Transcript J_Raymond_Cardiology Advances in 2015 ta... 12117KB Feb 23

Cardiology Advances in
2015
John Raymond MS, PA-C, MHP
February 5, 2016
HYPERTENSION
Systolic Blood Pressure Intervention Trial
Goals and Rationale
American Society of Hypertension
May 20, 2012
Karen C. Johnson, MD, MPH
University of Tennessee Health Science Center
Why is NIH Conducting SPRINT?
• High blood pressure is one of the most common
conditions among middle-aged and older adults, and is a
leading risk factor for stroke, heart disease, chronic
kidney disease, and other conditions.
• Previous trials demonstrate effectiveness of treating SBP
to about 140 mm Hg.
• Observational studies suggest benefits of SBP lowering
may extend to levels below 120 mm Hg.
• SPRINT will provide critical evidence regarding feasibility
and benefits and potential risks of more intensive BP
control.
Systolic Blood Pressure
Intervention Trial
• SPRINT is a randomized controlled clinical
trial examining the effect of a high blood
pressure treatment strategy aimed at
reducing systolic blood pressure (SBP) to
a lower goal than is currently
recommended.
SPRINT Important Goals
SPRINT will test whether a treatment strategy
aimed at reducing systolic blood pressure to:
• lower goal (SBP < 120 mm Hg)
compared with
• currently recommended (SBP < 140 mm Hg)
will reduce the occurrence of cardiovascular
disease (CVD).
N = 9250
SPRINT Primary Outcome
• Composite of
– MI
– Stroke
– Heart failure
– Acute coronary syndrome
– Cardiovascular death
The primary hypothesis is that CVD event rates will
be lower in the intensive intervention arm.
SPRINT Other Outcomes
•
Renal outcomes
– For Chronic Kidney Disease (CKD),
composite of:
•
ESRD or 50% decline in eGFR
– For non-CKD, progression to CKD:
•
ESRD or 30% decrease in eGFR to a
value of < 60 mL/min/1.73m2
Major Inclusion Criteria
• At least 50 years old
• Systolic blood pressure
–
–
–
–
SBP: 130 – 180 mm Hg on 0 or 1 medication
SBP: 130 – 170 mm Hg on up to 2 medications
SBP: 130 – 160 mm Hg on up to 3 medications
SBP: 130 – 150 mm Hg on up to 4 medications
• Risk (one or more of the following)
– Presence of clinical or subclinical CVD (not stroke)
– Chronic Kidney Disease (CKD), defined as eGFR 20 – 59 ml/min/1.73m2
– Framingham Risk Score for 10-year CVD risk ≥ 15%
– Not needed if eligible based on preexisting CVD or CKD
– Age ≥ 75 years
Major Exclusion Criteria
•
•
•
•
•
•
Stroke
Diabetes
Congestive heart failure (symptoms or EF < 35%)
Proteinuria >1g/d
CKD with eGFR < 20 mL/min/1.73m2 (MDRD)
Adherence flags
SPRINT Intensive Intervention
• Blood pressure medications are added
and/or titrated at each study visit to achieve
SBP <120 mm Hg
• Intervention goal is to create a minimum
mean difference between randomized
groups of at least 10 mm Hg
Medication Classes Provided by SPRINT
•
•
•
•
•
•
•
•
•
•
Angiotensin converting enzyme (ACE)-inhibitors
Angiotensin receptor blockers (ARBs)
Direct vasodilators
Thiazide-type diuretics
Loop diuretics
Potassium-sparing diuretics
Beta-blockers
Sustained-release calcium channel blockers (CCBs)
Alpha1-receptor blockers
Sympatholytics
The intervention in this trial, which carefully
adjusts the amount or type of blood pressure
medication to achieve a target systolic
pressure of 120 millimeters of mercury (mm
Hg), reduced rates of cardiovascular events,
such as heart attack and heart failure, as well
as stroke, by almost a third and the risk of
death by almost a quarter, as compared to the
target systolic pressure of 140 mm Hg.
NEWS
IN LIPIDS:
Background and Rationale

Despite the widespread availability of statins, many patients fail to
reach recommended LDL-C targets in clinical practice, even in
combination with other lipid lowering agents

In PCSK9 human population studies:
– Gain-of-function mutations result in hypercholesterolemia
– Loss-of-function mutations associated with low LDL-C and low
prevalence of CHD events

SAR236553/REGN727 is a highly specific, fully human monoclonal
antibody (mAb) to PCSK9

A SAR236553/REGN727 Phase 1 trial* in familial and non-familial
hypercholesterolemia:
– Demonstrated dose dependently reduced LDL-C by 36% to 58% either
with or without atorvastatin
– Safe and well-tolerated
*Stein EA, Mellis S, Yancopoulos GD et al. NEJM 2012; 366: 1108-1118.
LDL Receptor Function and Life Cycle
16
16
The Role of PCSK9 in the Regulation
of LDL Receptor Expression
17
17
Introduction
PCSK9 regulation
Both the LDL receptor and PCSK9 are up regulated by
statins through sterol regulatory element binding protein-2
(SREBP-2) stimulation
PCSK9 targeting
 Given these interrelationships, there has been considerable
interest in understanding the effect of statins on PCSK9
concentrations, particularly since agents designed to inhibit
PCSK9 are likely to be used as adjuncts to statin therapy
 Phase II and III clinical trials are currently being conducted
using PCSK9 antisense and inhibitors to lower LDL-C
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Summary and Conclusions

SAR236553 produced significant, dose-dependent LDL-C reductions
– Up to 72% LDL-C reduction with 150mg Q2W
– Improved ability to achieve LDL-C goal cut points
– LDL-C reductions were generally unaffected by baseline atorvastatin dose

Consistent and robust reductions for all other Apo B–containing lipoproteins
– Important reduction in Lp (a), consistent with prior studies

Trend towards decreases in TG and increases in HDL-C and Apo AI vs placebo

More sustained efficacy with Q2W vs. Q4W regimen

SAR236553 was well tolerated during this short study
– No signals for persistent or prevalent clinical or laboratory adverse events
including hepatic and muscle assessments.
– One patient experienced an occurrence of leukocytoclastic vasculitis; no similar
reactions reported in prior studies

These results support further evaluation of SAR236553 in larger, more diverse
patient populations with different background therapies to fully assess its efficacy
and safety.
OSLER Study Design
Standard of Care
N = 368
Evolocumab +
Standard of Care
Evolocumab +
Standard of Care
N = 736
Blinded
Stabilization
Period
Visits*
End of parent 4
study / Day 1
Primary
Objectives:
Years 2–5
8
Unblinded
Lipid
Treatment
12
Q4W
52
Q4W
OSLER Week
• Effects on LDL-C over 1 year
• Safety and Tolerability
Q4W, every 4 weeks. * Patients in the evolocumab + SOC group had in-person visits every 4 weeks. Patients in the
CONFIDENTIAL
NOT FOR
PROMOTIONAL
USEwith
– DO telephone
NOT COPY ORvisits
DISTRIBUTE
SOC group had in-person visits
at week 4,– then
every
3 months,
every 4 weeks.
End of Study
12-week studies:
MENDEL
(monotherapy)
LAPLACE-TIMI 57
(patients on statins)
GAUSS
(statin intolerance)
RUTHERFORD
(Familial hypercholesterolemia)
Randomization 2:1
Year 1
UC LDL-C Percentage Change from
Baseline to Week 52, Mean (SE)
OSLER: Percentage Change in LDL-C, by
UC, From Baseline to 1 Year
-2%
10
0
-10
-20
-30
-40
-50
-60
-3%
-52%
-52%
Baseline
Parent Study
Week 12
12
24
36
OSLER Study Week
48
52
Not Evolocumab / SOC Only (n = 96)
Not Evolocumab / Evolocumab + SOC (n = 192)
Evolocumab / Evolocumab + SOC (n = 544)
Evolocumab / SOC Only (n = 272)
SE, standard error; SOC, CONFIDENTIAL
standard of
care;
UC, ultracentrifugation
– NOT
FOR PROMOTIONAL
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< 70 mg/dL
SOC
Evolocumab + SOC
Proportion of Patients, %
< 100 mg/dL
Proportion of Patients, %
OSLER: LDL-C Goal Achievement
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LDL-C values by ultracentrifugation. SOC, standard of care
OSLER: Safety and Tolerability
Adverse events, %
Any adverse event
Serious
Possibly treatment-related (none serious)
Leading to discontinuation of evolocumab
Deaths
Most common adverse events
Nasopharyngitis
Upper respiratory tract infection
Arthralgia
Back pain
Muscle-related
Injection-site reactions
73.1
6.3
NA
NA
0.5
Evolocumab
+ SOC
N = 736
81.4
7.1
5.6*
3.7
0.1
9.8
7.6
4.3
5.4
9.8
NA†
12.2
7.7
6.9
6.5
9.2
5.2
SOC
N = 368
NA, not applicable; SOC, standard of care. *Percentage of adverse events. †Patients in the SOC group did not
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receive injections.
OSLER: Key Laboratory Results
SOC
N = 368
Evolocumab
+ SOC
N = 736
ALT or AST > 3 × ULN at any
post-baseline visit
6 (1.6)
13 (1.8)
Creatine kinase > 5 × ULN at any
post-baseline visit
7 (1.9)
7 (1.0)
Laboratory Results, n (%)
SOC, standard of care. ALT, alanine aminotransferase; AST, aspartate aminotransferase;
ULN, upper limit of normalCONFIDENTIAL – NOT FOR PROMOTIONAL USE – DO NOT COPY OR DISTRIBUTE
OSLER: Adjudicated Cardiovascular
Clinical Events
Event, Patient Incidence, n (%)
Any positively adjudicated cardiovascular
clinical event
Death
Myocardial infarction (fatal and non-fatal)
Hospitalization for unstable angina
Revascularization
Cerebrovascular event
Transient ischemic attack
Ischemic stroke
Hemorrhagic stroke
Hospitalization for heart failure
SOC, standard of care
SOC
N = 368
Evolocumab
+ SOC
N = 736
8 (2.2)
9 (1.2)
2 (0.5)
3 (0.8)
2 (0.5)
4 (1.1)
1 (0.3)
1 (0.3)
0 (0.0)
0 (0.0)
1 (0.3)
1 (0.1)
0 (0.0)
2 (0.3)
6 (0.8)
3 (0.4)
2 (0.3)
1 (0.1)
0 (0.0)
0 (0.0)
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OSLER: Conclusions


26
The 1 year OSLER analysis evaluated evolocumab in a
diverse patient population in the largest and longest
study of an anti-PCSK9 antibody reported to date.
Findings over > 1000 patient-years suggest a highly
effective, consistent, and well tolerated therapy.
– Evolocumab reduced LDL-C by an average of 50%
beyond that achieved with optimal SOC in various
hypercholesterolemic patient populations.
– AE profile was generally balanced.
– No adverse laboratory signals were observed.
– No major increase in AEs was observed in patients
who reached low or very low LDL-C levels.
NEWS
IN
CONGESTIVE HEART
FAILURE
27
Cardiac Resynchronization
Therapy for Heart Failure
Ventricular Dysynchrony and Cardiac
Resynchronization

Ventricular Dysynchrony1
– Electrical: Inter- or
Intraventricular conduction delays typically manifested as left bundle
branch block
– Structural: disruption of myocardial collagen matrix impairing electrical
conduction and mechanical efficiency
– Mechanical: Regional wall motion abnormalities with increased
workload and stress—compromising ventricular mechanics

Cardiac Resynchronization
– Therapeutic intent of atrial synchronized biventricular pacing
• Modification of interventricular, intraventricular, and atrial-ventricular
activation sequences in patients with ventricular dysynchrony
• Complement to optimal medical therapy
1
Tavazzi L. Eur Heart J 2000;21:1211-1214
Prevalence of Inter- or Intraventricular
Conduction Delay
General HF Population1,2
Moderate to Severe
HF Population3,4,5
IVCD >30%
IVCD 15%
1
2
3
4
5
Havranek E, Masoudi F, Westfall K, et al. Am Heart J 2002;143:412-417
Shenkman H, McKinnon J, Khandelwal A, et al. Circulation 2000;102(18 Suppl II): abstract 2293
Schoeller R, Andresen D, Buttner P, et al. Am J Cardiol. 1993;71:720-726
Aaronson K, Schwartz J, Chen T, et al. Circulation 1997;95:2660-2667
Farwell D, Patel N, Hall A, et al. Eur Heart J 2000;21:1246-1250
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Achieving Cardiac Resynchronization
Mechanical Goal: Atrial-synchronized bi-ventricular pacing

Transvenous Approach
– Standard pacing lead in RA
– Standard pacing or defibrillation lead in RV
– Specially designed left heart lead placed in a left ventricular
cardiac vein via the coronary sinus
Right Atrial
Lead
Right Ventricular
Lead
Left Ventricular
Lead
CRT Improves Quality of Life Score
and NYHA Functional Class
QoL
NYHA
PATH-CHF1 (n=41)
+
+
InSync (Europe)2 (n=103)
+
+
InSync ICD (Europe)3 (n=84)
+
+
MUSTIC4 (n=67)
+
MIRACLE5 (n=453)
+
+
MIRACLE ICD6 (n=364)
+
+
+

Blank
1 Auricchio
Statistically significant improvement with CRT (p  0.05)
Not statistically significant or No statistical analysis performed on data
Indicates test neither performed nor reported
A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39:2026-
2033
Gras D, Leclercq C, Tang A, et al. Eur J Heart Failure 2002;4:311-320
3 Kuhlkamp V. JACC 2002;39:790-797
4 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40:111-118
2
5 Abraham
W, Fisher W, Smith A, et al.
N Engl J Med. 2002;346:1845-1853
6 Leon A. NASPE Scientific Sessions – Late Breaking
Clinical Trials. May 2002; Medtronic Inc. data on file
CRT Improves Exercise Capacity
6 Min Walk
Peak VO2
PATH-CHF1 (n=41)
+
+
InSync (Europe)2 (n=103)
+
InSync ICD (Europe)3 (n=84)
+
MUSTIC4 (n=67)
+

MIRACLE5 (n=453)
+
+
+

+
+
MIRACLE ICD6 (n=364)
+

Blank
1 Auricchio
Statistically significant improvement with CRT (p  0.05)
Not statistically significant or No statistical analysis performed on data
Indicates test neither performed nor reported
A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39:2026-
2033
Gras D, Leclercq C, Tang A, et al. Eur J Heart Failure 2002;4:311-320
3 Kuhlkamp V. JACC 2002;39:790-797
4 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40:111-118
2
Exercise
Time
5 Abraham
W, Fisher W, Smith A, et al.
N Engl J Med. 2002;346:1845-1853
6 Leon A. NASPE Scientific Sessions – Late Breaking
Clinical Trials. May 2002; Medtronic Inc., data on file
CRT Improves Cardiac
Function/Structure
LVEF
MR
PATH-CHF1 (n=41)
+ LVEDP
+ LV dP/dtmax
InSync (Europe)2 (n=103)
+
InSync ICD (Europe)3 (n=84)
MUSTIC4 (n=67)
+


 LVEDD,LVESD
 Filling Time
MIRACLE5 (n=453)
+
+
+ LVEDD,
+ LVEDV, LVESV
MIRACLE ICD6 (n=362)

+
+ LVESV,
+ LVEDV
+

Blank
1 Auricchio
+ Filling Time
+ Filling Time
Statistically significant improvement with CRT (p  0.05)
Not statistically significant or No statistical analysis performed on data
Indicates test neither performed nor reported
A. Stellbrink C, Sack S., et al. J Am Coll Cardiol 2002;39:2026-
2033
Gras D, Leclercq C, Tang A, et al. Eur J Heart Failure 2002;4:311-320
3 Kuhlkamp V. JACC 2002;39:790-797
4 Linde C, Leclercq C, Rex S, et al. J Am Coll Cardiol 2002;40:111-118
2
Other
5 Abraham
W, Fisher W, Smith A, et al.
N Engl J Med. 2002;346:1845-1853
6 Young J. ACC Scientific Sessions – Late Breaking
Clinical Trials III. March 2002; Medtronic Inc.,
data on file
NEWS
IN
ANTICOAGULATION:
Non-Valvular Atrial Fibrillation
• 500,000 strokes/year in U.S.
• Up to 20% of ischemic strokes occur in
patients with atrial fibrillation
35
Percent of Total Strokes
Attributable to Atrial Fibrillation
30
25
%
20
15
10
5
0
Stroke 22(18), 1991
50-59
60-69
70-79
80-89
3000838-7
Non-Valvular Atrial Fibrillation Stroke Prevention
Medical Rx
• Warfarin cornerstone of therapy
• Assuming 51 ischemic strokes/1000 pt-yr
• Adjusted standard dose warfarin prevents
28 strokes at expense of 11 fatal bleeds
• Aspirin prevents 16 strokes at expense
of 6 fatal bleeds
• Warfarin
• 60-70% risk reduction vs no treatment
• 30-40% risk reduction vs aspirin
Cooper: Arch Int Med 166, 2006
Lip: Thromb Res 118, 2006
3000838-10
Primary Endpoints
Atrial Fibrillation Trials
Study
NOAC
VKA
Outcome
RE-LY
Dabigatran
1.1%
Warfarin
1.7%
RR 0.66
95% CI 0.53-0.82
P < 0.001
superiority
ARISTOTLE
Apixaban
1.3%
Warfarin
1.6%
HR 0.79
95% CI 0.66-0.95
P= < 0.001 Non- I
P= 0.01
Superiority
ROCKET-AF
Rivaroxaban
1.7%
Warfarin
2.2%
HR 0.79
95% CI 0.66-0.96
P = <0.001
Non-Inferiority
Major Bleeding
Atrial Fibrillation Trials
Study
NOAC
VKA
Outcome
RE-LY
Dabigatran
3.3%
Warfarin
3.6%
RR 0.93
95% CI 0.81-1.07
P = 0.31
ARISTOTLE
Apixaban
2.1%
Warfarin
3.1%
HR 0.69
95% CI 0.60-0.8
P = < 0.001
ROCKET-AF
Rivaroxaban
5.6%
Warfarin
5.4%
HR 1.04
95% CI 0.90-1.20
P = 0.58
Intracranial Hemorrhage
Atrial Fibrillation Trials
Study
NOAC
VKA
Outcome
RE-LY
Dabigatran
0.3%
Warfarin
0.7%
RR 0.40
95% CI 0.27-0.60
P= <0.001
ARISTOTLE
Apixaban
0.3%
Warfarin
0.8%
HR 0.42
95% CI 0.30-0.58
P = <0.001
ROCKET-AF
Rivaroxaban
0.5%
Warfarin
0.7%
HR 0.67
95% CI 0.47-0.93
P = 0.02
Dosing Schedules
Atrial Fibrillation
Agent
Dosing Recommendations
Dabigatran
75mg, 150mg
CrCl > 30 cc/min: 150 mg, BID
CrCl 15 to 30 cc/min: 75 mg, BID
Avoid < 15 cc/min
Apixaban
2.5mg, 5mg
CrCl > 15 cc/min: 5 mg, BID
Any 2 ( > 80 yrs, < 60 kg, SCr > 1.5mg/dL:
2.5 mg, BID)
Avoid < 15 cc/min
Rivaroxaban
CrCl > 50 cc/min: 20 mg, Qday
10mg, 15mg, 20mg CrCl 15-50 cc/min: 15 mg, Qday
Avoid CrCl < 15 cc/min
Pharmacologic Characteristics
Characteristics Dabigatran
Rivaroxaban
Apixaban
Target
IIa
Xa
Xa
Bioavailability
7%
60%-80%
80%
Half-Life
12-17 hrs
7-11 hrs
12 hrs
Clearance
80% renal
60% renal
33% biliary
25% renal
75% biliary
Metabolism
Conjugation to
active
glucuronides
CYP3A4
CYP2J2
CYP3A4
P-GP interaction
Yes
Yes
Yes minimal
Galanis T et al Thromb Thrombolysis 2011;31:310-320
INABILITY TO USE
ANTICOAGULATES
Non-Valvular Atrial Fibrillation
Stroke Pathology
• Major fatal bleed with age >75 = 3%/year
(30% over 10 years)
• Intracranial hemorrhage
• 0.3-0.5%/100 patient-years
• 3% in INR >4.0
• 10% if INR >4.5
Brass. Stroke 28(12), 1997
VanWalraven: JAMA 288, 2002
3000838-15
Non-Valvular Atrial Fibrillation
Stroke Pathology
• Insufficient contraction of LAA leads to
stagnant blood flow
• Most likely culprit: embolization of LAA clot
• 90% of thrombus found in LAA
• TEE-based risk factors
• Enlarged LAA
• Reduced inflow and outflow velocities
• Spontaneous Echo contrast
Blackshear: Ann Thoracic Surg 61, 1996
Johnson: Eur J Cardiothoracic Surg 17, 2000
Fagan: Echocardiography 17, 2000
3000838-9
WATCHMAN® LAA Closure Technology
3000838-20
Risk
/ Benefit
Analysis
Risk/Benefit
Analysis
Per-protocol analysis
• Superiority for the primary efficacy event rate
• Approximately 86% of patients in the device
group were able to be successfully implanted
and discontinue warfarin therapy
• Study demonstrates the role of the left atrial
appendage in the pathogenesis of stroke due
to AF
• Based on average age, patients will
experience a 56% reduction in safety events
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3000838-122
Summary
• Long-term warfarin treatment of patients with AF has been
found effective, but presents difficulties and risk
• PROTECT AF trial was a randomized, controlled,
statistically valid study to evaluate the WATCHMAN device
compared to warfarin
• In PROTECT AF, hemorrhagic stroke risk is significantly
lower with the device.
• When hemorrhage occurred, risk of death was
markedly increased
• In PROTECT AF, all cause stroke and all cause mortality
risk are equivalent to that with warfarin
• In PROTECT AF, there are early safety events, specifically
pericardial effusion; hese events have decreased over time
3000838-123
Conclusion
The WATCHMAN LAA Technology offers a safe and
effective alternative to warfarin in patients with nonvalvular atrial fibrillation at risk for stroke and who are
eligible for warfarin therapy
3000838-124
VALVULAR
DISEASE
HEART
Prevalence of Aortic Stenosis
16.5 Million People in US
Over the Age of 652


Aortic stenosis is estimated to
be prevalent in up to 7% of the
population over the age of 651
Percentage
Diagnosed with
Aortic Stenosis
It is more likely to affect men
than women; 80% of adults
with symptomatic aortic
stenosis are male3
51
Aortic Stenosis Demographics
 Aortic stenosis
2% US population >65yrs old
 Aortic sclerosis
29% US population> 65 yrs old
 Aortic sclerosis
50% greater risk of mortality
and myocardial infarction.
 Aortic sclerosis progresses to aortic stenosis in 9%
over 5 years
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What Causes Aortic Stenosis in
Adults?
More Common
Age-Related Calcific
Aortic Stenosis
Aortic stenosis in patients over the age of 65 is
usually caused by calcific (calcium) deposits
associated with aging
Rheumatic Fever
Adults who have had rheumatic fever may also be
at risk for aortic stenosis
Congenital
Abnormality
In some cases adults may develop aortic stenosis
resulting from a congenital abnormality
Less Common
53
3 Major Etiologies for aortic stenosis
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Signs and Symptoms



Heart Failure
Angina
Syncope





Carotid Parvus et
Tardus
Laterally displaced PMI
Soft A2
CrescendoDecrescendo systolic
murmur
Timing of peak murmur
and NOT intensity
predicts severity
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Sobering Perspective
8
35
5-Year Survival
30
30
28
Survival, %
25
20
23
15
12
10
5
4
3
0
Breast
Cancer
Lung
Cancer
Colorectal
Cancer
Prostate
Cancer
Ovarian
Cancer
Severe
Inoperable AS*
*Using constant hazard ratio. Data on file, Edwards Lifesciences LLC. Analysis courtesy of Murat Tuczu, MD, Cleveland Clinic
5 year survival of breast cancer, lung cancer, prostate cancer, ovarian
cancer and severe inoperable aortic stenosis
56
What is TAVR-Transcatheter Aortic
Valve Replacement?

An aortic valve replacement as an
alternative to traditional
thoracotomy.

Less invasive than traditional
thoracotomy for patients
considered too high risk for
traditional surgery.
57
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



Two TAVR Options
Edwards Sapien Valve
Stainless Steel Frame
More Aortic Regurg, less
AV block/PPM
Better for severe bulky
calcification.



Medtronic CoreValve
Nitinol Frame-self expanding
Less Aortic Regurg, More
heart block/PPM
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Edwards SAPIEN THV Improved Cardiac
Function
Error bars = ± 1 Std Dev
THE PARTNER TRIAL COHORT B
59
Complications
Stroke was defined as follows: Neurological deficit lasting ≥ 24 hours or lasting less than 24 hours with a brain imaging study showing an infarction.
Major vascular complications were defined as any thoracic aortic dissection, access site or access-related vascular injury (dissection, stenosis, perforation, rupture,
arterio-venous fistula, pseudoaneurysm, or hematoma) leading to either death, need for significant blood transfusion (> 3 units), or percutaneous or surgical
intervention, and/or distal embolization (non-cerebral) from a vascular source requiring surgery or resulting in amputation or irreversible end-organ damage.
Bleeding event is defined as ≥ 2 units within the index procedure.
THE PARTNER TRIAL COHORT B
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