Concomitant systemic thrombolytic therapy with tissue plasminogen activator for acute pulmonary embolism: a systematic review and meta-analysis

The standard therapyfor acute low- and intermediate-risk pulmonary embolism (PE) isanticoagulation, while concomitant systemic thrombolysis is reserved only forhigh-risk patients. Studies reporting thrombolysis in the former categorieshave yielded mixed results. Two databases andtwo trial registers were searched for randomized- and non-randomized trials.The Mantel-Haenszel method along with a fixed-effect model was used foranalysing dichotomous outcomes. Sixteen trials wereincluded. Concomitant use of tPA analogues resulted in lower all-causemortality (OR = 0.53;95%-CI:0.32-0.89;<i>p</i> = 0.02), PE recurrence(OR = 0.47;95%-CI:0.24-0.90; <i>p</i> = 0.01) and, treatment-escalations(OR = 0.39;95%-CI:0.25-0.61;<i>p</i> &lt; 0.00001) while causing a higher incidence ofmajor- (OR = 2.84;95%-CI:1.82-4.43; <i>p</i> &lt; 0.00001) and minor-bleeding(OR = 4.31;95%-CI:3.26-5.71;<i>p</i> &lt; 0.00001). Subgroup analysis based on the type oftPA used showed similar results except for the significantly lower major-bleedingwith alteplase compared to tenecteplase (<i>p</i> = 0.003) and a lower incidence ofbleeding events with low dosage while maintaining relatively similar treatmentefficacy. Systemicthrombolysis significantly reduced all-cause mortality, PE recurrence, and treatmentescalations but increased major and minor bleeding risk, with low-dosealteplase causing fewer bleeding complications compared to full-dosetherapy/tenecteplase. Although the included trials showcased substantial sample-sizesand standardized dosing protocols, their baseline imbalances introduced potentialconfounding bias. Notably, mortality reduction lost statistical-significance uponexcluding non-randomized trials and trials with baseline imbalances. This paper was registered on PROSPERO (CRD42024553660).