Updates in General Internal Medicine 2019 No conflicts of interest - - PowerPoint PPT Presentation

Updates in General Internal Medicine 2019

No conflicts of interest jeff.kohlwes@ucsf.edu

Topics!

CV Updates in Primary Care

• Anticoagulation in afib
• Risk factor reduction
• Steppin’ out for health
• WCH vs. WCE

Important Surgical Outcomes for Primary Care

• AAA repair

Public Health in Primary Care

• It’s legal
• Not the elixir of health

Epidemiology of Fear

Case #1- A 70-year-old asymptomatic diabetic man with CAD post PCI with DES stent in the LAD 14 months ago with rate controlled atrial fibrillation on apixaban, amlodipine, atorvastatin, metoprolol and aspirin presents for routine primary care. BP- 118/78, HR- 80, RR- 12, 99% saturation. You recommend: A- Continue all medications B- Add clopidogrel to ensure DAPT C- Increase amlodipine to lower SBP D- Stop aspirin for single anticoagulation agent E- Increase metoprolol for rate control

Case #1- A 70-year-old asymptomatic diabetic man with CAD post PCI with DES stent in the LAD 14 months ago with rate controlled atrial fibrillation on apixaban, amlodipine, atorvastatin, metoprolol and aspirin presents for routine primary care. BP- 118/78, HR- 80, RR- 12, 99% saturation. You recommend: A- Continue all medications B- Add clopidogrel to ensure DAPT C- Increase amlodipine to lower SBP D- Stop aspirin for single anticoagulation agent E- Increase metoprolol for rate control

• Common disorder, increases with age (mirrors CAD)

Circulation 2011: 103:162-182

• Warfarin vs. Placebo- 66% RRR INR 2-3

Annals I. M. Vol. 131, No. 7 October 5, 1999

What is the right anticoagulation plan post PCI?!

Afib+Anticoag in Stable CAD

• 18.2 million adults age 20 and older have CAD
• 1 in 4 deaths in the U.S.
• 5-7% of PCI pts with atrial fibrillation

Anticoagulation- Afib post PCI

• First 12 months

Canadian Guidelines (European similar) Restenosis risk first month- slowly decreases over 12 months

• Canadian Journal of Cardiology, Vol. 34, March 2018, Pages 214-233

Anticoagulation- Afib post PCI

• After 12 months
• Atrial Fibrillation and Ischemic events with Rivaroxaban in patiEnts

with stable CAD (AFIRE) Trial

• Open label RCT, Japan Ministry funded
• 74 yrs, 79% men, CHADS2=2, HAS-BLED=2

2236 patients >12 mos post PCI with afib

Stroke, Systemic Emboli, ACS/MI, Revascularization, death Yasuda et al- NEJM 2019 Sep 19;381(12):1103-1113

1107 rivaroxaban

1108 Rivaroxaban + antiplatelet (70% asa)

AFIER (afire) Results

ITT Analysis- stopped early for mortality benefit monotherapy rivaroxaban

• 2 years average follow up
• HR 0.72
• 4.1 % mono vs. 5.7% aPLT

NNT= 62.5 / 2 years NNT mortality = 67 / 2 years Major Bleeding- 2.8% vs. 1.6% NNH = 83 / 2 years with aPLT

Yasuda et al. NEJM 2019 Sep 19;381(12)

Case continued

You stop the patient’s asa and continue monotherapy

• rivaroxaban. He returns 2 months later for routine follow up.

His EP physician suggests a catheter-based ablation

• procedure. He wants to know if he can change his lifestyle to

maintain sinus rhythm. You tell him: A- Anticoagulation can be stopped immediately after procedure B- Paroxysmal afib has the same success rate as chronic afib post ablation C- Alcohol abstinence reduces atrial fibrillation in drinkers D- Two of the above

Case continued

You stop the patient’s asa and continue monotherapy

• rivaroxaban. He returns 2 months later for routine follow up.

His EP physician suggests a catheter-based ablation

• procedure. He wants to know if he can change his lifestyle to

maintain sinus rhythm. You tell him: A- Anticoagulation can be stopped immediately after procedure (Wait at least 2-3 months only with cards OK!) B- Paroxysmal afib (70-80%) has the same success rate as chronic afib (60-70%) post ablation C- Alcohol abstinence reduces atrial fibrillation in drinkers D- Two of the above

Cool study on ETOH-Afib

• RCT- open label

63 years, 85% men, 500 excluded

140 patients Freedom from A. Fib >30 sec Total Afib Burden

• Voskovoinik et al. NEJM Jan. 2, 2020

70 control 70 abstinence

Baseline drinking behaviors

Abstinence helps..

6 Months Follow Up:

• Abstinence group2 drinks/week (88% decrease), control 13/week (20%)
• Afib recurrence: 37 (53%) abstinence group vs. 51 (73%) control group
• NNT to not Drink- 5
• Clinical relevance? Likely! -Voskovoinik et al. NEJM Jan. 2, 2020

Case continued

3 months later the 70-year-old asymptomatic patient returns feeling great. He wants to walk with his partner but is intimidated by walking > 10K steps. How many steps does he need to take to start seeing mortality benefit over 4-5 years? Which of the following is true? A- Sorry its 10K or bust B- Mortality doesn’t reduce unless you make it 7500 steps C- Biggest incremental mortality benefit is seen over 7500 steps D- Mortality benefits begins at 3000 steps daily E- B and C

Case continued

3 months later the 70-year-old asymptomatic patient returns feeling great. He wants to walk with his partner but is intimidated by walking > 10K steps. How many steps does he need to take to start seeing mortality benefit over 4-5 years? Which of the following is true? A- Sorry its 10K or bust B- Mortality doesn’t reduce unless you make it 7500 steps C- Biggest incremental mortality benefit is seen over 7500 steps D- Mortality benefits begins at 3000 steps daily E- B and C

Step Volume and Mortality

• 17K pts WHS
• 7 days steps/day

accelerometer Survival Curve Levels

• 7500 steps

Difference at 3000 steps HR-0.75 Max effect at >7500 steps HR-0.45 Lee- JAMA IM 2019;179(8)

Afib/CAD updates

• Rivaroxaban monotherapy after one year

– Coordinate with cardiologists

• Alcohol abstinence with afib
• WALK!!

– 3,000 to 7,500 steps for max benefit

Case continued

The patient’s 65-year-old partner is your next patient and he has a BP=144/90. His BP has never been elevated before and on repeat he is 128/80. He says it is never high at home (he checks at pharmacy). What should you do? A- Nothing, he is normotensive on repeat B- Start low dose amlodipine C- Ambulatory BP monitoring D- Have him rest and repeat a third time

Case continued

The patient’s 65-year-old partner is your next patient and he has a BP=144/90. His BP has never been elevated before and on repeat he is 128/80. He says it is never high at home (he checks at pharmacy). What should you do? A- Nothing, he is normotensive on repeat B- Start low dose amlodipine C- Ambulatory BP monitoring D- Have him rest and repeat a third time

Hypertension (HTN)

• HTN dxed 80 million people in U.S.

– Only 54% controlled – Tightly a/w CV outcomes

• Measurement error common

– Cuff size, body position, talking, haste

– 2nd measure, (−)8mmHg

– Leads to less treatment

• Einstader JAMA Intern Med. 2018;178(6)
• Do we care about missing white coat

HTN?

Risk of stroke with HTN Rx

Relationship between Clinic/Ambulatory BP Measures

Banegas NEJM 2018; 378:1509-1520

White Coat HTN is not benign- HR 1.96 Cohort study from Spain

Cox CV and BP (rxed) Cox CV covariates

White Coat HTN

• Meta-analysis – 27 studies, 26K patients

– 56 years old, 8 years follow-up

• Predictors:

– untreated WCH or treated WC Effect (WCE)

• Outcomes:

– CV Events, all cause mortality, CV mortality

– Cohen et al. Ann Intern Med. 2019;170:853-862

White Coat Hypertension

Cohen et al. Ann Intern Med. 2019;170:853-862

• CV Outcomes
• Mortality Outcomes

36% increase CV

• utcomes

33% increased Mortality!!

Fewer WCH More WCH No difference for Treated White Coat HTN

Bottom Line HTN Screening

• Beware White coat

HTN

• Ambulatory (or

Home?) BP measures useful

• Good coaching to

measure correctly!

• Treat to guidelines

Stroke reduction!

Case #2- When talking about Abdominal Aortic Aneurysms which of the following statements is true?

A- Risk of rupture increases exponentially when AAA measures >4.5cm B- Smoking is the biggest risk factor for AAA C- Family history of AAA is not a risk factor D- Screening for AAA has no impact on disease specific mortality E- All of the above are false

Case #2- When talking about Abdominal Aortic Aneurysms which of the following statements is true?

A- Risk of rupture increases exponentially when AAA measures >4.5cm B- Smoking is the biggest risk factor for AAA C- Family history of AAA is not a risk factor D- Screening for AAA has no impact on disease specific mortality E- All of the above are false

Abdominal Aortic Aneurysm

• AAA >3.0 cm 6% at 65yo

– Increases 6%/decade – 90% smokers – Ehlers Danlos, Marfans – Familial (30%, 6%)

• Obvious risk=rupture

– 90% mortality!

9K deaths

– 2-6% operative mortality

1400-2800 deaths

www.pennhealth.com/ int_rad/health_info/aaa.html

Aorta Rupture

When to repair a AAA??

Powell et al. NEJM 348;19, May 8, 2003

Surgical benefit>>Surgical risk when aneurysm is 5.5-6cm >1cm expansion/12mos

How to repair a AAA?

DREAM Trial- >5 cms 345 patients

4.6% (8) 1.2% (2) EVR-171 Open-174 Mortality 9.8% (17) 4.7% (8) Mortality or severe complications @30 days

(Dutch Randomized EVR Aneurysm Trial)

www.marketwire.com/ mw/release_html_b1?release... NEJM 351;16, Oct 14, 2004

3 Possible Explanations 1- Chance driving outcomes since small study 2- Frail patients survived EVR but later died 3- Long term EV repair inferior to open?

NEJM 352:23 June 9 2005

Not so Sweet DREAM- 2-year outcomes

9 year follow up- EVAR vs. Open

Lederle FA, et al. N Engl J Med. 2019;380(22):2126‐2135

Large Vet Health Cohort No difference in mortality-

• all cause (70%)
• disease specific (3%)

No difference in mortality or secondary procedures

• Increase secondary

procedures EVAR

• 27% vs. 20%

Bottom Line- AAA

• Screen smoking men 65-75, +FH, Marfans

– Non-smokers, women??

• >5.4 cm refer for repair

– (or for >1cm expansion/yr) – Short term survival benefit for EVR – Endovascular repair high risk patients – Mortality risk even over 9 years

A 30-year-old man who runs a local cannabis dispensary was in a motor vehicle accident, broke his ankle and is now in your office for post-discharge visit. His pain is managed with

• acetaminophen. He is having trouble sleeping,

nausea, restlessness, night sweats and irritability but no pain since leaving the

• hospital. He stopped smoking marijuana in the

hospital as he was stoned during the accident. He asks if this could be marijuana withdrawal? A- There is no DSM 5 diagnosis for cannabinoid WD B- Hyperemesis is expected with cannabinoid WD C- Cannabinoid WD is very common in frequent users D- A and C are correct

Public Health Case 1

A 30-year-old man who runs a local cannabis dispensary was in a motor vehicle accident, broke his ankle and is now in your office for post-discharge visit. His pain is managed with

• acetaminophen. He is having trouble sleeping,

nausea, restlessness, night sweats and irritability but no pain since leaving the

• hospital. He stopped smoking marijuana in the

hospital as he was stoned during the accident. He asks if this could be marijuana withdrawal? A- There is no DSM 5 diagnosis for cannabinoid WD B- Hyperemesis is expected with cannabinoid WD C- Cannabinoid WD is very common in frequent users D- A and C are correct

Public Health Case 1

Cannabis- science behind society

• Genus Cannabis-> tetrahydrocannabinol
• Spiritual use Assyrians 2500 BC
• Smoking, vaporizing, eaten (tea, edibles), extracts
• Effect onset 5-40 minutes -> 2-6 hours
• Euphoric and medical effects
• Physical effects include:
• Pain relief, opiate reduction

https://en.wikipedia.org/wiki/Cannabis

Cannabinoids Effect

Endocannabanoids

Modify normal responses of cell: CB1 CNS receptors modify cell response to neuro-transmitters CB2- effect inflammation, vascular cells Phytocannabinoids or Synthetic- cannabanoids=> react with same receptors TCH agonist, CBD antagonist- creates the imbalance of response

https://www.youtube.com/watch?v=lkNIRZXraY4

Meta-Analysis Cannabinoids

• 79 RCTs (4 low risk of bias- lousy data)
• Benefits (heterogeneity diff preparations):
• Chronic Pain reduction 41% P=0.06

– Chemo N/V response (28): 47% v 20% (OR= 3.82) – Spasticity reduction (14): -0.76 scale (OR= 1.44) – HIV weight gain (4)- less than megestrol (1) – Sleep disorders (2- 13)- various indication- suggestive – Tourette Syndrome tic reduction (2)- small benefit – Psychosis, anxiety, depression, glaucoma- insufficient data to assess.

• Whiting, JAMA. 2015;313(24):2456-2473.

Cannabinoid Withdrawal

• Meta-Analysis of 47 observational studies

– 23K frequent users, 69% men, 30 years, 35% use disorder – Outcomes frequency, associated risk factors of Cannabis withdrawal syndrome (CWS)

• Diagnostic and Statistical Manual (DSM5)

– 3 of 7 criteria for CWS dx – (1) irritability, anger, or aggression; (2) nervousness or anxiety; (3) sleep disturbance; (4) appetite or weight disturbance; (5) restlessness; (6) depressed mood; and (7) somatic symptoms, such as headaches, sweating, nausea, vomiting, or abdominal pain.

– Bahji et al. JAMA Netw Open. 2020;3(4)

Cannabinoid Withdrawal Syndrome Results

• CWS 47%!!
• significant heterogeneity

– no gender/racial differences – Higher in inpatients

• Risk Factors:

– daily cannabis use (β = 0.004, P < .001), – cannabis use disorder (β = 0.005, P < .001) – comorbid tobacco use (β = 0.002, P = .02) – comorbid drug use (β = 0.003, P = .05).

– Bahji et al. JAMA Netw Open. 2020;3(4)

Withdrawal Symptoms

• Physical Symptoms

(headaches, sweating, nausea, vomiting, or abdominal pain)

• Generally peak in the

first week

• Mental Health

Symptoms

• Often last two weeks
• Depression/Anxiety

may last much longer

Treatment: Sleep, Rest, Avoid caffeine, drugs, CBT or Group Treatment Support

Cannabis Withdrawal

• Common and

missed

• Inpatient and clinic
• Screen!
• No current data for

synthetic cannabinoids to treat

Public Health Case #2 Soda and Health

45-year-old obese man comes to your office saying he wants to lose weight so last week he switched from drinking regular to diet sodas while at work. He drinks at least 3-4 daily. Will this reduce his risk of developing a heart attack? How do you advise him? A- Good start keep it up! B- Diet soda has similar metabolic syndrome risk C- Diet soda is proven to help lose weight D- Regular soda is not associated with vascular events

Soda and Health

45-year-old obese man comes to your office saying he wants to lose weight so last week he switched from drinking regular to diet sodas while at work. He drinks at least 3-4 daily. Will this reduce his risk of developing a heart attack? How do you advise him? A- Good start keep it up! B- Diet soda has similar metabolic syndrome risk C- Diet soda is proven to help lose weight D- Regular soda is not associated with vascular events

Diet or Regular

Component of the metabolic syndrome Multivariable- adjusted odds ratio (95% CI) Diet soft drink, ≥ 1/d 1.53 (1.10 - 2.15) Regular soft drink, ≥ 1/d 1.62 (0.96 - 2.75)

No difference!!!

Dhingra et al. Circulation July 31, 2007

Framingham Heart Study n=6154

• Adjusted for age, sex, smoking, diet

Examined risk of > 1 soda daily on dev. of metabolic syndrome

Soda and Mortality

• EPIC (European Prospective Investigation Cancer)

– 451K pts from10 European countries – 51 years, 71% women, over 16 yrs

• Predictor: Self reported soda intake

– Never, monthly, weekly, daily consumption

• Outcome: Mortality

Mullee A, et al. JAMA Intern

• Med. 2019;179(11):1479–1490

Soda Mortality

JAMA Intern Med. 2019;179(11)

• All sodas- (no gender difference)
• Sugar Sweetened Sodas
• Artificially Sweetened Sodas

Dose Response Mortality Increase <1 glass/month vs. 1-2 daily 17% increase 8% increase 26% increase!!

Soda Mortality Subgroups

Strongest association with CV Disease Mortality (CAD/CVA)

• Lesser extent digestive diseases, CRC, Parkinson’s JAMA Intern Med. 2019;179(11)

Biologic Plausibility?

• Vascular Risk and Diet Soda…

– Probably not just increased calories… – Confounders potentially at play (worse diet, sedentary) – Fluid decreased satiety over-eating later – Brown caramel syrup inflammation

• Bottom line:

Diet soda associated with vascular events. Cohorts prone to confounding BUT several studies show this now….

Allies and Antiracists- the data

• Police killed 1,098 people in 2019
• Black people were 24% of those killed

despite being only 13% of the population.

https://mappingpoliceviolence.org/

https://mappingpoliceviolence.org/

Thank you for your attention!