Sponsors Discussants Milan Gupta Narendra Singh Deepak Bhatt MD, - - PowerPoint PPT Presentation

Sponsors

Milan Gupta MD, FRCPC, FCCS, FACC, FAHA

Associate Clinical Professor McMaster University Medical Director, Canadian Collaborative Research Network Brampton, ON

Narendra Singh MD, FRCPC, FCCS, FACC, FAHA

Director, Clinical Research, Atlanta Heart Specialists Clinical Assistant Professor, Medical College of Georgia at Augusta University Clinician Scientist and Co-Director, Canadian Collaborative Research Network Atlanta, GA

Deepak Bhatt MD, MPH, FACC, FAHA, FSCAI, FESC

Executive Director, Interventional Cardiovascular Programs,Brigham and Women’s Hospital Heart & Vascular Center Professor of Medicine Harvard Medical School Boston, MA

Discussants

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• These are remarkable times.
• We hope you and your loved ones are all safe and healthy.
• We thank all frontline health care workers for their dedication during this

pandemic.

• For the first time in history, the live scientific sessions of the ACC were cancelled.
• Instead, ACC held a virtual meeting over 3 half days using a novel format.
• This program highlights the key clinical trials presented at ACC 2020, and explores

the clinical implications for cardiovascular care.

Introduction

Heart failure

• VICTORIA
• New data from PARAGON-HF

Lipids

• Homozygous FH
• EPA levels in REDUCE-IT
• New data from ODYSSEY Outcomes
• Evolocumab for HIV patients

Peripheral arterial disease

• VOYAGER-PAD
• COMPASS-DM

Structural heart disease

• Updates in TAVR

Key topics at ACC 2020

Heart failure

• VICTORIA
• New data from PARAGON-HF

Lipids

• Homozygous FH
• EPA levels in REDUCE-IT
• New data from ODYSSEY Outcomes
• Evolocumab for HIV patients

Peripheral arterial disease

• VOYAGER-PAD
• COMPASS-DM

Structural heart disease

• Updates in TAVR

Key topics at ACC 2020

Cardiovascular death

HR 0.82 (0.69, 0.98); p=0.029

Worsening HF event

HR 0.70 (0.59, 0.83); p=0.00003

CV prognosis remains unacceptably poor in HFrEF

Dapagliflozin Placebo Dapagliflozin Placebo

DAPA-HF study, 2019

ACC 2020: What You Need To Know

Discussion

Heart failure

• VICTORIA
• New data from PARAGON-HF

Lipids

• Homozygous FH
• EPA levels in REDUCE-IT
• New data from ODYSSEY Outcomes
• Evolocumab for HIV patients

Peripheral arterial disease

• VOYAGER-PAD
• COMPASS-DM

Structural heart disease

• Updates in TAVR

Key topics at ACC 2020

Back ckground

26

Hess…Hiatt et al. JACC 2020 Jones…Fowkes et al. Circulation 2017 Bonaca…Sabatine et al. JACC 2017 Bonaca…Morrow et al. Circulation 2016

N=393,017 Cumulative Incidence Years from Index Revascularization

Risk in Patients Undergoing Peripheral Revascularization

Major Adverse Limb Events 4x risk of ALI Long-term vs. no Revascularization MACE

“Acute” Post Revascularization “Stable” Phase

Outcomes in Patients with Acute Limb Ischemia

• Median hospitalization 8 days (IQR 5-15)
• ~4% die at presentation
• ~1/5  major amputation
• ~1/3  prolonged ICU stay
• ~3/4  major surgery
• Outcomes after hospitalization are poor with

~15% disabled or dead

VOYAGER P ER PAD

Vascul ular Out utcomes S Stud udy of

• f ASA A

Along with Ri h Rivaroxaba ban in n Endo ndovascula lar o

• r

Sur urgical L l Limb b Revasculariz izatio ions ns f for Periphe pheral Artery Disease

Marc P. Bonaca, Rupert M. Bauersachs, Manesh R. Patel, Sonia S. Anand, Eike Sebastian Debus, Mark N. Nehler, Fabrizio Fanelli, Warren H. Capell, Nicole Jaeger, Lihong Diao, Connie N. Hess, John

• M. Kittelson, Lloyd P. Haskell, Scott D. Berkowitz, William R. Hiatt,

for the VOYAGER PAD Steering Committee & Investigators

American College of Cardiology Virtual Scientific Sessions 2020 Late-Breaking Clinical Trial March 28, 2020

Trial De Design gn

6,564 Patients with Symptomatic Lower Extremity PAD* Undergoing Peripheral Revascularization

Primary Efficacy Endpoint: Acute limb ischemia, major amputation of vascular etiology, myocardial infarction, ischemic stroke or cardiovascular death Principal Safety Outcome: TIMI Major Bleeding Follow up Q6 Months, Event Driven, Median f/u 28 Months

Randomized 1:1 Double Blind

ASA 100 daily for all Patients Clopidogrel at Investigator’s Discretion NCT02504216 Stratified by Revascularization Approach (Surgical or Endovascular) and Use of Clopidogrel

*Ankle Brachial Index < 0.90 and Imaging Evidence

• f Occlusive

Disease

Capell WH, Bonaca MP, Nehler MR…Hiatt WR. AHJ 2018

Rivaroxaban 2.5 mg twice daily Placebo

Primary En Endpoint: Acut

ute l limb i b ischemia, m major amput utation for vascul ular caus use, m myocardial i l infarctio ion, , ische hemic ic s stroke, CV de death

Primary En Endpoint & & C Components

KM% 3 Years Rivaroxaban N=3286 KM% 3 Years Placebo N=3278 HR (95% CI) Primary Efficacy Outcome 17.3 19.9 0.85 (0.76 – 0.96) Acute Limb Ischemia 5.24 7.74 0.67 (0.55 – 0.82) Major Vascular Amputation 3.42 3.87 0.89 (0.68 – 1.16) Ischemic Stroke 2.70 3.01 0.87 (0.63 – 1.19) Myocardial Infarction 4.55 5.22 0.88 (0.70 – 1.12) CV Death 7.05 6.43 1.14 (0.93 – 1.40)

First E Events ts P Prevented / Cause sed f for

• r 10,

10,000 000 Patients ts Treated* f for

• r 1

1 Year

• 300
• 200
• 100

100 200 300

Favors Rivaroxaban 2.5 mg twice daily plus aspirin Favors aspirin monotherapy

• 181
• 110
• 20
• 42
• 19
• 10

29

• 6

Primary Efficacy Outcome

Acute Limb Ischemia Major Amputation of Vascular Etiology Myocardial Infarction Ischemic Stroke Cardiovascular Death

Principal Safety Outcome

Intracranial Hemorrhage Fatal Bleeding

(-269 – -94) (-165 – -56) (-53 – 12) (-84 – -1) (-50 – 13) (-48 – 28) (-2 – 60) (-22 – 11) (-10 – 11) *Efficacy and safety on-treatment

Summary & Conclusion

• In symptomatic PAD after revascularization, ~1 in 5 have acute limb ischemia, major

amputation of vascular etiology, MI, ischemic stroke or cardiovascular death at 3 years

• In this population and setting, rivaroxaban 2.5 mg twice daily with aspirin compared to

aspirin alone:  Significantly reduces this risk with…

• Benefits apparent early and continued over time
• Consistent benefit across major subgroups
• Broad benefits including reductions in unplanned index limb revascularization

 Increases bleeding: in VOYAGER PAD, there was a numerical increase in TIMI major bleeding and significantly increased ISTH major bleeding but no excess in intracranial

• r fatal bleeding

 Prevents ~6 times as many ischemic events relative to bleeds caused in PAD patients after revascularization

VOYAGE AGER P PAD Efficacy a and S Safety of R Rivaroxaban i in Patients with Symptomatic c PAD u undergoing R Revascularization with a and w without C Clopidogrel

William R. Hiatt, Marc P. Bonaca*, Manesh R. Patel, Mark R. Nehler, Eike Sebastian Debus, Sonia S. Anand, Warren H Capell, Lihong Diao, Nicole Jaeger, Connie N. Hess, Akos Ferenc Pap, Scott D. Berkowitz,Eva Muehlhofer, Lloyd Haskell, David Brasil, Juraf Madaric, Henrick Sillesen, David Szalay, Rupert Bauersachs on behalf of the VOYAGER PAD Investigators

American College of Cardiology Virtual Scientific Sessions 2020 Late-Breaking Clinical Trial 29 March 2020

Primary Endpoint

Acute limb ischemia, major amputation for vascular cause, myocardial infarction, ischemic stroke, CV death

ISTH M Major B Bleedi eding ng W With a h and W nd Witho hout ut C Clopi pido dogrel

Summa mmary

• In patients with symptomatic PAD undergoing

revascularization:

• The benefit of rivaroxaban plus aspirin versus aspirin alone is consistent regardless of

background clopidogrel

• Primary efficacy endpoint HR ~0.85 with rivaroxaban regardless of clopidogrel with NNT < 50

with or without clopidogrel

• The safety of rivaroxaban plus aspirin versus aspirin alone is consistent regardless of

background clopidogrel

• Principal safety outcome TIMI major bleeding HR ~1.3-1.5 regardless of clopidogrel with NNH >

90 with or without clopidogrel

• However, clopidogrel exposure was associated with higher rates of bleeding overall,

particularly with longer durations (e.g. > 30 days)

Discussion

Heart failure

• VICTORIA
• New data from PARAGON-HF

Lipids

• Homozygous FH
• EPA levels in REDUCE-IT
• New data from ODYSSEY Outcomes
• Evolocumab for HIV patients

Peripheral arterial disease

• VOYAGER-PAD
• COMPASS-DM

Structural heart disease

• Updates in TAVR

Key topics at ACC 2020

Alirocumab Efficacy And Safety In Adults With Homozygous Familial Hypercholesterolemia (ODYSSEY HoFH)

Dirk J. Blom

University of Cape Town, Cape Town, South Africa

Mariko Harada-Shiba, Paolo Rubba, Daniel Gaudet, John J.P. Kastelein, Min-Ji Charng, Robert Pordy, Stephen Donahue, Shazia Ali, Yuping Dong, Nagwa Khilla, Marie Baccara-Dinet, Robert S. Rosenson

Background

• HoFH is characterized by extremely high LDL-C levels and early onset atherosclerotic

cardiovascular disease despite treatment with conventional lipid lowering therapy1-3

• HoFH includes true homozygotes, compound heterozygotes and double heterozygotes1
• HoFH results from severely impaired LDLR function, most commonly due to mutations

in both copies of the LDLR gene1

• Mutation in other genes of the LDLR pathway (APOB, PCSK9, and LDLRAP1) may also

affect LDLR function1

• 1. Cuchel M et al. Eur Heart J. 2014;35:2146-2157. 2. Hovingh GK, Goldberg AC, Moriarty PM. J Clin Lipidol. 2017;11:602-616. 3. Raal FJ, Hovingh GK, Catapano AL. Atherosclerosis. 2018;277:483-492.

Baseline Characteristics

Alirocumab (n=45) Placebo (n=24) Age, years, mean (SD) 42.3 (14.1) 45.4 (15.8) Male, n (%) 21 (46.7) 13 (54.2) Race, n (%) White 36 (80.0) 18 (75.0) Black or African American 2 (4.4) Asian 7 (15.6) 5 (20.8) Body mass index, kg/m2, mean (SD) 25.1 (5.4) 25.1 (5.1) History of CHD, n (%) 21 (46.7) 9 (37.5)

Lipid-Lowering Therapy at Screeninga

n (%) Alirocumab (n=45) Placebo (n=24) Any statin 44 (97.8) 23 (95.8) High-intensity statinb 38 (84.4) 21 (87.5) Ezetimibe 31 (68.9) 19 (79.2) Statin + ezetimibe 30 (66.7) 19 (79.2) Lomitapide 7 (15.6) 3 (12.5) Apheresis + other LLT 6 (13.3) 4 (16.7)

Baseline Lipids

Alirocumab (n=45) Placebo (n=24) LDL-C, mmol/L, mean (SD) 7.6 (4.0) 6.7 (4.6) Non-HDL-C, mmol/L, mean (SD) 8.3 (4.1) 7.3 (4.6) Apolipoprotein B, g/L, mean (SD) 1.9 (0.8) 1.7 (0.9) HDL-C, mmol/L/L, mean (SD) 1.1 (0.4) 1.1 (0.3) Triglycerides, mmol/L, median (Q1:Q3) 1.24 (0.9:1.8) 0.90 (0.7:1.4) Lp(a), mg/dL, median (Q1:Q3) 36.0 (10.0:68.0) 32.5 (12.0:52.5)

Primary Endpoint: LDL-C % Change vs. Placebo at Week 12a

• 40
• 30
• 20
• 10

10 20 4 8 12 LS mean (SE) percent change from baseline in LDL-C (%) Time (weeks)

LS mean difference (SE) versus placebo: –35.6 (7.8)%, P<0.0001 –26.9 (4.6)% −62.8 (14.0) mg/dL 8.6 (6.3)% 8.9 (19.0) mg/dL

∆ Alirocumab 150 mg Q2W (n=45) ○ Placebo (n=24) 0.23 (0.49) mmol/L

• 1.62 (0.36) mmol/L

% Change in LDL-C at Week 12 by Genotype

• 100
• 80
• 60
• 40
• 20

20 40 60 80

Change from baseline in LDL-C at Week 12 (%) * * * **

Alirocumab 150 mg Q2W Placebo Null/null (LDLR activity <2%) Single null LDLR variant

* † † † † †

No mutation identified Double heterozygous (LDLR + APOB or PCSK9) Homozygous (LDLR) Compound heterozygous (LDLR) Heterozygous (LDLR + other benign variants) Homozygous (LDLRAP1) Homozygous (PCSK9)

Conclusions

• This is the largest randomized controlled interventional trial in HoFH patients to date
• Treatment with alirocumab resulted in a statistically significant and clinically meaningful reduction in

LDL-C at Week 12 versus placebo

• Consistent reductions in LDL-C were observed from baseline to Week 12 for all subgroups,

including patients on apheresis

• Alirocumab also significantly reduced ApoB, non-HDL-C, TC and Lp(a)
• LDL-C response more variable in patients with HoFH than in other forms of hypercholesterolemia
• Alirocumab was generally well tolerated with no distinct safety differences versus placebo

EPA Levels and Cardiovascular Outcomes in the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial

Deepak L. Bhatt, MD, MPH, Michael Miller, MD, Ph. Gabriel Steg, MD, Eliot A. Brinton, MD, Terry A. Jacobson, MD, Steven B. Ketchum, PhD, Rebecca A. Juliano, PhD, Lixia Jiao, PhD, Ralph T. Doyle, Jr., BA, Christina Copland, PhD, Richard L. Dunbar, MD, Craig Granowitz, MD, PhD, Fabrice MAC Martens, MD, PhD, Matthew Budoff, MD, John R. Nelson, MD, R. Preston Mason, PhD, Peter Libby, MD, Paul Ridker, MD, Jean-Claude Tardif, MD, Christie M. Ballantyne, MD,

• n Behalf of the REDUCE-IT Investigators

Bhatt DL, Steg PG, Miller M, et al. N Engl J Med. 2019; 380:11-22. Bhatt DL.AHA 2018, Chicago.

Primary Composite Endpoint:

CV Death, MI, Stroke, Coronary Revasc, Unstable Angina

Key Secondary Composite Endpoint:

CV Death, MI, Stroke

Primary and Key Secondary Composite Endpoints

Icosapent Ethyl Patients with an Event (%) 1 2 3 4 Years since Randomization 5 10

16.2%

Icosapent Ethyl Patients with an Event (%) 1 2 3 4 Years since Randomization 5 10

30

Hazard Ratio, 0.75

(95% CI, 0.68–0.83)

28.3%

30

Hazard Ratio, 0.74

(95% CI, 0.65–0.83) 20

RRR = 24.8% ARR = 4.8% NNT = 21 (95% CI, 15–33) P=0.00000001 23.0%

20

RRR = 26.5% ARR = 3.6% NNT = 28 (95% CI, 20–47) P=0.0000006 20. 0%

Baseline 26.1 26.1

Year 1 144 112.6 393.5 <0.0001 23.3

• 2.9
• 12.8

<0.0001 114.9 385.8 <0.0001 Year 2 169 137.3 478.6 <0.0001 28 0.5 2.8 <0.0001 137.1 457.4 <0.0001 Year 3 168 137.4 464.5 <0.0001 27.3

• 0.1
• 0.4

<0.0001 136.9 447.5 <0.0001 Year 4 162 132.6 452.1 <0.0001 26.2

• 1.1
• 5.2

0.15 133 439.8 <0.0001 Year 5 158 130.5 463.6 <0.0001 25.3

• 0.5
• 2

0.09 130.8 448.1 <0.0001 Last Visit 150 117.9 395.2 <0.0001 26.5

• 0.9
• 3.8

0.08 119 380.3 <0.0001 On- Treatment EPA Daily Average (derived) 135.2 103.9 363.9 <0.0001 27.7 0.2 <0.0001 103.8 347.7 <0.0001

Bhatt DL. ACC/WCC 2020, Chicago(virtual).

Levels of Eicosapentaenoic Acid (EPA) in Serum

Year 6 values are not included as the number of patients = 9.

Primary Composite Endpoint Key Secondary Composite Endpoint HR (95% CI) Significance P-value HR (95% CI) Significance P-value Overall Trial 0.75 (0.68–0.83) 0.00000001 0.74 (0.65–0.83) 0.0000006 Lipid/Biomarker Covariate HR (95% CI) for Treatment Comparison (Adjusting Covariate) Significance P-value HR (95% CI) for Treatment Comparison (Adjusting Covariate) Significance P-value EPA (µg/mL) 1.03 (0.91–1.16) <0.0001 0.98 (0.84–1.14) <0.0001 Triglycerides (mg/dL) 0.77 (0.70–0.85) <0.0001 0.75 (0.66–0.85) <0.0001 LDL-C derived (mg/dL) 0.75(0.68–0.83) 0.80 0.74 (0.65–0.84) 0.38 HDL Cholesterol-CDC (mg/dL) 0.73 (0.66–0.81) <0.0001 0.71 (0.63–0.80) <0.0001 Non-HDL Cholesterol (mg/dL) 0.78 (0.71–0.87) <0.0001 0.77 (0.68–0.87) <0.0001 Apolipoprotein B (mg/dL) 0.76 (0.69–0.84) 0.03 0.75 (0.66–0.85) 0.0004 hsCRP (mg/L) 0.76 (0.69–0.84) 0.004 0.74 (0.66–0.84) <0.0001 RLP-C (mg/dL) 0.78(0.71–0.87) <0.0001 0.77 (0.68–0.87) <0.0001

Bhatt DL. ACC/WCC 2020, Chicago(virtual).

Stratified Analysis of Time to Primary Endpoint by Adjusting Time-Varying Covariates of Post-Baseline Biomarkers

Primary Composite Endpoint Key Secondary Composite Endpoint HR (95% CI) Significance P-value HR (95% CI) Significance P-value Overall Trial 0.75 (0.68–0.83) 0.00000001 0.74 (0.65–0.83) 0.0000006 Lipid/Biomarker Covariate HR (95% CI) for Treatment Comparison (Adjusting Covariate) Significance P-value HR (95% CI) for Treatment Comparison (Adjusting Covariate) Significance P-value EPA (µg/mL) 1.03 (0.91–1.16) <0.0001 0.98 (0.84–1.14) <0.0001 Triglycerides (mg/dL) 0.77 (0.70–0.85) <0.0001 0.75 (0.66–0.85) <0.0001 LDL-C derived (mg/dL) 0.75(0.68–0.83) 0.80 0.74 (0.65–0.84) 0.38 HDL Cholesterol-CDC (mg/dL) 0.73 (0.66–0.81) <0.0001 0.71 (0.63–0.80) <0.0001 Non-HDL Cholesterol (mg/dL) 0.78 (0.71–0.87) <0.0001 0.77 (0.68–0.87) <0.0001 Apolipoprotein B (mg/dL) 0.76 (0.69–0.84) 0.03 0.75 (0.66–0.85) 0.0004 hsCRP (mg/L) 0.76 (0.69–0.84) 0.004 0.74 (0.66–0.84) <0.0001 RLP-C (mg/dL) 0.78(0.71–0.87) <0.0001 0.77 (0.68–0.87) <0.0001

Bhatt DL. ACC/WCC 2020, Chicago(virtual).

Stratified Analysis of Time to Primary Endpoint by Adjusting Time-Varying Covariates of Post-Baseline Biomarkers

Primary and Key Secondary Composite Endpoints, Cardiovascular Death, and Total Mortality by On- Treatment Serum EPA

• No. of

Primary Endpoint1-5 Key Secondary Endpoint1-5 Cardiovascular Death1,2,4-6 TotalMortality1,2,4-6 P*<0.001 for all

Bhatt DL. ACC/WCC 2020, Chicago(virtual).

Dose-Response of Hazard Ratio (95% CI) Primary Composite Endpoint by On-Treatment Serum EPA

Established Cardiovascular Disease or Diabetes with Risk Factors

• No. of Patients 3765

Primary Endpoint: Established Cardiovascular Disease

Primary Endpoint: Diabetes with Risk Factors P*<0.001 for all

Bhatt DL. ACC/WCC 2020, Chicago(virtual).

Compared with placebo, icosapent ethyl 4g/day significantly reduced first and total cardiovascular events by 25% and 30%, respectively.

• These benefits were beyond what can be explained by the degree of

triglyceride or other biomarker changes On-treatment EPA levels via icosapent ethyl correlate strongly with the primary endpoint, the key secondary endpoint, CV death, MI, stroke, coronary revascularization, unstable angina, sudden cardiac death, cardiac arrest, new heart failure, and all-cause mortality. These data provide a mechanistic underpinning for the large risk reductions seen in multiple endpoints with icosapent ethyl in REDUCE-IT.

Bhatt DL. ACC/WCC 2020, Chicago(virtual).

Conclusions

61

OO Guidelines

Landmesser U, McGinniss J, Steg G, Bhatt DL, Bittner VA, Diaz R, Dilic M, Goodman SG, Harrington RA, Wouter Jukema J, Laucevicius A, Pecin I, Pordy R, Poulsen SH, Roe MT, Szarek M, White HD, Zeiher AM, Schwartz GG, for the ODYSSEY OUTCOMES Investigators

ACC 2020 – Chicago, USA March 28–30, 2020

Achievemen ent o

• f New E

ew Europ

• pean Dyslip

lipid idemia ia-Guid idelin line Low

• w-Den

ensity L y Lipop

• prot
• tei

ein C Choles ester erol

• l T

Treatmen ent G Goals After A Acute C Coronary S Syndrome

Insights From ODYSSEY OUTCOMES

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ACC 2020

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OO Guidelines

• The 2019 ESC/EAS dyslipidemia guidelines have recalibrated targets of

lipid-lowering therapy, particularly for secondary prevention.1

• In patients considered very high risk (including those with ACS) a LDL-C

goal of <1.4 mmol/L (<55 mg/dL) is now recommended, with a goal of <1.0 mmol/L (40 mg/dL) for patients with recurrent cardiovascular events within 2 years.

• Using data from the ODYSSEY OUTCOMES trial,2 we examined how many

patients achieved these new goals with the PCSK9 inhibitor alirocumab, and projected how many would have achieved the goals with the use of ezetimibe.

Background and Aim

ACS, acute coronary syndromes; EAS, European Atherosclerosis Society; ESC, European Society of Cardiology; LDL-C, low-density lipoprotein cholesterol, PCSK9, proprotein convertase subtilisin−kexin type 9

• 1. Mach F, et al. Eur Heart J. 2020;41:111-188; 2. Schwartz G, et al. NEJM. 2019;379:2097−107

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ACC 2020

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OO Guidelines

Results

• At baseline, 89% of patients received intensive statin treatment; 3%

received ezetimibe.

• Median baseline LDL-C was 2.3 mmol/L [88.9 mg/dL] (interquartile range

1.9–2.7 [73.5 – 104.4 mg/dL])

54 77 101 124 147 170 193 217 240 263 286 309 333 356 379 402 425 449 472 495 518

[mg/dL]

64

ACC 2020

64

OO Guidelines

Percent of patients who achieved LDL-C <1.4 mmol/L on at least 1 post-baseline measurement according to baseline LDL-C level

• Of the patients treated with alirocumab, 94.6% achieved LDL-C

<1.4 mmol/L (<54 mg/dL) on at least one post-baseline measurement, compared with 17.3% in the placebo arm.

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ACC 2020

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OO Guidelines

Patients with prior ASCVD event who achieved LDL-C <1.0 mmol/L at any time post-baseline according to baseline LDL-C level

• Of patients with at least one prior ischemic cardiovascular event (in addition to

the index ACS), 84% assigned to alirocumab achieved LDL-C <1.0 mmol/L (<39 mg/dL) at any time after baseline, compared with 3.7% with placebo

Discussion

Heart failure

• VICTORIA
• New data from PARAGON-HF

Lipids

• Homozygous FH
• EPA levels in REDUCE-IT
• New data from ODYSSEY Outcomes
• Evolocumab for HIV patients

Peripheral arterial disease

• VOYAGER-PAD
• COMPASS-DM

Structural heart disease

• Updates in TAVR

Key topics at ACC 2020

Background

• Previous PARTNER trials have shown that TAVR

was superior to standard therapy in extreme-risk patients and non-inferior to surgery in high- and intermediate-risk patients with aortic stenosis.

• Results from the PARTNER 3 Trial in low-risk

patients demonstrated superiority for TAVR vs. surgery for the primary endpoint of death, stroke,

• r rehospitalization at 1 year.

Low Risk/TF ASSESSMENT by Heart Team (STS < 4%)

1:1 Randomization 1000 Patients TAVR

(SAPIEN 3 THV) Surgery

(Surgical Bioprosthetic Valve)

Symptomatic Severe Aortic Stenosis

Follow-up: 30 days, 6 mos, and annually through 10 years PRIMARY ENDPOINT: Composite of all-cause mortality, stroke, or CV re-hospitalization at 1 year post-procedure

PARTNER 3 Study Design

Baseline Patient Characteristics

Demographics & Vascular Disease TAVR (N=496) Surgery (N=454) Other Co-Morbidities TAVR (N=496) Surgery (N=454)

Age (years) 73.3 ± 5.8 73.6 ± 6.1 Diabetes 31.3% 30.2% Male 67.5% 71.1% COPD (any) 5.1% 6.2% BMI – kg/m2 30.7 ± 5.5 30.3 ± 5.1 Pulmonary Hypertension 4.6% 5.3% STS Score 1.9 ± 0.7 1.9 ± 0.6 Creatinine > 2mg/dL 0.2% 0.2% NYHA Class III or IV* 31.3% 23.8% Frailty (overall; > 2/4+) Coronary Disease 27.7% 28.0% Atrial Fibrillation (h/o) 15.7% 18.8% Prior CABG 3.0% 1.8% Permanent Pacemaker 2.4% 2.9% Prior CVA 3.4% 5.1% Left Bundle Branch Block 3.0% 3.3% Peripheral Vascular Disease 6.9% 7.3% Right Bundle Branch Block 10.3% 13.7% % or mean ± SD *P = 0.01

Primary Endpoint

6 12 18 24

496 462 452 436 454 378 370 352 Number at risk: TAVR Surgery

Months after Procedure

422 339

TAVR Surgery Death, Stroke, or Rehosp (%)

11.5% 17.4% 10 20 HR [95% CI] = 0.63 [0.45, 0.88] P = 0.007 HR [95% CI] = 0.52 [0.35, 0.76] P < 0.001 15.6% 8.5% ∆ 7.1%

Primary Endpoint

6 12 18 24

496 462 452 436 454 378 370 352 Number at risk: TAVR Surgery

Months after Procedure

422 339

TAVR Surgery Death, Stroke, or Rehosp (%)

11.5% 17.4% 10 20 HR [95% CI] = 0.63 [0.45, 0.88] P = 0.007 HR [95% CI] = 0.52 [0.35, 0.76] P < 0.001 15.6% 8.5% ∆ 7.1% ∆ 5.9%

The PARTNER 3 Trial

Conclusions

In a defined population of severe symptomatic aortic stenosis patients who were at low surgical risk, TAVR (using the SAPIEN 3 valve) compared to surgery @ 2 years demonstrated:

• Reduced primary endpoint events (37% reduction in death, stroke or

CV rehospitalization); BUT…

• More death and stroke events in TAVR patients from

1 to 2 years; no significant differences @ 2 years

• Reduced CV rehospitalizations favoring TAVR
• Increased valve thrombosis events in TAVR patients, esp. from 1 to 2

years

• Hemodynamic improvements and frequency of moderate or mild

paravalvular regurgitation were unchanged between 1 and 2 years in both TAVR and surgery patients

Discussion

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Program completion

Access your notes following the program in My Account

• n the MD-Online website

Download these slides from the PROGRAM PAGE

• n the MD-Online website

Links & Resources

Program Page

Sponsors