European Heart Journal Advance Access originally published online on October 17, 2005
European Heart Journal 2006 27(4):406-412; doi:10.1093/eurheartj/ehi604
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Post-discharge survival following pre-hospital cardiopulmonary arrest due to cardiac aetiology: temporal trends and impact of changes in clinical management
1Section of Cardiology, University of Glasgow, Level 4, Queen Elizabeth Building, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow G31 2ER, UK
2Robertson Centre for Biostatistics, University of Glasgow, Level 11, Boyd Orr Building, University Avenue, Glasgow G12 8QQ, UK
3Scottish Ambulance Service, Headquarters, 23 Tipperlinn Road, Edinburgh EH10 5UU, UK
4Department of Cardiology, Royal Infirmary of Edinburgh, Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SA, UK
Received 10 May 2005; revised 30 August 2005; accepted 29 September 2005; online publish-ahead-of-print 17 October 2005.
* Corresponding author. Greater Glasgow NHS Board, Dalian House, 350 St Vincents Street, Glasgow G3 8YU, UK. Tel: +44 141 201 4544; fax: +44 141 201 4539. E-mail address: jill.pell{at}gghb.scot.nhs.uk
See page 377 for the editorial comment on this article (doi:10.1093/eurheartj/ehi670)
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Abstract |
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Aims To determine whether survival after discharge following pre-hospital cardiopulmonary arrest has improved.
Methods and results The Heartstart Register was used to identify all 1659 patients discharged alive from Scottish hospitals during 1991–01 following pre-hospital arrest due to cardiac aetiology. The cohort was split into tertiles using year of arrest. A Cox proportional hazards model was used to determine risk of death relative to 1991–93. Patients who survived cardiopulmonary arrest in 1997–01 were less likely to die from any cause (unadjusted HR 0.60, 95% CI 0.48–0.75, P<0.001) or cardiac disease (unadjusted HR 0.50, 95% CI 0.38–0.65, P<0.001). After adjustment for case-mix, there remained significant declines in all-cause (adjusted HR 0.62, 95% CI 0.50–0.78, P<0.001) and cardiac death (adjusted HR 0.52, 95% CI 0.39–0.68, P<0.001). Clinical management had improved, with increased use of thrombolysis (47–63%, 
2 trend, P<0.001), beta-blockers (28–53%, 2 trend, P<0.001), ACE-inhibitors (48–69%, 2 trend, P<0.001), and anti-thrombotics (79–88%, 2 trend, P<001). Adjustment for recorded changes in management attenuated the decline in all-cause death (adjusted HR 0.77, 95% CI 0.60–0.98, P=0.03).
Conclusion Survival following cardiopulmonary arrest has improved after adjusting for changes in case-mix. Better clinical management has contributed to this improvement.
Key Words: Cardiopulmonary arrest • Survival • Epidemiology
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Introduction |
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Over the past decade, there have been many advances in both the acute management of coronary heart disease and secondary prevention. However, the anticipated improvement in long-term outcome in survivors of pre-hospital cardiopulmonary arrest may have been offset by changes in the risk profile of patients due, for example, to demographic trends. Published data are few and conflicting. Engdahl et al.1 demonstrated no improvement in long-term outcome following discharge in survivors of pre-hospital cardiopulmonary arrest in Goteborg, Sweden, between 1980 and 1998. In contrast, Rea et al.2 demonstrated improved age-, sex-stratified survival in Washington, USA, between 1976 and 2001. Rea et al. neither had access to information on other aspects of case-mix nor had access to information on clinical management. Therefore, they were unable to determine whether the observed improvements were due to changes in case-mix or management. The aim of this study was to determine whether survival after discharge has increased over time among patients surviving pre-hospital cardiopulmonary arrest and whether changes in clinical practice contributed to any improvements observed.
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Methods |
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We undertook a population-based retrospective cohort study of survival after discharge from hospital following pre-hospital cardiopulmonary arrest due to a cardiac aetiology.
Heartstart Register
In Scotland, which has a population of approximately five million, all emergency pre-hospital ambulance care is provided by the Scottish Ambulance Service. Since October 1988, the Scottish Ambulance Service has collected data prospectively on all pre-hospital cardiopulmonary arrests. Completed forms are sent to the Section of Cardiology in the University of Glasgow where the data are collated to form the Heartstart (Scotland) Register. The information collected by the Scottish Ambulance Service includes demographic characteristics and postcode of residence. Postcode of residence is used to derive the Carstairs socio-economic deprivation categories from census data on car ownership, social class, overcrowding, and male unemployment.3 The categories range from 1 (most affluent) to 7 (most deprived). Medical records staff at the hospitals to which patients are admitted send copies of discharge letters to the Heartstart Register. These are used to collect additional information on in-hospital drug therapies and investigations, diagnosis and therapy at discharge, and in-hospital death. Where necessary, electrocardiograms and biochemical assays are accessed to inform the classification of diagnosis.
Follow-up
The Registrar General's Office (RGO) collates information, from death certificates, on the date and cause of all deaths that occur in Scotland, irrespective of whether they occur in the community or in hospital. The Scottish Morbidity Record (SMR1) collects data on all admissions to Scottish acute hospitals, including information on diagnosis and procedures. We obtained permission from the Privacy Advisory Committee to link the Heartstart Register to the RGO and SMR1 databases to provide follow-up information on deaths, adverse events, and procedures following discharge from hospital. The SMR1 database also provided information on whether the patient has been admitted to hospital during the previous 10 years and the principal diagnosis on admission. Additional information on insertion of implantable cardioverter defibrillators (ICDs) was obtained directly from the units in Scotland where these devices are inserted.
Study cohort
The study cohort comprised everyone in Scotland who suffered a first pre-hospital cardiopulmonary arrest for a cardiac aetiology between 1991 and 2001 inclusive and was discharged alive from hospital. Aetiology was determined by a cardiologist (S.C., N.W., or J.C.) using information contained in the discharge letter, supplemented by electrocardiographic and biochemical data where necessary. Cardiac aetiology was defined as a discharge diagnosis of either
- Q-wave/ST-elevation myocardial infarction (STEMI),
- non-Q-wave/non-STEMI,
- myocardial infarction (unspecified),
- primary ventricular tachycardia/fibrillation due to old myocardial infarction,
- acute ischaemia, or
- other non-ischaemic cardiac diseases.
Statistical analyses
The cohort was split into tertiles according to year of arrest (1991–93, 1994–96, and 1997–01). To test for temporal trends, 1991–93 was used as the referent category against which the latter two time periods were compared. Changes in case-mix and management were tested using 2 and linear tests for trend.
Outcome was assessed in terms of all-cause death, cardiac death, fatal or non-fatal myocardial infarction, and coronary revascularization. Follow-up was measured from the date of discharge. For each of these four outcomes, the unadjusted cumulative event rates were determined using the Kaplan–Meier product limit estimator and the tertiles were compared using log-rank tests. We compared the results of the univariate analyses using year expressed as a continuous variable and as tertiles to check that the results were consistent, before undertaking the multivariate analyses using tertiles. All of the outcomes, except the use of coronary revascularization, were adjusted for differences in case-mix and management over time using multivariate Cox proportional hazard models. We forced into the Cox proportional hazards model all of the variables relating to case-mix and in-hospital management that were deemed to be potential confounders because they changed over time and were associated with one or more outcome in the univariate analyses. We did not include pre-hospital management, as this is likely to impact predominantly on survival to hospital. In the Cox models, ICDs and coronary revascularization were treated as time-dependent covariates. In the Kaplan–Meier and Cox analyses, follow-up was truncated at 5 years to ensure that the maximum period of follow-up was consistent across all three time periods. P-values are reported without adjustment for multiple testing. Statistical analyses were performed using SPSS (v11.0) and S-Plus (v6.1) software. We applied two methods to check the proportional hazards assumption with respect to the time period variable, namely the log cumulative hazard plots and the time-varying coefficients method.4 We checked the linearity assumption by plotting model coefficients after dividing age into quintiles and by fitting a non-linear age term using cubic splines.
Projection model
There has been a progressive increase in the use of elective coronary revascularization and ICDs in patients who have suffered cardiopulmonary arrest. The threshold for clinical interventions varies between countries. Owing to funding constraints, the proportion of patients in our study who received ICDs and coronary revascularization is lower than in some other countries such as Germany and the USA.5,6 For that reason, we modelled the potential impact on crude survival of increased use of ICDs and elective coronary revascularization following cardiopulmonary arrest. We obtained hazard ratios for all-cause death associated with these interventions from published sources. We applied a relative risk of 0.72 for ICD implantation, as reported by Connolly et al.7 in their meta-analysis of randomized trials of ICD implantation vs. amiodarone therapy in survivors of cardiac arrest or ventricular tachycardia. In a meta-analysis, elective coronary artery bypass grafting and percutaneous coronary intervention have been demonstrated to have similar impacts on survival.8 Therefore, we applied a relative risk of 0.62 for coronary revascularization, calculated from the numbers of deaths following coronary artery bypass grafting reported by Yusuf et al.9 For those discharged between 1997 and 2001, we modelled the impact on 5-year survival of increasing ICD coverage from the observed level to 100% of all eligible patients and increasing coronary revascularization from the observed level to both 50 and 100% of all eligible patients. We defined patients who had suffered a STEMI as being ineligible for ICD implantation, because these patients are not considered to require implantation according to current guidelines, and all other patients as being eligible. We defined all patients whose cardiac arrest was due to the acute or chronic consequences of coronary artery disease as being eligible for coronary revascularization. Those with non-ischaemic cardiac aetiologies were defined as ineligible. None of the patients in our cohort underwent primary angioplasty, and we have not attempted to model the impact of adopting primary angioplasty in this group of patients.
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Results |
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Between 1991 and 2001 inclusive, 1659 patients were discharged alive from Scottish hospitals following pre-hospital cardiopulmonary arrest due to a cardiac aetiology. Of these patients, 552 had suffered arrests in 1991–93, 549 in 1994–96, and 558 thereafter. The median age of patients was 65 years (inter-quartile range 56–72). Overall, there was no statistically significant trend in age (Table 1). However, the percentage of patients aged
55 years increased from 21.4 to 27.8% (2 trend, P=0.012). The percentage with an admission for myocardial infarction in the previous 10 years fell from 19.7 to 14.7% (2 trend, P=0.024). Over the period studied, there was a significant increase in the proportion of those discharged alive whose arrest had been witnessed (Table 2). In particular, the proportion of arrests witnessed by ambulance crew members increased from 33.4 to 51.3% (2 trend, P<0.001). As a result, the proportion requiring only a single shock increased from 41.6 to 50.8% (P=0.002) (Table 2). Use of thrombolysis and discharge therapy with beta-blockers, ACE-inhibitors, and anti-thrombotics increased significantly over the period studied (Table 3).
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The percentage of patients discharged with normal neurological function decreased from 87.5 to 81.3%, whereas those with moderate disability increased from 8.5 to 15.6% (
2 trend, P=0.001). Overall, 64 (3.9%) people were discharged with a severe neurological disability, vegetative state, or coma, and the incidence did not change significantly over time. Seventy-three (4.4%) patients had ICDs implanted following the arrest. Use of coronary revascularization after discharge increased between 1991–93 and 1994–96, but the difference did not reach statistical significance (Figure 1D).
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On univariate analysis, the risk of all-cause death fell significantly over time (Figure 1A). Among patients who arrested in 1991–93, 63.2% (95% CI 59.2–67.3%) were alive at 5 years. This compared to 76.0% (95% CI 72.1–79.9%) among those who arrested in 1997–01. This was due to a significant fall in the risk of cardiac death (Figure 1). There was no trend observed in non-cardiac deaths (log-rank 0.91, P=0.341). The risk of suffering fatal or non-fatal myocardial infarction within 5 years of discharge fell from 27.3 (95% CI 23.4–31.3%) to 14.0% (95% CI 11.0–17.1%) (Figure 1C). Following adjustment for case-mix, the fall in all-cause deaths remained statistically significant (HR 0.62, 95% CI 0.50–0.78, P<0.001) (Table 4). Following adjustment for in-hospital and discharge management, implantation of ICDs, and coronary revascularization, the reduction in risk of dying was attenuated but retained borderline statistical significance (Table 4). Treating year as a continuous variable produced similar results. In the univariate Cox proportional hazards model, year was significantly associated with risk of dying (HR 0.92, 95% CI 0.89–0.95, P<0.001).
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Both methods of testing the proportional hazards assumptions provided the same result. In comparing the second period with the first, there was some evidence that the hazard ratio was not constant over time, with the early hazard ratio being slightly lower. However, in the main comparison, namely the comparison of the third period against the first, the proportional hazards assumption held true. The only continuous variable in any of the models was age. We checked the linearity assumption by plotting model coefficients after dividing age into quintiles and by fitting a non-linear age term using cubic splines. There was no evidence of non-linearity.
On the basis of our projection model, increasing the use of ICDs from the status quo to 100% of all eligible patients would have increased 5-year survival among those discharged between 1997 and 2001 from the current figure of 76.0 to 79.3%. Similarly, increasing the use of coronary revascularization to 100% of those eligible would have increased 5-year survival to 83.4% (Table 5). If all of the eligible patients received both interventions, overall survival would have increased by 9.9%, to 85.9%.
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Discussion |
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Over the 10-year period studied, there were significant improvements in crude survival among patients discharged from hospital following pre-hospital cardiopulmonary arrest. Our findings are in line with those of Rea et al.2 who demonstrated significant improvements in survival in Washington, USA, between 1976 and 2001. In contrast, Engdahl et al.1 demonstrated no improvement in survival in Goteborg, Sweden, between 1980 and 1998. Our study demonstrated that the improvements observed in overall survival were due specifically to a reduction in the risk of cardiac deaths and that the improvements in survival were accompanied by a reduction in the risk of acute myocardial infarction following discharge.
Rea et al.2 were able to adjust survival for age and sex and demonstrated improvements in age–sex-adjusted survival but they did not have access to data on other aspects of case-mix or to data on clinical management. We had access to both and, therefore, were able to adjust for these factors in multivariate models. Engdahl et al.1 demonstrated no change over time in the age, sex, and comorbidity of patients discharged from hospital following pre-hospital cardiopulmonary arrest. In our study, the case-mix of patients remained constant over time in most regards. There was a significant decrease in the percentage of patients who had previously suffered a myocardial infarction. This may reflect improvements in secondary prevention or may simply be the result of the significant increase in patients under 55 years of age. Both the reduction in patients with a previous myocardial infarction and the increasing proportion of younger patients would tend to improve survival. However, adjustment for case-mix had relatively little impact on the observed improvements in outcome over time.
Skrifvars et al.10 demonstrated that survival among patients discharged following pre-hospital cardiopulmonary arrest is associated with in-hospital management. We demonstrated significant improvements over time in the in-hospital and discharge management of patients. These findings are supported by the results of Engdahl et al.1 The proportion of patients receiving drug therapies of proven efficacy, such as thrombolysis, beta-blockers, and anti-thrombotics, increased significantly over the period we studied. Similarly, the increase in use of ACE-inhibitors is more likely to reflect improved management than worsening case-mix. The proportion of patients undergoing coronary revascularization prior to or following discharge increased significantly between 1991–93 and 1994–96 and then plateaued. Adjustment for clinical management attenuated the improvements in outcome over time. This suggests that the improvements in survival and risk of myocardial infarction observed over time are due, at least in part, to improvements in clinical management.
Following adjustment for clinical management, trends in all-cause death were of borderline statistical significance, but trends in cardiac death and myocardial infarction remained statistically significant. It is likely that some of the residual improvements over time are, nonetheless, due to improvements in clinical management. We did not have access to data on some aspects of clinical management, in particular, secondary prevention and drug therapies commenced after discharge. Evidence suggests that the uptake of these is also likely to have improved over time. For example, in the study by Engdahl et al.,1 the prevalence of smoking among patients discharged from hospital following pre-hospital cardiopulmonary arrest halved over 10 years, whereas the proportion of patients who were treated with lipid-lowering therapy increased significantly. Over the period we studied, the proportion of patients in Scotland taking statins following acute myocardial infarction has increased 20-fold from 3.1 to 62.9% (T. MacDonald, University of Dundee, Scotland, personal communication).
Classification of cause of death was obtained from death certificates. It is likely that the proportion of deaths due to cardiac causes will be overestimated due to death being wrongly attributed to cardiac disease in some people who have previously suffered a cardiac event. However, this is unlikely to have changed over the time periods studied and, therefore, is unlikely to have introduced bias. Furthermore, the time trends observed in cardiac deaths were also observed for all-cause deaths and non-fatal myocardial infarction (data not shown), which are not affected by incorrect coding of cause of death. We have previously shown that prognosis is better following cardiopulmonary arrest due to myocardial infarction than other cardiac aetiologies.11 Therefore, in the Cox model, we adjusted for arrest due to myocardial infarction. This definition is derived primarily from information contained in the discharge letter. However, where the information was insufficient or imprecise, the investigators (S.C., N.W., J.C.) accessed electrocardiograms and biochemical assays prior to classification.
In our study, there was a significant increase in the proportion of patients discharged from hospital with moderate neurological disability. However, there was no trend in the proportion of patients with severe neurological disability or coma. Therefore, we can only speculate whether this is a real trend or reflects changing diagnostic thresholds. In the study by Engdahl et al.,1 the investigators did not have access to data on neurological status. However, they demonstrated that the proportion of patients requiring rehabilitation increased and concluded that neurological status had probably declined.
Over the period studied, the proportion of people suffering pre-hospital arrest who survived to discharge from hospital changed from 11.6% (552/4766) in 1991–93, and 10.5% (549/5216) in 1994–96, to 7.0% (558/8006) in 1997–01. The reasons for this are currently unclear and are being explored in a separate study. This could have introduced a systematic bias into the assessment of trends in crude outcome. However, the time trends in outcome remained after adjustment for changes in case-mix at discharge.
The results of our projection models suggested that, although we have achieved significant improvements in survival as a result of improvements in clinical management, still greater improvements could be achieved by greater access to such interventions. This is despite the fact that the 5-year survival in our cohort is already greater than that reported in previous studies. In our study, 76% of patients discharged from hospital between 1997 and 2001 were alive at 5 years compared with 
50% reported by Rea and Engdahl in the USA and Sweden, respectively.1,2 These differences may relate to differences in case-mix, the usage of medications for secondary prevention of coronary disease in different countries, or to other unexplained factors. Our projection model was based on an increase in the use of elective coronary revascularization. None of our patients underwent primary angioplasty. Adoption of primary angioplasty was not included in our model, but would increase survival further.
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Conclusions |
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There were relatively few discernable changes in the case-mix of patients discharged following pre-hospital cardiopulmonary arrests. Those changes that were observed, namely the increase in the proportion of young patients and decline in the previous admission for myocardial infarction, would tend to improve survival. However, adjustment for case-mix had little impact on the observed improvement in survival. There was an increase in the proportion of patients receiving drug therapies and other interventions known to be effective at improving survival. Adjustment for clinical management attenuated the increase in survival, suggesting that improvements in clinical practice have contributed to the observed improvement in survival. The residual improvement may nonetheless be due to improvements in management for which we had no data, such as increased use of statin therapy. In the UK, the use of many effective interventions such as ICDs and coronary revascularization is much lower than in many countries. Our model demonstrated that increased use of such interventions could produce further improvements in survival.
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Acknowledgements |
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The authors are grateful to the British Heart Foundation for funding the study, to the Scottish Ambulance Service and hospital medical records staff for providing baseline data, and to the Information Services Division of NHS National Services Scotland for providing follow-up data.
Conflict of interest: no conflict of interest.
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References |
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