality, overall bleeding risk, and haemorrhagic stroke risk.

Of the 263,955 acute pulmonary embolism patients, 1.63% (n=4,272) received systemic thrombolysis and 0.55% (n=1,455) received catheter-directed intervention. Systemic thrombolysis patients were older, had more chronic comorbidities, and higher rates of respiratory failure (27.9%, n=1,192; vs catheter-directed thrombolysis: 21.2%, n=308; p<0.001) and shock (systemic thrombolysis: 18.2%, n=779; catheter-directed intervention: 12%, n=174; p<0.001). Catheter patients saw higher rates of concurrent deep venous thrombosis (systemic thrombolysis: 35.8%, n=1,530; catheter-directed intervention: 45.9%, n=668; p<0.001) and vena cava filter placement (systemic thrombolysis: 31.1%, n=1,328; catheter-directed intervention: 57%, n=830; p<0.001). In the unmatched cohort, systemic thrombolysis patients had higher in-hospital mortality (16.7%, n=714; catheter-directed intervention: 9.4%, n=136; p<0.001) and haemorrhagic stroke rates (2.2%, n=96; catheter-directed intervention: 1.4%, n=20; p=0.041).

After propensity matching, 1,434 patients remained in each cohort; “baseline characteristics of the matched cohorts did not differ significantly using standardised difference comparisons,” Liang reported. Furthermore, Liang and colleagues’ analysis of the matched cohorts did not demonstrate a significant effect of catheter-directed intervention on in-hospital mortality or overall bleeding risk. Liang did note that the analysis did show “a significant protective effect against haemorrhagic stroke offset by an increased risk of procedural bleeding compared to systemic thrombolysis.”

Subgroup analysis showed decreased odds of haemorrhagic stroke for catheter-directed intervention in the non-shock subgroup, and increased procedural bleeding, but no difference in haemorrhagic stroke risk in the shock subgroup.

“Systemic thrombolysis for acute pulmonary embolism may not improve in-hospital mortality, but increases the overall risk of haemorrhagic stroke compared to catheter-directed intervention,” Liang concluded. “Further prospective studies should examine the comparative effectiveness and safety of these two treatments.”