Downloaded from heart.bmj.com on June 28, 2014 - Published by group.bmj.com
Heart Online First, published on June 10, 2014 as 10.1136/heartjnl-2014-306023 Coronary artery disease
ORIGINAL ARTICLE
Aborted myocardial infarction in ST-elevation myocardial infarction: insights from the STrategic Reperfusion Early After Myocardial infarction trial Neda Dianati Maleki,1 Frans Van de Werf,2 Patrick Goldstein,3 Jennifer A Adgey,4 Yves Lambert,5 Vitaly Sulimov,6 Fernando Rosell-Ortiz,7 Anthony H Gershlick,8 Yinggan Zheng,1 Cynthia M Westerhout,1 Paul W Armstrong1 1
Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada 2 Department of Cardiology, University Hospital Gasthuisberg, Leuven, Belgium 3 Emergency Department, Lille University Hospital France, Lille Cedex, France 4 The Heart Centre, Royal Victoria Hospital, Belfast, Ireland 5 Hôpital André Mignot, Centre Hospier de Versailles, Paris, France 6 Department of Internal Diseases, 1st Moscow State Medical University, Moscow, Russian Federation 7 Empresa Publica de Emergencias Sanitarias, Almería, Spain 8 Leicester Cardiovascular Biomedical Research Unit, University Hospital of Leicester, Leicester, UK Correspondence to Dr Paul W Armstrong, Canadian VIGOUR Centre, University of Alberta, 2–132 Li Ka Shing Centre for Health Research Innovation, Edmonton, AB, Canada T6G 2E1; [email protected] Received 16 April 2014 Revised 8 May 2014 Accepted 22 May 2014
ABSTRACT Background We evaluated the prespecified endpoint, aborted myocardial infarction (AbMI), according to the use of a pharmacoinvasive (PI) strategy versus primary percutaneous coronary intervention (PCI) in 1754 patients randomised within 3 h of symptom onset in the STrategic Reperfusion Early After Myocardial infarction (STREAM) trial. Methods Based on sequential ECG’s and biomarkers, AbMI was defined as ST-elevation resolution ≥50% (90 min posttenecteplase (TNK) in the PI arm or 30 min postprimary PCI) with minimal biomarker rise. Results In the PI arm 11.1% (n=99) had AbMI versus 6.9% (n=59) in primary PCI arm ( p18 years, presenting within 3 h from symptom onset were randomised to either (i) a strategy of fibrinolysis with tenecteplase (TNK) followed by scheduled or rescue PCI, based on achievement or failure to achieve at least 50% ST resolution in the single worst lead at baseline (PI) or (ii) primary PCI administered according to local standards (Primary PCI). STEMI was defined by ≥2 mV ST-elevation in two contiguous leads of the baseline ECG. Creatinine kinase (CK), creatinine kinase MB isoenzyme (CK-MB) and troponin levels were collected as multiples exceeding the upper limit of normal (ULN) at baseline, 8–12 h and 24 h after randomisation.
Dianati Maleki N, et al. Heart 2014;0:1–7. doi:10.1136/heartjnl-2014-306023 1 Copyright Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd (& BCS) under licence.
Downloaded from heart.bmj.com on June 28, 2014 - Published by group.bmj.com
Coronary artery disease Baseline ECGs were collected at each site on admission; additional ECGs were acquired for the PI group at 90 min post-TNK and postcatheterisation/PCI; and for primary PCI, prior to catheterisation/PCI and 30 min after PCI. A core ECG laboratory (Canadian VIGOUR Centre, Edmonton, Canada) analysed these ECGs according to methods previously documented.10 AbMI was defined by assessing whether there was ≥50% ST-elevation resolution in the ECG lead exhibiting the maximal baseline ST-elevation at either 90 min post-TNK or 30 min post-PCI in PI and primary PCI patients, respectively. In addition, biomarker analysis, using either CK-MB ≤2 times the ULN (n=74) or if CK-MB was not available, then total CK ≤2 times the ULN (n=77) on at least two measurements within the first 24 h. If neither CK-MB nor CK was available (n=7) then cardiac troponin I/T (cTn) levels ≤5 times the ULN was required.11 Serial ECGs of the patients who met the cardiac biomarker criteria were analysed and patients who developed significant new Q-waves in their post-treatment or discharge ECGs were excluded from the AbMI category. Patients with minimal or no rise in biomarker data simulating the AbMI patients but who did not exhibit evolutionary ECG changes between their qualifying and discharge ECGs were classified separately as infarct masquerade.4
Statistical analysis Patient and procedural characteristics were presented according to AbMI and non-AbMI, and then further according to randomised treatment strategy (ie, PI or primary PCI). Categorical variables were reported as percentages, and differences between groups were tested by the χ2 test; Fisher’s exact test was applied when the cell count was less than five patients. Continuous variables were summarised as medians with 25th and 75th centiles, and differences between groups were tested via Wilcoxon rank-sum test. Multivariable logistic regression analysis was applied to identify the factors significantly associated with AbMI. Baseline patient characteristics in table 1 were first tested using univariable logistic regression and then variables with p ≤ 0.20 were included in the full multivariable model and then stepwise selection ( p≤0.20 as ‘in’ criteria and p≤0.05 as ‘out’ criteria) was used to identify the final model. Variables considered in the full model were age >75 years, Killip class, previous MI, previous PCI, previous coronary artery bypass graft surgery, baseline Q-wave, ∑ST-deviation on the baseline ECG and time from symptom onset to first medical contact. The association between AbMI and the primary clinical outcomes (ie, the composite of all-cause death, cardiogenic shock, congestive heart failure (CHF), recurrent MI and the individual components) within 30 days was examined using Poisson regression model with robust error variance. Relative risks (RR) with 95% CI were reported. Given the small number of events in the AbMI group, the Thrombolysis In Myocardial Infarction (TIMI) risk score12 was used as an aggregate measure of risk to account for imbalances in baseline patient characteristics. The interaction between AbMI and randomised study treatment was tested to examine whether the treatment assignment modulated the association between AbMI and 30-day clinical outcomes. The Kaplan–Meier estimates for 1-year all-cause mortality are reported, and the log-rank test was applied to test the difference according to AbMI. A sensitivity analysis was performed to examine the outcomes according to whether AbMI was observed pre-PCI or post-PCI in the primary PCI arm. All statistical tests were two-sided, with p
Heart Online First, published on June 10, 2014 as 10.1136/heartjnl-2014-306023 Coronary artery disease
ORIGINAL ARTICLE
Aborted myocardial infarction in ST-elevation myocardial infarction: insights from the STrategic Reperfusion Early After Myocardial infarction trial Neda Dianati Maleki,1 Frans Van de Werf,2 Patrick Goldstein,3 Jennifer A Adgey,4 Yves Lambert,5 Vitaly Sulimov,6 Fernando Rosell-Ortiz,7 Anthony H Gershlick,8 Yinggan Zheng,1 Cynthia M Westerhout,1 Paul W Armstrong1 1
Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada 2 Department of Cardiology, University Hospital Gasthuisberg, Leuven, Belgium 3 Emergency Department, Lille University Hospital France, Lille Cedex, France 4 The Heart Centre, Royal Victoria Hospital, Belfast, Ireland 5 Hôpital André Mignot, Centre Hospier de Versailles, Paris, France 6 Department of Internal Diseases, 1st Moscow State Medical University, Moscow, Russian Federation 7 Empresa Publica de Emergencias Sanitarias, Almería, Spain 8 Leicester Cardiovascular Biomedical Research Unit, University Hospital of Leicester, Leicester, UK Correspondence to Dr Paul W Armstrong, Canadian VIGOUR Centre, University of Alberta, 2–132 Li Ka Shing Centre for Health Research Innovation, Edmonton, AB, Canada T6G 2E1; [email protected] Received 16 April 2014 Revised 8 May 2014 Accepted 22 May 2014
ABSTRACT Background We evaluated the prespecified endpoint, aborted myocardial infarction (AbMI), according to the use of a pharmacoinvasive (PI) strategy versus primary percutaneous coronary intervention (PCI) in 1754 patients randomised within 3 h of symptom onset in the STrategic Reperfusion Early After Myocardial infarction (STREAM) trial. Methods Based on sequential ECG’s and biomarkers, AbMI was defined as ST-elevation resolution ≥50% (90 min posttenecteplase (TNK) in the PI arm or 30 min postprimary PCI) with minimal biomarker rise. Results In the PI arm 11.1% (n=99) had AbMI versus 6.9% (n=59) in primary PCI arm ( p18 years, presenting within 3 h from symptom onset were randomised to either (i) a strategy of fibrinolysis with tenecteplase (TNK) followed by scheduled or rescue PCI, based on achievement or failure to achieve at least 50% ST resolution in the single worst lead at baseline (PI) or (ii) primary PCI administered according to local standards (Primary PCI). STEMI was defined by ≥2 mV ST-elevation in two contiguous leads of the baseline ECG. Creatinine kinase (CK), creatinine kinase MB isoenzyme (CK-MB) and troponin levels were collected as multiples exceeding the upper limit of normal (ULN) at baseline, 8–12 h and 24 h after randomisation.
Dianati Maleki N, et al. Heart 2014;0:1–7. doi:10.1136/heartjnl-2014-306023 1 Copyright Article author (or their employer) 2014. Produced by BMJ Publishing Group Ltd (& BCS) under licence.
Downloaded from heart.bmj.com on June 28, 2014 - Published by group.bmj.com
Coronary artery disease Baseline ECGs were collected at each site on admission; additional ECGs were acquired for the PI group at 90 min post-TNK and postcatheterisation/PCI; and for primary PCI, prior to catheterisation/PCI and 30 min after PCI. A core ECG laboratory (Canadian VIGOUR Centre, Edmonton, Canada) analysed these ECGs according to methods previously documented.10 AbMI was defined by assessing whether there was ≥50% ST-elevation resolution in the ECG lead exhibiting the maximal baseline ST-elevation at either 90 min post-TNK or 30 min post-PCI in PI and primary PCI patients, respectively. In addition, biomarker analysis, using either CK-MB ≤2 times the ULN (n=74) or if CK-MB was not available, then total CK ≤2 times the ULN (n=77) on at least two measurements within the first 24 h. If neither CK-MB nor CK was available (n=7) then cardiac troponin I/T (cTn) levels ≤5 times the ULN was required.11 Serial ECGs of the patients who met the cardiac biomarker criteria were analysed and patients who developed significant new Q-waves in their post-treatment or discharge ECGs were excluded from the AbMI category. Patients with minimal or no rise in biomarker data simulating the AbMI patients but who did not exhibit evolutionary ECG changes between their qualifying and discharge ECGs were classified separately as infarct masquerade.4
Statistical analysis Patient and procedural characteristics were presented according to AbMI and non-AbMI, and then further according to randomised treatment strategy (ie, PI or primary PCI). Categorical variables were reported as percentages, and differences between groups were tested by the χ2 test; Fisher’s exact test was applied when the cell count was less than five patients. Continuous variables were summarised as medians with 25th and 75th centiles, and differences between groups were tested via Wilcoxon rank-sum test. Multivariable logistic regression analysis was applied to identify the factors significantly associated with AbMI. Baseline patient characteristics in table 1 were first tested using univariable logistic regression and then variables with p ≤ 0.20 were included in the full multivariable model and then stepwise selection ( p≤0.20 as ‘in’ criteria and p≤0.05 as ‘out’ criteria) was used to identify the final model. Variables considered in the full model were age >75 years, Killip class, previous MI, previous PCI, previous coronary artery bypass graft surgery, baseline Q-wave, ∑ST-deviation on the baseline ECG and time from symptom onset to first medical contact. The association between AbMI and the primary clinical outcomes (ie, the composite of all-cause death, cardiogenic shock, congestive heart failure (CHF), recurrent MI and the individual components) within 30 days was examined using Poisson regression model with robust error variance. Relative risks (RR) with 95% CI were reported. Given the small number of events in the AbMI group, the Thrombolysis In Myocardial Infarction (TIMI) risk score12 was used as an aggregate measure of risk to account for imbalances in baseline patient characteristics. The interaction between AbMI and randomised study treatment was tested to examine whether the treatment assignment modulated the association between AbMI and 30-day clinical outcomes. The Kaplan–Meier estimates for 1-year all-cause mortality are reported, and the log-rank test was applied to test the difference according to AbMI. A sensitivity analysis was performed to examine the outcomes according to whether AbMI was observed pre-PCI or post-PCI in the primary PCI arm. All statistical tests were two-sided, with p
