The influence of time from symptom onset and reperfusion strategy on 1-year survival in ST-elevation myocardial infarction: A pooled analysis of an early fibrinolytic strategy versus primary percutaneous coronary intervention from CAPTIM and WEST

doi:10.1016/j.ahj.2010.10.033

American Heart Journal

Volume 161, Issue 2, February 2011, Pages 283-290

https://doi.org/10.1016/j.ahj.2010.10.033 Get rights and content

Background

The CAPTIM trial suggested a survival benefit of prehospital fibrinolysis (FL) compared to primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) with a presentation delay of <2 hours. We examined the relationship between reperfusion strategy and time from symptom onset on 1-year mortality in a combined analysis of 1,168 patients with STEMI.

Methods

Individual patient data from CAPTIM (n = 840, 1997-2000) and the more recent WEST trial (n = 328, 2003-2005) were pooled.

Results

Median age was 58 years, 81% were men, and 41% had anterior myocardial infarction; 640 patients were randomized to FL versus 528 patients to PCI. Both arms received contemporary adjunctive medical therapy. Presentation delay (ie, symptom onset to randomization) was similar in FL and PCI patients (median 105 [72-158] vs 106 [74-162] minutes, P = .712). Rescue PCI after FL occurred in 26% and 27%, and 30-day PCI, in 70% and 71% in CAPTIM and WEST, respectively. Mortality was not different between FL and PCI (4.6% vs 6.5%, P = .263); however, the interaction between presentation delay and treatment was significant (P = .043). Benefit with FL was observed with time <2 hours (2.8% [FL] vs 6.9% [PCI], P = .021, hazard ratio [HR] 0.43, 95% CI 0.20-0.91), whereas beyond 2 hours, no treatment difference was observed (6.9% [FL] vs 6.0% [PCI], P = .529, HR 1.23, 95% CI 0.61-2.46).

Conclusions

A strategy of early FL demonstrated a reduction in 1-year mortality compared to primary PCI in early presenters. Time from symptom onset should be a key consideration when selecting reperfusion therapy for STEMI.

Section snippets

Methods

The details and primary results of the CAPTIM and WEST trials have been previously published.8, 10 In brief, the CAPTIM trial randomized eligible patients at the site of initial management to prehospital FL or direct transfer for primary PCI. All patients received an intravenous bolus of 5,000 U heparin and 250 to 500 mg aspirin. Patients assigned to prehospital FL received an intravenous bolus of alteplase followed by an infusion over 90 minutes. Coronary angiography and subsequent

Results

Individual patient data from the CAPTIM, which enrolled 840 patients with STEMI between 1997 and 2000, and WEST trials, which enrolled 328 patients with STEMI between 2003 and 2005, were obtained for the current study (Figure 1). Baseline patient characteristics according to study treatment are presented in Table I for the individual trials as well as the pooled cohort. Overall, the patients enrolled in the CAPTIM and WEST trials were comparable across the trials and between the study

Discussion

Our novel findings not only support the critical relationship between time from symptom onset and 1-year survival after reperfusion, but also provide new evidence about the impact of this relationship on the relative efficacy of the 2 standard modes of therapy. A survival advantage existed for patients treated with FL within 2 hours of symptom onset relative to those treated with primary PCI (P interaction [unadjusted] = .043). When time from symptom onset was explored in a continuous fashion,

Conclusion

Given persisting evidence of failure to meet guideline-suggested times to PCI, especially among patients presenting to non-PCI hospitals, our data provide additional evidence to support the efficacy of an alternative reperfusion strategy, that is, fibrinolytic therapy (in patients without contraindications, coupled with contemporary adjunctive therapy, timely rescue PCI, and subsequent revascularization), especially in those presenting early after symptom onset either in the prehospital setting

Disclosures

The original WEST study was supported by an unrestricted grant from Hoffmann-LaRoche Limited; Aventis Pharma, a member of the Sanofi-Aventis group; as well as Eli-Lilly Canada. The original CAPTIM study was supported by a grant from the French Ministry of Health (Projet Hospitalier de Recherche Clinique, 96/045), by the Hospices Civils de Lyon, and by an unrestricted research grant from AstraZeneca France. Biotronic GmbH provided balloons and guidewires free of charge.

Drs Armstrong and Welsh

Acknowledgements

The authors would like to acknowledge the expert editorial assistance of Jo-An Padberg.

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Cited by (78)

Prognostic impact of prepercutaneous coronary intervention TIMI flow in patients with ST-segment and non-ST-segment elevation myocardial infarction: Results from the FAST-MI 2010 registry
2018, Archives of Cardiovascular Diseases
Citation Excerpt :
Myocardial perfusion grade predicts final infarct size and left ventricular function in patients with acute myocardial infarction (AMI) [1–5].
Thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3 before percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) is associated with improved outcomes. However, no recent data are available on its impact beyond 1 year and/or by type of AMI.
To assess the prognostic impact of prePCI TIMI flow at 30 days and 3 years in patients with ST-segment elevation (STEMI) or non-ST-segment elevation (NSTEMI) AMI.
We compared long-term outcomes associated with TIMI flow grade 2/3 versus 0/1 in patients referred for PCI in the nationwide French registry of acute ST-segment elevation or non-ST-segment elevation myocardial infarction (FAST-MI) 2010.
TIMI flow grade 2/3 was found in 41% of patients with STEMI and 69% of patients with NSTEMI; it was associated with a lower risk of 30-day death in patients with STEMI (odds ratio 0.30, 95% confidence interval [CI] 0.12–0.77; P = 0.01), but not in patients with NSTEMI (odds ratio 0.57, 95% CI 0.22–1.42; P = 0.23). TIMI grade flow 2/3 was also associated with a lower risk of 3-year death in patients with STEMI (hazard ratio 0.69, 95% CI 0.49–0.98; P = 0.04), but not in patients with NSTEMI (hazard ratio 0.79, 95% CI 0.56–1.11; P = 0.17).
TIMI flow grade 2/3 is observed more often in patients with NSTEMI; it is an independent predictor of early and late survival in patients with STEMI, but is not significantly related to early or long-term survival in patients with NSTEMI.
Le flux intracoronaire (TIMI) 2 ou 3 avant une angioplastie chez les patients pris en charge pour un infarctus du myocarde (IDM) est associé à un meilleur pronostic. Cependant, il n’existe pas de donnée récente après un an de suivi et selon le type d’IDM.
Évaluer l’impact pronostic du flux TIMI avant angioplastie à 30 jours et à 3 ans chez les patients présentant un IDM avec ou sans sus-décalage ST.
Comparaison du devenir clinique à long terme selon le flux TIMI avant angioplastie (2/3 versus 0/1) chez les patients hospitalisés pour un IDM en utilisant les données du registre FAST-MI 2010.
Le flux TIMI 2/3 est observé chez 41 % des IDM avec sus-décalage et 63 % des IDM sans sus-décalage. Il est associé à une mortalité plus faible à 30 jours dans la population des IDM avec sus-décalage (OR 0,30, IC 95 % 0,12–0,77 ; p = 0,01) mais pas dans la population des IDM sans sus-décalage (OR 0,57, IC 95 % 0,22–1,42 ; p = 0,23). Le flux TIMI 2/3 est également associé à une mortalité plus faible à 3 ans dans la population des IDM avec sus-décalage (HR 0,69, IC 95 % 0,49–0,98 ; p = 0,04) mais pas dans la population des IDM sans sus-décalage (HR 0,79, IC 95 % 0,56–1,11 ; p = 0,17).
Le flux TIMI 2/3 est plus fréquemment observé chez les patients avec un IDM sans sus-décalage. Il représente un facteur prédictif indépendant de survie précoce et à long terme chez les patients avec un IDM avec sus-décalage mais pas de manière significative dans la population des IDM sans sus-décalage.
Reperfusion therapy in ST-elevation myocardial infarction
2018, Coronary Microvascular Obstruction in Acute Myocardial Infarction: From Mechanisms to Treatment
Primary percutaneous coronary intervention (PPCI) with stenting has become the standard reperfusion strategy for the treatment of ST-segment-elevation myocardial infarction (STEMI) and it achieves superior outcomes compared to thrombolysis or balloon PCI alone. Yet, thrombolysis remains an effective reperfusion strategy, especially in the many parts of the world where PPCI is not available or geographical limitations prohibit timely access to it. Recombinant tissue plasminogen activators are the preferred fibrinolytic agents of choice and “accelerated” delivery has shown the greatest survival benefit of all thrombolytic regimens. Procedural safety and outcomes of PPCI have been improved by the contemporary use of radial (rather than femoral) artery access and new-generation drug-eluting stents, that reduce restenosis, reinfarction and stent thrombosis compared with older stent technologies, facilitated by potent antiplatelet agents. Other adjunctive pharmacotherapy and mechanical interventions have not been shown to consistently improve outcomes and their routine use is controversial. The optimal management of high-risk STEMI patients, particularly those with multivessel disease and/or cardiogenic shock, is undetermined and currently under investigation. The greatest challenges to optimizing prognosis following STEMI remain ischemia-reperfusion injury and suboptimal microvascular perfusion despite angiographically successful PPCI.
Impact of time of admission on short- and long-term mortality in the Vienna STEMI registry
2017, International Journal of Cardiology
Citation Excerpt :
As this factor did not translate into increased mortality, these findings reflect an appropriate clinical decision making to select fibrinolytic therapy when prompt PCI is not feasible. Hence, our results align with the results of clinical trials, suggesting that pre-hospital FT followed by rescue, facilitated or elective angiography in a well-organized system of care is at least equivalent in regards to outcome compared to pPCI [38–42]. 4) The rotational system between the tertiary hospitals offers several advantages: availability of experienced interventionists and other cath-lab personnel on-site (no call-in system as in the majority of international networks) also during “off-hours”, advanced experience of the participating centres following the higher case load, a higher likelihood of critical care unit beds and thus avoidance of early re-transfer to other hospitals.
Several studies have shown contradictive findings regarding mortality and hospital admission time in patients presenting with ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the impact of “on-” or “off-hour” admission on short- and long-term all-cause mortality of patients in the advanced Vienna STEMI network between 2003 and 2009.
In total, 2829 patients were included into this analysis. Patients were stratified according to admission time into “on-hour” admission (07:30 until 15:00 h on weekdays) and “off-hour” admission (15:00–7:30 h on weekdays and 24 h on weekends). As endpoint of interest, all-cause mortality was investigated after 30 days and 3 years of follow-up, the latter for all patients and as Landmark analysis for survivors of the index event.
Mean age was 60.5 ± 13.3 years, 2048 (72.4%) patients were male and 1260 (44.5%) patients presented with anterior wall infarction. 683 (24.1%) patients were admitted “on-hours”, 2146 (75.9%) patients were admitted “off-hours”. All-cause death occurred in 176 (6.2%) patients after a follow-up of 30 days and in 337 (11.9%) patients after 3 years.
For short- and long-term all-cause mortality no significant differences could be detected between “on-” and “off-hour” admission in univariate and multivariate Cox proportional hazard analyses as well as for propensity score adjusted outcome analysis.
In the Vienna STEMI network, “on-” or “off-hour” admission had no impact on short- and long-term mortality for all-comers presenting with acute STEMI. Our findings confirm the imperative need for well-structured STEMI networks of care, as previous data repeatedly demonstrated increased adverse cardiovascular outcome for “off-hour” admission.
Temporal Trends of Reperfusion Strategies and Hospital Mortality for Patients With STEMI in Percutaneous Coronary Intervention–Capable Hospitals
2017, Canadian Journal of Cardiology
The aim of this study was to examine temporal trends and provincial variations in reperfusion strategies and in-hospital mortality among patients presenting with ST-segment elevation myocardial infarction (STEMI) at hospitals in Canada capable of performing percutaneous coronary intervention (PCI).
We included patients aged ≥ 20 years who were hospitalized between fiscal years 2009 and 2013 in all provinces except Quebec. We categorized patients as receiving fibrinolysis (lysis), primary PCI (pPCI), or no reperfusion. Patients undergoing lysis were further categorized as (1) lysis + PCI ≤ 90 minutes, (2) lysis + PCI > 90 minutes, and (3) lysis only. Patients undergoing pPCI were further categorized as (1) pPCI ≤ 90 minutes and (2) pPCI > 90 minutes. We used logistic regression to examine the baseline-adjusted association between reperfusion strategy and in-hospital mortality.
Among 44,650 STEMI episodes in 44,373 patients, 66.3% received pPCI (annual increase of 7.8%; P < 0.001). British Columbia had the highest (81.4%) rates of pPCI and New Brunswick had the lowest rates (30.2%). In-hospital mortality ranged from a high of 16.3% among patients receiving no reperfusion to a low of 1.9% among patients receiving lysis + PCI > 90 minutes (adjusted odds ratio of 0.42; 95% confidence interval, 0.32-0.55 compared with pPCI ≤ 90 minutes).
The use of pPCI in STEMI has increased significantly in Canada; however, significant interprovincial variation remains. Changes in reperfusion strategies do not appear to have had an impact on in-hospital mortality rates. Patients who underwent lysis followed by PCI in a systematic fashion had the lowest mortality.
Cette étude avait pour but d'examiner les tendances temporelles et les variations interprovinciales en matière de stratégies de reperfusion et de mortalité hospitalière chez les patients victimes d'un infarctus du myocarde avec élévation du segment ST (STEMI) dans les hôpitaux canadiens offrant des interventions coronariennes par voie percutanée (ICP).
Nous avons inclus tous les patients âgés de 20 ans et plus hospitalisés entre les années financières 2009 et 2013 dans toutes les provinces du Canada, à l'exception du Québec. Les patients ont été classés par catégories en fonction du traitement reçu, soit fibrinolyse (lyse), ICP primaire (ICPp) et absence de reperfusion. Les patients soumis à la lyse ont été répartis en sous-catégories, soit 1) lyse + ICP ≤ 90 minutes, 2) lyse + ICP > 90 minutes et 3) lyse uniquement. De même, les patients soumis à une ICPp ont été répartis en sous-catégories, soit 1) ICPp ≤ 90 minutes et 2) ICPp > 90 minutes. Nous avons ensuite fait appel à une régression logistique pour examiner l'association, ajustée en fonction des données initiales, entre la stratégie de reperfusion utilisée et la mortalité hospitalière.
Parmi les 44 650 épisodes de STEMI survenus chez 44 373 patients, 66,3 % ont été traités par ICPp (augmentation annuelle de 7,8 %; p < 0,001). C'est en Colombie-Britannique que le plus fort taux d’ICPp a été enregistré (81,4 %), tandis que le plus faible taux a été observé au Nouveau-Brunswick (30,2 %). Le taux de mortalité hospitalière variait pour sa part de 16,3 % chez les patients n'ayant pas bénéficié d'une reperfusion à 1,9 % chez les patients ayant été traités par lyse + ICP > 90 minutes (rapport de cotes ajusté de 0,42; intervalle de confiance à 95 % de 0,32 à 0,55 comparativement avec l’ICPp ≤ 90 minutes).
Il y a eu une augmentation significative du recours à l’ICPp en cas de STEMI au Canada, mais d'importantes variations interprovinciales sont toujours présentes. Le changement de stratégie de reperfusion ne semble pas avoir eu d'incidence sur le taux de mortalité hospitalière. Les patients ayant bénéficié de manière systématique d'une lyse suivie d'une ICP ont présenté le plus faible taux de mortalité.
The Choice Is Reperfusion Therapy: But Which One?
2016, JACC: Cardiovascular Interventions
STEMI Treatment 2016: Is Outcome Improvement Stalling and If So, Why?
2016, Canadian Journal of Cardiology

View all citing articles on Scopus

: ClinicalTrials.gov Identifier: NCT00121446 (WEST).

^d: For the CAPTIM/WEST Investigators.

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Clinical InvestigationAcute Ischemic Heart DiseaseThe influence of time from symptom onset and reperfusion strategy on 1-year survival in ST-elevation myocardial infarction: A pooled analysis of an early fibrinolytic strategy versus primary percutaneous coronary intervention from CAPTIM and WEST

Background

Methods

Results

Conclusions

Section snippets

Methods

Results

Discussion

Conclusion

Disclosures

Acknowledgements

Lancet

Lancet

Am Heart J

J Am Coll Cardiol

Am J Cardiol

Circulation

Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation

Eur Heart J

Editor's commentary: one size does not fit all

Circulation

Does time matter? A pooled analysis of randomized clinical trials comparing primary percutaneous coronary intervention and in-hospital fibrinolysis in acute myocardial infarction patients

Eur Heart J

Duration of symptoms is the key modulator of the choice of reperfusion for ST-elevation myocardial infarction

Circulation

Development of systems of care for ST-elevation myocardial infarction patients. Policy recommendations

Circulation

Clinical Investigation
Acute Ischemic Heart Disease
The influence of time from symptom onset and reperfusion strategy on 1-year survival in ST-elevation myocardial infarction: A pooled analysis of an early fibrinolytic strategy versus primary percutaneous coronary intervention from CAPTIM and WEST