Transcript The Detrimental Impact of Chronic Renal Insufficiency

A Prospective, Randomized Comparison of
Bivalirudin vs. Heparin Plus Glycoprotein
IIb/IIIa Inhibitors During Primary
Angioplasty in Acute Myocardial Infarction
– 30 Day Results –
Gregg W. Stone MD
For the HORIZONS AMI Investigators
Disclosures

Gregg W. Stone MD
– Research support from The Medicines
Company and Boston Scientific
– Honoraria from Eli Lilly Co.
Background

In addition to suppressing periprocedural ischemia,
prevention of hemorrhagic complications has
emerged as a priority in patients undergoing PCI

In patients with stable angina and NSTEMI, the
direct thrombin inhibitor bivalirudin has been shown
to result in similar rates of composite ischemia as
heparin plus GP IIb/IIIa inhibitors, while significantly
reducing major bleeding

Whether bivalirudin has comparable safety and
efficacy in patients with STEMI undergoing primary
PCI is unknown
Harmonizing Outcomes with Revascularization and Stents in AMI
≥3400* pts with STEMI with symptom onset ≤12 hours
Aspirin, thienopyridine
R
1:1
UFH + GP IIb/IIIa inhibitor
(abciximab or eptifibatide)
Bivalirudin monotherapy
(± provisional GP IIb/IIIa)
Emergent angiography, followed by triage to…
CABG – Primary PCI – Medical Rx
3000 pts eligible for stent randomization
Bare metal stent
*To rand 3000 stent pts
R
1:3
TAXUS paclitaxel-eluting stent
Clinical FU at 30 days, 6 months,
1 year, and then yearly through 5 years
Harmonizing Outcomes with Revascularization and Stents in AMI
≥3400* pts with STEMI with symptom onset ≤12 hours
Aspirin, thienopyridine
UFH + GP IIb/IIIa inhibitor
(abciximab or eptifibatide)
R
1:1
Bivalirudin monotherapy
(± provisional GP IIb/IIIa)
Pharmacology Arm
Primary Endpoints*
30 Day
Intention to Treat Population
* All stent randomization results are still blinded
30 Day Study Objectives

In patients with STEMI undergoing a primary
PCI strategy, compared to UFH plus the
routine use of GP IIb/IIIa inhibitors,
bivalirudin monotherapy will result in:
– Similar or reduced rates of net adverse
clinical events (the composite of ischemic
major adverse cardiovascular events and
major bleeding) at 30 days
– Similar or reduced rates of major bleeding
at 30 days
2 Primary Endpoints (at 30 Days)
1) Net Adverse Clinical Events
and
2) Major Bleeding (non CABG)
• Intracranial bleeding
• intraocular bleeding
• Retroperitoneal bleeding
• Access site bleed requiring
intervention/surgery
• Hematoma ≥5 cm
• Hgb ≥3g/dL with an overt source
• Hgb ≥4g/dL w/o overt source
• Reoperation for bleeding
• Blood product transfusion
2 Primary Endpoints (at 30 Days)
1) Net Adverse Clinical Events
=
2) Major Bleeding (non CABG)
or
Major adverse
cardiovascular events
(major secondary endpoint)
• All cause death
• Reinfarction
• Ischemic TVR
• Stroke
Harmonizing Outcomes with Revascularization and Stents in AMI
3602 pts with STEMI
R
1:1
Randomized
UFH +
GP IIb/IIIa
N=1802
9
15
Bivalirudin
Monotherapy
N=1800
• • • Withdrew • • •
• • • Lost to FU • • •
10
13
30 day FU*
N=1778
(98.7%)
N=1777
(98.7%)
ITT population
N=1802
N=1800
* Range ±7 days
Primary Management Strategy*
UFH + GP IIb/IIIa Inhibitor
N=1802
Primary PCI
Deferred PCI
Bivalirudin Monotherapy
N=1800
CABG
*Primary ITT analysis includes all pts regardless of treatment
Medical Rx
Primary Outcome Measures (ITT)
Heparin + GPIIb/IIIa inhibitor (N=1802)
30 day event rates (%)
20
15
Bivalirudin monotherapy (N=1800)
Diff = -2.9% [-4.9,-0.8]
RR = 0.76 [0.63,0.92]
Diff = -3.3% [-4.0,-1.6]
RR = 0.60 [0.46,0.77]
Diff = 0.0% [-1.6,1.5]
RR = 0.99 [0.76,1.30]
PNI ≤ 0.0001
Psup = 0.006
PNI ≤ 0.0001
Psup ≤ 0.0001
Psup = 1.00
12.1
10
9.2
8.3
4.9
5
1 endpoint
1 endpoint
Net adverse clinical
events
Major bleeding*
5.5
5.4
0
*Not related to CABG
**MACE = All cause death, reinfarction, ischemic TVR or stroke
MACE**
30 Day MACE Components*
UFH + GP IIb/IIIa
(N=1802)
Bivalirudin
(N=1800)
P Value
3.1%
2.1%
0.058
- Cardiac
2.9%
1.8%
0.035
- Non cardiac
0.2%
0.3%
0.75
Reinfarction
1.8%
1.8%
0.90
- Q-wave
1.2%
1.4%
0.66
- Non Q-wave
0.7%
0.4%
0.50
1.9%
2.6%
0.18
- Ischemic TLR
1.8%
2.5%
0.14
- Ischemic remote TVR
0.3%
0.3%
1.0
0.6%
0.7%
0.69
Death
Ischemic TVR
Stroke
*CEC adjudicated
Conclusions

In this large scale, prospective, randomized trial
of pts with STEMI undergoing a primary PCI
management strategy, compared to UFH plus the
routine use of GP IIb/IIIa inhibitors, bivalirudin
monotherapy with GP IIb/IIIa inhibitors reserved
for suboptimal PCI outcomes resulted in:
– A significant 24% reduction in the 30 day
primary endpoint of net adverse clinical events
– A significant 40% reduction in the 30 day
primary endpoint of major bleeding