Association Between Use of Bleeding Avoidance Strategies and Risk of Periprocedural Bleeding Among Patients Undergoing Percutaneous Coronary Intervention

1
Association Between Use of Bleeding Avoidance
Strategies and Risk of Periprocedural Bleeding
Among Patients Undergoing Percutaneous Coronary
Intervention

• Marso et al. JAMA 20103032156-2164

2
Background

• Percutaneous coronary intervention (PCI) is
  performed approximately 1 million times annually
  in the United States.
• The safety of PCI continues to be excellent with
  very low rates of death, myocardial infarction
  (MI), and need for urgent revascularization.
• PCI-related bleeding occurs in approximately 2-6
  of patients in national PCI databases marked
  institutional variability in rates exists.
• Bleeding complications are associated with
  increased length of stay, hospital costs, and
  important clinical complications such as death
  and MI.

3
Objective

• To describe the use of 2 bleeding avoidance
  strategies1) vascular closure devices and 2)
  bivalirudinand associated post-PCl bleeding
  rates in a nationally representative PCI
  population.
• Examine clinical usage patterns of these
  strategies as a function of bleeding risk.

Marso et al. JAMA 20103032156-2164
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Study Patients Exclusions

• NCDR CathPCI Registry
• Patients undergoing PCI via the femoral artery
• Exclusion criteria
• gt1 PCI procedure during same stay
• Incomplete data on bleeding
• PCI via radial, brachial artery
• Cardiogenic shock
• Missing device data
• Death in cath lab
• Unknown bleeding event data

Marso et al. JAMA 20103032156-2164
5
Candidate Bleeding Avoidance Strategies

• Bivalirudin
• Vascular closure devices
• Both therapies (bivalirudin vascular closure)

Marso et al. JAMA 20103032156-2164
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Bleeding Risk Strata

• Bleeding risk score calculated for each patient
  using NCDR bleeding risk model1
• Clinical elements used to calculate bleeding risk
  score
• STEMI/non-STEMI
• Female sex
• Previous CHF
• No previous PCI
• NYHA/CCS Class IV CHF
• PVD
• Age
• Estimated glomerular filtration rate

Marso et al. JAMA 20103032156-2164
1 Mehta et al. Circ Cardiovasc Intervent
20092222-229
7
Study Outcomes

• In-hospital bleeding according to NCDR data
  definition
• Requiring transfusion and/or
• Prolonged hospital stay and/or
• Decrease in hemoglobin gt3 g/dL

Marso et al. JAMA 20103032156-2164
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Statistical Analysis

• Patients categorized into 3 groups of bleeding
  risk based on NCDR bleeding risk score
• Low (lt1)
• Intermediate (1-3)
• High (gt3)
• Propensity score matching with site adjustment
  using 26 clinical variables for each bleeding
  avoidance strategy performed to minimize
  confounding
• Population was well matched (standard difference
  plot on next slide)

Marso et al. JAMA 20103032156-2164
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Standardized Difference Before and After
Propensity Matching
Marso et al. JAMA 20103032156-2164
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Study Population
Marso et al. JAMA 20103032156-2164
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Patient Characteristics
Total (N1,522,935) Manual Compression (N 529,247) Vascular Closure Devices (N363,583) Bivalirudin N 353,769) Both (N 276,336)
Age, mean (SD), y 64.3 (12.1) 63.87 (12.33) 63.34 (12.26) 65.43 (11.86) 64.77 (11.80)
Male, N () 1,011,992 (66.5) 350,424 (66.21) 250,753 (68.97) 225,235 (63.67) 185,580 (67.16)
White, N () 1,289,673 (84.8) 449,617 (85.05) 301,908 (83.18) 303,317 (85.82) 234,831 (85.11)
Height, mean (SD), cm 171.30 (10.84) 171.22 (10.89) 171.73 (10.77) 170.81 (10.90) 171.50 (10.73)
Weight, mean (SD), kg 87.71 (20.45) 87.25 (20.42) 88.22 (20.28) 87.29 (20.71) 88.47 (20.40)
Body mass index, mean (SD), kg/m2 29.8 (6.3) 29.7 (6.3) 29.8 (6.2) 29.8 (6.4) 30.0 (6.3)
Obesity , N () 643,500 (42.25) 219,470 (41.47) 153,233 (42.15) 150,813 (42.63) 119,984 (43.42)
Current CHF, N () 136,489 (8.96) 48,658 (9.19) 30,799 (8.47) 33,173 (9.38) 23,859 (8.63)
NYHA class, N ()
I 480,785 (31.57) 160,016 (30.24) 125,209 (34.44) 107,678 (30.44) 87,882 (31.81)
II 355,937 (23.37) 107,093 (20.24) 79,475 (21.86) 90,682 (25.64) 78,687 (28.48)
III 415,651 (27.30) 146,439 (27.67) 87,352 (24.03) 107,952 (30.52) 73,908 (26.75)
IV 270,376 (17.76) 115,629 (21.85) 71,508 (19.67) 47,412 (13.40) 35,827 (12.97)
All Plt0.001
Marso et al. JAMA 20103032156-2164
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Patient Characteristics
Total (N1,522,935) Manual Compression (N 529,247) Vascular Closure Devices (N363,583) Bivalirudin (N 353,769) Both (N 276,336)
Coronary artery disease risk factors, N () Coronary artery disease risk factors, N () Coronary artery disease risk factors, N () Coronary artery disease risk factors, N () Coronary artery disease risk factors, N () Coronary artery disease risk factors, N ()
Diabetes 509,455 (33.45) 173,024 (32.69) 113,130 (31.12) 129,335 (36.56) 93,966 (34.00)
Hypertension 1,190,098 (78.15) 405,122 (76.55) 272,906 (75.06) 290,085 (82.00) 221,985 (80.33)
Dyslipidemia 1,167,108 (76.64) 392,248 (74.12) 269,478 (74.12) 283,174 (80.05) 222,208 (80.42)
Smoking , N ()
Never 600,315 (38.87) 196,423 (37.12) 143,554 (39.49) 138,026 (39.02) 114,318 (41.37)
Past 543,091 (35.17) 178,466 (33.72) 121,980 (33.55) 132,027 (37.32) 102,545 (37.11)
Current 400,845 (25.96) 154,297 (29.16) 97,995 (26.96) 83,681 (23.66) 59,439 (21.51)
Estimated glomerular filtration rate, mean (SD) 73.77 (29.62) 73.60 (29.88) 75.02 (30.48) 72.46 (29.06) 74.09 (28.61)
Family history of coronary artery disease , N () 392,815 (25.80) 135,320 (25.57) 100,704 (27.70) 86,660 (24.50) 70,131 (25.38)
Coronary artery disease history , N () Coronary artery disease history , N () Coronary artery disease history , N () Coronary artery disease history , N () Coronary artery disease history , N () Coronary artery disease history , N ()
PCI 576,207 (37.84) 182,518 (34.49) 125,649 (34.56) 151,835 (42.92) 116,205 (42.05)
CABG 291,773 (19.16) 98,038 (18.52) 59,980 (16.50) 79,189 (22.39) 54,566 (19.75)
Myocardial infarction 427,655 (28.08) 144,381 (27.28) 96,191 (26.46) 106,403 (30.08) 80,690 (29.20)
Other cardiovascular disease history , N () Other cardiovascular disease history , N () Other cardiovascular disease history , N () Other cardiovascular disease history , N () Other cardiovascular disease history , N () Other cardiovascular disease history , N ()
CHF 136,483 (8.96) 54,661 (10.33) 32,255 (8.87) 43,082 (12.18) 28,751 (10.40)
All Plt0.001
Marso et al. JAMA 20103032156-2164
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Patient Characteristics
Total (N1,522,935) Manual Compression (N 529,247) Vascular Closure Devices (N363,583) Bivalirudin (N 353,769) Both (N 276,336)
Cerebrovascular disease 174,811 (11.48) 60,260 (11.39) 34,638 (9.53) 48,214 (13.63) 31,699 (11.47)
Peripheral vascular disease 181,787 (11.74) 65,568 (12.39) 33,064 (9.09) 50,678 (14.33) 29,477 (10.67)
Previous valve surgery 17,267 (1.13) 5,929 (1.12) 3,672 (1.01) 4,505 (1.27) 3,161 (1.14)
Previous transplant 3,463 (0.23) 1,257 (0.24) 732 (0.20) 899 (0.25) 575 (0.21)
Chronic lung disease 248,918 (16.35) 86,586 (16.36) 52,995 (14.58) 6,5139 (18.41) 44,198 (15.99)
Renal failure 83,029 (5.45) 30,004 (5.67) 18,028 (4.96) 21,369 (6.04) 13,628 (4.93)
All data are N ()
All Plt0.001
Marso et al. JAMA 20103032156-2164
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Admission Characteristics
Total (N1,522,935) Manual Compression (N 529,247) Vascular Closure Devices (N363,583) Bivalirudin (N 353,769) Both (N 276,336)
No symptoms 196,190 (12.88) 55,961 (10.57) 42,224 (11.61) 54,346 (15.36) 43,659 (15.80)
Atypical chest pain 113,339 (7.44) 32,570 (6.15) 27,031 (7.44) 27,758 (7.85) 25,980 (9.40)
Stable angina 260,582 (17.11) 73,109 (13.81) 57,179 (15.73) 69,093 (19.53) 61,201 (22.15)
Unstable angina 527,624 (34.65) 168,813 (31.90) 113,413 (31.19) 142,473 (40.27) 102,925 (37.25)
Non-STEMI 238,305 (15.65) 98,866 (18.68) 64,921 (17.86) 43,239 (12.22) 31,279 (11.32)
STEMI 186,810 (12.27) 99,900 (18.88) 58,796 (16.17) 16,843 (4.76) 11,271 (4.08)
PCI type
Elective 758,110 (49.79) 220,576 (41.68) 157,348 (43.28) 212,562 (60.09) 167,624 (60.67)
Urgent 553,524 (36.35) 196,634 (37.16) 140,023 (38.52) 121,995 (34.49) 94,872 (34.34)
Emergency 209,465 (13.76) 110,990 (20.97) 65,758 (18.09) 19,011 (5.37) 13,706 (4.96)
Salvage 1,662 (0.11) 968 (0.18) 422 (0.12) 172 (0.05) 100 (0.04)
All data are N ()
All Plt0.001
Marso et al. JAMA 20103032156-2164
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Hospital Characteristics
Total (N1,522,935) Manual Compression (N 529,247) Vascular Closure Devices (N363,583) Bivalirudin (N 353,769) Both (N 276,336)
Region, N ()
West 244,853 (16.11) 71,085 (13.47) 73,065 (20.15) 41,801 (11.83) 58,902 (21.36)
Northeast 177,930 (11.71) 56,353 (10.68) 60,120 (16.58) 28,392 (8.04) 33,065 (11.99)
Midwest 505,125 (33.24) 198,609 (37.63) 119,220 (32.88) 104,043 (29.45) 83,253 (30.19)
South 591,568 (38.93) 201,679 (38.22) 110,237 (30.40) 179,071 (50.68) 100,581 (36.47)
Community type, N ()
Rural 177,441 (15.92) 59,727 (15.44) 54,008 (21.02) 31,542 (11.48) 32,164 (16.38)
Urban 937,476 (84.08) 327,222 (84.56) 202,931 (78.98) 243,165 (88.52) 164,158 (83.62)
Profit type, N ()
Government 23,838 (1.57) 7,895 (1.49) 4,948 (1.36) 5,988 (1.69) 5,007 (1.81)
Private/community 1,356,756 (89.09) 465,238 (87.91) 319,915 (87.99) 318,550 (90.04) 253,053 (91.57)
University 142,341 (9.35) 56,114 (10.60) 38,720 (10.65) 29,231 (8.26) 18,276 (6.61)
Annual PCI volume, mean (SD) 1095.81 (795.18) 1058.04 (704.88) 981.16(732.27) 1303.62(782.65) 1052.94(678.44)
All Plt0.001
Marso et al. JAMA 20103032156-2164
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Bleeding Rates
LowN475,152
High N301,056
Overall bleeding 30,429 (2)
Intermediate N746,727
NCDR bleeding risk lt1NCDR bleeding risk
1-3NCDR bleeding risk gt3
M Manual comp. C Closure only B Bival
only BC Bivalclosure
M
C
BC
B
M
C
BC
B
M
C
BC
B
M
C
BC
B
Plt0.001 allintra-risk groupcomparisons
Overall
Low(lt1)
Intermediate(1-3)
High(gt3)
17
Estimated Bleeding ReductionsAll Patients
(Propensity Adjusted)
Treatment(N) Treatment(N) Bleeding N () Odds Ratio (95 CI) NNT (95 CI) Reduction in Bleeding Events per 1,000 Patients Treated (95 CI)
Manual compression 508,455 13,597 (2.7) 13,597 (2.7) 1 Reference
Vascular closure devices 205,606 5,050 (2.5) 5,050 (2.5) 0.77 (0.73-0.80) 148 (130-175) 6.7 (5.7-7.7)
Bivalirudin 172,471 3,224 (1.9) 3,224 (1.9) 0.67 (0.63-0.70) 118 (107-132) 8.5 (7.6-9.3)
Both 130,378 1,361 (1.0) 1,361 (1.0) 0.38 (0.35-0.42) 70 (68-74) 14.2 (13.5-14.8)
Total 1,016,910 23,232 (2.3) 23,232 (2.3)
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Estimated Bleeding Reductions (Propensity
Adjusted)
Treatment(N) Bleeding N () Odds Ratio (95 CI) NNT (95 CI) Reduction in Bleeding Events per 1,000 Patients Treated (95 CI)
Low Risk, lt1 Low Risk, lt1 Low Risk, lt1 Low Risk, lt1 Low Risk, lt1 Low Risk, lt1
Manual compression 144,594 1,320 (0.9) 1 Reference
Vascular closure devices 54,217 532 (1.0) 1.07 (0.93-1.22) NS NS
Bivalirudin 48,378 296 (0.6) 0.65 (0.56-0.77) 315 (247-470) 3.2 (2.1-4.0)
Both 41,999 166 (0.4) 0.42 (0.34-0.51) 188( 167-222) 5.3 (4.5-6.0)
Total 289,188 2,314 (0.8)
Intermediate Risk, 1-3 Intermediate Risk, 1-3 Intermediate Risk, 1-3 Intermediate Risk, 1-3 Intermediate Risk, 1-3 Intermediate Risk, 1-3
Manual compression 252,898 5,722 (2.3) 1 Reference
Vascular closure devices 103,095 2,077 (2.0) 0.76 (0.71-0.81) 169 (141-217) 5.9 (4.6-7.1)
Bivalirudin 85,800 1,311 (1.5) 0.69 (0.63-0.74) 153 (131-187) 6.5 (5.3-7.6)
Both 64,003 573 (0.9) 0.39 (0.35-0.44) 80 (75-86) 12.5 (11.6-13.3)
Total 505,796 9,683 (1.9)
High Risk, gt3 High Risk, gt3 High Risk, gt3 High Risk, gt3 High Risk, gt3 High Risk, gt3
Manual compression 110,963 6,555 (5.9) 1 Reference
Vascular closure devices 48,294 2,441 (5.1) 0.79 (0.75-0.82) 81 (66-109) 12.3 (9.2-15.3)
Bivalirudin 38,293 1,617 (4.2) 0.67 (0.62-0.73) 56 (49-66) 17.9 (15.1-20.6)
Both 24,376 622 (2.6) 0.42 (0.38-0.47) 33 (31-36) 30.5 (27.9-32.8)
Total 221,926 11,235 (5.1)
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Bleeding Avoidance Strategy Use by Pre-PCI
Bleeding Risk
LowN475,152
High N301,056
Risk-Treatment Paradox
Intermediate N746,727
NCDR bleeding risk lt1NCDR bleeding risk
1-3NCDR bleeding risk gt3
M Manual comp. C Closure only B Bival
only BC Bivalclosure
M
C
BC
B
M
C
BC
B
M
C
BC
B
Plt0.001 for allintra-risk groupcomparisons
Low(lt1)
Intermediate(1-3)
High(gt3)
20
Limitations

• Observational, non-randomized study
• Potential unmeasured confounding
• No data on activated clotting time
• Contraindications to use of bleeding avoidance
  therapies
• Bivalirudin in the setting of other
  anticoagulants, PCI of chronic total occlusion
• Vascular closure devices high risk anatomy
• Data insufficient to warrant abandoning use of
  manual compression in favor of vascular closure
  devices
• Adequately powered randomized trial assessing
  bleeding endpoints is needed

21
Conclusions

• In 1.5 million PCI patients in the NCDR
• Post-PCI bleeding occurred in 2
• Use of bivalirudin plus vascular closure devices
  was associated with an absolute 3.8 lower rate
  in PCI related bleeding in high risk patients
• To prevent 1 bleeding event in high risk patients
  would require treating 33 patients with both
  therapies
• High risk patients were least likely to receive
  both strategies (risk-treatment paradox)

Marso et al. JAMA 20103032156-2164