8/5/2019 Q UESTION #2: Y OUR PATIENT IS CAPABLE P RETEST PROBABILITY - - PowerPoint PPT Presentation

8/5/2019

OUTPATIENT MANAGEMENT

OF CAD- A PRIMARY CARE

PERSPECTIVE

Michael G. Shlipak, MD, MPH

Scientific Director , Kidney Health Research Collaborative Professor of Medicine, Epidemiology & Biostatistics University of California, San Francisco Associate Chief of Medicine for Research Development San Francisco VA Medical Center August 5, 2019

DISCLOSURES

 I am on the Scientific Advisory Boards with

stock option compensation for the following companies:

 TAI Diagnostics  Cricket Health, Inc.

FEATURES OF THIS TALK

 Covers a broad array of topics  Greatest attention to common challenges in decision

making

 All recommendations supported by the following

Guideline: AHA Guideline for the Diagnosis and Management of Patients with Stable Ischemic Heart Disease (Circulation, 2012)

 Class 1 indication: we should do this  Class 2 indication: it’s reasonable to do this

QUESTION #1

YOUR PATIENT IS A 62YO MAN WITH HISTORY OF

CONTROLLED HYPERTENSION, MILD OVERWEIGHT (BMI 29), AND UNTREATED LDL OF 137MG/DL. HE REPORTS TO YOU THAT FOR ABOUT 2 MONTHS HE HAS EXPERIENCED LEFT- SIDED CHEST TIGHTNESS AFTER WORKING UP 2 FLIGHTS OF STAIRS . IT IS RELIEVED BY REST AND IS NOT PROGRESSING

• NOTICEABLY. THE SYMPTOMS HAVE NOT OCCURRED AT ANY

OTHER TIMES. WHAT IS THE PROBABILITY THAT THE PATIENT’S SYMPTOMS ARE CAUSED BY CAD?

• A. <50%
• B. 60%
• C. 80%
• D. >90%

< 5 % 6 % 8 % > 9 %

10% 39% 26% 25%

8/5/2019

PRETEST PROBABILITY OF CORONARY HEART

DISEASE IN PATIENTS WITH CHEST PAIN ACCORDING TO AGE, GENDER, AND SYMPTOMS

Age Nonanginal Chest Pain Atypical angina Typical angina Men Women Men Women Men Women 30-39 4 2 34 12 76 26 40-49 13 3 51 22 87 55 50-59 20 7 65 31 93 73 60-69 27 14 72 51 94 86

Diamond GA et al., N Engl J Med 1979 Weiner DA et al., N Engl J Med 1979

AHA definitions: low risk ~10% or less high risk ~90% or higher intermediate risk- anything in between

QUESTION #2: YOUR PATIENT IS CAPABLE

OF WALKING AND HAS A NORMAL RESTING

• ECG. WHICH OF THE FOLLOWING TESTS

SHOULD YOU ORDER NEXT?

• A. Exercise only stress test
• B. Exercise with perfusion imaging
• C. Exercise echo
• D. Coronary angiography
• E. None of the above

Exercise only stress test Exercise with perfusion... Exercise echo Coronary angiography None of the above

38% 24% 9% 14% 14%

NON INVASIVE TESTING FOR DIAGNOSIS OF ISCHEMIC HEART DISEASE

AHA recommendation is to limit testing to intermediate risk patients

If patient can exercise and has normal resting

ECG, then exercise only stress test

If abnormal ECG, then exercise/imaging or

exercise echo

If patient cannot exercise, then pharmacologic

stress with imaging/echo

WHY DO WE ONLY TEST PATIENTS WITH

INTERMEDIATE PROBABILITY OF CAD?

 Exercise only:

 LR+ = 3.0  LR- = 0.42

(Gianrossi R. et al. Circulation, 1989)  Exercise echo:

 LR+ = 3.7  LR- = 0.19

(Fleischmann KE. et al. JAMA 1998)  Exercise imaging:

 LR+ = 2.4  LR- = 0.20

(Fleischmann KE. et al. JAMA 1998)

0.1 0.9 0.5

+

(0.97)

• (0.65)

+

(0.77)

• (0.25)

+

(0.28)

• (0.02)

8/5/2019

PROMISE TRIAL Is coronary CT angio the best tests for evaluation of intermediate risk patients with chest pain?

Douglas P.S. et al N Engl J Med, 2015

TRIAL DESIGN

 10,000 participants in North America  193 sites  NIH-funded  Randomization:  CTA- coronary computed tomographic angiography  Functional Testing- (one of the 3 options)

 Exercise EGG  Nuclear stress  Stress echo

 Composite: death, MI, UA hospital procedure

complication

 Median follow-up 25 months

PATIENT CHARACTERISTICS

 Age: 60±8  Women: 53%  Mean: 2.4 risk factors  Typical angina: 17%  Atypical angina: 78%  Non-anginal symptoms: 10%  Individual predicted CAD risk: mean 0.53

QUESTION 3

AMONG THESE INTERMEDIATE RISK PATIENTS, WHAT

PERCENTAGE WOULD YOU GUESS HAD THE PRIMARY OUTCOME (DEATH OR MI) WITHIN 2 YEARS?

• A. <5%
• B. 5-10%
• C. 10-20%
• D. >20%

< 5 % 5

• 1

% 1

• 2

% > 2 %

41% 7% 14% 37%

8/5/2019

CT ANGIO IS NO BETTER THAN FUNCTIONAL TESTING

Incidence of death or MI was only 1%/year in each group

SUMMARY

 A lot of testing with very low yield  “Intermediate risk” is actually low risk  “…reflects an excellent prognosis for patients

with similar, new-onset, stable chest pain in real- world settings.”

QUESTION #4

• A. ACE inhibitors (ARBs)
• B. Aspirin
• C. Beta blockers
• D. Statins

Based on his symptoms of typical angina, you inform your patient that he has CAD. You explain the proven value of “optimal medical therapy”

A C E i n h i b i t

• r

s ( A R B s ) A s p i r i n B e t a b l

• c

k e r s S t a t i n s

68% 0% 20% 13%

Which of the following is not considered part of

• ptimal medical therapy for a patient with

anginal symptoms?

ASPIRIN

 All patients with CAD should use 81-162mg of

aspirin (class 1)

 Clopidigrel (plavix) should be offered to patients

who cannot tolerate aspirin (class 1)

 Aspirin + clopidigrel for severe patients is

reasonable (class 2B)

8/5/2019

BETA BLOCKERS

 Improved survival in patients with prior MI  If patient has prior MI, BB is class 1  If MI >3 years ago, BB is class 2A  Best choice for angina symptoms

STATINS (MORE ON THIS TOPIC LATER)

 LDL target <100 mg/dL - class 1  LDL target <70 mg/dL - class 2A  “No evidence to suggest LDL targets of 70 vs.

100mg/dL in patients with ASCVD”

ACE INHIBITORS

 Not clearly indicated in patients with angina

because no effect on symptoms

 Considered a “reasonable choice” (2A)  ACE inhibitors (Class I) must be used for

patients with:

 Reduced ejection fraction  CKD with albuminuria

CASE CONTINUED

 Your patient worries that something bad might

happen with his heart. He asks you to assess the likelihood of him having a heart attack or dying from his heart disease. How do you determine risk in the secondary prevention setting?

8/5/2019

RISK PREDICTION IN CAD

 Primary prevention:  Patients without CAD or CVD  CVD risk calculator  Secondary prevention:  Patients who have CAD  No risk score for ambulatory patients with

established CAD

 CVD risk calculators do not work

RISK FACTORS FOR ADVERSE OUTCOMES IN PATIENTS WITH CAD

 Feared adverse outcomes in CAD patients:  Recurrent MI  Heart failure  Sudden death  Traditional CVD risk factors are still important:

• Blood pressure control
• Smoking cessation
• Weight loss
• Diabetes control
• Lipid management
• Encourage exercise

 Although important, cardiac status matters more

for prognosis than metabolic risk factors

CARDIAC-SPECIFIC RISK FACTORS IN PATIENTS WITH CAD

1.

Exercise capacity

2.

Number and size of MIs

3.

Reduced ejection fraction

4.

HF symptoms

5.

BNP/NT-pro-BNP

6.

High sensitivity troponins

TREATMENT OF ANGINAL SYMPTOMS

RANKING ANTI-ISCHEMIC AGENTS (PER AHA GUIDELINES) 1.

BBs- top choice

2.

CCBs or long acting nitrates (if BB intolerant)

3.

Use combinations if necessary

4.

NTG (sl or spray) for immediate relief

5.

Ranolozine as lesser alternative (class 2A)

8/5/2019

FOLLOW UP IN CAD PATIENTS

Routine

 Assess anginal symptoms and physical function  Assess signs of heart failure or arrythmia  Risk factor management  Lifestyle

Situational

 If heart failure signs or repeat MI echo  If new or worsening angina exercise testing or

coronary angiography

CASE STUDY FOLLOW UP

 Your patient is still frustrated by the concept of

medical management and concerned that his symptoms indicate an impending heart attack. He asks you “why can’t I just get a stent and fix this problem?” This seems logical- why not proceed to PCI?

INTERVENTIONS IN STABLE ANGINA

 Interventions should be limited to patients who

fail optimal medical therapy

 Currently, 85% of all percutaneous coronary

intervention (PCI) procedures are elective in patients with stable angina

 The COURAGE trial demonstrated that PCI does

not improve outcomes

COURAGE TRIAL

 Conducted to compare OMT with and without

PCI in 2,287 patients with stable angina

 Funded by the US VA R&D/Canadian Institutes

• f Health Research

 Outcome:  All-cause mortality  Non-fatal MI  Initial trial: mean of 4.6 years  Extended follow-up: 12 years Boden et al. NEJM 2007 Sedlis et al. NEJM 2015

8/5/2019

COURAGE OUTCOMES

Sedlis et al. NEJM 2015

CASE STUDY FOLLOW UP

 Your patient insists on talking with a specialist  You refer to a cardiologist  The patient returns to your office 8 weeks later

for a follow-up visit… …after having received a stent. What happened?

What are cardiologists thinking?

CARDIOLOGISTS’ USE OF PCI FOR STABLE CAD

 Design: focus groups of cardiologists in N. Cal  Research Question: Why do cardiologists

ignore COURAGE results?

 Reasons given for performing PCI in stable

angina:

 Belief in the benefits of treating ischemia and in the

• pen artery hypothesis

 Potential regret (psychological and legal) for not

intervening if a cardiac event could be averted

 Alleviation of patient anxiety  Belief that referring PCP expects a procedure Lin et al. Arch Intern Med. 2007

8/5/2019 WHY STATINS ARE BETTER THAN STENTS

 Severity of stenosis ≠ MI risk  Stents are small (1-2 cm) relative to length of 3

major coronary arteries (~30cm) and their branches (>30cm)

 Statins stabilize all the plaques

CONCLUSIONS

 We need to fully implement OMT (β-blocker,

statin, aspirin) first, before referring to cardiologists

 We need to resist the urge to “fix” patients’

angina by stenting

 We need to educate patients that stents do not

prevent adverse outcomes

 We need to be clear about our expectations prior

to referring patients to cardiologists

QUESTION 5

YOUR PATIENT RETURNS FOR FOLLOW UP. HE HAS BEEN

TAKING 20MG SIMVASTATIN. LDL IS 110MG, HDL 25MG.

WHICH IS THE BEST NEXT STEP?

• A. ↑ simvastatin
• B. Change to pravastatin
• C. Change to atorvastatin
• D. Add gemfibrozil
• E. Add niacin

C h a n g e t

• p

r a v a s t a t i n C h a n g e t

• a

t

• r

v a s t a t i n A d d g e m f i b r

• z

i l A d d n i a c i n

34% 1% 0% 1% 64%

NEW RECOMMENDATIONS FOR LIPID MANAGEMENT IN PERSONS WITH CVD

 2013 ACC/AHA Guideline on the Treatment of Blood

Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

 “High intensity statin therapy should be first line in persons

with clinical ASCVD, aged ≤ 75, unless contraindicated”

 High- atorvastatin 40-80, rosuvastatin 20-40  Moderate- simvastatin 20-40, pravastatin 40, lovastatin 40  Low- simvastatin 10, pravastatin 10-20, lovastatin 20  Our patient should be on atorvastatin or rosuvastatin

8/5/2019

SHOULD WE STILL USE SIMVASTATIN?

 June 8, 2011: FDA restricts use of 80mg

simvastatin because of increased risk of myopathy

 FDA recommends:  No new patients on simvastatin 80mg  Okay to maintain patients on 80mg if >1 year

without symptoms of muscle toxicity

 Beware of drug interactions  Based on the SEARCH Trial (Lancet, 2010)  Simvastatin 80mg vs. 20mg in RCT of 12,000 with

CAD

SEARCH TRIAL RESULTS

 Difference in myopathy risk:  Myopathy (muscle weakness + CK >10x ULN)

 80 mg: 52 patients (0.9%)  20 mg: 1 patient (0.02%)

 Rhabdomyolysis (muscle weakness + CK>40x ULN)

 80 mg: 22 patients (0.4%)  20 mg: 0 patients

 Risk 5-fold higher in year 1 compared with

subsequent years

 Key drug interactions noted  Calcium channel blockers, Amiodarone, Ranolazine,

and others

SEARCH Study Group The Lancet, 2010

QUESTION 6

YOU DECIDE YOUR PATIENT SHOULD SWITCH TO ATORVASTATIN. HOWEVER, HE HAS NOW STOPPED HIS STATIN DUE TO ADVERSE

PUBLICITY AND WILL NOT RESTART.

HE TELLS YOU THAT HE IS NOW TAKING NIACIN BECAUSE IT IS “A

NATURAL OPTION.”

YOU RECHECK HIS LIPIDS; HIS HDL IS 50MG/DL AND HIS LDL IS 140

MG/DL.

A.

Reinforce to the patient that statins are by far the best treatment for lipid disorders.

B.

Congratulate him on his choice because niacin has made his HDL go up beautifully

C.

Offer a fibrate (e.g. gemfibrozil), as it is an evidence-based treatment for patients like him

D.

Any of the above approaches is fine. Your best management option is:

R e i n f

• r

c e t

• t

h e p a t i e n t . . . C

• n

g r a t u l a t e h i m

• n

h i s . . . O f f e r a f i b r a t e ( e . g . g e m f . . . A n y

• f

t h e a b

• v

e a p p r

• .

. .

92% 5% 3% 0%

WHY IS NIACIN IN DISFAVOR?

 AIM-HIGH trial (NEJM 2011)  HPS2-THRIVE trial (NEJM, July 17, 2014) http://www.aimhigh-heart.com/ AIM-HIGH Investigators, NEJM 2011 http://www.ctsu.ox.ac.uk/hps2-thrive/ HPS2-THRIVE Investigators, NEJM 2014

8/5/2019

AIM-HIGH TRIAL (NIH, ABBVIE)

 Participants: N=3,414 in US and Canada  Inclusion criteria:  Prior CVD  On a statin  Low HDL and high TG  Design: Placebo-controlled RCT  Intervention: Niaspan – 2 g/day or placebo  Outcomes: CVD death, MI, CVA, ACS,

revascularization

 Follow-up: 3 years http://www.aimhigh-heart.com/ AIM-HIGH Investigators, NEJM 2011

AIM-HIGH FINDINGS

 Trial stopped early  Event rate was same in both groups http://www.aimhigh-heart.com/ AIM-HIGH Investigators, NEJM 2011

HPS2-THRIVE TRIAL (MERCK)

 Participants: N=25,673 in UK, Scandinavia,

and China

 Inclusion criteria:  Prior CVD  On a statin  Design: Placebo-controlled RCT  Intervention: 2g ext-release niacin + 40mg

laropiprant vs. placebo

 Outcomes: CVD death, MI, CVA, and

revascularization

 Follow-up: 4 years http://www.ctsu.ox.ac.uk/hps2-thrive/ HPS2-THRIVE Investigators, NEJM 2014

HPS2-THRIVE FINDINGS

 Primary outcome RR= 0.96 (0.90-1.03)  All-cause mortality RR= 1.09 (0.99 to 1.21)

http://www.ctsu.ox.ac.uk/hps2-thrive/ HPS2-THRIVE Investigators, NEJM 2014

But, there is more to the story…

8/5/2019

NIACIN INCREASES RISK FOR SERIOUS ADVERSE EVENTS AND DIABETES

http://www.ctsu.ox.ac.uk/hps2-thrive/ HPS2-THRIVE Investigators, NEJM 2014

Event Rate Ratio (95% CI) Extra Events/100 Users Serious adverse event GI Event 1.28 (1.13-1.44) 1.0 Musculoskeletal event 1.26 (1.10-1.44) 0.7 Skin-related event 1.67 (1.20-2.34) 0.3 Infection event 1.22 (1.12-1.34) 1.4 Bleeding events 1.38 (1.17-1.62) 0.7 Diabetes mellitus New-onset 1.32 (1.16-1.51) 1.3 Worsened condition 1.55 (1.34-1.78) 3.7  “On the basis of the weight of available evidence

showing net clinical harm, niacin must be considered to have an unacceptable toxicity profile for the majority of patients, and it should not be used routinely.”

 “…[the study] lends further evidence to the notion

that HDL cholesterol is unlikely to be causal.”

Do fibrates improve clinical outcomes?

EFFECTS OF FIBRATES ON CARDIOVASCULAR OUTCOMES

 Design: systematic review and meta-analysis  Analysis: 18 RCTs from 1950-2010  Participants: N=45,058 Jun et al. The Lancet 2010

8/5/2019

FIBRATE VS. PLACEBO AND CVD RISK

Outcome Relative Risk 95% CI P Value

All-cause mortality

1.00 0.98-1.08 0.92

Cardiovascular death

0.97 0.88-1.07 0.59

Non-fatal coronary events

0.81 0.75-0.89 <0.0001

Total stroke

1.03 0.91-1.16 0.69

Jun et al. The Lancet 2010

DATA SUMMARY

 For patients with low HDL:  Statins are treatment of choice to decrease CVD risk,

regardless of LDL

 Do not add either niacin or fibrates to statin treatment  For patients who cannot tolerate statins:  Fibrates appear to lower MI risk, but no other CVD

endpoints

 Niacin has clear harmful effects and uncertain benefits

among statin non-users.

 AHA guidelines state that for statin untreated patients

fibrates are a “reasonable choice” (2A)

CASE STUDY FOLLOW UP

 Now that your patient with stable CAD is on

OMT, he has increased exercise, as you recommended.

 However, he has developed persistent knee pain

and wants to take “prescription-strength”

• ibuprofen. The label says to ask a doctor before

use if you have heart disease.

 Is the risk real?

NSAIDS IN CAD PATIENTS

 Meta-analysis demonstrated increased risk for

incident CAD

 Are they clinically harmful in patients with

established CAD?

 No RCT evidence in CAD patients (Trelle et al. BMJ 2011)

8/5/2019

BEST EVIDENCE FROM DENMARK

 National registry of MI patients and pharmacy data  Patients with first MI (2002-2011); N= 61,971  34% received NSAIDS; average age = 68, 63% men  Follow-up for MI/CHD death  Follow-up for bleeding risk

Olsen AM et al. JAMA 2015

NSAID ASSOCIATION WITH CVD RISK

 Outcome: CVD death, MI, stroke  No NSAID: 8.3%/year  NSAID: 11.2%  Adjusted HR: 1.40 (1.3-1.5)  Risks similar across NSAIDS; naproxen rarely

used

Olsen AM et al. JAMA 2015

NSAID ASSOCIATION WITH BLEEDING RISK

 Outcome: Intra-cranial, GI, respiratory, or

urinary bleeding

 No NSAID: 2.2%/year  NSAID: 4.2%  Adjusted HR: 2.0 (1.8-2.3)  Risks similar across NSAIDS

Olsen AM et al. JAMA 2015

NSAID CONCLUSIONS

 MI risk from NSAIDs appears real  NSAIDs should be used at most for short-term in

CAD patients

 Evidence supports FDA’s “Black Box” warning (FDA

update 7-9-2015):

 NSAIDs cause MI and stroke, even in first weeks  Increased risk with higher dose and duration  Uncertain whether risk varies by particular NSAID  NSAIDs also cause HF

8/5/2019

THANK YOU! ANY QUESTIONS?