Abstract: We included three trials involving 538 participants. We found low quality of evidence indicating uncertainty whether pre-hopsital thrombolysis reduces all-cause mortality in individuals with STEMI compared to in-hospital thrombolysis (risk ratio 0.73, 95% confidence interval 0.37 to 1.41). We found high-quality evidence (two trials, 438 participants) that pre-hospital thrombolysis reduced the time to receipt of thrombolytic treatment compared with in-hospital thrombolysis. For adverse events, we found moderate-quality evidence that the occurrence of bleeding events was similar between participants receiving in-hospital or pre-hospital thrombolysis (two trials, 438 participants), and low-quality evidence that the occurrence of ventricular fibrillation (two trials, 178 participants), stroke (one trial, 78 participants) and allergic reactions (one trial, 100 participants) was also similar between participants receiving in-hospital or pre-hospital thrombolysis. We considered the included studies to have an overall unclear/high risk of bias. Pre-hospital thrombolysis reduces time to treatment, based on studies conducted in higher income countries. In settings where it can be safely and correctly administered by trained staff, pre-hospital thrombolysis may be an appropriate intervention. Pre-hospital thrombolysis has the potential to reduce the burden of STEMI in lower- and middle-income countries, especially in individuals who have limited access to in-hospital thrombolysis or percutaneous coronary interventions. We found no randomised controlled trials evaluating the efficacy of pre-hospital thrombolysis for STEMI in lower- and middle-income countries. Large high-quality multicentre randomised controlled trials implemented in resource-constrained countries will provide additional evidence for the efficacy and safety of this intervention. Local policy makers should consider their local health infrastructure and population distribution needs. These considerations should be taken into account when developing clinical guidelines for pre-hospital thrombolysis.

Plain-language summary: The aim of this review was to compare the effect of pre-hospital and in-hospital administration of thrombolytic therapy on all-cause death and disability in individuals having a heart attack. We carried out a comprehensive search for all trials that have investigated this outcome. Two authors worked independently to ensure we found all of the trials and obtained the relevant information from them. Overall, we found three trials with 538 participants which could be included in this review. We found low-quality evidence indicating uncertainty whether the numbers of people dying were different when therapy was given before hospital compared to in hospital (3 trials). We found high-quality evidence that giving therapy before hospital reduced the time taken for an individual to receive thrombolytic therapy by more than 30 minutes (two studies) and generally low-quality evidence that side effects, such as allergic reactions and bleeding, were similar whether therapy was given pre-hospital or in hospital. The main limitations of the evidence were the unclear/high risk of bias in the studies and the low numbers of people recruited. We conclude that clot-busting therapy given before arriving at a hospital reduces the time taken for an individual to receive thrombolytic treatment. The limitations of the evidence we have found should be considered carefully, especially in settings where thrombolysis can be safely and correctly administered by trained staff. We found that there were no trials evaluating pre-hospital thrombolytic therapy in poorer countries, and therefore further research in such settings will provide more information to advise on whether giving this therapy for heart attacks is safe and effective.