Supplementary Online Content - JAMA€¦ · Stent thrombosis was defined according to the definite or probable criteria of the Academic Research Consortium (Circulation 2007;115:2344-51)

Supplementary Online Content Han Y, Guo J, Zheng Y, et al. Bivalirudin versus Heparin with or without Tirofiban during Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction: The BRIGHT randomized clinical trial. JAMA. doi:10.1001/jama.2015.2323.

eTable 1. Definitions of endpoint events (adjudicated), 2 eTable 2. Access site and non-access site BARC types 2-5 bleeding through 30 days, 6 eTable 3. Baseline characteristics in the STEMI population, 7 eTable 4. Treatment and procedural characteristics in the STEMI population, 8 eTable 5. Clinical outcomes in the STEMI population, 10 eFigure 1. Subgroup analyses for NACE at 30 days for the entire study population, 11 eFigure 2. Subgroup analyses for MACCE at 30 days for the entire study population, 12 eFigure 3. Subgroup analyses for any bleeding at 30 days for the entire study population, 13 eFigure 4. Subgroup analyses for BARC types 2-5 bleeding at 30 days for the entire study population, 14 eFigure 5. Time-to-event curves for NACE in the STEMI population, 15 eFigure 6. Time-to-event curves for MACCE in the STEMI population, 16 eFigure 7. Time-to-event curves for any bleeding in the STEMI population, 17eAppendix 1. Search strategy for Medline (using PubMed)

This supplementary material has been provided by the authors to give readers additional information about their work.

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eTable 1. Definitions of endpoint events (adjudicated)

Death. The cause of death was adjudicated as cardiac or non-cardiac. All deaths were considered

cardiac-related unless non-cardiac causes were clearly identified.

Myocardial infarction. Myocardial infarction was defined according to the third Universal Definition of

Myocardial Infarction (European Heart Journal. 2012;33:2551–2567).

Type 1: Spontaneous myocardial infarction.

Spontaneous myocardial infarction related to atherosclerotic plaque rupture, ulceration, fissuring,

erosion, or dissection with resulting intraluminal thrombus in one or more of the coronary arteries

leading to decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis.

The patient may have underlying severe CAD but on occasion non-obstructive or no CAD.

Type 2: Myocardial infarction secondary to an ischaemic imbalance

In instances of myocardial injury with necrosis where a condition other than CAD contributes to an

imbalance between myocardial oxygen supply and/or demand, e.g. coronary endothelial dysfunction,

coronary artery spasm, coronary embolism, tachy-/brady-arrhythmias, anaemia, respiratory failure,

hypotension, and hypertension with or without LVH.

Type 3: Myocardial infarction resulting in death when biomarker values are unavailable

Cardiac death with symptoms suggestive of myocardial ischaemia and presumed new ischaemic ECG

changes or new LBBB, but death occurring before blood samples could be obtained, before cardiac

biomarker could rise, or in rare cases cardiac biomarkers were not collected.

Type 4a: Myocardial infarction related to percutaneous coronary intervention (PCI)

Myocardial infarction associated with PCI is arbitrarily defined by elevation of cTn values >5 x 99th

percentile URL in patients with normal baseline values (≤99th percentile URL) or a rise of cTn

values >20% if the baseline values are elevated and are stable or falling. In addition, either (i)

symptoms suggestive of myocardial ischaemia, or (ii) new ischaemic ECG changes or new LBBB, or (iii)

angiographic loss of patency of a major coronary artery or a side branch or persistent slow- or

no-flow or embolization, or (iv) imaging demonstration of new loss of viable myocardium or new

regional wall motion abnormality are required.

Type 4b: Myocardial infarction related to stent thrombosis

Myocardial infarction associated with stent thrombosis is detected by coronary angiography or

autopsy in the setting of myocardial ischaemia and with a rise and/or fall of cardiac biomarkers values

with at least one value above the 99th percentile URL.

Type 5: Myocardial infarction related to coronary artery bypass grafting (CABG)

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Myocardial infarction associated with CABG is arbitrarily defined by elevation of cardiac biomarker

values >10 x 99th percentile URL in patients with normal baseline cTn values (≤99th percentile URL).

In addition, either (i) new pathological Q waves or new LBBB, or (ii) angiographic documented new

graft or new native coronary artery occlusion, or (iii) imaging evidence of new loss of viable

myocardium or new regional wall motion abnormality.

Stent thrombosis: Stent thrombosis was defined according to the definite or probable criteria of the

Academic Research Consortium (Circulation 2007;115:2344-51).

1. Definite stent thrombosis

Presence of an acute coronary syndrome with angiographic or autopsy evidence of thrombus or

occlusion.

2. Probable stent thrombosis

Unexplained deaths within 30 days after the procedure or acute myocardial infarction involving the

target-vessel territory without angiographic confirmation.

3. Possible stent thrombosis

All unexplained death occurring at least 30 days after the procedure.

Stent thrombosis classification by time frame

1. Acute stent thrombosis

Occurring within 24 hours after the index PCI.

2. Subacute stent thrombosis

Occurring between 24 hours and 30 days after the index PCI.

3. Late stent thrombosis

Occurring between 31 and 360 days after the index PCI.

4. Very late stent thrombosis

Occurring later than 360 days after the index PCI.

Ischemia-driven Target Vessel Revascularization. Ischemia-driven target vessel revascularization was

defined as repeat PCI or bypass surgery of the target lesion(s) and any additional lesions in the main

epicardial coronary artery or branches containing the target lesion with one or more of the following

conditions:

1. Patient had ischemic symptoms and ECG-changes at rest referable to the target lesion.

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2. Diameter stenosis ≥50% at follow-up angiography and a positive functional study corresponding to

the area served by the target vessel.

3. Diameter stenosis <50% at follow-up angiography but a markedly positive functional study or

ECG-changes corresponding to the territory supplied by target vessel.

4. Diameter stenosis ≥70% at follow-up angiography in absence of documented clinical or functional

ischemia.

Stroke. Stroke was defined as an acute event of non-hemorrhagic cerebrovascular origin causing focal or

global neurologic dysfunction lasting > 24 hours, which is confirmed by both clinical and radiographic

means.

Bleeding. Bleeding was defined according to the Bleeding Academic Research Consortium(Circulation

2011;123:2736-47).

Type 0: no bleeding.

Type 1: bleeding that is not actionable and does not cause the patient to seek unscheduled

performance of studies, hospitalization, or treatment by a healthcare professional; may include

episodes leading to self-discontinuation of medical therapy by the patient without consulting a

healthcare professional.

Type 2: any overt, actionable sign of hemorrhage (eg, more bleeding than would be expected for a

clinical circumstance, including bleeding found by imaging alone) that does not fit the criteria for type

3, 4, or 5 but does meet at least one of the following criteria: (1) requiring nonsurgical, medical

intervention by a healthcare professional, (2) leading to hospitalization or increased level of care, or

(3) prompting evaluation.

Type 3:

Type 3a: Overt bleeding plus hemoglobin drop of 3 to <5 g/dL (provided hemoglobin drop is related

to bleed); any transfusion with overt bleeding.

Type 3b: Overt bleeding plus hemoglobin drop ≥5 g/dL (provided hemoglobin drop is related to

bleed); cardiac tamponade; bleeding requiring surgical intervention for control (excluding

dental/nasal/skin/hemorrhoid); Bleeding requiring intravenous vasoactive agents.

Type 3c: Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation,

does include intraspinal); Subcategories confirmed by autopsy or imaging or lumbar puncture;

Intraocular bleed compromising vision.

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Type 4: CABG-related bleeding: Perioperative intracranial bleeding within 48 h; Reoperation after

closure of sternotomy for the purpose of controlling bleeding; Transfusion of ≥5 U whole blood or

packed red blood cells within a 48-h period; Chest tube output ≥2L within a 24-h period.

Type 5: fatal bleeding.

Type 5a: Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious.

Type 5b: Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation.

Acquired thrombocytopenia. Acquired thrombocytopenia was defined as a platelet count decrease by >50% or by >150×109/L from baseline.

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eTable 2. Access site and non-access site BARC types 2-5 bleeding through 30 days according to randomized treatment

Bivalirudin

(n=735) Heparin (n=729)

Heparin + tirofiban (n=730)

P value

Access site bleeding 2 (0.3) 8 (1.1) 12 (1.6) 0.03

Radial 1 (0.1) 3 (0.4) 3 (0.4)

Femoral 1 (0.1) 5 (0.7) 9 (1.2)

Non-access site bleeding 7 (1.0) 18 (2.5) 25 (3.4) 0.005

Intracranial 0 0 0

Gastrointestinal 4 (0.5) 10 (1.4) 14 (1.9)

Other 3 (0.4) 8 (1.1) 11 (1.5)

BARC denotes Bleeding Academic Research Consortium.

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eTable 3. Baseline characteristics in the STEMI population according to the randomized treatment

Characteristic Bivalirudin (N = 655)

Heparin alone (N = 641)

Heparin plus tirofiban (N = 629)

Age, years 57.1 ± 11.7 57.8 ± 11.8 58.0 ± 11.7

Male (%) 558 (85.2) 529 (82.5) 518 (82.4)

Body mass, kg 71.8 ± 11.0 71.3 ± 11.6 70.4 ± 10.8

Body mass index (kg/m2) 25.5 ± 3.5 25.3 ± 3.5 25.1 ± 3.6

Medical history (%)

Diabetes 149 (22.7) 106 (16.5) 136 (21.6)

Hypertension 261 (39.8) 262 (40.9) 255 (40.5)

Hyperlipidemia 231 (35.3) 247 (38.5) 229 (36.4)

Current smoker 418 (63.8) 383 (59.8) 390 (62.0)

Previous MI 21 (3.2) 19 (3.0) 20 (3.2)

Previous PCI 33 (5.0) 27 (4.2) 28 (4.5)

Previous stroke 58 (8.9) 56 (8.7) 43 (6.8)

Symptom onset to hospital arrival, hrs 6.1 [4.1, 8.9] 6.2 [4.3, 8.9] 5.9 [4.2, 8.8]

Killip class ≥II (%) 100 (15.3) 107 (16.7) 107 (17.0)

Anemia (%) 37/616 (6.0) 25/597 (4.2) 31/590 (5.3)

Creatinine clearance ≤60 ml/min (%) 58/612 (9.5) 63/594 (10.6) 65/580 (11.2)

CRUSADE bleeding score* 19.5 ± 11.9 19.8 ± 12.2 20.9 ± 12.2

>30 (moderate or high bleeding risk) 106/585 (18.1) 110/566 (19.4) 106/550 (19.3)

There were no significant differences between groups. Anemia was defined as hemoglobin < 13 g/dL for men or < 12

g/dL for women. MI denotes myocardial infarction, PCI denotes percutaneous coronary intervention, STEMI denotes

ST-segment elevation myocardial infarction, NSTEMI denotes non-ST-segment elevation myocardial infarction, and

CRUSADE denotes Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early

implementation of the ACC/AHA guidelines. Continuous data are mean ± SD or median (interquartile range). *The

Crusade bleeding scale can range from 1-96, with higher numbers representing a greater risk of bleeding. In the Bright

study population the Crusade scores ranged from 1-65.

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eTable 4. Treatment and procedural characteristics in the STEMI population according to the randomized treatment

Characteristic Bivalirudin (N = 655)

Heparin alone (N = 641)

Heparin plus tirofiban (N = 629)

Aspirin before randomization (%) 655 (100) 641 (100) 626 (99.5)

Clopidogrel before randomization (%) 655 (100) 641 (100) 628 (99.8)

Loading dose

None 1 (0.2) 0 (0) 0 (0)

300 mg 182 (27.8) 189 (29.5) 176 (28.0)

600 mg 472 (72.1) 452 (70.5) 453 (72.0)

Study medications (%)

Bivalirudin 655 (100) 2 (0.3) 1 (0.2)

Unfractionated heparin 2 (0.3) 641 (100) 629 (100)

Tirofiban 30 (4.6) 36 (5.6) 629 (100)

Activated clotting time*, seconds 298.6 ± 93.3 261.6 ± 62.2 266.4 ± 80.6

Additional bolus of study medication† 27 (4.1) 82 (12.8) 36 (5.7)

Door to device time, mins 66.1 ± 29.5 68.6 ± 28.6 69.8 ± 27.8

Arterial access (%)

Transfemoral 140 (21.4) 141 (22.0) 138 (21.9)

Transradial 515 (78.6) 500 (78.1) 491 (78.1)

Multivessel disease (%) 416 (63.5) 405 (63.2) 424 (67.4)

Revascularization strategy (%)

None (medical therapy only) 6 (0.9) 2 (0.3) 4 (0.6)

Coronary artery bypass graft surgery 5 (0.8) 2 (0.3) 4 (0.6)

Any PCI 644 (98.3) 637 (99.4) 621 (98.7)

Balloon angioplasty only 15 (2.3) 17 (2.7) 12 (1.9)

Stent implantation 629 (96.0) 620 (96.7) 609 (96.8)

Drug-eluting stents 624/629 (99.2) 615/620 (99.2) 606/609 (99.5)

Drug-eluting stent type‡

Sirolimus-eluting 596/717 (83.1) 589/701 (84.0) 557/679 (82.0)

Paclitaxel-eluting 6/717 (0.8) 2/701 (0.3) 2/679 (0.3)

Zotarolimus-eluting 29/717 (4.0) 23/701 (3.2) 25/679 (3.7)

Everolimus-eluting 86/717 (12.0) 87/701 (12.1) 95/679 (14.0)

Bare metal stents only 5/629 (0.8) 5/620 (0.8) 3/609 (0.5)

Culprit vessel treated with PCI (%)

Left main coronary artery 5/644 (0.8) 4/637 (0.6) 3/621(0.5)

LAD coronary artery 344/644 (53.4) 353/637 (55.4) 327/621 (52.7)

Left circumflex coronary artery 142/644 (22.0) 136/637 (21.4) 139/621 (22.4)

Right coronary artery 153/644 (23.8) 144/637 (22.6) 152/621 (24.5)

Mean culprit lesion RVD, mm 3.13 ± 0.81 3.16 ± 0.72 3.10 ± 0.77

Number of stents per patient 1.15 ± 0.46 1.14 ± 0.44 1.1 2± 0.43

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Mean stent length, mm 27.8 ± 12.4 28.5 ± 11.6 27.8 ± 10.7

Thrombus aspiration (%) 179/644 (27.8) 178/637 (27.9) 178/621 (28.7)

TIMI flow

Pre-PCI (%)

0/1 510/620 (82.3) 509/602 (84.6) 481/597 (80.6)

2 42/620 (6.8) 49/602 (8.1) 59/597 (9.9)

3 68/620 (11.0) 44/602 (7.3) 57/597 (9.5)

Post-PCI (%)

0/1 9/620 (1.5) 14/602 (2.3) 14/597 (2.3)

2 16/620 (2.6) 12/602 (2.0) 4/597 (0.7)

3 595/620 (96.0) 576/602 (95.7) 579/597 (97.0)

Medications at discharge (%)

Aspirin 648 (98.9) 630 (98.3) 620 (98.6)

Clopidogrel 651 (99.4) 630 (98.3) 622 (98.9)

Statin 581 (88.7) 585 (91.3) 555 (88.2)

Beta-blocker 483 (73.7) 457 (71.3) 462 (73.4)

Calcium channel blocker 46 (7.0) 50 (7.8) 40 (6.4)

ACEI/ARB 356 (54.4) 360 (56.2) 326 (51.8)

Proton pump inhibitor 139 (21.2) 152 (23.7) 122 (19.4) There were no significant differences between groups except for study medications administered, activated clotting time,

and additional bolus of study medication administered (each P<0.001). *5 minutes after bolus. †Administered for an

activated clotting time measured 5 minutes after the first bolus of <225 seconds in the bivalirudin and heparin only arms,

or <200 seconds in the heparin plus tirofiban arm. ‡The denominator represents the total number of drug-eluting stents

implanted in each group. PCI denotes percutaneous coronary intervention, LAD denotes left anterior descending, RVD

denotes reference vessel diameter, TIMI denotes Thrombolysis In Myocardial Infarction, ACEI denotes

angiotensin-converting enzyme inhibitor, and ARB denotes angiotensin receptor II blocker.

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eTable 5. Clinical outcomes in the STEMI population according to the randomized treatment

Events, n (%) Bivalirudin

(N = 655)

Heparin alone

(N =641)

Heparin plus

tirofiban (N = 629)

Difference (%)

(95% CI)

Biv vs. H

Difference (%)

(95% CI)

Biv vs. H+T

Difference (%)

(95%CI)

H vs. H+T

30-day outcomes

NACE (primary endpoint) 56 (8.5) 89 (13.9) 105 (16.7) -5.3 (-8.8 – -1.9) -8.1 (-11.8 – -4.5) -2.8 (-6.8 – 1.1)

MACCE 31 (4.7) 39 (6.1) 31 (4.9) -1.4 (-3.8 – 1.1) -0.2 (-2.5 – 2.2) 1.2 (-1.4 – 3.7)

All-cause death 9 (1.4) 13 (2.0) 14 (2.2) -0.7 (-2.1 – 0.8) -0.9 (-2.3 – 0.6) -0.2 (-1.8 – 1.4)

Cardiac death 8 (1.2) 13 (2.0) 14 (2.2) -0.8 (-2.2 – 0.6) -1.0 (-2.4 – 0.4) -0.2 (-1.8 – 1.4)

Reinfarction 7 (1.1) 8 (1.2) 5 (0.8) -0.2 (-1.3 – 1.0) 0.3 (-0.8 – 1.3) 0.5 (-0.7 – 1.6)

Stroke 5 (0.8) 6 (0.9) 4 (0.6) -0.2 (-1.2 – 0.8) 0.1 (-0.8 – 1.0) 0.3 (-0.7 – 1.3)

Ischemic TVR 10 (1.5) 12 (1.9) 8 (1.3) -0.3 (-1.8 – 1.1) 0.3 (-1.0 – 1.5) 0.6 (-0.8 – 2.0)

All Bleeding 27 (4.1) 51 (8.0) 76 (12.1) -3.8 (-6.4 – -1.2) -8.0 (-10.9 – -5.0) -4.1 (-7.4 – -0.8)

BARC 2-5 8 (1.2) 23 (3.6) 33 (5.2) -2.4 (-4.0 – -0.7) -4.0 (-6.0 – -2.1) -1.7 (-3.9 – 0.6)

BARC 3-5 3 (0.5) 10 (1.6) 15 (2.4) -1.1 (-2.2 – 0) -1.9 (-3.2 – -0.6) -0.8 (-2.4 – 0.7)

Acquired thrombocytopenia 1 (0.2) 4 (0.6) 7 (1.1) -0.5 (-1.2 – 0.2) -1.0 (-1.8 – 0) -0.5 (-1.5 – 0.5)

Stent thrombosis* 4 (0.6) 6 (1.0) 5 (0.8) -0.3 (-1.3 – 0.7) -0.2 (-1.1 – 0.8) 0.1 (-0.9 – 1.2)

Definite 3 (0.5) 5 (0.8) 4( 0.7) -0.3 (-1.2 – 0.6) -0.2 (-1.0 – 0.7) 0.1 (-0.8 – 1.1)

Probable 1 (0.2) 1 (0.2) 1 (0.2) 0 (-0.4 – 0.4) 0 (-0.5 – 0.4) 0 (-0.5 – 0.4)

Acute (<24 hours) 2 (0.3) 2 (0.3) 2 (0.3) 0 (-0.6 – 0.6) 0 (-0.6 – 0.6) 0 (-0.6 – 0.6)

Subacute (1-30 days) 2 (0.3) 4 (0.6) 3 (0.5) -0.3 (-1.1 – 0.4) -0.2 (-0.9 – 0.5) 0.2 (-0.7 – 1.0)

1-year outcomes

NACE 83 (12.7) 111 (17.3) 125 (19.9) -4.6 (-8.5 – -0.8) -7.2 (-11.2 – -3.2) -2.6 (-6.8 – 1.7)

MACCE 42 (6.4) 48 (7.5) 42 (6.7) -1.1 (-3.8 – 1.7) -0.3 (-3.0 – 2.4) 0.8 (-2.0 – 3.6)

Death 12 (1.8) 16 (2.5) 17 (2.7) -0.7 (-2.2 – 0.9) -0.9 (-2.5 – 0.8) -0.2 (-2.0 – 1.5)

Cardiac death 10 (1.5) 15 (2.4) 15 (2.4) -0.8 (-2.3 – 0.7) -0.9 (-2.4 – 0.7) 0 (--1.7 – 1.6)

Reinfarction 12 (1.8) 11 (1.7) 10 (1.6) -0.1 (-1.3 – 1.6) 0.2 (-1.2 – 1.7) 0.1 (-1.3 – 1.5)

Stroke 6 (0.9) 10 (1.6) 6 (1.0) -0.6 (-1.8 – 0.6) 0 (-1.1 – 1.0) 0.6 (-0.6 – 1.8)

Ischemic TVR 13 (2.0) 13 (2.0) 11 (1.7) 0 (-1.6 – 1.5) 0.2 (-1.2 – 1.7) 0.3 (-1.2 – 1.8)

All bleeding 42 (6.4) 67 (10.5) 87 (13.8) -4.0 (-7.2 – -1.0) -7.4 (-10.7 – -4.1) -3.4 (-7.0 – 0.2)

BARC 2-5 10 (1.5) 25 (3.9) 35 (5.6) -2.4 (-4.1 – -0.6) -4.0 (-6.1 – -2.0) -1.7 (-4.0 – 0.7)

BARC 3-5 3 (0.5) 10 (1.6) 16 (2.5) -1.1 (-2.2 – 0) -2.1 (-3.4 – -0.8) -1.0 (-2.5 – 0.6)

Stent thrombosis* 7 (1.1) 11 (1.8) 7 (1.1) -0.7 (-2.0 – 0.7) 0 (-1.2 – 1.1) 0.6 (-0.7 – 2.0)

Definite 6 (1.0) 10 (1.6) 6 (1.0) -0.7 (-1.9 – 0.6) 0 (-1.1 – 1.1) 0.6 (-0.6 – 1.9)

Probable 1 (0.2) 1 (0.2) 1 (0.2) 0 (-0.4 – 0.4) 0 (-0.5 – 0.4) 0 (-0.5 – 0.4)

*Among patients receiving stents (n=629 for bivalirudin, n=620 for heparin alone, and n=609 for heparin plus tirofiban). BIV denotes bivalirudin.

H denotes heparin. H+T denotes heparin plus tirofiban. NACE denotes net adverse clinical events, MACCE denotes major adverse cardiac and

cerebral events, TVR denotes target vessel revascularization, and BARC denotes Bleeding Academic Research Consortium. BARC bleeding is

graded on a scale of 1-5, ranging from minor bleeding that is not actionable (type 1) to fatal bleeding (type 5). The detailed definitions for the

BARC bleeding types are reported in Table 1 of the supplemental appendix.

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eFigure 1. Subgroup analyses for the primary composite outcome of net adverse clinical events (NACE)

at 30 days among patients randomized to bivalirudin vs. heparin alone or with tirofiban (pooled).

Previous cardiovascular (CV) events are defined as prior myocardial infarction, coronary revascularization

or stroke. LAD denotes left anterior descending coronary artery. Data are binary proportions. The

CRUSADE score is a validated model that quantifies the risk for in-hospital major bleeding from 8 baseline

variables. The Crusade bleeding scale ranges from 1-96, with higher numbers representing a greater risk

of bleeding. A Crusade score of >30 predicts a moderate or high risk of bleeding.

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eFigure 2. Subgroup analyses for the secondary composite outcome of major adverse cardiac and

cerebral events (MACCE) at 30 days among patients randomized to bivalirudin vs. heparin alone or with

tirofiban (pooled). Previous cardiovascular (CV) events are defined as prior myocardial infarction,

coronary revascularization or stroke. LAD denotes left anterior descending coronary artery. Data are

binary proportions. The CRUSADE score is a validated model that quantifies the risk for in-hospital major

bleeding from 8 baseline variables. The Crusade bleeding scale ranges from 1-96, with higher numbers

representing a greater risk of bleeding. A Crusade score of >30 predicts a moderate or high risk of

bleeding.

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eFigure 3. Subgroup analyses for the secondary endpoint of any bleeding at 30 days among patients

randomized to bivalirudin vs. heparin alone or with tirofiban (pooled). Previous cardiovascular (CV)

events are defined as prior myocardial infarction, coronary revascularization or stroke. LAD denotes left

anterior descending coronary artery. Data are binary proportions. The CRUSADE score is a validated

model that quantifies the risk for in-hospital major bleeding from 8 baseline variables. The Crusade

bleeding scale ranges from 1-96, with higher numbers representing a greater risk of bleeding. A Crusade

score of >30 predicts a moderate or high risk of bleeding.

13


eFigure 4. Subgroup analyses for the tertiary endpoint of medically actionable bleeding (BARC types 2-5)

at 30 days among patients randomized to bivalirudin vs. heparin alone or with tirofiban (pooled).

Previous cardiovascular (CV) events are defined as prior myocardial infarction, coronary revascularization

or stroke. LAD denotes left anterior descending coronary artery. Data are binary proportions. The

CRUSADE score is a validated model that quantifies the risk for in-hospital major bleeding from 8 baseline

variables. The Crusade bleeding scale ranges from 1-96, with higher numbers representing a greater risk

of bleeding. A Crusade score of >30 predicts a moderate or high risk of bleeding. BARC denotes Bleeding

Academic Research Consortium.

14


eFigure 5. Time-to-event curves for net adverse clinical events through 1-year follow-up, comparing outcomes in patients with STEMI randomized to bivalirudin, heparin alone, or heparin plus tirofiban. The large graph represents the cumulative estimated time to first event rates with follow-up through 1 year. The small inset in each panel displays a landmark analysis demonstrating the cumulative estimated time to first event rates within the first 30 days after randomization, and then between 30 days and 1 year (having censored all events which occurred before 30 days). Net adverse clinical events is a composite of measure major adverse cardiac or cerebral events (all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke) or any bleeding as defined by the Bleeding Academic Research Consortium (BARC) definition (grades 1-5). Event rates were estimated by the Kaplan-Meier method, and thus may vary slightly from the binary proportions shown in Table 5 of the supplemental appendix.

15


eFigure 6. Time-to-event curves for major adverse cardiac or cerebral events through 1-year follow-up, comparing outcomes in patients with STEMI randomized to bivalirudin, heparin alone, or heparin plus tirofiban. The large graph represents the cumulative estimated time to first event rates with follow-up through 1 year. The small inset in each panel displays a landmark analysis demonstrating the cumulative estimated time to first event rates within the first 30 days after randomization, and then between 30 days and 1 year (having censored all events which occurred before 30 days). Major adverse cardiac or cerebral events is a composite of all-cause death, reinfarction, ischemia-driven target vessel revascularization, or stroke. Event rates were estimated by the Kaplan-Meier method, and thus may vary slightly from the binary proportions shown in Table 5 of the supplemental appendix.

16


eFigure 7. Time-to-event curves for any bleeding through 1-year follow-up, comparing outcomes in patients with STEMI randomized to bivalirudin, heparin alone, or heparin plus tirofiban. The large graph represents the cumulative estimated time to first event rates with follow-up through 1 year. The small inset in each panel displays a landmark analysis demonstrating the cumulative estimated time to first event rates within the first 30 days after randomization, and then between 30 days and 1 year (having censored all events which occurred before 30 days). Any bleeding was defined by the Bleeding Academic Research Consortium (BARC) definition (grades 1-5). Event rates were estimated by the Kaplan-Meier method, and thus may vary slightly from the binary proportions shown in Table 5 of the supplemental appendix.

17


Documents

Supplementary Online Content - JAMA€¦ · Stent thrombosis was defined according to the definite or probable criteria of the Academic Research Consortium (Circulation 2007;115:2344-51)