Letters RESEARCH LETTER
Clinical Trial Participation After Myocardial Infarction in a National Cardiovascular Data Registry Randomized clinical trials of patients with acute myocardial infarction (MI) enroll selected populations, with low enrollment in the United States, raising questions whether findings are generalizable.1,2 We evaluated whether participants in cardiovascular trials are representative of contemporary patients with MI.
Methods | The National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines is an ongoing, voluntary, quality improvement registry of consecutive patients with MI treated at participating centers across the United States. Registry design, inclusion and exclusion criteria, and data definitions have been described.3 Institutional review boards at participating hospitals approved the registry, and informed consent was waived. Trained abstractors determined registry data, including trial partici-
Table 1. Characteristics of Trial Participants, Eligible Nonparticipants, and Ineligible Nonparticipants Nonparticipantsa Trial Participants (n = 4008)a
Eligible (n = 93 274)
Ineligible (n = 43 853)
Clinical presentation STEMI
1586 (39.6)
31 888 (34.2)
16 204 (37.0)
NSTEMI
2422 (60.4)
61 386 (65.8)
27 649 (63.0)
Age, median (IQR), y
60 (52-69)
Female sex
63 (53-74)
67 (57-78)
1258 (31.4)
30 364 (32.6)
16 937 (38.6)
White
3322 (82.9)
78 094 (83.7)
35 414 (80.8)
Black
472 (11.8)
8601 (9.2)
Asian
36 (0.9)
1409 (1.5)
669 (1.5)
126 (3.1)
3940 (4.2)
1845 (4.2)
25 (0.6)
535 (0.6)
302 (0.7)
Race/ethnicityb
Hispanic Other or unknown
5304 (12.1)
History Myocardial infarction
857 (21.4)
23 392 (25.1)
12 092 (27.6)
1148 (28.6)
29 129 (31.2)
14 707 (33.5)
Stroke
215 (5.4)
6271 (6.7)
4598 (10.5)
Congestive heart failure
306 (7.6)
9770 (10.5)
8269 (18.9)
Coronary revascularization (PCI or CABG surgery)
Inhospital mortality risk score, median (IQR)
28 (22-34)
30 (25-36)
Abbreviations: CABG, coronary artery bypass graft; IQR, interquartile range; NSTEMI, non–ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction. a
Data are presented as number (percentage) unless otherwise indicated. All comparisons were significant with P < .001. Patients with missing data for classification of the exposure of interest (ie, trial participation; n = 472), or who had incomplete or missing data for determining trial eligibility (n = 48 869) were excluded. There were no clinically relevant differences between patients included in the study and excluded due to missing data.
b
Self-reported.
c
Indicates treatment within the first 24 hours of hospitalization among patients without a documented contraindication to treatment or receiving blinded study drug.
d
Includes patients who were transferred prior to discharge, did not survive, or were managed with comfort measures only. Patients discharged to hospice or against medical advice were excluded.
31 (22-42)
Region West
209 (5.2)
11 329 (12.2)
Northeast
344 (8.6)
8127 (8.7)
3814 (8.7)
Midwest
695 (17.3)
29 685 (31.8)
13 759 (31.4)
2760 (68.9)
44 133 (47.3)
21 052 (48.0)
1191 (29.7)
24 168 (25.9)
11 839 (27.0)
Aspirin
3841 (97.4)
89 671 (98.0)
40 106 (95.9)
Clopidogrel
2798 (73.5)
59 683 (66.5)
24 679 (60.4)
Diagnostic angiography
3852 (96.1)
82 011 (87.9)
34 257 (78.1)
South Teaching hospital
5228 (11.9)
In-hospital carec
Primary PCI (STEMI patients only)
1281 (86.3)
29 407 (93.6)
10 351 (65.7)
PCI within first 24 h (among NSTEMI patients only)
1015 (41.9)
18 886 (30.8)
5332 (19.3)
Ventricular function evaluated
3833 (95.6)
86 863 (93.1)
39 741 (90.6)
Length of stay, median (IQR), d
3 (2-4)
3 (2-5)
4 (3-7)
Discharge care (if eligible)d Exercise counseling
3261 (92.9)
72 362 (87.8)
Cardiac rehabilitation referral
2850 (85.4)
60 035 (78.0)
30 327 (87.4) 23 786 (75.4)
Discharged home
3583 (90.7)
79 499 (87.3)
32 352 (80.1)
jama.com
JAMA August 27, 2014 Volume 312, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Nanyang Technological University User on 05/20/2015
841
Letters
Table 2. Risk of Inhospital Cardiovascular Events Among Trial Participants, Eligible Nonparticipants, and Ineligible Nonparticipants Nonparticipants
Trial Participants (n = 3789)
Deathc
Eligible (n = 89 305)
No. (%)a
No. (%)a
Adjusted OR (95% CI)b
58 (1.5)
1 [Reference]
2213 (2.5)
1.63 (1.11-2.41)d
.01
d
Adjusted OR (95% CI)b
P Valueb
3473 (8.4)
1.91 (1.29-2.83)d
.001
No. (%)a
Death or myocardial infarction
90 (2.4)
1 [Reference]
2887 (3.2)
1.41 (1.05-1.89)
.02
3798 (9.1)
1.60 (1.19-2.16)d
.002
Cardiogenic shock
87 (2.3)
1 [Reference]
3070 (3.4)
1.52 (1.15-2.01)d
.003
2547 (6.1)
1.41 (1.06-1.87)d
.02
Congestive heart failure
168 (4.4)
1 [Reference]
4780 (5.4)
1.02 (0.86-1.21)d
.83
3693 (8.9)
1.05 (0.89-1.26)d
.55
Major bleedinge
244 (6.4)
1 [Reference]
5844 (6.5)
1.12 (0.95-1.31)f
.17
4840 (11.6)
1.19 (1.01-1.39)f
.04
Abbreviation: OR, odds ratio. a
Among patients who were not transferred prior to discharge.
b
Represents the risk associated with each group of patients compared with trial participants (reference).
c
The mortality model C statistic was 0.855 (95% CI, 0.850-0.860).
d
Adjusted for demographic variables (age, sex, ethnicity/race, and weight), signs and symptoms at presentation (heart failure, heart rate, systolic blood pressure, electrocardiographic findings), medical history (hypertension, diabetes mellitus, current or recent tobacco use, hypercholesterolemia, and prior myocardial infarction, coronary revascularization, heart failure, stroke, and peripheral artery disease), laboratory results (baseline hemoglobin, serum creatinine, and troponin ratio to the upper limit of the local assay normal reference), medical insurance type, and within-center correlation and clustering of variable responses using an exchangeable correlation structure covariance matrix.
pation, in 190 476 patients with MI at 609 registry centers between July 1, 2008, and March 31, 2011. Patients with missing or incomplete data for classification of trial participation (n = 472) or eligibility (n = 48 869) were excluded. There were no clinically relevant differences between patients included and excluded. Trial participation was defined as patients who provided informed consent and enrolled in a trial during hospitalization, even if the investigational medication, device, or procedure was never initiated. Among nonparticipants, we determined whether trial exclusion criteria were met for 3 antiplatelet therapy trials in patients with MI during the study period,4-6 including age younger than 18 years, uncontrolled hypertension (systolic blood pressure >180 mm Hg), stage 5 kidney disease or dialysis-dependent renal failure, cardiogenic shock, major bleeding within 24 hours of presentation, impaired hemostasis (international normalized ratio [INR] >1.5), severe anemia (hemoglobin
Clinical Trial Participation After Myocardial Infarction in a National Cardiovascular Data Registry Randomized clinical trials of patients with acute myocardial infarction (MI) enroll selected populations, with low enrollment in the United States, raising questions whether findings are generalizable.1,2 We evaluated whether participants in cardiovascular trials are representative of contemporary patients with MI.
Methods | The National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcomes Network Registry–Get With The Guidelines is an ongoing, voluntary, quality improvement registry of consecutive patients with MI treated at participating centers across the United States. Registry design, inclusion and exclusion criteria, and data definitions have been described.3 Institutional review boards at participating hospitals approved the registry, and informed consent was waived. Trained abstractors determined registry data, including trial partici-
Table 1. Characteristics of Trial Participants, Eligible Nonparticipants, and Ineligible Nonparticipants Nonparticipantsa Trial Participants (n = 4008)a
Eligible (n = 93 274)
Ineligible (n = 43 853)
Clinical presentation STEMI
1586 (39.6)
31 888 (34.2)
16 204 (37.0)
NSTEMI
2422 (60.4)
61 386 (65.8)
27 649 (63.0)
Age, median (IQR), y
60 (52-69)
Female sex
63 (53-74)
67 (57-78)
1258 (31.4)
30 364 (32.6)
16 937 (38.6)
White
3322 (82.9)
78 094 (83.7)
35 414 (80.8)
Black
472 (11.8)
8601 (9.2)
Asian
36 (0.9)
1409 (1.5)
669 (1.5)
126 (3.1)
3940 (4.2)
1845 (4.2)
25 (0.6)
535 (0.6)
302 (0.7)
Race/ethnicityb
Hispanic Other or unknown
5304 (12.1)
History Myocardial infarction
857 (21.4)
23 392 (25.1)
12 092 (27.6)
1148 (28.6)
29 129 (31.2)
14 707 (33.5)
Stroke
215 (5.4)
6271 (6.7)
4598 (10.5)
Congestive heart failure
306 (7.6)
9770 (10.5)
8269 (18.9)
Coronary revascularization (PCI or CABG surgery)
Inhospital mortality risk score, median (IQR)
28 (22-34)
30 (25-36)
Abbreviations: CABG, coronary artery bypass graft; IQR, interquartile range; NSTEMI, non–ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction. a
Data are presented as number (percentage) unless otherwise indicated. All comparisons were significant with P < .001. Patients with missing data for classification of the exposure of interest (ie, trial participation; n = 472), or who had incomplete or missing data for determining trial eligibility (n = 48 869) were excluded. There were no clinically relevant differences between patients included in the study and excluded due to missing data.
b
Self-reported.
c
Indicates treatment within the first 24 hours of hospitalization among patients without a documented contraindication to treatment or receiving blinded study drug.
d
Includes patients who were transferred prior to discharge, did not survive, or were managed with comfort measures only. Patients discharged to hospice or against medical advice were excluded.
31 (22-42)
Region West
209 (5.2)
11 329 (12.2)
Northeast
344 (8.6)
8127 (8.7)
3814 (8.7)
Midwest
695 (17.3)
29 685 (31.8)
13 759 (31.4)
2760 (68.9)
44 133 (47.3)
21 052 (48.0)
1191 (29.7)
24 168 (25.9)
11 839 (27.0)
Aspirin
3841 (97.4)
89 671 (98.0)
40 106 (95.9)
Clopidogrel
2798 (73.5)
59 683 (66.5)
24 679 (60.4)
Diagnostic angiography
3852 (96.1)
82 011 (87.9)
34 257 (78.1)
South Teaching hospital
5228 (11.9)
In-hospital carec
Primary PCI (STEMI patients only)
1281 (86.3)
29 407 (93.6)
10 351 (65.7)
PCI within first 24 h (among NSTEMI patients only)
1015 (41.9)
18 886 (30.8)
5332 (19.3)
Ventricular function evaluated
3833 (95.6)
86 863 (93.1)
39 741 (90.6)
Length of stay, median (IQR), d
3 (2-4)
3 (2-5)
4 (3-7)
Discharge care (if eligible)d Exercise counseling
3261 (92.9)
72 362 (87.8)
Cardiac rehabilitation referral
2850 (85.4)
60 035 (78.0)
30 327 (87.4) 23 786 (75.4)
Discharged home
3583 (90.7)
79 499 (87.3)
32 352 (80.1)
jama.com
JAMA August 27, 2014 Volume 312, Number 8
Copyright 2014 American Medical Association. All rights reserved.
Downloaded From: http://jama.jamanetwork.com/ by a Nanyang Technological University User on 05/20/2015
841
Letters
Table 2. Risk of Inhospital Cardiovascular Events Among Trial Participants, Eligible Nonparticipants, and Ineligible Nonparticipants Nonparticipants
Trial Participants (n = 3789)
Deathc
Eligible (n = 89 305)
No. (%)a
No. (%)a
Adjusted OR (95% CI)b
58 (1.5)
1 [Reference]
2213 (2.5)
1.63 (1.11-2.41)d
.01
d
Adjusted OR (95% CI)b
P Valueb
3473 (8.4)
1.91 (1.29-2.83)d
.001
No. (%)a
Death or myocardial infarction
90 (2.4)
1 [Reference]
2887 (3.2)
1.41 (1.05-1.89)
.02
3798 (9.1)
1.60 (1.19-2.16)d
.002
Cardiogenic shock
87 (2.3)
1 [Reference]
3070 (3.4)
1.52 (1.15-2.01)d
.003
2547 (6.1)
1.41 (1.06-1.87)d
.02
Congestive heart failure
168 (4.4)
1 [Reference]
4780 (5.4)
1.02 (0.86-1.21)d
.83
3693 (8.9)
1.05 (0.89-1.26)d
.55
Major bleedinge
244 (6.4)
1 [Reference]
5844 (6.5)
1.12 (0.95-1.31)f
.17
4840 (11.6)
1.19 (1.01-1.39)f
.04
Abbreviation: OR, odds ratio. a
Among patients who were not transferred prior to discharge.
b
Represents the risk associated with each group of patients compared with trial participants (reference).
c
The mortality model C statistic was 0.855 (95% CI, 0.850-0.860).
d
Adjusted for demographic variables (age, sex, ethnicity/race, and weight), signs and symptoms at presentation (heart failure, heart rate, systolic blood pressure, electrocardiographic findings), medical history (hypertension, diabetes mellitus, current or recent tobacco use, hypercholesterolemia, and prior myocardial infarction, coronary revascularization, heart failure, stroke, and peripheral artery disease), laboratory results (baseline hemoglobin, serum creatinine, and troponin ratio to the upper limit of the local assay normal reference), medical insurance type, and within-center correlation and clustering of variable responses using an exchangeable correlation structure covariance matrix.
pation, in 190 476 patients with MI at 609 registry centers between July 1, 2008, and March 31, 2011. Patients with missing or incomplete data for classification of trial participation (n = 472) or eligibility (n = 48 869) were excluded. There were no clinically relevant differences between patients included and excluded. Trial participation was defined as patients who provided informed consent and enrolled in a trial during hospitalization, even if the investigational medication, device, or procedure was never initiated. Among nonparticipants, we determined whether trial exclusion criteria were met for 3 antiplatelet therapy trials in patients with MI during the study period,4-6 including age younger than 18 years, uncontrolled hypertension (systolic blood pressure >180 mm Hg), stage 5 kidney disease or dialysis-dependent renal failure, cardiogenic shock, major bleeding within 24 hours of presentation, impaired hemostasis (international normalized ratio [INR] >1.5), severe anemia (hemoglobin
