rapid fire review of acc.17 late-breaking clinical trials · study design aim: compare the efficacy...

Rapid Fire Review of ACC.17 Late-Breaking Clinical Trials

Akhil Narang, MDAdvanced Cardiac Imaging Fellow, University of ChicagoImmediate Past Chair, ACC Fellows-in-Training Section

2017 ACC Illinois/Wisconsin Annual MeetingLake Geneva, WIMay 7, 2017

@AkhilNarangMD

Michael J. Reardon, MD

For the SURTAVI Investigators

Transcatheter Aortic Valve Replacement with a Self-Expanding Prosthesis or Surgical Aortic Valve

Replacement in Intermediate-Risk Patients:First Results from the SURTAVI Clinical Trial

• TAVR is is superior in patients at high risk for operative mortality at 30 days.1

• Comparative efficacy of TAVR and SAVR has been less well studied in AS patients at lower surgical risk.

Background

1Adams D, Popma J, Reardon M, et al. New Engl J Med 2014

3

Objective

Assess the safety and efficacy of TAVR with the self-expanding valve vs. surgical AVR in patients

with symptomatic, severe AS at intermediate surgical risk

4

Intermediate Surgical Risk Predicted risk of operative mortality ≥3% and <15%

Heart Team EvaluationAssess inclusion/exclusion

Risk classification

RandomizationStratified by need for revascularization

TAVR SAVR

TAVR + PCI SAVR + CABGTAVR only SAVR only

Baseline neurological assessments

Screening CommitteeConfirmed eligibility

5

Trial Design

• 17 sites in Europe• 5 sites Canada• 65 sites in the

United States

894 patients

796 patients

First patient enrolled June 19, 2012

Primary endpointassessment Dec 2016

CoreValve (n=724) Evolut R (n=139)

2012 2013 2014 2015 2016

Enrollment completed June 30, 2016

Evolut R (US)

CoreValve: 23, 26 and 29 mm (CAN, EU)

CoreValve: 31 mm (US, CAN, EU)

94% TF4% DA2% SCA

6

CoreValve: 23, 26 and 29 mm (US)

April

Study Timeline

0%

5%

10%

15%

20%

25%

30%

0 6 12 18 24

All-

Cau

se M

ort

alit

y o

r D

isab

ling

Stro

ke

Months Post-ProcedureNo. at Risk796 674 555 407 241

864 755 612 456 272TAVR

SAVR

Primary Endpoint: All-Cause Mortality or Disabling Stroke

24 Months

TAVR SAVR12.6% 14.0%

7

Meetsnoninferiority

0%

5%

10%

15%

20%

25%

30%

0 6 12 18 24

24 Months

TAVR SAVR95% CI for Difference

11.4% 11.6% -3.8, 3.3

0%

5%

10%

15%

20%

25%

30%

0 6 12 18 24

All-

Cau

se M

ort

alit

y

Months Post-Procedure

TAVR SAVR

No. at Risk796 690 569 414 249

864 762 621 465 280TAVR

SAVR

All-Cause Mortality

30 DaySAVR 1.7% O:E 0.38TAVR 2.2% O:E 0.50

8

0%

2%

4%

6%

8%

10%

0 6 12 18 24

Dis

ablin

g St

roke

Months Post-ProcedureNo. at Risk

796 674 555 407 241

864 755 612 456 272TAVR

SAVR

Disabling Stroke

24 Months

TAVR SAVR95% CI for Difference

2.6% 4.5% -4.0, 0.1

9

• SURTAVI met its primary endpoint: TAVR with a self-expanding CoreValve or Evolut R bioprosthesis is noninferior to SAVR for all-cause mortality or disabling stroke at 24 months.

• TAVR had significantly less 30 day stroke, AKI, atrial fibrillation and transfusion use and a superior quality of life at 30 days.

• TAVR resulted in significantly improved AV hemodynamics with lower mean gradients and larger aortic valve areas than SAVR through 24 months.

• SAVR had less residual aortic regurgitation, major vascular complications and fewer new pacemakers.

• Need for a new pacemaker after TAVR was not associated with increased mortality.

Summary

10

• In SURTAVI, TAVR with the self-expanding valve was safe and effective treatment for patients with symptomatic severe AS at intermediate risk for surgical mortality

Summary

11

Dr. Phil Wells on behalf of the EINSTEIN CHOICE Steering Committee and Investigators

Weitz JI et al. N Engl J Med 2017 (DOI: 10.1056/NEJMoa1700518)

Rivaroxaban or Aspirin for Extended Treatment

of Venous Thromboembolism

NCT02064439

Background

Risk of recurrent VTE is up to 10% in the first year if anticoagulation (AC) is

stopped in patients without reversible risk factors for VTE

ASA has been previously shown to reduced rates of recurrent VTE

Although extended AC prevents recurrent VTE, there is reluctance to extend

treatment beyond 6-12 months due to bleeding

Study Design

Aim: Compare the efficacy and safety of once daily rivaroxaban (20 or 10 mg)

with aspirin (100 mg) in VTE patients who completed 6 to 12 months of

treatment

Randomized, double-blind, active-comparator, event-driven, superiority study

1 month

observation

period

Rivaroxaban 20 mg od (1121 patients)

Rivaroxaban 10 mg od (1127 patients)N=3396Patients with confirmed

symptomatic DVT/PE who completed 6–12 months of anticoagulation

R

Aspirin 100 mg od (1069 patients)

12-month treatment duration

Weitz JI et al. Thromb Haemost 2015;114:645–50

Recurrent VTE – Cumulative Incidence

VTE, Venous thromboembolism; HR, hazard ratio

Aspirin 4.4% (50/1131)

Rivaroxaban 20 mg 1.5% (17/1107)


Days

0

1

2

3

4

5

Cu

mu

lati

ve

in

cid

en

ce

(%

)

1 30 60 90 120 150 180 210 240 270 300 330 367

Number of patients at risk

Rivaroxaban 20 mg 1107 1102 1095 1090 1084 1079 997 876 872 860 794 718 0

Rivaroxaban 10 mg 1126 1124 1119 1118 1111 1109 1029 890 886 867 812 723 0

Aspirin 1131 1121 1111 1103 1094 1088 1010 859 857 839 776 707 0

Major Bleeding – Cumulative Incidence

Treatment-emergent major bleeding: onset during study treatment up to 2 days after stop of study treatment

Number of patients at risk

Rivaroxaban 20 mg 1107 1081 1063 1048 1036 1024 963 818 801 780 712 642 449 10 0 0 0

Rivaroxaban 10 mg 1126 1103 1080 1070 1058 1046 988 823 812 790 733 653 469 8 0 0 0

Aspirin 1131 1096 1075 1058 1040 1023 970 800 791 768 709 645 445 5 2 2 0

0

1

2

4

5

3

1 30 60 120 150 180 240 270 300 360 390 420 45090 210 330 480Days

Aspirin 0.3% (3/1131)



Cu

mu

lati

ve

in

cid

en

ce

(%

)

Summary and Conclusions

In patients with VTE who completed 6 to 12 months of treatment, rivaroxaban

(20 or 10 mg once daily) is superior to ASA for recurrent VTE and are

associated with similar rates of bleeding

Compared with aspirin, NNT to prevent one VTE without increase in bleeding for

rivaroxaban 20 mg QD = 33 and rivaroxaban 10 mg QD = 30

Rivaroxaban 10 mg once daily provides an additional option for extended

VTE treatment

*Number needed to treat (NNT) compared with aspirin for primary efficacy outcome up to 1 year

COMPARE-ACUTE

Randomised trial of

FFR-guided complete revascularization

versus

infarct artery only treatment in

multivessel STEMI patients

On behalf of all COMPARE-ACUTE investigators

Pieter Smits

Maasstad Hospital

Rotterdam, The Netherlands

Introduction

• ~50% of the STEMI patients have multivessel disease at

presentation (≥50% stenosis in ≥1 non-infarct-related

arteries (non-IRAs)

• Management of these non-IRAs lesions an unresolved

clinical dilemma

Trial design

885 stable multivesselSTEMI pts. randomized

295 pts

Acute FFR-guided complete revascularization of non-IRA lesions

590 pts

Infarct related artery only treatment + blinded FFR of non-IRA lesions

1 : 2 randomization

Follow-up at 30 days, 12, 24 and 36 months

45 day treatment window for

elective clinically indicated PCI

Acute STEMI patients

undergoing primary PCI

FFR was

measured

by Pd/Pa in

rest and after

adenosine iv

or ic

Primary outcome

No. at risk

FFR guided complete

295 286 281 264 215

Culprit lesion only 590 512 492 457 371

HR = 0.35 (95% CI 0.22 - 0.55),

p<0.001

Log-rank p<0.001

7.8%

20.5%

Driven by the

decreased need

for subsequent

revascularization

Conclusions

• In multivessel STEMI patients, FFR-guided complete

revascularization of non-IRA in the acute phase reduced

the risk of the composite MACCE outcome compared to

treatment of the IRA only

• This reduction was mainly driven by the decreased need

for subsequent revascularization

DECISION-CTO

Optimal Medical Therapy With or Without

Stenting For Coronary Chronic Total Occlusion

Seung-Jung Park, MD., PhD.

Heart Institute, University of Ulsan College of Medicine

Asan Medical Center, Seoul, Korea

Background

• Benefits of successful CTO-PCI include reduced angina and

improvements in QOL, LVEF, or survival.

• CTO-PCI can lead to procedure-related complications.

• Evidence for CTO-PCI mostly from observational studies,

most of which compared successful and failed CTO-PCI

without a control group receiving optimal medical treatment.

DECISION CTO Trial

• OBJECTIVE: To compare the outcomes of OMT alone with

PCI coupled with OMT in patients with CTO.

• DESIGN: a prospective, open-label, randomized trial

• Inclusion Criteria:

- Silent ischemia, stable angina, or ACS

- De novo CTO located in a proximal to mid epicardial coronary artery with a

reference diameter of ≥2.5 mm

Study Procedures

• Patients who were assigned to PCIs underwent CTO-PCI using DES within 30

days after randomization

• In cases of failed CTO-PCI, additional attempts were allowed within 30 days

after the index procedure.

• Patients were prescribed guideline derived OMT including aspirin, P2Y12

receptor inhibitors (>12months in case of PCI), BB, CCB, nitrate, ACEi/ARB,

and statin.

• Blood pressure and diabetic control, smoking cessation, weight control, and

regular exercise were recommended.

Noninferiority Test for Primary End Point at 3-Year

Prespecified non-inferiority margin: 0.7

Lower 1-sided 97.5% CI

0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5

Event Rate Ratio 1.05

Non-inferiority P=0.008

Estimated 3-year Event Rate OMT: 19.6% PCI: 20.6%

Event Rate Ratio of 3-year MACE rate (PCI/OMT)

ITT Population

Non-inferiority met with ITT (not in as-treated

analysis or in per-protocol analysis)

Primary End Point(Death, MI, Stroke, Any Repeat Revascularization)

ITT Population

No. at Risk

OMT 398 305 246 178 129 72

PCI 417 293 241 175 117 65

Y e a rs S in c e R a n d o m iz a t io n

Pro

ba

bil

ity

(%

)

0 1 2 3 4 5

0

1 0

2 0

3 0

4 0

5 0

6 0

Crude HR 0.95 (95% CI, 0.74-1.22), P=0.67

Adjusted HR 0.91 (95% CI, 0.68-1.23), P=0.54

20.6%

19.6%25.1%

26.3%

PCIOMT

Conclusion

• DECISION-CTO trial is the first RCT to compare the strategy of OMT alone with that of

PCI in patients with coronary CTO.

• The ITT analysis showed that OMT as an initial strategy was non-inferior to PCI with

respect to the primary endpoint of the composite of death, MI, stroke, or any

revascularization at 3 years.

• Quality of life in the OMT and the PCI groups were comparable.

• OMT could be a reasonable initial treatment strategy for coronary CTO compared

with CTO-PCI.

Relationship between highsensitivity Troponin T

measurements and 30-day mortality after noncardiac surgery

PJ Devereaux, MD, PhD

McMaster University

Background• >5 Million Americans >45 years old undergo in-patient noncardiac surgery/year

and 1.3% die in hospital

– Cardiac complications are leading cause

• Myocardial injury after noncardiac surgery (MINS) is

– Defined as myocardial injury caused by ischemia that occurs during or within 30 days after surgery and is independently associated with mortality

• Little is known about relationship between perioperative hsTnT measurements and 30-day mortality and MINS

Design and Methods • Prospective, international, cohort study

• >45 yrs underwent in-patient noncardiac surgery

• Participating countries (23 centers in 13 countries)

• Patients had hsTnT measurements 6-12 hours after surgery and daily for 3 days

– 40.4% had preoperative hsTnT measurement

Results• 21,842 participants

– Mean age 63 years, 49% were female

• Most common types of surgery

– Major orthopedic (16%)

– Major general (20%)

– Low-risk (35%)

• 21,050 (96.4%) completed 30-day follow-up

– 266 patients (1.2%; 95% CI, 1.1-1.4) died within 30 days of surgery

Peak postoperative hsTnT thresholds associated with 30-day mortality

• No interaction b/w postop hsTnT threshold ≥20 ng/L and eGFR or sex (interaction p=0.83 and 0.20)

hsTnT thresholds % of PatientsMortality Rate

(%)aHR (95% CI) p-value

<5 ng/L 24.4 0.1 1.00 -

5 to <14 ng/L 40.1 0.5 3.73 (1.58-8.82) 0.003

14 to <20 ng/L 11.6 1.1 9.11 (3.76-22.09) <0.001

20 to <65 ng/L 18.6 3.0 23.63 (10.32-54.09) <0.001

65 to <1000 ng/L 5.1 9.1 70.34 (30.60-161.71) <0.001

≥1000 ng/L 0.2 29.6 227.01 (87.35-589.92) <0.001

• Among 4385 patients with elevated postop hsTnT

– 481 (11.0%) had non-ischemic (e.g., sepsis) non-MINS hsTnT elevation

– 13.8% of patients with elevated perioperative hsTnT had their peak value before surgery

Conclusions• Elevated postoperative hsTnT measurements strongly associated with 30-

day mortality (regardless of eGFR and sex)

• 13.8% of patients had their peak value before surgery suggests

– Physicians should consider obtaining preoperative hsTnT measurement in patients who they plan to measure hsTnT after surgery

• MINS may explain 24% of perioperative deaths

• 93% of MINS would probably go undetected without troponin monitoring

Subclinical Leaflet Thrombosis in Surgical and

Transcatheter Bioprosthetic Aortic ValvesResults from RESOLVE and SAVORY registries

Raj R. Makkar, MD

On Behalf of RESOLVE and SAVORY Investigators

• Subclinical leaflet thrombosis (reduced leaflet motion on CT) reported in ~10-15% of

patients after TAVR and surgical bioprosthetic AV

– Less common in patients on therapeutic anticoagulation with warfarin and resolves with

initiation of warfarin.

• No data on differences between SAVR and TAVR, impact of NOACs on prevention,

treatment, and outcomes

• Objective: Characterize incidence of leaflet thrombosis in SAVR/TAVR and role of

NOACs in management

Background

Makkar R. et al. NEJM 2015; Pache G. et al. EHJ 2015; Yanagisawa R. et al. JACC: Cardiovascular

Interventions 2016; Hansson NC. et al. JACC 2016; Ruile P. et al. Clin Res Cardiol 2017

Valve types and timing of CTTime from TAVR to CT vs. SAVR to CT: p<0.0001

890 patients with CTs (RESOLVE and SAVORY Registry)

Median time from AVR to CT 83 days (IQR 32-281 days)

752 transcatheter valves

Median time from TAVR to CT

58 days (IQR 32–236 days)

138 surgical valves

Median time from SAVR to CT

162 days (IQR 79–417 days)

Hypoattenuated leaflet thickening assessed using 2D and 3D volume-rendered (VR) imaging. Leaflet motion was assessed using 4D VR imaging.

Reduced leaflet motion was defined as the presence of at least 50% restriction of leaflet motion.

Prevalence of reduced leaflet motionTranscatheter vs. surgical bioprosthetic aortic valves: p=0.001

Reduced leaflet motion was present in 106

(11.9%) patients

Transcatheter valves

13.4% (101 out of 752)

Surgical valves

3.6% (5 out of 138)

Anticoagulation and reduced leaflet motionAnticoagulation vs. no anticoagulation

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

Pre

va

len

ce o

f re

du

ced

lea

flet

mo

tio

n

Anticoagulation NOACs WarfarinNo

anticoagulation

8/224

(3.6%) 3/107

(2.8%)

5/117

(4.3%)

98/666

(14.7%)Anticoagulation vs. no anticoagulation: p<0.0001

NOACs vs. no anticoagulation: p=0.0002

Warfarin vs. no anticoagulation: p=0.001

NOACs vs. warfarin: p=0.72

Anticoagulation and reduced leaflet motionAnticoagulation vs. antiplatelet therapy

0.0

2.0

4.0

6.0

8.0

10.0

12.0

14.0

16.0

18.0

Pre

va

len

ce o

f re

du

ced

lea

flet

mo

tio

n

Anticoagulation NOACs Warfarin DAPT

8/224

(3.6%) 3/107

(2.8%)

5/117

(4.3%)

31/208

(14.9%)Anticoagulation vs. DAPT: p<0.0001

Anticoagulation vs. monoantiplatelet therapy: p<0.0001

63/405

(15.6%)

Monoantiplatelet

therapy

Impact of initiation of anticoagulation on

reduced leaflet motion

0.0

20.0

40.0

60.0

80.0

100.0

120.0

Pre

va

len

ce o

f re

du

ced

lea

flet

mo

tio

n

Resolution

36/36

(100%) • Resolution in 36 out of

36 patients treated with

anticoagulation

(NOACs, n=12;

warfarin, n=24)

• Persistence/progression

in 20 out of 22 patients

not treated with

anticoagulation

P<0.0001No change or

progressionResolution No change or

progression

0/36

(0%)

2/22

(9.1%)

20/22

(89.1%)

Anticoagulation initiated No anticoagulation initiated

Conclusions

• In a heterogeneous cohort of bioprosthetic AV, reduced leaflet motion occurred 12% on CT.

• SAVR vs TAVR, had lower incidence of reduced leaflet motion (3.6% vs. 12%; p<0.04).

However, SAVR patients younger and fewer comorbidities.

• Anticoagulation with both warfarin and NOACs and not DAPT which is the standard of care

were effective in prevention and treatment of reduced leaflet motion.

• Cases of subclinical leaflet thrombosis diagnosed by CT are hemodynamically silent and hence

missed by TTE

• While the death, MI and stroke rates were not significantly different between the 2 groups,

subclinical leaflet thrombosis was associated with increased rates of TIAs and strokes/TIAs.

Background

• Management of stable coronary disease: optimize risk factors, OMT

– Revascularize those with resistant symptoms and proven ischemia

• FAME & DEFER showed FFR to invasive angiography has

prognostic benefits

• Combination of OMT + FFR-guided revascularization current best

invasive management strategy for patients with stable angina

Optimal Non-Invasive Strategy

• Non-invasive ischemia testing with perfusion imaging accurately

predicts flow-limiting stenosis and outcomes

• CMR perfusion imaging highest accuracy of non-invasive testing

– No radiation

– Gives anatomy, function, and myocardial structure

• Combination of OMT + CMR perfusion current best non-invasive

management strategy for patients with stable angina

Hypothesis

• In patients with stable angina and intermediate to high

risk of CAD, guiding the initial management with OMT

+ CMR-perfusion imaging is non-inferior to OMT +

invasive angiography with FFR

Optimal Medical Therpy

• All patients received OMT

– ASA or Clopidogrel

– Statin (goal LDL <2 mmol/L (77 mg/dL), total chol <4 mmol/L (154 mg/dL))

– ACE-I or ARB (goal BP <130/80)

– Counseling (goal BMI <25, random glucose <6 mmol/L (108 mg/dL), non-

smoking)

918 patients total randomized (groups well matched)-27% with diabetes-13% with known CAD

FFR arm (464)CMR arm (454)

Follow-up 1-year

MACE at 1-year-FFR vs. CMR: 3.9% vs. 3.3%, P=0.62

-Death: 0.22% vs. 0.89%-MI: 1.7% vs. 1.8%-Repeat revasc: 1.9% vs. 0.7%

Conclusions

• CMR-perfusion guided management of stable angina is

noninferior for the MACE endpoint at 1 year compared with

invasive angiography and FFR

• First trial to show that CMR-perfusion imaging could guide

patient management in a high-risk population with the same

effectiveness as invasive angiography with FFR

An Academic Research Organization of

Brigham and Women’s Hospital and Harvard Medical School

FOURIERFurther cardiovascular OUtcomes

Research with PCSK9 Inhibition in

subjects with Elevated RiskMS Sabatine, RP Giugliano, AC Keech, N Honarpour,

SM Wasserman, PS Sever, and TR Pedersen,

for the FOURIER Steering Committee & Investigators



Sever P & Mackay J. Br J Cardiol 2014;21:91-3

Giugliano RP, et al. Lancet 2012;380:2007-17

Sabatine MS, et al. NEJM 2015;372:1500-9

Proprotein convertase subtilisin/kexin type 9 (PCSK9)

• Chaperones LDL-R to destruction circulating LDL-C

Evolocumab

• Fully human anti-PCSK9 mAb

• ~60% LDL-C

• Safe & well-tolerated in Ph 2 & 3 studies

• Exploratory data suggested CV events

Objective: In patients with CV disease on statin therapy, test whether

evolocumab reduces incidence of major CV events; long-term safety

Background & Objective

evolocumab



Trial Design

Evolocumab SC 140 mg Q2W or 420 mg QM

Placebo SCQ2W or QM

LDL-C ≥70 mg/dL or

non-HDL-C ≥100 mg/dL

Follow-up Q 12 weeks

Screening, Lipid Stabilization, and Placebo Run-in

High or moderate intensity statin therapy (± ezetimibe)

27,564 high-risk, stable patients (49 countries) w/ established

CV disease (prior MI, prior stroke, or symptomatic PAD)

RANDOMIZED

DOUBLE BLIND

Sabatine MS et al. Am Heart J 2016;173:94-101



Lipid Lowering Therapy

& Lipid Levels at BaselineCharacteristic Value

Statin use (%)*

High-intensity 69

Moderate-intensity 30

Ezetimibe use (%) 5

Median lipid measures (IQR) – mg/dL

LDL-C 92 (80-109)

Total cholesterol 168 (151-189)

HDL-C 44 (37-53)

Triglycerides 133 (100-182)

*Per protocol, patients were to be on atorva ≥20 mg/d or equivalent.

1% were on low intensity or intensity data were missing.

Statin intensity defined per ACC/AHA 2013 Cholesterol Guidelines.

Pooled data; no differences between treatment arms



0

10

20

30

40

50

60

70

80

90

100

0 12 24 36 48 60 72 84 96 108 120 132 144 156 168

LD

L C

ho

les

tero

l (m

g/d

l)

Weeks

LDL Cholesterol

Evolocumab

(median 30 mg/dl, IQR 19-46 mg/dl)

Placebo

59% mean reduction (95%CI 58-60), P<0.00001

Absolute reduction: 56 mg/dl (95%CI 55-57)



0%

2%

4%

6%

8%

10%

12%

14%

16%

Primary Endpoint

Evolocumab

Placebo

Months from Randomization

CV

Death

, M

I, S

tro

ke,

Ho

sp

fo

r U

A,

or

Co

rR

evasc

0 6 12 18 24 30 36

Hazard ratio 0.85

(95% CI, 0.79-0.92)

P<0.0001 12.6%

14.6%



Lower LDL-C Is Better

P<0.0001

Patients divided by quartile of baseline LDL-C and by treatment arm

Q4

Q3

Q2

Q1

Q4Q3

Q2

Q1

PlaceboEvolocumab



0%

2%

4%

6%

8%

0%

2%

4%

6%

8%

Landmark Analysis

Evolocumab

Placebo

Months from Randomization

CV

Death

, M

I, S

tro

ke

0 3 9 12 24 30 366 12 18

16% RRR

HR 0.84 (95%CI 0.74-0.96)

P=0.008

25% RRR

HR 0.75 (95%CI 0.66-0.85)

P<0.00001



Summary for Evolocumab

• LDL-C by 59%

– Consistent throughout duration of trial

– Median achieved LDL-C of 30 mg/dl (IQR 19-46 mg/dl)

• CV outcomes in patients already on statin therapy

– 15% broad primary endpoint; 20% CV death, MI, or stroke

– Consistent benefit, incl. in those on high-intensity statin, low LDL-C

– 25% reduction in CV death, MI, or stroke after 1st year

• Safe and well-tolerated

– Similar rates of AEs, incl DM & neurocog events w/ evolocumab & placebo

– Rates of evolocumab discontinuation low and no greater than pbo

– No neutralizing antibodies developed



Conclusions

In patients with known cardiovascular disease:

1. PCSK9 inhibition with evolocumab significantly &

safely major cardiovascular events when added to

statin therapy

2. Benefit was achieved with lowering LDL cholesterol

well below current targets

rapid fire review of acc.17 late-breaking clinical trials · study design aim: compare the efficacy...

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