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The Appropriate Management of Rural Patientswith ST-Segment Elevation Myocardial InfarctionWhen Delays are Expected Due to Long-DistanceTransfersKelsi ColtomPacific University

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Recommended CitationColtom, Kelsi, "The Appropriate Management of Rural Patients with ST-Segment Elevation Myocardial Infarction When Delays areExpected Due to Long-Distance Transfers" (2014). School of Physician Assistant Studies. Paper 496.

The Appropriate Management of Rural Patients with ST-SegmentElevation Myocardial Infarction When Delays are Expected Due to Long-Distance Transfers

AbstractBackground: Current guidelines recommend primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) as long as it can be performed quickly by an experiencedprovider. Unfortunately as time from the onset of symptoms increases, so does the incidence of adversecardiac events. For patients in rural areas who face inevitable delays due to long-distance transfers, primaryPCI is a less than perfect option. Other options include full-dose fibrinolytic therapy with routine transfer to aPCI capable hospital and a relatively new reperfusion strategy called pharmaco-invasive PCI. With multipletreatment options available, what is the most appropriate management of rural patients with STEMIs whendelays are expected due to long-distance transfers?

Methods: An exhaustive search of available medical literature was conducted using Medline-OVID,CINAHL, and Web of Science using the keywords: myocardial infarction, fibrinolytic agents, myocardialreperfusion, and patient transfer. Articles evaluating the efficacy and safety of treatment options for STEMIpatients in rural locations were included. Relevant articles were assessed for quality using GRADE.

Results: Two studies met inclusion criteria and were included in this systematic review. A retrospectiveobservational study with 259 rural STEMI patients found that in-hospital mortality was higher in patientswith primary PCI (9.3%) compared with fibrinolysis patients (1.9%; P=0.03). A prospective observationalstudy with 2634 patients found that there was no significant difference in 30-day mortality (5.5 vs 5.6%; P=0.94), stroke (1.1 vs 1.3%; P= 0.66) or major bleeding (1.5 vs 1.8%; P= 0.65), or re-infarction/ischemia (1.2vs 2.5%; P= 0.088) in rural patients receiving a pharmaco-invasive therapy compared with patients presentingdirectly to the PCI center.

Conclusion: In rural patients with STEMIs, as delays in transfer time increase due to long-distance travel, theuse of fibrinolytic or pharmaco-invasive therapy may be more effective and beneficial than primary PCIreperfusion therapy.

Keywords: Myocardial infarction, myocardial reperfusion, fibrinolytic agents, transfer time, rural healthcare

Background: Current guidelines recommend primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) as long as it can be performed quickly by an experiencedprovider. Unfortunately as time from the onset of symptoms increases, so does the incidence of adversecardiac events. For patients in rural areas who face inevitable delays due to long-distance transfers, primaryPCI is a less than perfect option. Other options include full-dose fibrinolytic therapy with routine transfer to aPCI capable hospital and a relatively new reperfusion strategy called pharmaco-invasive PCI. With multipletreatment options available, what is the most appropriate management of rural patients with STEMIs whendelays are expected due to long-distance transfers?

Methods: An exhaustive search of available medical literature was conducted using Medline-OVID,CINAHL, and Web of Science using the keywords: myocardial infarction, fibrinolytic agents, myocardialreperfusion, and patient transfer. Articles evaluating the efficacy and safety of treatment options for STEMIpatients in rural locations were included. Relevant articles were assessed for quality using GRADE.

This capstone project is available at CommonKnowledge: http://commons.pacificu.edu/pa/496

Results: Two studies met inclusion criteria and were included in this systematic review. A retrospectiveobservational study with 259 rural STEMI patients found that in-hospital mortality was higher in patientswith primary PCI (9.3%) compared with fibrinolysis patients (1.9%; P=0.03). A prospective observationalstudy with 2634 patients found that there was no significant difference in 30-day mortality (5.5 vs 5.6%; P=0.94), stroke (1.1 vs 1.3%; P= 0.66) or major bleeding (1.5 vs 1.8%; P= 0.65), or re-infarction/ischemia (1.2vs 2.5%; P= 0.088) in rural patients receiving a pharmaco-invasive therapy compared with patients presentingdirectly to the PCI center.

Conclusion: In rural patients with STEMIs, as delays in transfer time increase due to long-distance travel, theuse of fibrinolytic or pharmaco-invasive therapy may be more effective and beneficial than primary PCIreperfusion therapy.

Keywords: Myocardial infarction, myocardial reperfusion, fibrinolytic agents, transfer time, rural healthcare

Degree TypeCapstone Project

Degree NameMaster of Science in Physician Assistant Studies

KeywordsMyocardial infarction, myocardial reperfusion, fibrinolytic agents, transfer time, rural healthcare

Subject CategoriesMedicine and Health Sciences

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NOTICE TO READERS This work is not a peer-reviewed publication. The Master’s Candidate author of this work has made every effort to provide accurate information and to rely on authoritative sources in the completion of this work. However, neither the author nor the faculty advisor(s) warrants the completeness, accuracy or usefulness of the information provided in this work. This work should not be considered authoritative or comprehensive in and of itself and the author and advisor(s) disclaim all responsibility for the results obtained from use of the information contained in this work. Knowledge and practice change constantly, and readers are advised to confirm the information found in this work with other more current and/or comprehensive sources. The student author attests that this work is completely his/her original authorship and that no material in this work has been plagiarized, fabricated or incorrectly attributed.

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The Appropriate Management of Rural Patients with ST-Segment Elevation Myocardial Infarction When Delays

are Expected Due to Long-Distance Transfers

Kelsi Coltom

A Clinical Graduate Project Submitted to the Faculty of the

School of Physician Assistant Studies

Pacific University

Hillsboro, OR

For the Masters of Science Degree, August 8th, 2014

Faculty Advisor: Duc Vo, MD

Clinical Graduate Project Coordinator: Annjanette Sommers, PA-C, MS

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Biography [Redacted for privacy]

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Abstract Background: Current guidelines recommend primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) as long as it can be performed quickly by an experienced provider. Unfortunately as time from the onset of symptoms increases, so does the incidence of adverse cardiac events. For patients in rural areas who face inevitable delays due to long-distance transfers, primary PCI is a less than perfect option. Other options include full-dose fibrinolytic therapy with routine transfer to a PCI capable hospital and a relatively new reperfusion strategy called pharmaco-invasive PCI. With multiple treatment options available, what is the most appropriate management of rural patients with STEMIs when delays are expected due to long-distance transfers? Methods: An exhaustive search of available medical literature was conducted using Medline-OVID, CINAHL, and Web of Science using the keywords: myocardial infarction, fibrinolytic agents, myocardial reperfusion, and patient transfer. Articles evaluating the efficacy and safety of treatment options for STEMI patients in rural locations were included. Relevant articles were assessed for quality using GRADE. Results: Two studies met inclusion criteria and were included in this systematic review. A retrospective observational study with 259 rural STEMI patients found that in-hospital mortality was higher in patients with primary PCI (9.3%) compared with fibrinolysis patients (1.9%; P=0.03). A prospective observational study with 2634 patients found that there was no significant difference in 30-day mortality (5.5 vs 5.6%; P= 0.94), stroke (1.1 vs 1.3%; P= 0.66) or major bleeding (1.5 vs 1.8%; P= 0.65), or re-infarction/ischemia (1.2 vs 2.5%; P= 0.088) in rural patients receiving a pharmaco-invasive therapy compared with patients presenting directly to the PCI center. Conclusion: In rural patients with STEMIs, as delays in transfer time increase due to long-distance travel, the use of fibrinolytic or pharmaco-invasive therapy may be more effective and beneficial than primary PCI reperfusion therapy. Keywords: Myocardial infarction, myocardial reperfusion, fibrinolytic agents, transfer time, rural healthcare

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Acknowledgements

[Redacted for privacy]

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Table of Contents Biography ............................................................................................................................ 2 Abstract ............................................................................................................................... 3 Acknowledgements ............................................................................................................. 4 Table of Contents ................................................................................................................ 5 List of Tables ...................................................................................................................... 6 List of Abbreviations .......................................................................................................... 6 BACKGROUND ................................................................................................................ 7 METHODS ......................................................................................................................... 8 RESULTS ........................................................................................................................... 8 DISCUSSION ................................................................................................................... 13 CONCLUSION ................................................................................................................. 16 Table I. Characteristics of Reviewed Studies ................................................................... 23 Table II. Summary of Findings Beri et al8 ........................................................................ 24 Table III. Summary of Findings Larson et al9 .................................................................. 25

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List of Tables Table I: Characteristics of Reviewed Studies Table II: Summary of Findings Beri et al8 Table III: Summary of Findings Larson et al9

List of Abbreviations AMI………………………………….…………………….…Acute Myocardial Infarction GRADE………Grading of Recommendations, Assessment, Development and Evaluation MHI-ANW…………………………..Minneapolis Heart Institute at Abbott Northwestern PCI…………………………………………………...Percutaneous Coronary Intervention PCMH………………………………………………...….. Pitt County Memorial Hospital STEMI………………………………………ST-segment Elevation Myocardial Infarction TNK…………………………………………………………………………. Tenecteplase

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The Appropriate Management of Rural Patients with ST-Segment Elevation Myocardial Infarction When Delays are Expected Due to Long-Distance Transfers

BACKGROUND

Almost 1 million acute myocardial infarctions (AMI) occur in the United States

annually.1 The gold standard of treatment for patients that are diagnosed with a ST-

segment elevation myocardial infarction (STEMI) is primary percutaneous coronary

intervention (PCI) as long as it can be performed quickly by an experienced provider.2,3

Rapid initiation of reperfusion with primary PCI for patients with a STEMI limits the

infarct size and improves the survival rates.4 Unfortunately, for patients requiring primary

PCI, as time from the onset of symptoms increases, so does the incidence of death, re-

infarction, and stroke.5 The American College of Cardiology and American Heart

Association guidelines4 currently recommend that primary PCI be performed within 90

minutes from the patient presentation to the emergency room. However, only 25% of

hospitals in the United States have the capability to perform primary PCI, and most of

these are located in urban settings,6 making primary PCI a less than perfect option for

rural patients with long-distance transfer times.

Other treatment options include full-dose fibrinolytic therapy with routine transfer

to a PCI capable hospital for ischemia-guided rescue PCI. Concerns over the safety and

efficacy of this treatment when compared to primary PCI have overall made it a second-

line reperfusion strategy for the average STEMI patient.7 However, fibrinolytic therapy

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might allow for the advantage of early reperfusion over primary PCI in rural patients that

are facing long transfer times.8 Recently, a hybrid method called pharmaco-invasive PCI

that aims to combine the benefits of both strategies (fibrinolytic therapy followed by

transfer for early PCI) has shown promise as a new management strategy.9 With multiple

treatment options available, what is the most appropriate management of rural patients

with STEMI when delays are expected due to long-distance transfers?

METHODS

An exhaustive literature search of available medical literature was conducted

using Medline-OVID, CINAHL, and Web of Science using the following search terms:

myocardial infarction, fibrinolytic agents, myocardial reperfusion, and patient transfer.

Articles with primary data evaluating the efficacy and safety of treatment options for

STEMI patients in rural locations were included. Relevant articles were assessed for

quality using the Grading of Recommendations, Assessment, Development and

Evaluation (GRADE).10

RESULTS

The initial search of medical literature generated 40 articles for review. Further

evaluation of relevant data from the generated search yielded a total of two articles that

met inclusion criteria. Both of these articles were observational studies analyzing the

treatment of rural patients diagnosed with STEMI. One evaluated the use of fibrinlyitcs,8

while the other the use of a pharmaco-invasive reperfusion strategy.9 These studies are

summarized in Table I and their findings are summarized in Tables II and III.

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Beri et al

This retrospective observational study8 assessed whether or not the administration

of fibrinolytics in rural STEMI patients prior to a long-distance hospital transfer resulted

in transfer delays or worse outcomes when compared with direct transfers for primary

PCI. Data was collected using information from the National Registry of Myocardial

Infarction 5 as well as the Acute Coronary Treatment and Intervention Outcomes

Network. All patients included in this study were transferred from 14 non-PCI capable

referral hospitals to Pitt County Memorial Hospital (PCMH), a 24 hour PCI-capable

hospital in eastern North Carolina. The median distance from the non-PCI hospital to the

PCI-capable center was 52 miles (interquartile range [IQR], 38-69), with an average

travel time of 72 minutes (IQR, 50-86) by ground.8

Patients with STEMI or new left bundle branch block within 12 hours of

symptom onset were included in the study. The administration of intravenous

fibrinolytics to STEMI patients was left to the discretion of the admitting ED physician.

Standard protocols for administration of fibrinolytics, as well as contraindications were

applied, including uncontrolled hypertension, malignant disease, recent major surgery or

bleeding, prolonged cardiopulmonary resuscitation, and severe heart failure. Patients that

qualified for fibrinolysis were given either full-dose tenecteplase (64.4%) or reteplase

(35.6%) and were eligible for transfer immediately after completion of fibrinolysis.

Patients who did not meet criteria for fibrinolysis, or had transfer times less than 30

minutes, were referred for primary PCI.8

The authors reviewed 259 patients presenting with a STEMI diagnosis to

participating non-PCI capable hospitals and were then transferred to PCMH between

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December 2006 and June 2008. Of these patients, 43 (16.6%) were transferred for

primary PCI, while the remaining 216 (83.4%) were transferred after administration of

fibrinolysis for further management. The mean age of patients transferred for primary

PCI was 65.2 ± 13.5 years, while the mean age for patients transferred after fibrinolysis

was 58.7 ± 12.5 years. There was a higher rate of congestive heart failure in the primary

PCI group (20.9%) as compared to the fibrinolytic group (3.7%; P < 0.001). Cardiogenic

shock was also higher in the primary PCI group (14.0% vs 0.5%; P < 0.001).8

The incidence of in-hospital mortality was 9.3% in patients with primary PCI

compared with 1.9% in patients treated with fibrinolysis (P = 0.03). This results in a risk

ratio reduction of 80%. Stroke occurred in 3 patients (1 was hemorrhagic) that received

fibrinolysis as compared with 0 patients that underwent primary PCI. The number of

major bleeding events that justified transfusion was 4.6% in both the primary PCI and

fibrinolytic groups.8 A summary of these findings can be found in Table II.

The median door to door time was 135 minutes for the primary PCI patients,

compared with 128 minutes in patients transferred following fibrinolysis (P = 0.71). Door

to door to balloon time in the primary PCI group was 182 minutes and the door to balloon

time was 49 minutes from the time of arrival at PCMH. Median door to needle time in the

fibrinolysis group was 30 minutes, with 51.4% being performed in less than 30 minutes.

Rescue PCI has to be performed in 81 (37.5%) of the fibrinolytic patients, and coronary

stents were placed in 75 (92.6%) of these patients.8

Larson et al

In this prospective observational study,9 the authors compared the safety and

efficacy of pharmaco-invasive PCI with immediate transfer for primary PCI in rural

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patients with STEMI. In 2003, a regional system called the “Level 1 MI programme” was

established to help with the management of STEMI patients transferred to the

Minneapolis Heart Institute at Abbott Northwestern (MHI-ANW) Hospital in

Minneapolis, Minnesota, a tertiary cardiovascular center, from community hospitals up to

210 miles away. At the time of study, 11 referral hospitals were < 60 miles from MHI-

ANW (designated as Zone 1 hospitals) and 20 referral hospitals were 60-120 miles from

MHI-ANW (designated as Zone 2 hospitals). Data was prospectively entered into a

registry and clinical outcomes were extracted from the electronic medical record at 30

days and 1 year. A propensity-score method was used to identify comparable patients

treated with pharmaco-invasive reperfusion and those receiving primary PCI, in groups A

and D. A nearest-neighbor 1:1 matching algorithm was used to match subjects on the

basis of the logit of the propensity score.9

A standardized protocol with pre-printed standing orders was implemented at

each hospital. Patients who presented to the PCI hospital (MHI-ANW) or were

transferred from Zone 1 hospitals (< 60 miles), received primary PCI reperfusion therapy.

Patients transferred from Zone 2 hospitals (> 60 miles) received half-dose fibrinolytic

followed by emergent transfer for primary PCI (pharmaco-invasive PCI). The decision of

type of fibrinolytic to administer was left up to individual hospital protocol, but

tenecteplase (TNK) was the most frequently used (97% TNK, 3% reteplase).

Contraindications to fibrinolysis included: active bleeding, significant closed head injury

within 3 months, suspected aortic dissection, ischemic stroke within 3 months, known

intracranial neoplasm or prior intracranial hemorrhage, and out of hospital cardiac arrest

with prolonged CPR.9

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From April 2003 to December 2009, 2634 consecutive STEMI patients in the

Level 1 MI database were enrolled. This study established five patients groups to help

with comparison. Group A (n=600) – primary PCI patients who presented directly to the

PCI hospital (MHI-ANW). Group B (n=1163) – primary PCI patients transferred from

Zone 1 (< 60 miles) hospitals. Group C (n=32) – pharmaco-invasive PCI patients

transferred from Zone 1 (< 60 miles) hospitals with anticipated delays due to weather.

Group D (n=660) – pharmaco-invasive PCI patients transferred from Zone 2 (> 60 miles)

hospitals. Group E (n=179) – primary PCI patients transferred from Zone 2 (> 60 miles).9

Pharmaco-invasive PCI with half-dose fibrinolysis was used in 692 (26.3%)

patients including 660 from Zone 2 hospitals and 32 from Zone 1 hospitals with weather

related transfer delays. For the most part groups were prognostically balanced. The

pharmaco-invasive treated patients (Group C and D) were slightly older than Group A

and B, while the patients from Zone 2 that were transferred for primary fibrinolysis

(Group D) were older and had more risk factors.9

A pre-specified prospective comparison of patients treated with primary PCI that

presented directly to the PCI hospital (Group A) with patients treated with pharmaco-

invasive PCI transferred from Zone 2 hospitals (Group D) showed no significant

differences with respect to 30-day mortality (5.5 vs 5.6%; P=0.94), recurrent

ischemia/AMI (2.5 vs 1.2%; P=0.088), stroke (1.3 vs 1.1%; P=0.66), or major bleeding

(1.8 vs 1.5%; P=0.65). Also, when comparing the total number of patients that were

treated with primary PCI from the PCI hospital and Zone 2 (Group A and B) with the

total number of patients treated with pharmaco-invasive PCI (Group C and D) again

showed no significant difference in 30-day mortality (5.6 vs 5.8%; P=0.87), stroke (0.9

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vs 1.2%; P=0.48), recurrent ischemia/myocardial infarction (1.5 vs 1.3%; P=0.67) or

major bleeding (1.4 vs 1.6%; P=0.76). After adjustment using the propensity-score

method, these results were confirmed with similar outcomes when comparing Group A

and D.9 A summary of these findings can be found in Table III.

Of the original group of patients that presented to Zone 2 hospitals, 21.3% did not

receive fibrinolyic therapy and were transferred for primary PCI. Contraindications for

fibrinolysis were the most common reason. These patients had higher 30-day mortality

(10.6 vs 5.6%; P=0.17) compared with patients transferred from Zone 2 with pharmaco-

invasive PCI. These patients were higher risk as they were older, had more risk factors,

and more likely to have had an out-of-hospital cardiac arrest (11.7 vs 7.0%; P=0.037).9

Median door to balloon times were 62 minutes for patients presenting directly to a

PCI capable hospital (Group A), 92 minutes for primary PCI patients transferred from

Zone 1 hospitals (Group B), and 122 minutes for pharmaco-invasive treated patients from

Zone 2 hospitals (Group D). The median door to needle time was 29 minutes for patients

receiving fibrinolytic therapy prior to transfer.9

DISCUSSION

For all patients with STEMIs, both urban and rural, the recommended standard of

treatment of primary PCI within 90 minutes of presenting to the hospital remains the gold

standard for reperfusion therapy. However, of the thousands of patients that are

diagnosed with STEMI every year in the United States, almost 75% of them present to

hospitals lacking the staff and resources to preform primary PCI.11 Furthermore, with

approximately 20% of the general population12 and more than 52% of the rural

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population12 living more than 60 minutes from a primary PCI facility, achieving door to

balloon times within 90 minutes remains a significant challenge.

Treatment of STEMI patients with fibrinolytic reperfusion therapy is a second-

line strategy due to its increase risk for bleeding and overall efficacy when compared to

primary PCI.7 However, most would agree that the benefits of primary PCI decrease

when there is a significant delay due to transfer.13-15 A recent study showed that patients

who are transferred for primary PCI with delays to reperfusion greater than 90 minutes

have significantly greater 30-day mortality.16 The study Beri et al8 found that rural

STEMI patients who received fibrinolysis as an initial reperfusion strategy did not have

overall worse outcomes like majoring bleeding, stroke, or death when compared to

patients transferred directly for primary PCI. However, due to the overall very low

quality, results from this article should be interpreted cautiously and a strong

recommendation cannot be made on this article alone. Findings similar to Beri et al8 were

reported in the DANAMI-2 trial,17 while the PRAGUE-218 and CAPTIM trials19 showed

that thrombolysis might be an equally effective or better strategy than primary PCI in

patients who could be reperfused within 2 to 3 hours of symptom onset. Other studies

showed that as delays in transfers increased so did the benefit of fibrinolysis over primary

PCI.13-15 Although these trials did not specifically study rural populations, transfer delay

was the issue being addressed, which is the important problem at hand for rural patients.

Multiple articles with similar findings help to strengthen the overall recommendation. In

rural patients with STEMIs facing delays greater than 90 minutes, fibrinolytics appears to

have no adverse effect in patients and may lead to better outcomes.

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An alternative strategy to these traditional methods of reperfusion is a treatment

that combines the advantages of the availability of fibrinolysis with the effectiveness of

primary PCI. The study Larson et al9 found that STEMI patients that presented to rural

hospitals greater than 60 miles from PCI capable facilities routinely had delays in transfer

times greater than 120 minutes. The results from this study for these patients indicate

pharmaco-invasive PCI treatment being equally effective and safe with outcomes similar

to patients presenting directly to a PCI-capable hospital.9 A recent meta-analysis20

revealed that “routine early PCI, following fibrinolysis, in patients presenting to non-PCI

hospitals, leads to significant reduction in re-infarction, recurrent ischemia, and the

combined endpoint of death and re-infarction at 30 days with no significant increase in

bleeding complications” compared with standard reperfusion therapy. The results found

in the meta-analysis lead to a class 1a recommendation by the 2010 European Society of

Cardiology and the European Association for Cardio-Thoracic Surgery guidelines on

myocardial revascularization for transfer of all post-fibrinolysis STEMI patients to a PCI-

capable hospital for immediate rescue PCI if fibrinolysis is unsuccessful or coronary

angiography within 3-24 hours and delayed PCI as needed.20 Despite these promising

results, more research needs to be conducted on the exact pharmacologic regimen,

dosing, and timing of PCI following fibrinolysis before any firm recommendations can be

made.

While both studies8,9 demonstrated the safety and efficacy of alternative

reperfusion strategies for rural STEMI patients, they are not without limitations. The Beri

et al study8 was a retrospective observational study, automatically making it a low

quality. The study was further downgraded to a very low due to the fact that the study

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group was prognostically different then the control group and no statistical adjustment

was done to make the groups equivalent. There may also been a selection bias due to the

fact that there was a higher percentage of patients with heart failure and related

cardiogenic shock in the primary PCI group compared to the fibrinolysis group.

This may have led to sicker patients being designated for primary PCI rather than

thrombolytics, resulting in delays in transfer and worse outcome. However, older patients

with severe heart failure are more likely to have contraindications for fibrinolysis. This

study was also limited to hospitals in the eastern part of North Carolina, and similar

results may not be attained in other regions of the country.8

The Larson et al study9 was a registry investigational study and was therefore

automatically a low quality to begin with. However, registry data does have the

advantage of including a higher risk patient population not included in randomized

trials,22 and recent research shows that it is difficult to enroll STEMI patients in a

randomized control trial because of the lack of research support in rural hospitals.22,23

Also results were obtained through an “organized STEMI system of care” that required

significant physician and nurse training, and similar results may not be applicable to other

areas that do not have similar systems.9

CONCLUSION

When managing rural STEMI patients, direct transfer for primary PCI remains the

strategy of choice for patients with contraindications to fibrinolysis or short transfer

times. The benefit of primary PCI over fibrinolysis is reduced when there is a significant

delay related to transfer,13-15 making on-site fibrinolytic therapy a more practical option

for reperfusion as transfer times increase. The relatively new method of pharmaco-

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invasive therapy may be a safe and effective reperfusion strategy for rural STEMI

patients when delays are expected due to long-distance travel. Further studies reinforcing

the safety and efficacy, as well as establishing a standardized protocol will help to

strengthen this recommendation.

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Table I. Characteristics of Reviewed Studies

Quality Assessment

Importance Downgrade Criteria

Quality No. of Studies Design Limitations Indirectness Imprecision Inconsistency Publication

bias likely

Mortality

2

Observational Serious limitationsa

No serious indirectness

No serious imprecision

No serious inconsistencies

No bias likely Very Low Critical

Re-infarction

1 Observational No serious limitations

No serious indirectness

Serious imprecisionb

No serious inconsistencies

No bias likely Very Low Critical

Stroke

2 Observational Serious limitationsa

No serious indirectness

No serious imprecision

No serious inconsistencies

No bias likely Very Low Critical

Major Bleeding

2 Observational Serious limitationsa

No serious indirectness

No serious imprecision

No serious inconsistencies

No bias likely Very Low Critical

a Study group is prognostically different then control group in Beri et al,8 with no statistical adjustment done bOnly one study evaluated this outcome

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Table II. Summary of Findings Beri et al8

Number of Patients Outcomes

Group pPCI (total) Mortality (%) Effect Stroke Major Bleed

Fibrinolytic 216 4 (1.9) Relative Risk Reduction: 0.80 3 (1.4) 10 (4.6)

Primary PCI 43 4 (9.3) Number Needed to Treat: 14 0 (0.0) 2 (4.7) pPCI, primary percutaneous coronary intervention.

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Table III. Summary of Findings Larson et al9

Study Number of Patients Outcomes

Larson et al9 Treatment (total) Mortality Re-infarction Stroke Major Bleed Relative Risk

Group A (pPCI, PCI hospital) 600 33 (5.5) 15 (2.5) 8 (1.3) 11 (1.8)

Group B (pPCI, Zone 1) 1163 66 (5.7) 12 (1.0) 7 (0.6) 14 (1.2)

Total pPCI (A + B) 1763 99 (5.6) 27 (1.5) 15 (0.9) 25 (1.4)

Group C (PI, Zone 1) 32 3 (9.6) 1 (3.1) 1 (3.1) 1 (3.1)

Group D (PI, Zone 2) 660 37 (5.6) 8 (1.2) 7 (1.1) 10 (1.5)

Total PI (C +D) 692 40 (5.8) 9 (1.3) 8 (1.2) 11 (1.6)

Group E (pPCI, Zone 2) 179 19 (10.6) 2 (1.1) 2 (1.1) 3 (1.7) pPCI, primary percutaneous coronary intervention; PCI, percutaneous coronary intervention; PI, pharmaco-invasive. Mortality Relative Risk when comparing Group A to Group D is 1.02