Timely treatment for acute myocardial infarction and health outcomes: An integrative review of the literature

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Timely treatment for acute myocardial infarction and health outcomes: An integrative review of the literature Lorelle Martin RN, MNSc a,b,∗ , Maria Murphy PhD b,a , Andrew Scanlon DNP b,c , Carolyn Naismith MN a , David Clark MBBS (Hons), FRACP a , Omar Farouque MBBS (Hons), PhD, FRACP a a b c

Department of Cardiology, Austin Health, Australia LaTrobe University School of Nursing, Australia Department of Neurosurgery, Austin Health, Australia

article information Article history: Received 28 August 2012 Received in revised form 24 November 2013 Accepted 26 November 2013 Available online xxx Keywords: Myocardial infarction Time factors Percutaneous coronary intervention Door to balloon time

a b s t r a c t Background: Coronary heart disease is the most common condition affecting Australians. The time sensitive nature of treating ST-segment elevation myocardial infarction (STEMI) has been the subject of extensive research for several years. Despite important advances in strategies to reduce time to treatment, time continues to represent a major determinant of mortality and morbidity. Door to balloon time (DTBT) is a key indicator of quality of care for STEMI. Nurses play a pivotal role in streamlining the care processes to influence timely management of STEMI. Purpose: The aim of this paper is to review the evidence on the time to treat STEMI, the associated factors impacting upon health outcomes and explore systems of care that reduce time to treatment, using an integrative review approach. Method: Established databases were searched from 2000 to 2012. The search terms ‘myocardial infarction’, ‘emergency medicine’, ‘angioplasty balloon’, ‘time factors’, ‘treatment outcome’, ‘mortality’, ‘prognosis’, ‘female’, ‘age factors’, and ‘readmission’, were used in various combinations. Research studies that addressed the aims of this paper were examined. Findings: Twenty-nine papers were included in this integrative review. The literature demonstrates a strong relationship between shorter DTBT and reduced in-hospital mortality. Factors such as age, gender, time of presentation and co-morbid condition were associated with increased in-hospital mortality. There is sparse literature examining the effect timely reperfusion has on longer-term mortality and other longer-term outcomes such as readmission rates and occurrence of heart failure. Additionally, strategies that effectively reduced DTBT were identified, yet little has been reported on the impact reduced DTBT has had upon health outcomes and whether these improvements were sustained. Conclusion: Whilst the importance of timely reperfusion is now well recognised, additional efforts to streamline the process of care and demonstrate sustained improvement for STEMI patients is required. Nurses in the areas of emergency medicine and cardiac care, play an essential role in facilitating this. Crown Copyright © 2013 Published by Elsevier Australia (a division of Reed International Books Australia Pty Ltd) on behalf of Australian College of Critical Care Nurses Ltd. All rights reserved.

Introduction

∗ Corresponding author at: Department of Cardiology, Austin Health, Australia. Tel.: +61 0421106296. E-mail addresses: [email protected], [email protected] (L. Martin), [email protected] (M. Murphy), [email protected] (A. Scanlon), [email protected] (C. Naismith), [email protected] (D. Clark), [email protected] (O. Farouque).

Cardiovascular disease (CVD) refers to all diseases of the heart and blood vessels.1 Coronary heart disease (CHD) is the largest subset of CVD accounting for 14.6% of all deaths in Australia in 2011.2 In terms of burden of disease, CVD was responsible for 18% of the total burden of disease and injury in Australia in 2003, second only to cancer.1,3 The Australian expenditure on CVD for 2004–2005 was recorded as $5.94 billion, more than any other

1036-7314/$ – see front matter. Crown Copyright © 2013 Published by Elsevier Australia (a division of Reed International Books Australia Pty Ltd) on behalf of Australian College of Critical Care Nurses Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.aucc.2013.11.005

Please cite this article in press as: Martin L, et al. Timely treatment for acute myocardial infarction and health outcomes: An integrative review of the literature. Aust Crit Care (2014), http://dx.doi.org/10.1016/j.aucc.2013.11.005

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disease group, and accounted for 11% of the total health care expenditure.4,5 Whilst mortality from CHD is decreasing, it remains the single largest cause of mortality in Australia for both men and women. Further, almost half of these deaths were attributed to acute myocardial infarction (AMI).2 CHD spans the spectrum from clinical presentations with stable coronary disease to acute coronary syndromes (ACS). The focus of this paper will have particular emphasis on the subset of ACS known as ST-segment elevation myocardial infarction (STEMI). It is recognised that gender and age are contributing factors to a presentation to hospital with STEMI. In Australia during 2007 there were 55,997 hospitalisations for STEMI; two thirds were male, with 40% aged 55–74 years and an additional 40% aged 75 and over.5 The prevalence of STEMI and costs attributed are likely to increase due to the ageing demographic of Australia. It is clear that advancing treatments for CHD are having a direct impact on mortality rates; in particular for patients presenting with STEMI. In 2009 63% of people who suffered a STEMI survived, compared with 47% in 1997.3 Prompt reperfusion of the culprit coronary lesion using primary percutaneous coronary intervention (PPCI) is the preferred treatment, with national and international guidelines for STEMI management suggesting a timeframe of ≤90 min from presentation to first balloon inflation or door to balloon time (DTBT).6–8 The importance of time has become a key measure of quality of care. The past decade has seen an intense focus on systems of care that best deliver these treatments in a timely manner. However systems of care that reduce DTBT require first and foremost, institutional drive with active participation and leadership across multiple disciplines. Given the delicate balance of providing this timely management, a deeper understanding of the factors that influence time to treatment and their associated clinical health outcomes, along with strategies that reduce DTBT are worthy of further examination. Aim The aim of this paper is to review the literature that demonstrates the impact time to treatment has on determining health outcomes for STEMI patients, examine the associated factors that influence these clinical health outcomes and delivery of timely treatment, and outline the systems of care that can be applied in the clinical setting to reduce DTBT. Methods An integrative review was used to synthesise the literature identified. An integrative review uses a broad review method that incorporates simultaneous inclusion of experimental and non-experimental research in order to understand the area of concern.9 A multi-database search was carried out using Ovid Medline, CINAHL and Cochrane databases using the terms ‘myocardial infarction’, ‘emergency medicine’, ‘angioplasty balloon’, ‘time factors’, ‘treatment outcome’, ‘mortality’, ‘prognosis’, ‘female’, ‘age factors’ and ‘patient readmission’. The inclusion criteria for this review were (1) articles published in English between 2000 and 2012, (2) studies that examined the impact time to treatment in STEMI had on mortality and other health outcomes, (3) studies that explored the associated factors that influenced health outcomes and delivery of timely management of STEMI, (4) studies that explored system based strategies that reduced time to treatment in STEMI. Exclusion criteria included (1) discussion papers and book chapters, and (2) small studies with fewer than 450 participants. These aforementioned search terms were used in various combinations using AND.

The electronic search strategy produced 624 potential studies. This list was read by title and abstract to confirm alignment of content to the purpose of this manuscript using the inclusion/exclusion criteria. A manual search of reference texts and other resources held in the university library was also undertaken, some of which fell outside the restriction of 2000–2012. The final number of relevant publications included in this review was 29 articles (refer to Fig. 1 for the study selection process). Results The synthesised literature was grouped into three themes: the impact time to treatment has on mortality and morbidity in STEMI, associated factors that influence mortality and timely treatment, and strategies to reduce DTBT. The primary research included in this review comprised both experimental and non-experimental studies (see Table 1). The impact time to treatment has on mortality and morbidity The time sensitive nature of achieving reperfusion of coronary vessels is well recognised and precedes the introduction of PPCI as front line treatment. A PPCI involves the urgent opening of the infarct related epicardial coronary artery with balloon angioplasty and/or insertion of a metal stent to maintain patency, restore blood flow and reduce the size of the infarct.10 A great deal of the initial evidence linking delay to treatment to higher mortality was generated prior to the wide spread acceptance of PPCI when thrombolytic therapy was considered the ‘gold standard’ in treatment.11 This research gave credence to the concept of the ‘golden hour’ in offsetting damage from an acute myocardial infarction. The adage ‘time is muscle’ became a familiar axiom, drawing attention to the importance of expedited care, along with routine measurement of the time from Emergency Department presentation to the commencement of thrombolytic therapy referred to as the door-to-needle time. Two landmark quantitative reviews contributed to a major shift in thinking on the best reperfusion strategy for STEMI patients.12,13 These reviews compared thrombolysis to PPCI and concluded that PPCI was better than thrombolytic therapy at reducing short-term major adverse cardiac events, resulting in an absolute decrease of approximately 2% risk of in-hospital and 30 day death with PPCI12 and PPCI being associated with a 37% relative risk reduction in 30day mortality.13 A plethora of literature followed the shift in reperfusion therapy strategy to PPCI, along with extensive examination of the relationship between time to reperfusion and patient mortality. De Luca and colleagues were able to show the risk of one-year mortality increased by 7.5% for every 30 min of delay to treatment.14 McNamara and colleagues also concluded that in-hospital mortality increased significantly with a longer DTBT, but went further breaking it down into timeframe categories. The in-hospital mortality was 3.0% for DTBT ≤ 90 min as compared to 7.4% for a DTBT ≥ 150 min.15 McNamara et al., also found each 15-min reduction in DTBT from 150 min to less than 90 min was associated with 6.3 fewer deaths per 1000 patients; this was seen regardless of the length of time from onset of symptoms. More recently a study by Rathore and colleagues concurred with previous studies, highlighting the independent association between a delay to the commencement of treatment and higher mortality.16 Results demonstrated a decrease in mortality of 0.8% with a reduction of DTBT from 90 min to 60 min, and a further decrease in mortality of 0.5% with a reduction of DTBT from 60 min to 30 min.16 Examples in the literature of mortality follow up outside the acute setting are few. Brodie and colleagues followed 2322

Please cite this article in press as: Martin L, et al. Timely treatment for acute myocardial infarction and health outcomes: An integrative review of the literature. Aust Crit Care (2014), http://dx.doi.org/10.1016/j.aucc.2013.11.005

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Fig. 1. Study selection process.

patients for seven years. They were able to demonstrate that prolonged DTBTs were associated with a higher mortality in hospital (p < 0.001), and at seven years (p < 0.001). Furthermore, DTBT was found to be an independent predictor of late mortality using cox regression (p < 0.0004).17 A longitudinal study by Dromburg and colleagues followed 533 patients for 27 years. During 1980–1985 these patients were randomised to either reperfusion therapy or conventional therapy. Results demonstrated that life expectancy for the reperfusion therapy group was 15.6 years vs. 12.5 years for conventional therapy (p < 0.02). Therefore the reperfusion therapy group demonstrated sustained long term benefits and an increase in life expectancy of three years. Further, they identified that independent predictors of mortality were age, impaired left ventricular function, multi-vessel disease and infarct size.18 Thus, the literature provides evidence linking time delay in treatment of STEMI to increased mortality; with few papers reporting the effect on longer-term mortality. Given the chronic nature of CHD, and the consequences of left ventricular dysfunction when time to percutaneous treatment is

inadequate, it is interesting there has been little reported in the published literature of long-term health outcomes other than mortality. Terkelsen et al., in 2011 evaluated a large registry of patients up to seven years following PPCI. They concluded that a shorter time to treatment was associated with a lower risk for readmission or, outpatient contacts due to the development of secondary congestive heart failure.19 Furthermore, a study by Hannan and colleagues, which focused primarily on non-urgent percutaneous coronary intervention, reported an overall readmission rate of 17.3% for patients with an admission of STEMI, compared to a 15.3% rate for patients presenting without STEMI.20 More recently, Ishihara and Sato, reviewed outcomes using a database of 2782 patients over a 30-year period. Although the therapies used for STEMI have evolved over this period, they reported a reduction in the incidence of congestive heart failure ranging from 5% to 10% until the early 2000s, to 2.8% in the late 2000s.21 Whilst the literature is sparse, these authors were able to demonstrate a reduction in morbidity over time when patients received rapid access to proven treatments. The literature also identified reduced hospital readmissions and less development of

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Boersma et al.

• Evaluated 22 randomised trials that compared fibrinolytic therapy with placebo. Reported a 24% reduction in mortality in patients who presented to hospital within 2 h compared to patients presenting later (p < 0.001)

Keeley et al. 12

2003

Quantitative review 23 randomised trials n = 7739 patients

• A landmark review that compared thrombolysis to primary percutaneous coronary intervention (PPCI). Reported an absolute decrease of approximately 2% in risk of in hospital and 30-day mortality with PPCI (p < 0.0002)

Boersma13

2006

Pooled analysis 22 randomised trials n = 6763

• Compared PPCI and thrombolysis and demonstrated that PPCI was associated with a 37% relative risk reduction in 30-day mortality. Adjusted OR 0.63; 95% CI (0.42–0.84)

De Luca et al.14

2004

Cohort study n = 1791

• Studied a population undergoing PPCI for STEMI. Concluded that the risk of one year mortality increased by 7.5% for every 30 min of delay to treatment

McNamara et al.15

2006

Cohort study n = 29,222

• In hospital mortality was 3.0% for door to balloon time (DTBT) < 90 min as compared to 7.5% for a DTBT > 150 min • When adjusted, each 15 min reduction in DTBT from 150 min to less than 90 min was associated with 6.3 fewer deaths per 1000 patients, regardless of length of time from onset of symptoms

Rathore et al.16

2009

Cohort study n = 43,801

• Demonstrated that a reduction in DTBT <90 min to 60 min was associated with a 0.8% reduction in mortality, and a reduction from 60 min to 30 min was associated with a 0.5% reduction in mortality (p < 0.001).

Brodie et al.17

2006

Cohort study n = 2322

• Examined a consecutive sample of STEMI patients. Concluded that a prolonged DTBT was associated with higher in-hospital mortality (p < 0.0001)

Dromburg et al.18

2012

Longitudinal study n = 533

Terkelsen et al.19

2011

Follow-up study using population based registry n = 7952

• Examined outcomes of patients treated who were randomised to conventional therapy or reperfusion therapy. Concluded that the life expectancy was 12.5 years vs. 15.6 years respectively (p < 0.02). Identified independent predictors of mortality were age, impaired LV function, multivessel infarct and infarct size • Followed patients up to a median of 3.1 years. Concluded that system delay to PPCI was an independent predictor of readmission or outpatient contact due to secondary congestive heart failure (HR 1.10; 95% CI 1.02–1.17)

Hannan et al. 20

2011

Retrospective cohort study n = 40,093

• Concluded a 17.3% overall readmission rate for patients at the index admission with STEMI compared to a 15.3% rate for patients presenting without STEMI (p < 0.0005)

Ishihara and Sato21

2012

Longitudinal database study n = 2782

• Examined STEMI patients between 1981 and 2010 • Divided patients into 6 groups in chronological order • In hospital mortality was >10% in the 1980s and decreased by half in the late 1990s • Post infarct angina occurred in 30% in the 1980s decreasing to <1% in the 2000s • Reinfarction occurred in 8.8% in the 1980s decreasing to <3% in the 2000s • Incidence of congestive heart failure ranged from 5 to 10% until the early 2000s which decreased to 2.8% in the late 2000s

Sussenbacher et al.22

2008

Registry study n = 1087

• Concluded using univariate analysis that in-hospital mortality was higher in women than men, 13.7% vs. 7.2% (p < 0.001)

Movahed et al.23

2009

Database study (1988–2004) n = 1,316,216

• Concluded that there was a significant decrease in the age-adjusted mortality rate from acute STEMI regardless of gender. Women had a persistently double mortality rate in comparison to men over the years studied (p < 0.01)

Koeth et al.24

2009

Registry study n = 36,643

• Females were more often complicated by cardiogenic shock despite adjusting for confounding variables • For those whose recovery was completed by cardiogenic, in-hospital mortality for female vs. males was 67.7% vs. 57.2% (p < 0.0001)

Canto et al.25

2007

Systematic review n = 69 studies

• Recorded the data of symptom presentation. Approximately one third of patients in the large cohort studies and one quarter of patients in smaller studies presented without chest pain or discomfort. This was more common in women than in men in the large cohort (37% vs. 27%) and in smaller studies (30% vs. 17%)

Ishihara et al.

2011

Observational study n = 2677

• Compared gender specific mortality in patients <70 years vs. >70 years with STEMI • Concluded mortality was significantly increased for the female gender in the age group >70 years (OR 1.78; 95% CI 1.05–3.00; p = 0.03)

Mehta et al.27

2001

Registry study n = 163,140

• Suggested a strong independent association between age and mortality following a STEMI • Thirty-day mortality rates increased for each age-based quintiles measured in years (p < 0.001)

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Main findings

Quantitative review 22 randomised trials n = 50,246 patients

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Design/sample

1996

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Year

Author(s)

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Table 1 Summary of the 29 research articles used in integrative review.

Author(s)

Year

Morrow et al.28

Design/sample

Main findings

Validation study

• Developed a bedside clinical risk score for predicting 30-day mortality at presentation. Used an arithmetic sum of independent predictors of mortality weighted according to adjusted odds ratio. Concluded that a score ranging from 0 to 8 showed a >40 fold graded increase in mortality (p < 0.0001) compared to mortality of <1% among patients with a score of 0

2009

Mini-registry study n = 459

• Concluded that high-risk patients derived more mortality benefit from a shorter balloon time when compared to low-risk patients. OR 2.41; 95% CI 1.14–5.06; p = 0.02

Magid et al.31

2005

Cohort study n = 1,02,086

• Concluded that presentation during off hours was more common and was associated with a substantially longer time to treatment for PCI

Kruth et al.33

2008

Cohort study

• Concluded that pre hospital delay and DTBT’s were significantly longer on weekends and at nights than regular working hours (p < 0.001). There was also a significantly higher in hospital mortality for weekends (11.1% vs. 9.4%; p = 0.01)

Kostis et al.32

2007

Jneid et al.34

2008

n = 11,516

n = 231,164 Clinical registry study n = 62,814 Prospective cohort study

• This study found that patients admitted on weekends were less likely to undergo invasive revascularisation (p < 0.001). Mortality was significantly higher for patients admitted on weekends (12.9% vs. 12.0%; p = 0.006). However this difference became non significant once adjusted for invasive cardiac procedures (p = 0.009) • Examined differences between patients arriving during off hours and in hours in terms of timely treatment and mortality. Concluded that those who arrived during off hours were more likely to have a longer DTBT (median 110 vs. 85 min, p = 0.0001). However no measurable difference in in-hospital mortality was found when comparing the two groups • Examined and compared patients who were treated for STEMI/NSTEMI in hours vs. out hours. Concluded that for the STEMI population DTBT’s were lower for those patients treated during regular hours compared to out of hours (97 vs. 157 min). Survival rate (93% vs. 87%, p = 0.1), and rate of survival free from major adverse coronary events (MACE) (85% vs. 80%, p = 0.20) were not statistically significant

Berger et al.

2006

Chew et al.36

2007

ACACIA registry study

• Demonstrated that 32% of Australian ACS patients did not receive early invasive management, with this associated with almost 50% increase in there mortality at 12 months (p < 0.01)

Krumholz et al.37

2011

US National Registry of STEMI patients from January-2005 through to September-2010

• Concluded that United States National efforts to improve DTBT in patients undergoing PPCI were being achieved • DTBT declined from 96 min (median) in 2005 to 64 min (median) in 2010 • Percentage of patients treated within 90 min (44.2–91.4%) and within 75 min (27.3–70.4%)

Bradley et al.38

2006

Cross sectional study

• Evaluated system based determinants of STEMI care for 365 hospitals. Concluded that six specific strategies were significantly associated with a reduced DTBT. 1. Activation of Cath Lab by Emergency Department Physicians 2. Single call page for activation of Cath Lab 3. Expecting staff to be 20 min away from the hospital 4. Having pre-hospital activation of the Cath Lab 5. Having an attending cardiologist on site 6. Real time data feedback of DTBT for quality assurance purposes

35

n = 510

n = 365 hospitals

Camp-Rogers et al.39

2012

Review study of Bradley et al. system based strategies

• Examined Bradley et al., six strategies referred to above, in addition to two additional strategies (1) senior management commitment and (2) team based approach • Found that 4 of the 8 strategies had quantitative evidence to support a reduction in DTBT • In particular Pre-Hospital Notification of the STEMI alert system and Emergency Physician activation of the Cath Lab demonstrated substantial evidence • Real time data feedback and team based approaches to STEMI management demonstrated moderate evidence

Jollis et al.41

2012

Survey study of 381 unique systems based approaches for STEMI

• Identified the widespread application of a number of interventions likely to improve DTBT • Direct activation of the Cath Lab by paramedics and emergency physicians, destination or hospital bypass protocols, interhospital transfer protocols, data collection using national instruments and timely feedback

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Cohort study

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Kong et al.30

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Table 1 (Continued)

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congestive heart failure when time to treatment was shorter and modern day reperfusion therapies were employed. Associated factors that influence health outcomes and delivery of timely treatment The efficacy of percutaneous revascularisation is not only dependent upon time to treatment, but also risk factors of the individual, including age, gender, co-morbid condition, along with onset of symptoms and context of the coronary event. The literature identifies non-modifiable and modifiable cardiac risk factors that affect mortality. Gender has been examined as a factor affecting mortality in STEMI. There is conflicting data on the impact of gender on outcomes after adjustment for confounding variables. In an Austrian registry of 1087 STEMI patients, in-hospital mortality rates were higher in women than in men (13.7% versus 7.2%; p < 0.001). However when adjusted for co-morbid conditions, gender was not associated with increased mortality.22 In contrast, Movahed and colleagues in 2009 reported a difference in mortality by gender using data from the US National Registry of Myocardial Infarction of 1,316,216 patients over a 14-year period. They found that women had a consistently higher age-adjusted mortality rate when compared to men.23 Similarly in 2009 Koeth and colleagues reported in a German cohort of 36,643 consecutive STEMIs, that female patients with STEMI were more complicated by cardiogenic shock despite adjusting for confounding variables (OR 1.19, 95% CI 1.09–1.30; p < 0.0001). In addition, patients whose recovery was complicated by cardiogenic shock, the in-hospital mortality for females versus males was 67.7% versus 57.2% (p < 0.0001).24 Reasons for this disparity between the genders have been investigated. Symptom presentation has been explored as a contributing factor to the higher mortality demonstrated in women. Canto and colleagues concluded that women were significantly less likely to report the typical STEMI symptoms of chest pain or discomfort when compared to men.25 Ishihara and colleagues compared gender specific mortality in patients <70 years compared to ≥70 years with STEMI. Mortality was increased for women ≥70 years (OR 1.78; 95% CI 1.05–3.00; p < 0.03).26 Advancing age had been identified as a factor affecting mortality in STEMI. A study conducted by Mehta and colleagues included 160,140 patients hospitalised for STEMI in the United States of America, evaluated the clinical characteristics and outcomes of elderly patients, with the aim to describe differences by age.27 The study reported that older age was associated with a greater proportion of patients with functional limitations, heart failure, prior coronary disease and renal insufficiency, with a lower proportion of males and diabetes. Additionally, a difference was identified (p < 0.001) in the 30-day mortality rates using aged-based quintiles were 65–69 years (10.9%); 70–74 years (14.1%); 75–79 years (18.5%); 80–84 years (23%); and ≥85 years (31.2%). Similar trends were observed for one-year mortality data. These authors concluded that these results reflected the influence of many factors including significant cardiovascular structural and physiological changes, decrease in systemic vascular compliance and coagulopathic changes with advancing age, leading to greater risk of thrombosis.27 Further, the lower proportion of diabetics and males was considered a survivor effect. Outcomes suggested a strong independent association of age with mortality, and explored a cohort of patients underrepresented in clinical studies. Every STEMI patient will have variability in mortality risk independent of time to treatment. In 2000 Morrow and colleagues developed the ‘Thrombolysis In Myocardial Infarction’ (TIMI) risk score to address this problem. Using data from the logistic regression analysis of the clinical ‘INTIME’ trial, a simple arithmetic sum of independent predictors of mortality was developed.28 There are

two categories; a low-risk TIMI score (<5) and a high-risk TIMI risk score (≥5). It has become a convenient and practical bedside clinical risk tool whose validity has been reported.29 Evidence supports high-risk patients derive more mortality benefit from timely reperfusion treatment when compared to low-risk patients when DTBTs are prolonged. Brodie et al. found that prolonged DTBT was associated with higher late mortality in high-risk patients but not low-risk patients; p < 0.0002 vs. p < 0.53.17 A smaller study by Kong and colleagues in 2009 reported similar results.30 These findings have implications for the triage of STEMI patients with time to treatment being important for high-risk patients, and suggest that low-risk patients would tolerate delays in their management in terms of mortality. Event time is also considered a factor affecting time to treatment and mortality. People who present to hospital with STEMI at the weekend or out of operating hours of the cardiac catheterisation laboratory are associated with a significantly higher mortality.31–33 Magid and colleagues identified that presentation during these ‘off hours’ were associated with significantly longer DTBT and higher adjusted in-hospital mortality rates.31 In their examination of 59,786 patients, Kostis and colleagues found statistically significant higher mortality at 30 days for patients admitted on weekends.32 This difference persisted at one year with 1% absolute difference in mortality, however when adjusted for completion of an invasive procedure the findings became non-significant; HR 1.04; 95% CI 0.997–1.049; p = 0.09. Kostis attributed this difference to the lower rates of revascularisation therapy during these hours.32 Additionally, Kruth and colleagues found prolonged DTBT for those admitted at night and on weekends, had statistically significantly higher in-hospital mortality for patients admitted on the weekend; 11.1% vs. 9.4%.33 Not all studies have demonstrated a relationship between time of presentation and in hospital mortality. Jneid and colleagues found similar results to the previous authors and noted that patients presenting during off peak-hours had less revascularisation rates and were less likely to achieve a DTBT <90 min. There was no measurable difference in mortality between in hours and off hours.34 Additionally, Berger and colleagues reported no significant difference between major adverse events at one year for regular hours vs. off hours in a cohort of 510 patients.35 Thus, the literature indicates an association between factors such as female gender, advanced age, co morbid condition, highrisk STEMI as determined by TIMI risk score, and event time with increased mortality and prolonged DTBT. Strategies to reduce door to balloon time Despite evidence for the timely treatment of STEMI presentations, compliance with national and international ACS guidelines remain sub-optimal. There is a complex balance. The ACACIA (Acute Coronary Syndrome Prospective Audit) study in 2007 demonstrated approximately 32% of Australian ACS patients did not receive early invasive management as part of their hospital care in a PPCI capable facility. This finding was associated with an almost 50% increase in their risk of mortality at 12 months; p < 0.01.36 This trend is reflected in the United States of America, although there have been impressive improvements in recent years. Based on nationwide quality assurance audit data, Krumholz and colleagues, in 2011, reported an improvement in median DTBT over a 5-year period from 96 min to 64 min. An additional measurement of quality assessing percentage of patients treated <90 min also improved from 44% to 91%,37 the recommended target recommended was 75%. Recent years have witnessed increased promotion of evidencedbased ACS guidelines and in particular strategies to improve access to timely percutaneous treatment for STEMI patients. Evaluation of

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these system-based determinants of STEMI care with practical recommendations for improving health outcomes has been reported in the literature. One of the earliest published reports in 2006 by Bradley and colleagues assessed the systems of activation for the cardiac catheterisation laboratory in 365 United States hospitals. A hierarchical generalised linear model was used to determine association between hospital strategies and door to balloon time. Six strategies were identified that were significantly associated with reduced DTBT. These strategies included the activation of the catheterisation laboratory by emergency physicians (p < 0.01), having a single call page to activate the catheterisation laboratory (p < 0.001), having pre-hospital activation of catheterisation services (p < 0.001); expecting staff to be 20 min away (p < 0.01), and having an attending cardiologist onsite (p < 0.01) and employing a real-time data feedback system as a quality assurance measure (p < 0.001).38 Whilst each one of these strategies was associated with a reduced median DTBT, only a minority of hospitals utilised these strategies at the time. More recently in 2012 Camp-Rogers and colleagues reviewed Bradley’s prospective work and found no causality using the six strategies described.39 Camp-Rogers et al., reviewed the latest supporting evidence against each strategy of Bradley’s, including two extra strategies: senior management commitment and a team based-approach, which were an addition to another publication by Bradley and colleagues around a similar time.40 Camp-Rogers et al., found that among the eight strategies, there was strong evidence for two strategies in reducing DTBT: (1) emergency physician activation of the catheterisation laboratory (p < 0.001) and (2) pre hospital activation of STEMI services (p < 0.001). Additionally, Camp-Rogers et al., found there was moderate evidence to support real-time data feedback to team members and a team based approach to STEMI management, with no quantitative evidence to support the remaining four strategies.39 Whilst this work was a thorough examination of the supporting evidence, a limitation was that it failed to clearly define what was considered strong or moderate evidence. Additionally, some of the studies that provided the ‘strong evidence’ researched small cohorts. Jollis and colleagues have further explored these system-based approaches to STEMI management, reporting on a survey carried out on 899 hospitals in United States, who performed primary PCI for the management of STEMI. Jollis et al., found that the barriers to system implementation were hospital competition (37%); emergency medical service transport to hospital (26%); competition between cardiology groups (21%); lack of data collection and feedback (18%); lack of infrastructure support and funding (16%); and lack of bed availability (16%).41 Whilst this survey only examined systems of care that used at least two hospitals and one emergency medical service transport system, it highlights the importance of coordination and collaboration for rapid diagnosis and treatment of STEMI. The literature is explicit in what strategies work to reduce DTBT, with the greatest opportunity for improvement existing in the front lines of cardiac care, however the direct impact upon health outcomes resulting from implementation of these strategies remains poorly understood.

Discussion Rapid coronary reperfusion reduces mortality in patients presenting with STEMI. Whilst it is evident that some of the published data has been around for a decade, several examples in the literature explored the impact time to treatment has on mortality.15,16 The axiom, time is muscle, irrespective of improvements in interventions to restore epicardial patency, still remains the point for expedited care today. Measurement of DTBT is not a true reflection

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of the total time to reperfusion and scrutinises only the hospital dependent delays.42 Measuring onset of symptoms to reperfusion results in selection bias by relying on patients to recall the time of onset. Often this is poorly documented. A more reliable indicator may be measuring time from first contact with the health care system (paramedics and general practitioners), which will allow for the analysis of modifiable delays of the total health care system. There is a shortage of literature that measures morbidity when time to treatment is inadequate; this gap needs addressing. Registries that gather quality assurance audit data clearly exist, however expansion of this data to include morbidity will further enhance understanding. Outcomes such as readmission rates are an important measure as they are perceived as failure of initial care and hence are a surrogate of quality.43 Additionally there are subsequent and significant financial implications on the health care system with readmission of a patient.43 Longitudinal data collection is required to measure readmission rates and their causes, which in turn, could potentially identify patients most likely to re-present. This review highlights the complexity when examining factors that increase mortality and delay to timely treatment. There was conflicting literature that supported increased mortality for females in the STEMI population.22–25 Physiological differences in the microcirculation and size of vessels are possible reasons for the under treatment of females, and potential increased risk of mortality.44 Other reported explanations include the protective influence sex hormones have on endothelial function and vascular tone, resulting in CVD developing later in life for females.45 Apt management also requires consideration of co morbid conditions and time of event,17,30–33 although the effect time of event has on mortality reported in this review was contentious.34,35 Consideration of these co-morbid factors adds complexity when juxtaposed with the need for timely treatment. This review also clearly outlined the evidence of using systems based approaches to improve timely management in STEMI.38,39 Lack of data collection and feedback was deemed one of the barriers to reducing time to treatment.41 Efforts need to include not just the creation of locally led audit systems but resource the support and ongoing structures required to sustain the feedback systems on a larger scale. Supporting the feedback structure across multiple disciplines within the greater community will drive sustained improvement and enrich the information that can be derived from such data collection. It is acknowledged that this integrative review focused primarily on system based strategies for a single tertiary site hospital that provides PPCI. It is noted that there are a large number of regional and remote area hospitals, particularly in Australia, that rely heavily on transport of the STEMI patient to a PPCI facility for reperfusion therapy or indeed use thrombolysis as their first line treatment. Discussions of the barriers to timely provision of care for this group of patients are beyond the scope of this review.46,47

Conclusion This paper has reviewed the evidence on the time to treat STEMI, the associated factors impacting upon health outcomes and explored systems of care that reduce time to treatment, using an integrative review approach. The efficacy of revascularisation therapies for patients with STEMI and delivery of timely treatment on mortality is evident. The effectiveness of achieving timely treatment is not an exclusive process with several factors contributing to increased mortality. Calculation of TIMI-risk score at triage would be a useful tool to predict clinical risk, with high-risk patients deriving better mortality benefit. Whilst some gains have been made in recognising the importance of time, it is clear that the adoption of

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system based approaches tailored to recognise contributing factors that delay care are required to improve compliance to guidelines. Additionally, the ongoing monitoring of the effect these systems have on sustaining improvements for time to treatment is essential. Nurses play a pivotal role in the determination of this system-based care and have the capacity to not only actively participate but also influence the outcomes. Raising awareness of the current literature assists in influencing professional practice and health outcomes. References 1. Australian Institute of Health and Welfare. Australia’s health 2010. Canberra: Australian Institute of Health and Welfare; 2010. 2. Australian Bureau of Statistics. Causes of death 2011. Canberra: Australian Bureau of Statistics; 2013 [Report No.: Cat. no.3303.0]. 3. Australian Institute of Health and Welfare. Cardiovascular disease: Australian facts 2011. Canberra: Australian Institute of Health and Welfare; 2011. 4. 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Please cite this article in press as: Martin L, et al. Timely treatment for acute myocardial infarction and health outcomes: An integrative review of the literature. Aust Crit Care (2014), http://dx.doi.org/10.1016/j.aucc.2013.11.005