Abstract
Background
Primary percutaneous coronary intervention (PCI) is the most common method of reperfusion in patients with ST‐segment elevation myocardial infarction (STEMI) in the United States. The intersection between processes of care and performance measures such as door‐to‐balloon (D2B) times and clinical trials evaluating novel therapies for STEMI has not been fully investigated.
Hypothesis
Processes of STEMI care, incorporating clinical trial enrollment and randomization, in patients undergoing reperfusion with primary PCI in the Counterpulsation Reduces Infarct Size Pre–Percutaneous Coronary Intervention Acute Myocardial Infarction trial (CRISP‐AMI) will conform to current standards of care.
Methods
Patients enrolled in CRISP‐AMI were included in the current analysis. Processes of care during reperfusion were recorded prospectively and compared between groups.
Results
A total of 337 patients with anterior STEMI without cardiogenic shock were randomized in CRISP‐AMI. Complete processes‐of‐care data were available for 303 patients (89.9%). In this cohort, 68.0% of patients underwent reperfusion within 90 minutes of hospital contact, and the median D2B time was 71 minutes. Time from hospital contact to informed consent was significantly different across different regions (North America, 45 minutes; India, 35 minutes; Europe, 20 minutes).
Conclusions
In CRISP‐AMI, reperfusion was accomplished in a timely fashion while incorporating informed consent and randomization among patients with anterior myocardial infarction. Further study of patients' comprehension and preferences during the informed‐consent process in STEMI patients is warranted so that innovative drugs and devices can be safely and ethically tested.
Introduction
Over the past 2 decades, primary percutaneous coronary intervention (PCI) has become the most common method of reperfusion in patients with ST‐segment elevation myocardial infarction (STEMI) in the United States.1 The introduction of performance measures in STEMI has altered the landscape of quality improvement and the delivery of cardiovascular care.2, 3, 4 Currently, the door‐to‐balloon (D2B) time has become the most widely accepted quality metric, and Medicare and other payers have used it to determine hospital reimbursement for STEMI care.5 Concurrently, the development and introduction of novel pharmacologic therapies and mechanical devices for the treatment of STEMI have necessitated the conduct of clinical trials in this critically ill patient population. This intersection of high‐quality, efficient clinical care and innovative clinical research has led some academic investigators to question whether patients with STEMI can adequately be consented, enrolled, and randomized in randomized controlled trials.6, 7
The aim of the current analysis is to evaluate the processes of STEMI care and the relationships of these processes with infarct size as measured by cardiac magnetic resonance imaging (cMRI) and outcomes in patients randomized to intra‐aortic balloon counterpulsation (IABC) or standard care in the multicenter, international Counterpulsation to Reduce Infarct Size pre‐PCI for Acute Myocardial Infarction (CRISP‐AMI) clinical trial.
Methods
The clinical trial design and methods for the CRISP‐AMI trial have been previously reported.8, 9, 10 In brief, CRISP‐AMI was a prospective, international, randomized controlled trial to determine whether a routine strategy of IABC insertion before primary PCI reduced infarct size in patients with acute anterior STEMI at 30 centers in the United States, Europe, India, and Australia. Patients were randomized to pre‐reperfusion initiation of IABC and PCI (IABC + PCI) or primary PCI alone. Institutional review boards and ethics committees approved the trial, and each enrolled patient provided written informed consent. The Duke Clinical Research Institute (Durham, NC) coordinated the trial and carried out data management, manuscript proposals, and statistical analyses with oversight from the trial steering committee.
Adult patients with ischemic chest pain (within 6 hours of symptom onset) and anterior STEMI with planned primary PCI were included in the study. The primary intent of the study was to determine whether IABC, when compared with standard care, reduces infarct size by cMRI. Exclusion criteria included cardiogenic shock, inability to undergo IABC implantation, fibrinolysis within 72 hours of presentation, or known contraindication to cMRI for endpoint assessment. Due to the cMRI infarct size endpoint, only patients with no known prior myocardial infarction (MI) or coronary artery bypass graft (CABG) surgery were included.
The processes of care included in the current analysis include total ischemic time (time from symptom onset to first device), symptom onset to first hospital contact, hospital contact to informed consent, hospital contact to randomization, hospital contact to vascular access, and hospital contact to first device.
The interventions and procedures used in the CRISP‐AMI trial have been previously reported.8, 9, 10 Sites with the proven ability to meet guideline standards were chosen (median door‐to‐device times <90 minutes). For participants randomized to receive IABC + PCI, balloon counterpulsation was recommended for ≥12 hours and for a maximum of 24 hours after PCI. For patients with hemodynamic instability, counterpulsation could be continued for longer periods at the discretion of the investigators. Cardiac MRI was recommended ≥3 to 5 days after PCI.
The cMRI protocol to determine infarct size has been described.8, 9, 10 A central cMRI laboratory at the University of Leipzig Heart Center (Leipzig, Germany) examined the quality of cMRI images from prospective sites, performed quality assessment on images during the conduct of the study, and manually performed blinded assessment for left ventricular myocardial mass, microvascular obstruction, area at risk, and infarct size.
Statistical Analysis
Baseline characteristics and procedural characteristics were described by randomized treatment group using medians (25th, 75th percentiles) for continuous variables; frequencies and proportions were used for categorical variables. The same statistics were applied to summarize important time intervals in the processes of care by randomized treatment. Time intervals were also summarized by randomized treatment using box‐and‐whisker plots that display the medians (25th, 75th percentiles) as well as the minimum and maximum values. Comparisons between the randomized treatment groups were performed using a 2‐sample t test for the continuous intervals and a χ2 test for the dichotomized (≤90 vs >90 minutes) D2B time interval. Four groups of interest were defined by the combination of randomized treatment (IABC + PCI vs PCI only) and dichotomized D2B time (≤90 vs >90 minutes). Infarct size on cMRI was summarized by group with the median (25th, 75th percentiles) and minimum and maximum. Occurrence of clinical outcomes was summarized by group by counting the number and cumulative percentage of patients with ≥1 events through 180 days postrandomization.
To investigate differences in the relationship of D2B time with infarct size between patients randomized to IABC + PCI or PCI only, 2 linear models of infarct size were applied. In the first model, we compared the 4 groups defined by dichotomized D2B time (≤90 vs >90 minutes) and randomized treatment. In the second model, we included D2B time as a continuous covariate and modeled infarct size as a function of randomized treatment, D2B time, and the interaction of those 2 factors.
Missing values were excluded from calculations. All statistical comparisons were performed using 2‐sided significance tests and were considered significant at P ≤ 0.05. No adjustment was made for inflation in false‐positive findings that might result from testing of multiple statistical hypotheses. All statistical analyses were performed using SAS version 9.2 (SAS Institute Inc., Cary, NC).
Results
A total of 337 patients with anterior STEMI without cardiogenic shock were enrolled and randomized in the CRISP‐AMI trial from June 2009 to February 2011. A total of 161 patients were randomized to the IABC + PCI group, and 176 patients were randomized to the PCI‐alone group. A flow diagram demonstrates the number of patients that were assigned to each group, were lost to follow‐up, and withdrew consent (Figure 1). Complete processes‐of‐care data were available for 303 patients (89.9% of the total population).
Figure 1.
Flow diagram of patients enrolled in the CRISP‐AMI study. Abbreviations: CRISP‐AMI, Counterpulsation to Reduce Infarct Size pre‐PCI for Acute Myocardial Infarction; PCI, percutaneous coronary intervention.
The 2 study groups were well balanced in terms of baseline characteristics (Table 1). Patients randomized to IABC + PCI were slightly younger, were less likely to have a history of hypertension or diabetes mellitus, had a lower systolic blood pressure on presentation, and were more likely to have >6 mm of ST‐segment elevation on initial electrocardiogram when compared with patients randomized to primary PCI alone.
Table 1.
Baseline Characteristics of Patients Enrolled in the CRISP‐AMI Study
| Total, N = 337 | IABC + PCI, n = 161 | PCI Alone, n = 176 | |
|---|---|---|---|
| Age, y, median (25th, 75th percentiles) | 56.6 (48.4, 65.6) | 56.1 (48.3, 64.3) | 57.7 (48.6, 66.4) |
| Male sex, n (%) | 276 (81.9) | 132 (82.0) | 144 (81.8) |
| Race, n (%) | |||
| Asian | 152 (45.1) | 75 (46.6) | 77 (43.8) |
| Black | 16 (4.7) | 3 (1.9) | 13 (7.4) |
| White | 161 (47.8) | 81 (50.3) | 80 (45.5) |
| Medical history, n (%) | |||
| Prior PCI | 5 (1.5) | 3 (1.9) | 2 (1.1) |
| Hypertension (receiving drug therapy) | 99 (29.4) | 39 (24.2) | 60 (34.1) |
| Stroke | 1 (0.3) | 0 (0.0) | 1 (0.6) |
| TIA | 1 (0.3) | 0 (0.0) | 1 (0.6) |
| Current nicotine use | 107 (31.8) | 53 (33.1) | 54 (30.7) |
| Dyslipidemia (receiving drug therapy) | 42 (12.5) | 20 (12.5) | 22 (12.5) |
| Prior AF | 4 (1.2) | 3 (1.9) | 1 (0.6) |
| Renal insufficiency | 6 (1.8) | 2 (1.2) | 4 (2.3) |
| DM | 63 (18.7) | 27 (16.8) | 36 (20.5) |
| Insulin‐dependent | 7 (11.1) | 5 (18.5) | 2 (5.6) |
| Non–insulin‐dependent | 56 (88.9) | 22 (81.5) | 34 (94.4) |
| Prior PAD | 1 (0.3) | 0 (0.0) | 1 (0.6) |
| Presenting SBP, mm Hg, median (25th, 75th percentiles) | 131.0 (118.0, 150.0) | 130.0 (113.0, 150.0) | 135.0 (120.0, 151.0) |
| Presenting DBP, mm Hg, median (25th, 75th percentiles) | 80.0 (70.0, 92.0) | 80.0 (70.0, 92.0) | 80.0 (71.5, 92.0) |
| Heart rate, bpm, median (25th, 75th percentiles) | 81.0 (71.0, 94.0) | 81.0 (71.0, 93.0) | 80.0 (70.0, 94.0) |
| Degree of ST elevation in anterior leads, mm, n (%) | |||
| 0– < 2 | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| 2– < 4 | 1 (0.3) | 0 (0.0) | 1 (0.6) |
| 4– < 6 | 135 (40.1) | 61 (37.9) | 74 (42.0) |
| ≥6 | 201 (59.6) | 100 (62.1) | 101 (57.4) |
Abbreviations: AF, atrial fibrillation; CRISP‐AMI, Counterpulsation to Reduce Infarct Size pre‐PCI for Acute Myocardial Infarction; DBP, diastolic blood pressure; DM, diabetes mellitus; IABC, intra‐aortic balloon counterpulsation; PAD, peripheral arterial disease; PCI, percutaneous coronary intervention; SBP, systolic blood pressure; TIA, transient ischemic attack.
The angiographic and procedural characteristics were also similar between the 2 study groups (Table 2). The left anterior descending artery was the infarct‐related artery in 99.4% of IABC + PCI patients and 96.0% of primary PCI‐alone patients, and the infarct‐related artery stenosis location was designated as proximal in 64.8% and 61.2% of patients, respectively. Similar proportions of patients in each group were treated with atherectomy/thrombectomy as a first device for reperfusion, and similar proportions of patients underwent drug‐eluting stent placement. Pre‐intervention and postintervention TIMI (Thrombolysis In Myocardial Infarction) flows were similar between study groups, and TIMI‐3 flow was restored in 94.2% of all patients in the study.
Table 2.
Procedural Characteristics of Patients Enrolled in the CRISP‐AMI Study
| Total, N = 337 | IABC + PCI, n = 161 | PCI Alone, n = 176 | |
|---|---|---|---|
| IABC placement, n (%) | 168 (50.0) | 153 (95.6) | 15 (8.5) |
| Infarct‐related artery, n (%) | |||
| LAD | 328 (97.6) | 159 (99.4) | 169 (96.0) |
| RCA | 1 (0.3) | 0 (0.0) | 1 (0.6) |
| No infarct‐related artery identified | 7 (2.1) | 1 (0.6) | 6 (3.4) |
| Infarct‐related artery stenosis location, n (%) | |||
| Proximal | 207 (62.9) | 103 (64.8) | 104 (61.2) |
| Mid | 132 (40.1) | 56 (35.2) | 76 (44.7) |
| Distal | 19 (5.8) | 11 (6.9) | 8 (4.7) |
| PCI, n (%) | |||
| Performed | 317 (94.3) | 154 (96.3) | 163 (92.6) |
| Not performed | 19 (5.7) | 6 (3.8) | 13 (7.4) |
| CABG instead | 6 (1.8) | 2 (1.3) | 4 (2.3) |
| No infarct artery identified | 7 (2.1) | 1 (0.6) | 6 (3.4) |
| Technical limitations | 6 (1.8) | 3 (1.9) | 3 (1.7) |
| Infarct‐related artery TIMI flow, n (%) | |||
| Preintervention grade | |||
| 0 | 215 (65.3) | 105 (66.0) | 110 (64.7) |
| 1 | 34 (10.3) | 18 (11.3) | 16 (9.4) |
| 2 | 50 (15.2) | 26 (16.4) | 24 (14.1) |
| 3 | 30 (9.1) | 10 (6.3) | 20 (11.8) |
| Postintervention grade | |||
| 0 | 5 (1.5) | 1 (0.6) | 4 (2.4) |
| 1 | 6 (1.8) | 5 (3.2) | 1 (0.6) |
| 2 | 8 (2.5) | 5 (3.2) | 3 (1.8) |
| 3 | 306 (94.2) | 145 (92.9) | 161 (95.3) |
| First device used on infarct‐related artery, n (%) | |||
| Atherectomy/thrombectomy | 115 (36.2) | 54 (34.8) | 61 (37.4) |
| Balloon | 152 (47.8) | 78 (50.3) | 74 (45.4) |
| Stent | 51 (16.0) | 23 (14.8) | 28 (17.2) |
| Type of stent, n (%) | 309 (96.9) | 147 (94.2) | 162 (99.4) |
| DES | 149 (48.2) | 69 (46.9) | 80 (49.4) |
| BMS | 165 (53.4) | 79 (53.7) | 86 (53.1) |
| Anticoagulant use, n (%) | |||
| Unfractionated heparin | 261 (77.7) | 127 (79.4) | 134 (76.1) |
| Bivalirudin | 57 (17.0) | 24 (15.0) | 33 (18.8) |
| GP IIb/IIIa inhibitor | 154 (45.8) | 79 (49.4) | 75 (42.6) |
Abbreviations: BMS, bare‐metal stent; CABG, coronary artery bypass graft; DES, drug‐eluting stent; GP, glycoprotein; IABC, intra‐aortic balloon counterpulsation; LAD, left anterior descending artery; PCI, percutaneous coronary intervention; RCA, right coronary artery; TIMI, Thrombolysis In Myocardial Infarction.
When examining the processes‐of‐care measures between groups (Figure 2 and Table 3), the total ischemic time (symptom onset to reperfusion), time from symptom onset to first hospital contact, time from hospital contact to informed consent, and time from hospital contact to randomization were similar between the IABC + PCI group and the primary PCI‐alone group. The median time from hospital contact to vascular access was longer in the IABC + PCI group compared with the primary PCI‐alone group (60 vs 53 minutes, P = 0.052), as the IABC group had 2 vascular access sites. The median time from hospital contact to first device (D2B time) was also longer in the IABC + PCI group compared with the primary PCI‐alone group (77 vs 68 minutes, P = 0.031). When considering both treatment groups, 68.0% of patients underwent reperfusion within 90 minutes of hospital contact.
Figure 2.
Processes‐of‐care measurements in patients enrolled in the CRISP‐AMI study. The 25th and 75th percentiles within each group are represented by the top and bottom of each box. The median is indicated by the horizontal line within each box. The minimum and maximum values are indicated by the horizontal lines outside each box. Abbreviations: CRISP‐AMI, Counterpulsation to Reduce Infarct Size pre‐PCI for Acute Myocardial Infarction; IABC, intra‐aortic balloon counterpulsation; IRA, infarct‐related artery.
Table 3.
Processes‐of‐Care Measurements in Patients Enrolled in the CRISP‐AMI Study
| Total, N = 337 | IABC + PCI, n = 161 | PCI Alone, n = 176 | P Value | |
|---|---|---|---|---|
| Process‐of‐care intervals in min, median (25th, 75th percentiles) | ||||
| Symptom onset to first hospital contact | 112 (62, 173) | 109 (65, 170) | 114 (61, 174) | 0.8084 |
| Hospital contact to informed consent | 35 (15, 64) | 34 (16, 65) | 35 (15, 62) | 0.5359 |
| Hospital contact to randomization | 46 (25, 74) | 49 (26, 72) | 44 (21, 74) | 0.2593 |
| Hospital contact to vascular access | 57 (34, 84) | 60 (37, 93) | 53 (32, 78) | 0.0524 |
| Hospital to first device (IRA) | 71 (47, 105) | 77 (53, 114) | 68 (40, 100) | 0.0314 |
| Hospital to device (dichotomous), n/N (%) | 0.5774 | |||
| ≤ 90 min | 206/303 (68.0) | 97/146 (66.4) | 109/157 (69.4) | |
| > 90 min | 97/303 (32.0) | 49/146 (33.6) | 48/157 (30.6) | |
| Symptom onset to device (total ischemic time) | 196 (140, 272) | 203 (145, 272) | 193 (136, 275) | 0.5665 |
Abbreviations: IABC, intra‐aortic balloon counterpulsation; IRA, infarct‐related artery; PCI, percutaneous coronary intervention.
Processes of care did vary across regions, as sites in Europe had significantly faster times from hospital contact to informed consent, randomization, and reperfusion compared with sites in North America (see Supporting Table 1 in the online version of this article).
The cMRI measures and clinical outcomes are associated with D2B times ≤90 and >90 minutes by treatment group (see Supporting Table 2 in the online version of this article). Clinical event rates were extremely low in all groups at 6 months. Overall, there was a significant difference in infarct size on cMRI among the 4 groups defined by treatment (IABC + PCI vs PCI alone) and dichotomized D2B time (≤90 or >90 minutes, P = 0.02). Median infarct size on cMRI was markedly larger in patients in the IABC + PCI group compared with other groups when the time from first hospital contact to device was >90 minutes. When infarct size was analyzed with D2B time as a continuous variable, results were similar, and with every 10‐minute delay there was an estimated 0.76% (95% confidence interval [CI]: 0.19%‐1.33%) increase in infarct size in IABC + PCI patients and a 0.10% (95% CI: −0.73%‐0.53%) decrease in infarct size in PCI‐alone patients (see Supporting Figure in the online version of this article). The difference between these 2 estimates of slope was significant (P = 0.047).
Discussion
There is significant interest in the cardiology community to develop innovative therapies for patients presenting with STEMI. The ability of clinicians to randomize STEMI patients into clinical trials of novel therapies while maintaining reperfusion times within the clinical guidelines has not been extensively studied. In this analysis of CRISP‐AMI, we examined the processes of care of STEMI patients who were randomized to IABC + PCI and primary PCI alone. The principal finding of the current study is that reperfusion can occur in a timely fashion while incorporating efforts to obtain informed consent, randomly assign patients to treatment groups, and perform the randomized intervention. Processes of enrollment and randomization (eg, informed consent, randomization) did vary regionally, as more expedient randomization and reperfusion occurred in Europe when compared with North America and India.
Over the past decade, D2B time has emerged as the primary measure to judge quality and determine reimbursement for STEMI patients undergoing reperfusion.3, 5 Partially due to the success of initiatives such as D2B Alliance and Mission: Lifeline, operators and hospitals have been highly focused and quite successful in achieving D2B times within 90 minutes of medical contact, as recommended by the current clinical guidelines.11, 12, 13 There is little argument that delays occur when patients are enrolled and randomized into clinical studies (due to the time required to consent, randomize, and perform the study treatment); however, few data exist to measure either the impact of this delay on infarct size, quality metrics, or patient outcomes. Recently, the Centers for Medicare & Medicaid Services (CMS) introduced reasons for exclusion from CMS reporting to ensure that performance can be accurately compared across institutions. One of these exclusions from CMS reporting is patient recruitment and involvement in a clinical trial. Whether this exclusion is necessary and whether clinicians avoid participating in clinical studies in STEMI remain topics of debate.
Many studies have randomly assigned STEMI patients to investigational treatments; however, few data exist on the processes of enrollment and randomization at the critical time point of hospital entry, catheterization laboratory entry, and primary reperfusion. One observational, single‐center study reported that reperfusion times, including D2B times in patients presenting and transferred to their own center, were not significantly different between patients enrolled vs patients not enrolled in clinical studies.7 The largest randomized trial in STEMI patients in the current era (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction [HORIZONS‐AMI]) reported a median D2B time of 99 minutes (interquartile range [IQR], 73–135 minutes), a finding that does not meet the current standards.14 In 2009, the median D2B time reported in the US National Cardiovascular Data Registry (NCDR) CathPCI Registry was 67 minutes.15 Results from this substudy of CRISP‐AMI show that median D2B time was 71 minutes (IQR, 47–105 minutes). Although multiple factors can contribute to the differences among these median D2B times, the D2B time observed in CRISP‐AMI confirms that patients can be enrolled in clinical studies without compromising quality metrics and ischemic times.
Though not the primary intent of this analysis, there was significant regional variation observed in the time required to obtain informed consent, randomize, and perform the randomized treatment. In patients treated in Europe, the times from hospital contact to informed consent, randomization, and reperfusion were approximately half of those observed in other regions. Interestingly, the total ischemic time was fairly balanced across regions, but differences in processes of care did suggest room for improvement in North America and India. Due to low clinical‐event rates, the ability to detect a significant difference in clinical outcomes as a result of these faster processes of care was limited.
There are really 2 aspects of clinical trials in STEMI patients that warrant further investigation: processes of care and the actual informed‐consent process. The recently reported study How Effective Are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention (HEAT‐PPCI) reported very fast D2B times and utilized a delayed informed‐consent process that may have allowed more expeditious randomization and reperfusion; however, the current US regulatory groups (eg, institutional review boards, US Food and Drug Administration) are unlikely to allow delayed informed consent at this time.16 Additionally, given the recent institution of quality metrics (ie, D2B time) and the development of regional and local STEMI networks designed to improve reperfusion times, our ability to understand the impact of participation in clinical trials during STEMI is somewhat limited when using data from clinical trials such as CRISP‐AMI, because published clinical trials span multiple years and have different D2B time goals. Because the NCDR CathPCI Registry does capture these process measures and whether patients participate in a clinical trial for STEMI, it would seem that using NCDR data could shed light on this issue on a national level. Furthermore, the association between delays in reperfusion and clinical outcomes such as all‐cause mortality would be a valuable addition to the current literature.
The current analysis does not address issues around patients' perceptions or understanding of the informed‐consent process. Prior randomized studies have examined these factors and concluded that patients do not have sufficient time or knowledge to provide informed consent for inclusion into clinical studies during the acute phase of STEMI care.17, 18, 19 Further study of patients' actual understanding of the randomized‐treatment and informed consent‐process is absolutely needed, especially as physicians, patients, and patient advocates continue to focus on patient‐centered outcomes such as patient perception, recall, and comprehension.
Study Limitations
There are multiple limitations of the current analysis. First, the small sample size limits any concrete conclusions from being drawn. Second, this retrospective analysis of prospectively collected data in the CRISP‐AMI study was not a prespecified analysis and, thus, was not powered to demonstrate differences between groups. Third, we were unable to directly measure the amount of time that it took to screen, enroll, and randomize patients, and we recognize that other aspects of clinical care took place during these time intervals. Fourth, the CRISP‐AMI study was international, and the impetus to drive D2B times <90 minutes in non‐US countries may have affected the D2B times observed in the study. Finally, the CRISP‐AMI study only enrolled patients with acute anterior STEMI; therefore, the generalizability to all patients with STEMI is questionable.
Conclusion
Patients in the CRISP‐AMI study were enrolled, randomized, and treated in an efficient manner that, in general, meets the current guideline recommendations for D2B times of <90 minutes, suggesting that clinical investigation with informed consent is possible in STEMI patients. Further investigation of the processes of care and informed‐consent process in STEMI patients is warranted to ensure patient understanding, evaluate novel therapies to improve reperfusion, and ensure they do not compromise performance measures that are designed to lead to improved patient outcomes.
Supporting information
Scatterplot of the association of time from first hospital contact to device and infarct size determined by cMRI by treatment group. Abbreviations: cMRI, cardiac magnetic resonance imaging; IABC, intra‐aortic balloon counterpulsation.
Processes‐of‐Care Measurements Based on Region of Enrollment in CRISP‐AMI Study
Clinical Outcomes at 180 Days by Elapsed Time Between Presentation and Device Placement (≤90 vs. >90 minutes) Among Patients Randomized to IABC + PCI vs. PCI Alone
Acknowledgments
The authors acknowledge Morgan deBlecourt (who is a salaried employee of the Duke Clinical Research Institute) for her editorial support with the preparation of the manuscript. She did not receive compensation for her contributions apart from those received in exchange for her regular duties as a medical editor.
The authors disclose the following: W. Schuyler Jones has received research grants from AstraZeneca, Boston Scientific Corporation, Bristol‐Myers Squibb, and the American Heart Association, and has served as a consultant/received honoraria from the American College of Physicians and American Physician Institute. Divaka Perera has received research funding and speaker's fees from Maquet (<$10 000 in past 3 years). Nico Pijls has received an institutional research grant, speaker's fee and travel reimbursement from Maquet. Disclosures for E. Magnus Ohman are available at https://dcri.org/about‐us/conflict‐of‐interest. Manesh R. Patel has received research grants from Johnson & Johnson, Pluristem, and AstraZeneca, and has served as a consultant for Baxter, Genzyme, Bayer, and Ortho‐McNeil‐Janssen.
Funding for the CRISP‐AMI trial was provided by Maquet (formerly Datascope). The sponsor had no role in the design and conduct of the study; in the collection, analysis, and interpretation of the data; or in the preparation, review, or approval of the manuscript. All statistical analyses were independently performed at the Duke Clinical Research Institute.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
References
- 1. O'Gara PT, Kushner FG, Ascheim DD, et al; CF/AHA Task Force. 2013 ACCF/AHA guideline for the management of ST‐elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2013;127:529–555. [DOI] [PubMed] [Google Scholar]
- 2. Pinto DS, Kirtane AJ, Nallamothu BK, et al. Hospital delays in reperfusion for ST‐elevation myocardial infarction: implications when selecting a reperfusion strategy. Circulation. 2006;114:2019–2025. [DOI] [PubMed] [Google Scholar]
- 3. Bradley EH, Roumanis SA, Radford MJ, et al. Achieving door‐to‐balloon times that meet quality guidelines: how do successful hospitals do it? J Am Coll Cardiol. 2005;46:1236–1241. [DOI] [PubMed] [Google Scholar]
- 4. Krumholz HM, Anderson JL, Brooks NH, et al; American College of Cardiology/American Heart Association Task Force on Performance Measures; Writing Committee to Develop Performance Measures on ST‐Elevation and Non‐ST‐Elevation Myocardial Infarction. ACC/AHA clinical performance measures for adults with ST‐elevation and non–ST‐elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures (Writing Committee to Develop Performance Measures on ST‐Elevation and Non–ST‐Elevation Myocardial Infarction). Circulation. 2006;113:732–761. [DOI] [PubMed] [Google Scholar]
- 5. Krumholz HM, Herrin J, Miller LE, et al. Improvements in door‐to‐balloon time in the United States, 2005 to 2010. Circulation. 2011;124:1038–1045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Mandawat A, Shah SJ, Rathore SS. ST‐elevation myocardial infarction patients can be enrolled in randomized trials before emergent coronary intervention without sacrificing door‐to‐balloon time. Am Heart J. 2010;159:e1. [DOI] [PubMed] [Google Scholar]
- 7. Blankenship JC, Skelding KA, Scott TD, et al. ST‐elevation myocardial infarction patients can be enrolled in randomized trials before emergent coronary intervention without sacrificing door‐to‐balloon time. Am Heart J. 2009;158:400–407. [DOI] [PubMed] [Google Scholar]
- 8. Patel MR, Smalling RW, Thiele H, et al. Intra‐aortic balloon counterpulsation and infarct size in patients with acute anterior myocardial infarction without shock: the CRISP AMI randomized trial. JAMA. 2011;306:1329–1337. [DOI] [PubMed] [Google Scholar]
- 9. Patel MR, Thiele H, Smalling RW, et al. A multicenter, randomized, controlled study of mechanical left ventricular unloading with counterpulsation to reduce infarct size pre–percutaneous coronary intervention for acute myocardial infarction: rationale and design of the Counterpulsation Reduces Infarct Size Acute Myocardial Infarction trial. Am Heart J. 2011;162:47.e1–55.e1. [DOI] [PubMed] [Google Scholar]
- 10. Vemulapalli S, Zhou Y, Gutberlet M, et al. Importance of total ischemic time and preprocedural infarct‐related artery blood flow in predicting infarct size in patients with anterior wall myocardial infarction (from the CRISP‐AMI Trial). Am J Cardiol. 2013;112:911–917. [DOI] [PubMed] [Google Scholar]
- 11. Krumholz HM, Bradley EH, Nallamothu BK, et al. A campaign to improve the timeliness of primary percutaneous coronary intervention: Door‐to‐Balloon: An Alliance for Quality. JACC Cardiovasc Interv. 2008;1:97–104. [DOI] [PubMed] [Google Scholar]
- 12. Jollis JG, Granger CB, Henry TD, et al. Systems of care for ST‐segment‐elevation myocardial infarction: a report from the American Heart Association's Mission: Lifeline. Circ Cardiovasc Qual Outcomes. 2012;5:423–428. [DOI] [PubMed] [Google Scholar]
- 13. Bradley EH, Nallamothu BK, Herrin J, et al. National efforts to improve door‐to‐balloon time: results from the Door‐to‐Balloon Alliance. J Am Coll Cardiol. 2009;54:2423–2429. [DOI] [PubMed] [Google Scholar]
- 14. Blankenship JC, Skelding KA, Scott TD, et al. Predictors of reperfusion delay in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention from the HORIZONS‐AMI trial. Am J Cardiol. 2010;106:1527–1533. [DOI] [PubMed] [Google Scholar]
- 15. Menees DS, Peterson ED, Wang Y, et al. Door‐to‐balloon time and mortality among patients undergoing primary PCI. N Engl J Med. 2013;369:901–909. [DOI] [PubMed] [Google Scholar]
- 16. Shahzad A, Kemp I, Mars C, et al. Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT‐PPCI): an open‐label, single centre, randomised controlled trial. Lancet. 2014; doi: 10.1016/S0140-6736(14)60924-7. [DOI] [PubMed] [Google Scholar]
- 17. Agård A, Hermerén G, Herlitz J. Patients' experiences of intervention trials on the treatment of myocardial infarction: is it time to adjust the informed consent procedure to the patient's capacity? Heart. 2001;86:632–637. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Gammelgaard A, Mortensen OS, Rossel P; DANAMI‐2 Investigators. Patients' perceptions of informed consent in acute myocardial infarction research: a questionnaire based survey of the consent process in the DANAMI‐2 trial. Heart. 2004;90:1124–1128. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Williams BF, French JK, White HD; HERO‐2 consent substudy investigators. Informed consent during the clinical emergency of acute myocardial infarction (HERO‐2 consent substudy): a prospective observational study. Lancet. 2003;361:918–922. [DOI] [PubMed] [Google Scholar]
Associated Data
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Supplementary Materials
Scatterplot of the association of time from first hospital contact to device and infarct size determined by cMRI by treatment group. Abbreviations: cMRI, cardiac magnetic resonance imaging; IABC, intra‐aortic balloon counterpulsation.
Processes‐of‐Care Measurements Based on Region of Enrollment in CRISP‐AMI Study
Clinical Outcomes at 180 Days by Elapsed Time Between Presentation and Device Placement (≤90 vs. >90 minutes) Among Patients Randomized to IABC + PCI vs. PCI Alone