Updates in Coronary Artery Disease Disclosure Statement of and - - PowerPoint PPT Presentation

Updates in Coronary Artery Disease and Interventional Cardiology

Lucas S Zier, MD, MS

Assistant Clinical Professor of Medicine Division of Cardiology Zuckerberg San Francisco General Hospital University of California San Francisco

Disclosure Statement of Financial Interest

None

Outline

Prevention

1. Understand the use of aspirin in the prevention of coronary artery disease 2. Understand the use of fish oil in the prevention of coronary artery disease

Stable Ischemic Heart Disease

1. Define the role of percutaneous coronary intervention in the management

• f stable ischemic heart disease

2. Review current guidelines for dual antiplatelet therapy duration following percutaneous coronary intervention and acute coronary syndrome

Structural Heart Disease

1. Define the expanding role of Transcatheter Aortic Valve Replacement in the management of aortic stenosis 2. Review the role of percutaneous mitral valve therapies in the clinical management of patients with mitral regurgitation

Outline

Prevention

1. Understand the use of aspirin in the prevention of coronary artery disease 2. Understand the use of fish oil in the prevention of coronary artery disease

Stable Ischemic Heart Disease

1. Define the role of percutaneous coronary intervention in the management

• f stable ischemic heart disease

2. Review current guidelines for dual antiplatelet duration following percutaneous coronary intervention and acute coronary syndrome

Structural Heart Disease

1. Define the expanding role of Transcatheter Aortic Valve Replacement in the management of aortic stenosis 2. Review the role of percutaneous mitral valve therapies in the clinical management of patients with mitral regurgitation

An ounce of prevention is worth a pound of cure

• Benjamin Franklin

Audience Response Question: Aspirin

Low dose daily aspirin should be prescribed to which of the following patient(s) to reduce the risk of primary cardiovascular events:

• A. 66 year old man with diabetes and a strong family

history of coronary artery disease

• B. 72 year old woman with non anginal, chronic chest

pain, no significant cardiovascular risk factors, and a negative stress test

• C. 46 year old man with no cardiovascular risk factors

who presents to your office wanting to reduce his lifetime risk of cardiovascular disease

• D. None of the above
• E. All of the above

6 6 y e a r

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. . N

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e

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58% 0% 0% 42% 0%

Primary Prevention: Aspirin

Gaziano JM, Brotons C, Coppolecchia R, et al., on behalf of the ARRIVE Executive Committee. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo- controlled trial. Lancet 2018;Aug 26:

Primary Prevention: Aspirin

ARRIVE Trial

Clinical Question: What is the clinical benefit of 100 mg per day of aspirin in reducing the risk of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischemic attack in patients at moderate risk of cardiovascular events without diabetes?

Primary Prevention: Aspirin

ARRIVE Trial

Primary Prevention: Aspirin

ARRIVE Trial Aspirin Placebo p Value

Composite Outcome of Cardiovascular Death, Myocardial Infarction, Unstable Angina, Stroke, or TIA

4.3% 4.5% p = 0.60 Gastrointestinal Bleeding 0.97% 0.43% p = 0.0007

The ASCEND Study Collaborative Group. Effects of Aspirin for Primary Prevention in Persons With Diabetes Mellitus. N Engl J Med 2018;379:1529-39.

Primary Prevention: Aspirin

ASCEND Trial

Clinical Question: What is the clinical benefit of 100 mg per day of aspirin in reducing the risk of vascular death, myocardial infarction,

• r

stroke/transient ischemic attack in patients with known diabetes but no history of cardiovascular disease?

Primary Prevention: Aspirin

ASCEND Trial

Primary Prevention: Aspirin

ASCEND Trial Aspirin Placebo p Value

Composite Outcome of Cardiovascular Death, Myocardial Infarction, Stroke, or TIA

8.5% 9.6% p = 0.01 Major Bleeding 4.1% 3.2% p = 0.003

Primary Prevention: Aspirin

ASCEND Trial

Aspirin resulted in a 1.1% absolute risk reduction in major adverse cardiovascular events Aspirin resulted in a 0.9% absolute increase in major bleeding

NNT: 1000 NNH: 1111

Primary Prevention: Aspirin

ASCEND Trial Aspirin Placebo p Value Gastrointestinal Cancer 2.0% 2.0% p = 1 All Cancer 11.6% 11.5% p = 0.98

What about cancer?... Primary Prevention: Aspirin

Primary Prevention: Aspirin

Aspirin and All Cause Mortality in 14 Primary Preventions Trials

Primary Prevention: Aspirin Summary An aspirin a day… Should not routinely be prescribed to patients without prior cardiovascular events due to a lack of clinical benefit and/or increased risk

• f bleeding that offsets the reduction in

cardiovascular events Primary Prevention: Aspirin Summary

2019 ACC/AHA Guidelines

Arnett, Donna K., et al. "2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease." Journal of the American College of Cardiology (2019): 26029.

Secondary Prevention: Fish Oil

Audience Response Question: Fish Oil

A 72 year old woman presents to your office for a follow up appointment. She has a history of diabetes, hypertension, hyperlipidemia and recently had a STEMI treated with PCI to her mid LAD. She is on appropriate guideline directed medical therapy for CAD including a statin. She wants to further reduce her risk of future cardiovascular events and asks whether she should take fish oil. The most appropriate advice is:

• A. It is reasonable to take any over the counter fish oil

supplement at 2 grams per day to reduce her risk of future cardiovascular events

• B. There is no data supporting the use of fish oil for

secondary prevention of cardiovascular events

• C. Pharmaceutical grade DHA derived from fish oil will

reduce her risk of cardiovascular events

• D. Pharmaceutical grade EPA derived from fish oil will

reduce her risk of cardiovascular events

I t i s r e a s

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a b l e t

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a k e a . . T h e r e i s n

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a t a s u p p

• r

t i . . P h a r m a c e u t i c a l g r a d e D . . P h a r m a c e u t i c a l g r a d e E . .

8% 22% 11% 58%

Bhatt DL, Steg G, Miller M, et al., on behalf of the REDUCE-IT Investigators. Cardiovascular Risk Reduction With Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med 2019;380:11-22.

Secondary Prevention: Fish Oil

REDUCE-IT Trial

Clinical Question: What is the clinical benefit of icosapent ethyl in reducing the risk of cardiovascular death, non fatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina in patients with established cardiovascular disease

• r diabetes and one additional risk factor already

receiving a stable dose of a statin?

Secondary Prevention: Fish Oil

REDUCE-IT Trial

Secondary Prevention: Fish Oil

REDUCE-IT Trial Icosapent Ethyl Placebo p Value

Composite Outcome of Cardiovascular Death, Non Fatal Myocardial Infarction, Nonfatal Stroke, Coronary Revascularization, or Unstable Angina

17.2% 22% p < 0.0001 Adverse Bleeding Events 2.7% 2.1% p = 0.06

Secondary Prevention: Fish Oil

REDUCE-IT Trial

No Benefit in Reducing Cardiovascular Events

Secondary Prevention: Fish Oil

REDUCE-IT Trial

Secondary Prevention: Fish Oil Summary Icosapent ethyl… Consider prescribing this medication to patients with a history of cardiovascular disease or diabetes with additional risk factors who are already receiving ACC/AHA guideline directed lipid lowering therapy and want to further reduce their cardiovascular risk Stable Ischemic Heart Disease

Outline

Prevention

1. Understand the use of aspirin in the prevention of coronary artery disease 2. Understand the use of fish oil in the prevention of coronary artery disease

Stable Ischemic Heart Disease

1. Define the role of percutaneous coronary intervention in the management

• f stable ischemic heart disease

2. Review current guidelines for dual antiplatelet duration following percutaneous coronary intervention and acute coronary syndrome

Structural Heart Disease

1. Define the expanding role of Transcatheter Aortic Valve Replacement in the management of aortic stenosis 2. Review the role of percutaneous mitral valve therapies in the clinical management of patients with mitral regurgitation

Audience Response Question: CAD

Percutaneous coronary intervention in combination with medical therapy has been shown to have the following clinical benefits in the management of stable ischemic heart disease compared to medical therapy alone:

• A. Reduction in the risk of death, myocardial

infarction and urgent revascularization

• B. Reduction in the frequency and severity of angina
• C. Statements 1 and 2 are both correct
• D. None of the above statements are correct

R e d u c t i

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i n t h e r i s k

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t h e a b

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16% 41% 27% 16%

Stable Ischemic Heart Disease: Prognosis Stable Ischemic Heart Disease The problem with coronary revascularization…

Stable Ischemic Heart Disease

Fractional Flow Reserve (FFR) and Physiologic Guided PCI

FFR tests for:

• 1. Objective ischemia
• 2. Viability

Stable Ischemic Heart Disease

FAME 2

Xaplanteris P , Fournier S, Pijls NH, et al., on behalf of the F AME 2 Investigators. Five-Year Outcomes With PCI Guided by Fractional Flow Reserve. N Engl J Med 2018;379:250-9.

Stable Ischemic Heart Disease

FAME 2

Clinical Question: What is the clinical benefit of percutaneous coronary intervention in reducing the risk of death, myocardial infarction,

• r

urgent revascularization in patients with stable ischemic heart disease and at least one hemodynamically significant coronary stenosis?

FFR Guided PCI plus Medical Therapy Medical Therapy p Value

Composite Outcome of Death, Myocardial Infarction, or Urgent Revascularization

13.9% 27% p < 0.001

Components of Primary End Point

• Death
• Myocardial Infarction
• Urgent Revascularization

5.1% 8.1% 11.9% 5.2% 12.0% 16.1%

Not Significant Borderline Significant

Stable Ischemic Heart Disease

FAME 2

What about angina?…

Results: Quality of Life

% of Patients with Class II-IV Angina at each Time Point

% with CCS II-IV Angina

Stable Ischemic Heart Disease

FAME 2

Physiologic (i.e. FFR) guided PCI… Stable Ischemic Heart Disease Summary Reduces the composite risk of death/myocardial infarction/urgent revascularization and the severity

• f angina compared to medical therapy alone in

patients with stable ischemic heart disease Know your cardiologist’s practice patterns! Dual Antiplatelet Therapy: Duration of Treatment

2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease Glenn N. Levine, Eric R. Bates, John A. Bittl, Ralph G. Brindis, Stephan D. Fihn, Lee A. Fleisher, Christopher B. Granger, Richard

• A. Lange, Michael J. Mack, Laura Mauri, Roxana Mehran, Debabrata Mukherjee, L. Kristin Newby, Patrick T. O’Gara, Marc S.

Sabatine, Peter K. Smith, Sidney C. Smith Journal of the American College of Cardiology Sep 2016, 68 (10) 1082-1115; DOI: 10.1016/j.jacc.2016.03.513

Bare Metal Stent Drug Eluting Stent CABG Stable Ischemic Heart Disease 1 Month 6 Months 12 Months Acute Coronary Syndrome 12 Months 12 Months 12 Months

Dual Therapy vs Triple Therapy Post PCI

Meta Analysis

Angiolillo, Dominick J., et al. "Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation undergoing percutaneous coronary intervention: a North American perspective–2018 update." Circulation 138.5 (2018): 527-536.

Dual Therapy Triple Therapy p Value Major and Minor Bleeding 17.2% 28.0% p < 0.001 Ischemic Events 11.4% 12.4% p = 0.16

Dual Therapy vs Triple Therapy Post PCI Summary In patients with an indication for systemic anticoagulation who have undergone PCI it is reasonable to prescribe the anticoagulant with a P2Y12 (clopidogrel, prasugrel, ticagrelor) inhibitor alone

Structural Heart Disease

Outline

Prevention

1. Understand the use of aspirin in the prevention of coronary artery disease 2. Understand the use of fish oil in the prevention of coronary artery disease

Stable Ischemic Heart Disease

1. Define the role of percutaneous coronary intervention in the management

• f stable ischemic heart disease

2. Review current guidelines for dual antiplatelet duration following percutaneous coronary intervention and acute coronary syndrome

Structural Heart Disease

1. Define the expanding role of Transcatheter Aortic Valve Replacement in the management of aortic stenosis 2. Review the role of percutaneous mitral valve therapies in the clinical management of patients with mitral regurgitation

Audience Response Question: TAVR

You visit one of your long term clinic patients in the hospital after an admission for syncope and a new diagnosis of severe aortic stenosis. Your patient is otherwise healthy with no major comorbidities. During the visit your patient seeks your advice as to whether transcatheter aortic valve replacement (TAVR) is a reasonable treatment option. The most appropriate response is:

• A. TAVR should only be considered for patients at

prohibitive surgical risk because surgery is the gold standard treatment for severe aortic stenosis

• B. TAVR is a reasonable treatment option only for

patients who are at high and intermediate risk of surgical complications

• C. TAVR is a reasonable treatment for all patients with

severe aortic stenosis

T A V R s h

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a b l e t r e . . .

3% 65% 32%

Structural Heart Disease: TAVR Structural Heart Disease: TAVR Surgical Mortality

(STS Prom Risk Calculator)

Frailty Assessment

Major Organ System Compromise Not Likely to be Improved Postprocedurally

Procedure Specific Impediments

(ex. Morbid Obesity)

Domains of Aortic Valve Intervention Risk Assessment...

Structural Heart Disease: TAVR

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

ESTIMATED RISK

Inoperable High Intermediate Low

TIME

PARTNER 1B

n=358

CoreValve ER

n=489

PARTNER 1A

n=699

CoreValve HR

n=795

SURTAVI

n=1746

PARTNER 2A

n=2032

NOTION

n=280

NOTION II, Evolut R LR, PARTNER III

Risk Spectrum in TAVR Trials over Time

Structural Heart Disease: Low Risk TAVR

PARTNER 3 Trial

Mack, Michael J., et al. "Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients." New England Journal of Medicine (2019). APA

Clinical Question: What is the clinical benefit of TAVR compared with SAVR in reducing the risk of death from any cause, stroke, or rehospitalization at one year after the procedure? Structural Heart Disease: Low Risk TAVR

PARTNER 3 Trial TAVR SAVR p Value

Composite of Death From Any Cause, Stroke, or Rehospitalization at 1 Year After the Procedure

8.5% 15.1%

p < 0.001 for Non Inferiority p = 0.001 for Superiority Key Secondary Endpoints

• New Onset Atrial Fibrillation
• Length of Hospitalization
• Stroke at 30 days

5% 3% 0.6% 39.5% 8% 2.4% p < 0.001 p < 0.001 p = 0.02

Structural Heart Disease: Low Risk TAVR

PARTNER 3 Trial

Structural Heart Disease: TAVR Summary

Transcatheter Aortic Valve Replacement…

Is equivalent to surgical aortic valve replacement in high, intermediate, and low risk patients with severe aortic stenosis and may be superior to surgical aortic valve replacement in low risk patients

But…

Structural Heart Disease: TAVR Summary

Long term valve durability remains unknown especially in younger patients Referral to a high volume center with a multidisciplinary heart team remains critical

Audience Response Question: Mitral Valve Disease

Percutaneous mitral valve repair (MitraClip) has been shown to have clinical benefit in which of the following patients:

• A. 61 year old woman with severe symptomatic

mitral regurgitation from mitral valve prolapse

• B. 72 year old man with heart failure with reduced

ejection fraction, severe symptomatic mitral regurgitation, currently receiving maximal medical therapy by a heart failure specialist

6 1 y e a r

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d m a n w i t h h e a . .

61% 39%

Structural Heart Disease: MitraClip

2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease

Structural Heart Disease: MitraClip versus

MitraClip may be considered for severely symptomatic patients with severe mitral regurgitation who are at prohibitive surgical risk because of severe comorbidities

Structural Heart Disease: MitraClip

Mitral Regurgitation: Valve Problem vs Ventricular Problem

Structural Heart Disease: MitraClip

COAPT Trial

Stone, Gregg W., et al. "Transcatheter mitral-valve repair in patients with heart failure." New England Journal of Medicine 379.24 (2018): 2307-2318.

Clinical Question: What is the clinical benefit of MitraClip plus maximal medical therapy compared to maximal medical therapy alone in reducing hospitalizations for heart failure in patients? Structural Heart Disease: MitraClip

COAPT Trial

Structural Heart Disease: MitraClip

COAPT Trial MitraClip plus Medical Therapy Medical Therapy p Value

Hospitalizations for Heart Failure

35.8% 67.9%

p < 0.001 Key Secondary Endpoints

• Death from any cause
• NYHA functional class I or II

19.1% 72.2% 23.3% 49.6%

p < 0.001 p < 0.001

Structural Heart Disease: MitraClip Summary

MitraClip… Should be considered in heart failure patients with severe mitral regurgitation who are severely symptomatic despite maximal guideline directed medical therapy

Structural Heart Disease: MitraClip Summary

Heart Failure Toolbox

Thank You

lucas.zier@ucsf.edu

Key Points

• 1. Low dose daily aspirin should NOT be routinely prescribed for primary prevention of

cardiovascular disease.

• 2. Icosapent ethyl, a fish oil derivative, should be considered as an adjunctive therapy to

reduce the risk of secondary cardiovascular events in patients already taking a statin.

• 3. Physiologic (FFR) guided PCI reduces the composite risk of death, myocardial

infarction and urgent revascularization in patients with stable ischemic heart disease and durably reduces the presence and severity of angina compared to medical therapy alone.

• 4. Transcatheter aortic valve replacement (TAVR) is equivalent to surgical aortic valve

replacement in high, intermediate, and low risk patients with severe aortic stenosis and may be superior to surgical aortic valve replacement in low risk patients.

• 5. Percutaneous mitral valve repair should be considered in heart failure patients with

severe mitral regurgitation who are severely symptomatic despite maximal guideline directed medical therapy.

References

• 1. Gaziano, J. Michael, et al. "Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular

disease (ARRIVE): a randomised, double-blind, placebo-controlled trial." The Lancet 392.10152 (2018): 1036-1046.

• 2. ASCEND Study Collaborative Group. "Effects of aspirin for primary prevention in persons with diabetes mellitus." New

England Journal of Medicine 379.16 (2018): 1529-1539.

• 3. Bhatt, Deepak L., et al. "Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia." New England Journal of

Medicine 380.1 (2019): 11-22.

• 4. Xaplanteris P, Fournier S, Pijls NH, et al., on behalf of the FAME 2 Investigators. Five-Year Outcomes With PCI Guided by

Fractional Flow Reserve. N Engl J Med 2018;379:250-9.

• 5. 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease
• 6. Glenn N. Levine, Eric R. Bates, John A. Bittl, Ralph G. Brindis, Stephan D. Fihn, Lee A. Fleisher, Christopher B. Granger,

Richard A. Lange, Michael J. Mack, Laura Mauri, Roxana Mehran, Debabrata Mukherjee, L. Kristin Newby, Patrick T. O’Gara, Marc S. Sabatine, Peter K. Smith, Sidney C. Smith Journal of the American College of Cardiology Sep 2016, 68 (10) 1082-1115; DOI: 10.1016/j.jacc.2016.03.513.

• 7. Angiolillo, Dominick J., et al. "Antithrombotic therapy in patients with atrial fibrillation treated with oral anticoagulation

undergoing percutaneous coronary intervention: a North American perspective–2018 update." Circulation 138.5 (2018): 527-536.

• 8. Mack, Michael J., et al. "Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients." New

England Journal of Medicine (2019).

• 9. Stone, Gregg W., et al. "Transcatheter mitral-valve repair in patients with heart failure." New England Journal of Medicine

379.24 (2018): 2307-2318.