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European Heart Journal Advance Access originally published online on June 7, 2006
European Heart Journal 2006 27(13):1539-1549; doi:10.1093/eurheartj/ehl066
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© The European Society of Cardiology 2006. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Factors explaining the under-use of reperfusion therapy among ideal patients with ST-segment elevation myocardial infarction

David A. Alter1,2,3,4,*, Dennis T. Ko1,2,3, Alice Newman1 and Jack V. Tu1,2,4

1 Institute for Clinical Evaluative Sciences, G106-2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5
2 University of Toronto Clinical Epidemiology and Health Care Research Program, Sunnybrook Health Science Centre, Canada
3 Division of Cardiology, Schulich Heart Centre, Sunnybrook Health Science Centre, and the, University of Toronto, Canada
4 Department of Health Policy, Management, and Evaluation, University of Toronto, Canada

Received 26 January 2006; revised 1 May 2006; accepted 12 May 2006; online publish-ahead-of-print 7 June 2006.

* Corresponding author. Tel: +1 416 480 5838; fax: +1 416 480 6048. E-mail address: david.alter{at}ices.on.ca

See page 1513 for the editorial comment on this article (doi:10.1093/eurheartj/ehl007)


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 
Aims To determine the relative impact of time to hospital arrival, baseline cardiovascular risk (i.e.TIMI mortality risk index), intracerebral haemorrhage risk, and comorbid disease burden on the likelihood of not receiving reperfusion therapy among ST-segment elevation myocardial infarction (STEMI) patients without contraindications to treatment.

Methods and results Retrospective population-based cohort of 3994 patients admitted to 103 acute care hospitals with chest pain and STEMI within 12 h of symptom onset in Ontario, Canada, between 1999 and 2001. Patients with one or more documented absolute or relative contraindication (n=909) were excluded from the analyses. Reperfusion therapy was defined as the receipt of either fibrinolysis or primary percutaneous coronary intervention. Multivariable analysis and likelihood {chi}2 was used to quantify the importance of each factor in predicting the non-utilization of therapy. In total, 23.1% of patients received no reperfusion therapy. Listed in order from greatest to least importance, predictors of non-utilization of reperfusion therapy included increasing time to hospital presentation (likelihood {chi}2 31.6, P<0.001), higher intracerebral haemorrhage risk (likelihood {chi}2 27.1, P<0.001), higher baseline cardiovascular risk (likelihood {chi}2 25.4, P<0.001), and greater number of chronic comorbid conditions (likelihood {chi}2 15.4, P<0.001). The importance of each factor on non-utilization was independent, additive, not explained by age effects alone, or driven by subgroups traditionally under-represented in clinical trials.

Conclusion Care gaps in the use of reperfusion therapy widen with both increasing baseline cardiovascular risk and increasing intracerebral haemorrhage risk. Future studies should examine whether the implementation of clinical decision tools which allow for more accurate risk–benefit tradeoff predictions improve the treatment gaps when using life-saving therapies in this patient population.

Key Words: Reperfusion therapy • ST-segment elevation acute myocardial infarction • Utilization


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 Acknowledgements
 References
 
Acute reperfusion therapy [i.e. thrombolytic therapy or primary percutaneous coronary intervention (PCI)] has been shown to reduce mortality among patients presenting with ST-segment elevation myocardial infarction (STEMI).1–3 Although debate over the relative merits of primary angioplasty vs. fibrinolytic therapy continues, available evidence suggests that the more pronounced care gap relates to the withholding of reperfusion therapy regardless of its therapeutic modality.4–7 For example, data from the Global Registry of Acute Coronary Events (GRACE) have demonstrated that up to 30% of eligible patients receive no reperfusion therapy and were not explained by documented absolute or relative contraindications to therapy.4

Understanding the reasons behind the under-utilization of reperfusion therapy is a prerequisite for reducing or eliminating such care gaps. Delays in hospital presentations, high-risk clinical features, increasing intracerebral haemorrhage risk, and comorbidity have all been shown to be associated with lower utilization rates of reperfusion therapy.4,7–15 However, most of the previous studies have identified simple factors, such as age, race, and diabetes as determinants of under-use of reperfusion therapy.4,7,15,16 In contrast, no large-scale population study has examined more complex characteristics, such as baseline cardiovascular risk, intracerebral haemorrhage risk, and comorbid disease burden, and determined their relative importance as factors that might explain reperfusion care gaps in the population. Given the impact of baseline risk as a determinant of the projected survival benefits of therapies in the population,17 care gaps which widen with both increasing baseline cardiovascular risk (i.e. projected benefits) and increasing intracerebral bleeding risk (i.e. projected harms) may require the implementation of clinical decision tools which better allow the physicians to estimate benefit–harm tradeoffs when extrapolating clinical trial evidence to real-world populations.

Accordingly, the objective of our study was to determine the relative importance of baseline cardiovascular risk, intracerebral hamorrhage risk, time to hospital arrival, and comorbid disease burden on explaining the under-utilization of reperfusion therapy among patients presenting with STEMI within 12 h of chest pain onset. We analysed data from the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) project, which abstracted information on acute myocardial infarction (AMI) patients hospitalized in Ontario, Canada, between 1999–2001.18 Because there was very limited availability of primary angioplasty in Ontario at the time of this study, our focus was predominantly on the projected risks and benefits associated with fibrinolytic therapy.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 Acknowledgements
 References
 
Data
EFFECT is part of a province-wide AMI quality care improvement initiative, designed to examine whether feedback related to hospital-specific processes of care and outcomes results in improved quality of care with detailed clinical when compared with administrative databases. EFFECT consists of a large population-based sample of AMI patients hospitalized in (i.e. all medium-, large-, and many small-volume) acute care hospitals throughout Ontario between 1999 and 2001. Very small-volume hospitals (i.e. hospitals treating fewer than 30 AMI cases per year) were excluded from the EFFECT study. Among the 104 institutions approached, 103 hospitals ultimately participated in the EFFECT study.

EFFECT AMI patients were identified as those discharged from hospital with a most-responsible diagnosis of AMI (ICD-9 of 410) using the Canadian Institutes of Health Information (CIHI) hospital discharge databases. Patients who sustained an AMI as a post-hospitalization complication (e.g. post-operative), those transferred-in from outside institutions, those with invalid health card numbers, and those patients of age <20 or >105 were excluded. Patient consent for participation was waived because there was no direct patient contact, and because all data were de-identified and collected through chart reviews. Additional details related to the exclusion/exclusion criteria and validation of the AMI coding has been published elsewhere.18–20

Detailed clinical data and processes of care (e.g. administration of reperfusion therapy, door-to-needle times, aspirin, B-blockers) related to the index AMI hospitalization were abstracted by trained cardiology research nurses. Mortality data were obtained by linking all patients to the Registered Persons Data Base (RPDB) and the CIHI hospital discharge databases. Additional details related to the rationale and study design are described elsewhere.18 Research Ethics approval was received at each of the participating hospitals.

Patients
This current study examined all patients presenting with STEMI within 12 h of chest pain symptom onset. Although chest pain was present among all study participants, patients with uninterpretable ECGs (i.e. paced rhythms, left bundle branch block) were excluded.

Contraindications
Information regarding the presence or absence of absolute and relative contraindications to reperfusion therapy (fibrinolysis or primary angioplasty) was abstracted using hospital chart data. With a few exceptions (i.e. previous AV malformations or the pre-hospitalization blood pressure control among patients with chronic hypertension), all contraindications to fibrinolysis, as specified in the 2005 ACC/AHA STEMI guidelines,21 were present and available through hospital chart data.

Baseline cardiovascular risk
A baseline risk score, which predicted 30-day AMI mortality rates, was calculated for each patient using the TIMI mortality risk index.22 The TIMI risk score, consisting of (age/10)2*heart rate/systolic blood pressure, has been validated in the EFFECT STEMI populations, with good discriminatory characteristics (c-statistic=0.81).

Intracerebral bleeding risk
Patients with neither absolute nor relative contraindications may still have an increased inherent risk of intracerebral bleeds. Accordingly, we calculated the risk of an intracerebral bleed, as estimated using the risk algorithm derived and validated by Selker et al.23 [risk of intracerebral bleed=100*(1/(1+(1/exp (0.0591*age points))+(0.0729*pulse-pressure points)–7.7784))].

Number of chronic comorbid conditions
Previous studies have demonstrated that the number (rather than the type) of pre-existing comorbid conditions was an important determinant of physician decision-making behaviour in this setting.24 Given that we were already examining an independent measure of baseline cardiovascular risk (i.e. TIMI mortality risk index), we examined the number of pre-existing conditions (i.e. cardiovascular and non-cardiovascular combined) and their effect on treatment non-utilization.

Time to hospital presentation
Previous studies have also demonstrated that the interval of time between symptom onset and hospital presentation correlates inversely with both the likelihood of receiving and efficacy once having received reperfusion therapy.4 Time to hospital presentation was obtained through hospital chart data and was subdivided into five categories for analytic purposes: <1 h, 1–2.9 h, 3–5.9 h, 6–8.9 h, and 9–12 h. As specified above, patients presenting >12 h after symptom onset were excluded from our study. In total, 857 (15%) STEMI patients had missing times related to time to presentation and were excluded from the analysis.

Admitting hospital and physician characteristics
Hospitals were categorized according to the presence or absence of on-site revascularization and according to academic affiliation. Attending physician specialty was identified through the hospital medical charts. These factors have been previously shown to correlate with the quality of AMI care in Canada and elsewhere.25,26

Outcomes
The primary outcome of this analysis was the non-utilization of reperfusion therapy within 12 h of symptom onset. Reperfusion therapy consisted of either fibrinolytic therapy or primary PCI. Thirty-day mortality was examined as a secondary outcome.

Analytic techniques
We compared the baseline characteristics of those who received and those who did not receive reperfusion therapy in univariate fashion, using {chi}2 analysis. After excluding patients with absolute or relative contraindications, we examined the relationship between the non-utilization of reperfusion therapy and age, gender, TIMI mortality risk index, intracerebral haemorrhage risk, comorbidity number, and time to hospital presentation using multivariable logistic regression analysis. Although all six patient-level variables were forced into the statistical models, admitting hospital and attending physician specialty characteristics were examined using stepwise variable selection techniques.

Similar multivariable logistic regression techniques were incorporated when examining the relationship between reperfusion therapy and 30-day mortality after adjustment for baseline characteristics. Probability plots were constructed to illustrate how the non-utilization of reperfusion therapy was correlated with two care-gap determinants simultaneously (e.g. baseline cardiovascular risk and the number of comorbid factors) after adjusting for all factors, by imputing ‘average values’ for the remaining covariates in the multivariable logistic regression models.

To help tease apart age from the effects of the TIMI mortality risk index and intracerebral haemorrhage risk (as age was present as a variable in both risk indices), all analyses were repeated within three pre-specified age-specific subgroups (age <60 years, age 60–75 years, and age 76+ years). The correlations between the TIMI mortality risk index, intracerebral haemorrhage risk, time to hospital arrival, and the number of comorbid diseases ranged from negligible to modest (correlation between any two of four variables ranged from r=–0.005 to r=0.31). Formal diagnostic testing demonstrated no evidence of multicollinearity, even where multivariable models included all of the following variables: TIMI mortality risk index, intracerebral haemorrhage risk, the number of comorbid conditions, time to hospital presentation, age, gender, and the remaining independent clinical and admitting hospital characteristics (variance inflation factor less than 5 for any variable).

To examine the extent to which under-utilization of reperfusion therapy was driven by patient subgroups traditionally under-represented in clinical trials, we re-analysed our data after excluding patients who presented beyond 6 h from symptom onset and those aged 75 and older. Finally, as an additional sensitivity analysis, we excluded patients who may not have had the opportunity to receive reperfusion therapy because they died within the initial hours of hospital presentation.

Statistical significance was defined as a two-tailed alpha <0.05. All analyses were undertaken using SASTM version 8.2.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 Acknowledgements
 References
 
Baseline characteristics
In total, 3994 STEMI patients presented within 12 h of symptom onset; 55 patients (0.5% of the cohort) had one or more absolute contraindications, and 909 patients (7.9%) of the cohort had one or more absolute or relative contraindications. After excluding all patients with one or more contraindication (absolute or relative), 3085 STEMI patients remained and comprised the cohort of interest for our study. The average age of our cohort was 62.6 years; 28% were female. In total, 23.1% of all such STEMI patients did not receive reperfusion therapy. Hospital-specific non-utilization rates of reperfusion therapy among ideal candidates without contraindications varied from 5 to 50%.

Of the 2371 patients without absolute or relative contraindications who received reperfusion therapy, 2330 patients (98.3%) received fibrinolysis and 41 patients (1.7%) received primary PCI. Table 1 illustrates the baseline characteristics categorized according to those who received and those who did not receive reperfusion therapy among ideal candidates without absolute or relative contraindications.


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  		Table 1 Baseline characteristics of 3085 patients presenting to hospital with STEMI within 12 h of chest pain in Ontario between 1999 and 2001 with no absolute or relative contraindications to reperfusion therapy

 
Determinants of non-utilization of reperfusion therapy
Table 2 illustrates the independent determinants of reperfusion non-utilization among patients without any absolute or relative contraindications. Determinants of non-utilization of reperfusion therapy listed in order of their respective contribution to the overall model included increasing time to hospital presentation (likelihood {chi}2 31.6, P<0.001), increasing intracerebral haemorrhage risk (likelihood {chi}2 27.1, P<0.001), increasing TIMI mortality risk index (likelihood {chi}2 25.4, P<0.001), and greater number of comorbid conditions (likelihood {chi}2 15.4, P<0.001).


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  		Table 2 Relative importance of explanatory factors of non-reperfusion among ideal STEMI patients presenting within 12 h of chest pain symptom onset listed in order of their {chi}2 contribution to the modela

 
Moreover, the importance of each factor on non-utilization was additive (Figures 1–3). For example, the probability of non-utilization among patients without any absolute or relative contraindications who presented within 1 h of symptoms, with a TIMI mortality risk index score of 1.15 (corresponding to an estimated in-hospital mortality rate of under 0.9%) and a negligible estimated intracerebral haemorrhage risk (0.04%), ranged between 6.2% (i.e. one or fewer chronic comorbid conditions) and 11.4% (six or more chronic comorbid conditions). Finally, all four factors remained important predictors of reperfusion therapy non-utilization within each of the pre-specified age subgroups, with statistical significance achieved for both TIMI mortality risk index and intracerebral haemorrhage risk in all but the youngest subgroup (age <60) (Table 3).


Figure 0661
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  		Figure 1 (A) Estimated probablity of non-reperfusion according to the number of comorbid factors and intracerebral bleeding risk among typical patients at low baseline cardiovascular risk (TIMI mortality risk index with predicted in-hospital mortality <0.9%) presenting within 1 h of symptom onset. (B) Estimated probablity of non-reperfusion according to the number of comorbid factors and intracerebral bleeding risk among typical patients at low baseline cardiovascular risk (TIMI mortality risk index with predicted in-hospital mortality <0.9%) presenting within 3–6 h of symptom onset.

 

Figure 0663
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  		Figure 3 (A) Estimated probablity of non-reperfusion according to intracerebral bleeding risk and baseline cardiovascular risk (TIMI mortality risk index) among typical patients with average number of comorbid factors3 presenting within 1 h of symptom onset. (B) Estimated probablity of non-reperfusion according to intracerebral bleeding risk and baseline cardiovascular risk (TIMI mortality risk index) among typical patients with average number of comorbid factors3 presenting within 3–6 h of symptom onset.

 

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  		Table 3 Relative importance of explanatory factors of non-reperfusion among ideal STEMI patients presenting within 12 h of chest pain symptom onset across age-specific subgroups listed in order of their {chi}2 contribution to the modela

 
All four factors remained as independent determinants of non-utilization of reperfusion therapy after excluding patients aged ≥75 and those presenting beyond 6 h of symptom onset—subgroups traditionally under-represented in clinical trials (Table 4). Moreover, the importance of each of these factors remained unchanged after adjusting for individual clinical factors listed in Table 1. Finally, neither increasing age, gender, admitting hospital nor attending physician specialty was significant independent predictors of non-utilization after adjusting for the remaining significant baseline factors.


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  		Table 4 Relative importance of explanatory factors of non-reperfusion among ideal STEMI patients presenting within 12 h of chest pain symptom onset among patients under age 75 years old presenting within 6 h of symptom onset listed in order of their {chi}2 contribution to the modela

 
Mortality
Only the TIMI mortality risk index, age, and the number of chronic comorbid conditions were significant independent predictors of 30-day mortality (P<0.001 for all). In contrast, neither time to hospital presentation nor receipt of reperfusion therapy was significant independent determinants of 30-day mortality after adjusting for the remaining patient-level characteristics (Table 5).


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  		Table 5 Independent determinants of 30-day mortality among ideal STEMI patients within 12 h of symptom onset listed in order of their {chi}2 contribution to the modela

 
Sensitivity analysis
Patients who died within the initial hours of hospital presentation might have theoretically succumbed to their illness prior to having been given the opportunity to receive reperfusion therapy, leading to a biased estimate and disproportionately greater under-utilization rates among high-risk populations than otherwise expected. However, a sensitivity analysis in which we excluded all reperfusion-eligible STEMI patients who died within 24 h of hospital arrival having not received reperfusion therapy generated results similar to those of our main analyses above.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
Acknowledgements
 References
 
Our study has demonstrated that baseline cardiovascular risk, intracerebral haemorrhage risk, comorbidity burden, and time to hospital presentation could account for the vast majority of under-utilization of reperfusion therapy observed among ideal patients presenting to hospital with STEMI within 12 h of chest pain symptom onset. The associations between these factors and reperfusion therapy non-utilization were independent, additive, and not explained by absolute or relative contraindications to therapy. Furthermore, these determinants of under-utilization were not driven by subgroups which have been traditionally under-represented in clinical trials, because their importance persisted even among younger ideal patients presenting within 6 h of symptom onset—subgroups who comprise the majority of patients enrolled into clinical trials. Neither age, gender, admitting hospital characteristics nor attending physician specialty was significant predictors of reperfusion therapy non-utilization after adjusting for remaining baseline factors.

In our population-based cohort, we observed that 23% of patients who presented to hospital within 12 h of symptom onset and who were considered ideal candidates were not given reperfusion therapy. The under-utilization rate of reperfusion therapy observed in our study is consistent with or lower than those rates reported elsewhere. For example, among the GRACE, 30% of eligible STEMI patients did not receive reperfusion therapy after excluding patients with absolute or relative contraindications.4 Similarly, Canto et al.27 determined that ~25% of ideal patients enrolled in the National Registry of Myocardial Infarction 2 (NRMI-2) did not receive reperfusion therapy.

In our study, each per cent rise in TIMI mortality risk index (our measure of baseline cardiovascular risk) and intracerebral haemorrhage risk was associated with a 3 and 23% fall in the use of reperfusion therapy, respectively. Indeed, such measures of prognosis and harm overshadowed the importance of other potential explanatory factors, such as age and gender, suggesting that previously demonstrated age–gender treatment disparities in the use of reperfusion therapy may be attributable to perceptions regarding benefit–harm tradeoffs more so than to age or gender treatment inequities or biases per se.28–31

The inverse relationship between baseline cardiovascular risk and the utilization of reperfusion therapy is consistent with a ‘treatment-risk paradox’, which has been demonstrated for other chronically administered cardiovascular therapies in ischaemic heart disease and congestive heart failure populations.12,13,32,33 The term ‘paradox’ reflects the counter-intuitive phenomenon whereby care gaps progressively widen rather than narrowing with increasing baseline cardiovascular risk severity. However, until now, the existence of a treatment-risk paradox with respect to the administration of acute life-saving reperfusion therapies among a representative STEMI population was unknown. Given that the absolute survival impact of evidence-based therapy correlates most strongly with baseline cardiovascular risk, the treatment-risk paradox implies that the maximum survival benefits associated with acute reperfusion therapy cannot be fully realized in the population.13,17

Notwithstanding the missed survival opportunities, solutions to the treatment-risk paradox may be complex. For example, delays to hospital presentation, higher intracerebral haemorrhage risk, and increasing number of comorbid conditions were also independent predictors of therapeutic non-utilization, and each may alter the benefit–harm tradeoffs associated with reperfusion therapy among high-risk populations. Consequently, any marginal survival advantages associated with reperfusion therapy among high-risk populations may be partially offset by increasing hospital arrival times and adverse therapeutic side effects, which also rise with progressive increases in comorbidity and baseline cardiovascular risk measures. However, the overall correlation between baseline cardiovascular risk and intracerebral haemorrhage risk for any given patient was small. Accordingly, disentangling the benefit–risk tradeoffs using automated clinical decision tools, which estimate expected net survival gains through the incorporation of baseline cardiovascular and intracerebral haemorrhage risk indices, may assist physician and patient decision-making at the bedside.23

Available evidence has demonstrated that the absolute risks of life-threatening complications from evidence-based therapies, rarely if ever, exceed their anticipated survival benefits when applied to high-risk populations.17 Therefore, regardless of the rationale used to withhold reperfusion therapy, some may argue that any care gaps among ideal candidates are unjustified and discordant with the projected risk–benefit tradeoff treatment gains. Nonetheless, we believe that our study underscores the need to implement and disseminate risk algorithms, which may allow physicians to better estimate the absolute risk–benefit tradeoffs at the bedside.14

The importance of time to hospital presentation as a determinant of reperfusion decision-making also emphasizes the need for better public awareness with regard to symptom recognition and its implications on access to acute life-saving therapies. Additional solutions may include the implementation of pre-hospital thrombolysis,34 which might address the impact of symptom delays on reperfusion therapy care gaps.

In contrast to the powerful impact of age and baseline cardiovascular risk on survival models, the administration of reperfusion therapy was only associated with a trend toward lower mortality. It is possible that the treatment-risk paradox and the consequential selection of lower risk patients for reperfusion therapy might have explained why reperfusion therapy itself was not significantly associated with survival in our study, despite clinical trial evidence to the contrary.35

There are important study limitations. First, the extent to which determinants of non-utilization reflect actual physician decision-making processes is unknown, as data regarding physician perspectives and patient preferences at the point of care were not available. However, consistency in medical decision-making perspectives may not always account for inter-physician variations in utilization patterns.36 Secondly, our study was retrospective; some patients may have had undocumented contraindications to therapy. Nonetheless, detailed clinical information was abstracted using a standardized process, which is a common and well-accepted method of data collection.7,37 Moreover, prospective data registries may require patient consent, which may lead to selection bias limitations.38 Thirdly, hospitals treating fewer than 30 AMI patients were excluded from the study. Nonetheless, the extent to which the inclusion of very small-volume hospitals may have significantly altered our results is unknown.39 Finally, primary angioplasty comprised a very low proportion of all reperfusion therapy in our study. Consequently, our results may have differed, had the prevalence of primary angioplasty matched or exceeded the utilization rates of fibrinolysis. However, the prevalence of primary angioplasty in Canada, as elsewhere, remains low.40 Moreover, available evidence has demonstrated the presence of a treatment-risk paradox for a number of cardiovascular pharmacotherapies and interventions.13,32 Accordingly, there is no reason why our results should not be generalizable to a more angioplasty-intensive region.

In conclusion, the under-utilization of reperfusion therapy among treatment-eligible candidates presenting within 12 h of symptom onset with STEMI was predominantly attributable to increasing hospital arrival times, intracerebral bleeding risk, chronic comorbid disease burden, and the treatment-risk paradox, and not by obvious contraindications to therapy. Care gaps in the use of reperfusion therapy may be explained by misconceptions over the benefit–harm treatment tradeoffs in high-risk populations. Future studies must examine whether the implementation of clinical decision tools, which allow for more accurate risk–benefit tradeoff assessments, and/or the administration of pre-hospital thrombolysis improve the treatment gaps when using acute reperfusion therapies in the population.


Figure 0662
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  		Figure 2 (A) Estimated probablity of non-reperfusion according to the baseline cardiovascular risk (TIMI mortality risk index) and the number of comorbid factors among typical patients at low risk of intracerebral bleeding risk (0.23%) presenting within 1 h of symptom onset. (B) Estimated probability of non-reperfusion according to the baseline cardiovascular risk (TIMI mortality risk index) and the number of comorbid factors among typical patients at low risk of intracerebral (0.23%) presenting within 3–6 h of symptom onset.

 


   Acknowledgements
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
References
 
This work was supported in part by grants from the Canadian Institutes of Health Research and the Heart and Stroke Foundation of Ontario (Grant No. NA5703). The Institute for Clinical Evaluative Sciences is supported in part by a grant from the Ontario Ministry of Health. The results, conclusions, and opinions are those of the authors, and no endorsement by the Ministry or the Institute is intended or should be inferred. Dr. Alter is a New Investigator at the Canadian Institutes of Health Research. Dr. Tu is a Canada Research Chair in Health Services Research and is a Career Investigator of the Heart and Stroke Foundation of Ontario.

Conflict of interest: none declared.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Acknowledgements
 References
 

  1. Armstrong PW and Collen D. (2001) Fibrinolysis for acute myocardial infarction: current status and new horizons for pharmacological reperfusion, part 2. Circulation 103:2987–2992.[Free Full Text]
  2. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. (1994) Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 343:311–322.[CrossRef][Web of Science][Medline]
  3. Keeley EC, Boura JA, Grines CL. (2003) Primary angioplasty vs intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 361:13–20.[CrossRef][Web of Science][Medline]
  4. Eagle KA, Goodman SG, Avezum A, Budaj A, Sullivan CM, Lopez-Sendon J. (2002) Practice variation and missed opportunities for reperfusion in ST-segment-elevation myocardial infarction: findings from the Global Registry of Acute Coronary Events (GRACE). Lancet 359:373–377.[CrossRef][Web of Science][Medline]
  5. Burwen DR, Galusha DH, Lewis JM, Bedinger MR, Radford MJ, Krumholz HM, Foody JM. (2003) National and state trends in quality of care for acute myocardial infarction between 1994–1995 and 1998–1999: the medicare health care quality improvement program. Arch Intern Med 163:1430–1439.[Abstract/Free Full Text]
  6. Rogers WJ, Canto JG, Lambrew CT, Tiefenbrunn AJ, Kinkaid B, Shoultz DA, Frederick PD, Every N. (2000) Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the US from 1990 through 1999: the National Registry of Myocardial Infarction 1, 2 and 3. J Am Coll Cardiol 36:2056–2063.[Abstract/Free Full Text]
  7. Krumholz HM, Murillo JE, Chen J, Vaccarino V, Radford MJ, Ellerbeck EF, Wang Y. (1997) Thrombolytic therapy for eligible elderly patients with acute myocardial infarction. JAMA 277:1683–1688.[Abstract/Free Full Text]
  8. Jha P, Deboer D, Sykora K, Naylor CD. (1996) Characteristics and mortality outcomes of thrombolysis trial participants and nonparticipants: a population-based comparison. J Am Coll Cardiol 27:1335–1342.[Abstract]
  9. Bjorklund E, Lindahl B, Stenestrand U, Swahn E, Dellborg M, Pehrsson K, Van De Werf F, Wallentin L. Swedish ASSENT-2, RIKS-HIA Investigators. (2004) Outcome of ST-elevation myocardial infarction treated with thrombolysis in the unselected population is vastly different from samples of eligible patients in a large-scale clinical trial. Am Heart J 148:566–573.[CrossRef][Web of Science][Medline]
  10. Lincoff AM and Topol EJ. (1993) Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction? Circulation 88:1361–1374.[Abstract/Free Full Text]
  11. Tanne D, Gottlieb S, Hod H, Reicher-Reiss H, Boyko V, Behar S. (1997) Incidence and mortality from early stroke associated with acute myocardial infarction in the prethrombolytic and thrombolytic eras. Secondary Prevention Reinfarction Israeli Nifedipine Trial (SPRINT) and Israeli Thrombolytic Survey Groups. J Am Coll Cardiol 30:1484–1490.[Abstract]
  12. Lee DS, Tu JV, Juurlink DN, Alter DA, Ko DT, Austin PC, Chong A, Stukel TA, Levy D, Laupacis A. (2005) Risk-treatment mismatch in the pharmacotherapy of heart failure. JAMA 294:1240–1247.[Abstract/Free Full Text]
  13. Ko DT, Mamdani M, Alter DA. (2004) Lipid-lowering therapy with statins in high-risk elderly patients: the treatment-risk paradox. JAMA 291:1864–1870.[Abstract/Free Full Text]
  14. Selker HP, Beshansky JR, Griffith JL. (2002) Use of the electrocardiograph-based thrombolytic predictive instrument to assist thrombolytic and reperfusion therapy for acute myocardial infarction. A multicenter, randomized, controlled, clinical effectiveness trial. Ann Intern Med 137:87–95.[Abstract/Free Full Text]
  15. Manhapra A, Canto JG, Barron HV, Malmgren JA, Taylor H, Rogers WJ, Weaver WD, Every NR, Borzak S. (2001) Underutilization of reperfusion therapy in eligible African Americans with acute myocardial infarction: role of presentation and evaluation characteristics. Am Heart J 142:604–610.[CrossRef][Web of Science][Medline]
  16. Franklin K, Goldberg RJ, Spencer F, Klein W, Budaj A, Brieger D, Marre M, Steg PG, Gowda N, Gore JM. GRACE Investigators. (2004) Implications of diabetes in patients with acute coronary syndromes. The Global Registry of Acute Coronary Events. Arch Intern Med 164:1457–1463.[Abstract/Free Full Text]
  17. Alter DA, Manuel DG, Gunraj N, Anderson G, Naylor CD, Laupacis A. (2004) Age, risk-benefit trade-offs, and the projected effects of evidence-based therapies. Am J Med 116:540–545.[CrossRef][Web of Science][Medline]
  18. Tu JV, Donovan L, Lee D, Austin PC, Ko D, Wang J, Newman AM. (2004) Quality of cardiac care in Ontario: EFFECT (Enhanced Feedback for Effective Cardiac Treatment). (Institute for Clinical Evaluative Sciences, Toronto, ON).
  19. Schull MJ, Vermeulen M, Donovan L, Newman A, Tu JV. (2005) Can the wrong statistic be bad for health? Improving the reporting of door-to-needle time performance in acute myocardial infarction. Am Heart J 150:583–587.[Medline]
  20. Bradshaw PJ, Ko DT, Newman AM, Donovan LR, Tu JV. Validity of the GRACE acute coronary syndrome prediction model for 6-month post-discharge death in an independent data set. Heart (in press).
  21. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, Hochman JS, Krumholz HM, Kushner FG, Lamas GA, Mullany CJ, Ornato JP, Pearle DL, Sloan MA, Smith SC Jr, Alpert JS, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Gregoratos G, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK. (2004) ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Circulation 110:e82–e292.[Free Full Text]
  22. Morrow DA, Antman EM, Giugliano RP, Cairns R, Charlesworth A, Murphy SA, de Lemos JA, McCabe CH, Braunwald E. (2001) A simple risk index for rapid initial triage of patients with ST-elevation myocardial infarction: an InTIME II substudy. Lancet 358:1571–1575.[CrossRef][Web of Science][Medline]
  23. Selker HP, Griffith JL, Beshansky JR, Schmid CH, Califf RM, D'Agostino RB, Laks MM, Lee KL, Maynard C, Selvester RH, Wagner GS, Weaver WD. (1997) Patient-specific predictions of outcomes in myocardial infarction for real-time emergency use: a thrombolytic predictive instrument. Ann Intern Med 127:538–556.[Abstract/Free Full Text]
  24. Schneeweiss S, Seeger JD, Maclure M, Wang PS, Avorn J, Glynn RJ. (2001) Performance of comorbidity scores to control for confounding in epidemiologic studies using claims data. Am J Epidemiol 154:854–864.[Abstract/Free Full Text]
  25. Jollis JG, DeLong ER, Peterson ED, Muhlbaier LH, Fortin DF, Califf RM, Mark DB. (1996) Outcome of acute myocardial infarction according to the specialty of the admitting physician. N Engl J Med 335:1880–1887.[Abstract/Free Full Text]
  26. Alter DA, Naylor CD, Austin PC, Tu JV. (2001) Long-term MI outcomes at hospitals with or without on-site revascularization. JAMA 285:2101–2108.[Abstract/Free Full Text]
  27. Canto JG, Zalenski RJ, Ornato JP, Rogers WJ, Kiefe CI, Magid D, Shlipak MG, Frederick PD, Lambrew CG, Littrell KA, Barron HV. (2002) Use of emergency medical services in acute myocardial infarction and subsequent quality of care: observations from the National Registry of Myocardial Infarction 2. Circulation 106:3018–3023.[Abstract/Free Full Text]
  28. Rathore SS, Mehta RH, Wang Y, Radford MJ, Krumholz HM. (2003) Effects of age on the quality of care provided to older patients with acute myocardial infarction. Am J Med 114:307–315.[CrossRef][Web of Science][Medline]
  29. Williams RI, Fraser AG, West RR. (2004) Gender differences in management after acute myocardial infarction: not ‘sexism’ but a reflection of age at presentation. J Public Health (Oxf) 26:259–263.
  30. Bond M, Bowling A, McKee D, Kennelly M, Banning AP, Dudley N, Elder A, Martin A. (2003) Does ageism affect the management of ischaemic heart disease? J Health Serv Res Policy 8:40–47.[CrossRef][Medline]
  31. Dudley NJ, Bowling A, Bond M, McKee D, McClay Scott M, Banning A, Elder AT, Martin AT, Blackman I. (2002) Age- and sex-related bias in the management of heart disease in a district general hospital. Age Ageing 31:37–42.[Abstract/Free Full Text]
  32. Bhatt DL, Roe MT, Peterson ED, Li Y, Chen AY, Harrington RA, Greenbaum AB, Berger PB, Cannon CP, Cohen DJ, Gibson CM, Saucedo JF, Kleiman NS, Hochman JS, Boden WE, Brindis RG, Peacock WF, Smith SC Jr, Pollack CV Jr, Gibler WB, Ohman EM. CRUSADE Investigators. (2004) Utilization of early invasive management strategies for high-risk patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. JAMA 292:2096–2104.[Abstract/Free Full Text]
  33. Bhatt DL, Steg PG, Ohman EM, Hirsch AT, Ikeda Y, Mas JL, Goto S, Liau CS, Richard AJ, Rother J, Wilson PW. REACH Registry Investigators. (2006) International prevalence, recognition, and treatment of cardiovascular risk factors in outpatients with atherothrombosis. JAMA 295:180–189.[Abstract/Free Full Text]
  34. Pedley DK, Bissett K, Connolly EM, Goodman CG, Golding I, Pringle TH, McNeill GP, Pringle SD, Jones MC. (2003) Prospective observational cohort study of time saved by prehospital thrombolysis for ST elevation myocardial infarction delivered by paramedics. BMJ 327:22–26.[Abstract/Free Full Text]
  35. ISIS Pilot Study Investigators. (1987) Randomized factorial trial of high-dose intravenous streptokinase, of oral aspirin and of intravenous heparin in acute myocardial infarction. Eur Heart J 8:849–857.
  36. Poses RM, De Saintonge DM, McClish DK, Smith WR, Huber EC, Clemo FL, Schmitt BP, Alexander-Forti D, Racht EM, Colenda CC III, Centor RM. (1998) An international comparison of physicians' judgments of outcome rates of cardiac procedures and attitudes toward risk, uncertainty, justifiability, and regret. Med Decis Making 18:131–140.[Web of Science][Medline]
  37. Krumholz HM, Chen J, Wang Y, Radford MJ, Chen YT, Marciniak TA. (1999) Comparing AMI mortality among hospitals in patients 65 years of age and older: evaluating methods of risk adjustment. Circulation 99:2986–2992.[Abstract/Free Full Text]
  38. Tu JV, Willison DJ, Silver FL, Fang J, Richards JA, Laupacis A, Kapral MK. Investigators in the Registry of the Canadian Stroke Network. (2004) Impracticability of informed consent in the Registry of the Canadian Stroke Network. N Engl J Med 350:1414–1421.[Abstract/Free Full Text]
  39. Willison DJ, Soumerai SB, Palmer RH. (2000) Association of physician and hospital volume with use of aspirin and reperfusion therapy in acute myocardial infarction. Med Care 38:1092–1102.[CrossRef][Web of Science][Medline]
  40. Ghali WA, Donaldson CR, Knudtson ML, Lewis SJ, Maxwell CJ, Tu JV. (2003) Rising to the challenge: transforming the treatment of ST-segment elevation myocardial infarction. CMAJ 169:35–37.[Free Full Text]

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