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Cochrane corner: prehospital versus in-hospital thrombolysis for ST-elevation myocardial infarction
  1. Michael McCaul1,
  2. Andrit Lourens2,
  3. Tamara Kredo3
  1. 1Centre for Evidence-Based Health Care, Stellenbosch University, Cape Town, Western Cape, South Africa
  2. 2Division of Emergency Medicine, Stellenbosch University, Cape Town, Western Cape, South Africa
  3. 3Cochrane South Africa, South African Medical Research Council, Cape Town, Western Cape, South Africa
  1. Correspondence to Dr Michael McCaul, Centre for Evidence-Based Health Care, Stellenbosch University, Cape Town, Western Cape, PO Box 241, Cape Town, 8000, South Africa; mmccaul{at}sun.ac.za

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The WHO reports that cardiovascular disease is the leading cause of death worldwide, with >80% of these deaths occurring in lower-income and middle-income countries (LMICs).1 ST-elevation myocardial infarction (STEMI) can be treated either with percutaneous coronary interventions (PCIs) or thrombolytic agents, which are most effective if given in the first few minutes to hours after onset of symptoms. While traditionally thrombolysis is given in-hospital, prehospital thrombolysis is proposed as an effective intervention to save time and reduce mortality and morbidity in individuals with STEMI. Despite some evidence that prehospital thrombolysis may be delivered safely, there is a paucity of data from controlled trials to indicate whether the timing of delivery can be effective in reducing key clinical outcomes specifically in STEMI in LMICs.

In this Cochrane Corner, we highlight a Cochrane review2 that assessed the effect of prehospital compared with in-hospital thrombolysis for STEMI. A comprehensive search conducted in June 2014 identified all relevant randomised controlled trials (RCTs) comparing prehospital versus in-hospital thrombolysis in adults with STEMI diagnosed by a healthcare provider. Three RCTs were included involving 538 participants, all of which provided data for meta-analysis.

We found low quality of evidence (indicating uncertainty) that all-cause mortality in individuals with STEMI is similar for prehospital compared with in-hospital thrombolysis (risk ratio 0.73, 95% CI 0.37 to 1.41, three trials, n=538, table 1). High-quality evidence was found that prehospital thrombolysis reduced the time to receipt of thrombolytic treatment compared with in-hospital thrombolysis (mean difference 37.95 (min), 95% CI 14.77 to 61.12, two trials, n=438). For adverse events, moderate-quality evidence was found that the occurrence of bleeding events was similar between participants receiving in-hospital or prehospital 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 prehospital thrombolysis.

Table 1

GRADE summary of findings table for all-cause mortality only

We were unable to obtain requested STEMI-specific data from a potentially eligible study3 and therefore excluded it. This study could have contributed to the power of the meta-analysis to detect a difference between the groups for the primary outcome. The included studies had potential for high risk of bias due to unclear randomisation practices, high risk in blinding practices, incomplete outcome data and possible selective-outcome reporting. We considered the included studies to have an overall high risk of bias.

Implications for practice

Prehospital thrombolysis reduces time to thrombolytic treatment, based on the results of three studies conducted in high-income countries. In settings where it can be safely and correctly administered by trained staff, prehospital thrombolysis may therefore be an appropriate intervention. We were unable to determine whether prehospital thrombolysis is superior to in-hospital thrombolysis with regard to mortality, EF or adverse effects as the meta-analysis included few studies and was therefore potentially underpowered. Prehospital thrombolysis for STEMI has the potential to reduce the burden of disease in LMICs, especially in individuals who have limited access to in-hospital thrombolysis or PCI (eg, those living in rural areas). Local policymakers and clinical directors should consider their local health infrastructure and population distribution needs (rural compared with urban), emergency care system and the availability of thrombolytic therapy compared with surgical alternatives (eg, the availability of PCI). These considerations should be taken into account when developing clinical guidelines for prehospital thrombolysis. In Weaver et al,4 prehospital thrombolysis was performed by paramedics (emergency care professionals) with physician guidance, highlighting the advantage of a paramedic-led team (with physician collaboration) as an alternative to a physician-led thrombolysis team, especially when considering physician availability in LMICs.

Implications for research

Earlier thrombolysis availability is biologically likely to impact on clinical endpoints, but due to the small studies to date, this has not been proven. We found no RCTs that evaluated the efficacy of prehospital thrombolysis for STEMI in LMICs. Large, high-quality multicentre RCTs implemented in LMICs have the potential to develop health infrastructure and service-delivery capacity in those countries. From our review, two areas of further research may be indicated—adequately sized pragmatic RCTs and feasibility studies to understand the core features of when this intervention might work, under what circumstances and how. These should take into consideration issues faced by various income settings, including LMICs.

Pragmatic RCTs and related feasibility studies could inform planning of infrastructure, health system coordination, training models and policy development necessary for the implementation and facilitation of prehospital thrombolysis in LMICs.

References

Footnotes

  • Twitter Follow Michael McCaul at @MikeMcCaul3

  • Contributors All authors contributed equally to the design, writing and editing of this article.

  • Provenance and peer review Commissioned; externally peer reviewed.