Ios V Exam 2

Front 1

What is CAM?

Back 1

complementary alternative medicine
 “A group of diverse medical and health care
systems, practices, and products that are
not generally considered to be part of
conventional medicine.” (NCCAM definition)
 Complementary: together with conventional
medicine
 Alternative: instead of conventional
medicine

Front 2

CAM History

Back 2

 15th century B.C. – Saw palmetto used
for male urinary symptoms
 5th century B.C. – St. John’s Wort used
for mood ailments
 100 B.C. – Traditional Chinese herbs
described
 1820 – 2/3 of the entries in the US
Pharmacopoeia (USP) were herbal

Front 3

What was the outcome of DSHEA (Dietary Supplement Health
and Education Act) in 1994

Back 3

– Manufacturer responsible for product safety
– Do not need FDA approval
– FDA must show product to be “unsafe” before it
can take action for restriction or removal

Front 4

What are the CAM Disclaimers?

Back 4

– “This statement has not been evaluated by the
FDA.”
– “This product is not intended to diagnose, treat,
cure, or prevent any disease.”

Front 5

2002 survey (NHIS) CAM findings

Back 5

identified 10,572
pts with CVD
– 36% had used CAM in past 12 months
– 18% (of 36%) used herbal products*
 Echinacea, garlic, ginseng, ginkgo biloba,
glucosamine ± chondroitin
– 80% (of 18%) thought herbs were helpful
*Note: majority of CAM use was for non-CVD indications…

Front 6

2003 survey of 107 patients in Nova Scotia Findings

Back 6

– 40% using herbal + non-herbal supplement
– 32% using herbal supplement (i.e. garlic)
– 22% using non-herbal supplement (i.e. omega-3)
– 65% cited use was for underlying CVD

Front 7

What are the omega 3 FAs we are concerned with?

Back 7

Eicosapentaenoic acid (EPA) &
docosahexaenoic acid (DHA)

Front 8

What are possible MOAs for O3 FAs?

Back 8

– Inhibition of acyl coA:1,2 diacylglycerol
acyltransferase
– ↑ hepatic β oxidation
– ↓ hepatic TG synthesis
– ↑ plasma lipoprotein lipase activity

Front 9

Potential O3 FAs uses:

Back 9

↓ TG’s, primary prevention,
secondary prevention in HF
 Ongoing studies: OMEGA, effects on
atherosclerotic plaque formation

Front 10

O3 FAs in CVD risk reduction

Back 10

 Overall data is mixed for CVD reduction…
 Primary prevention
– Physicians’ Health Study: approx 50% RRR in
sudden death with small amt fish intake
– Mostly cohort data; mixed
 Secondary prevention
– Population-based research showed dietary fish
intake  slightly ↓ risk of death
– Diet & Reinfarction trial: no difference in
reinfarction in men s/p MI who were
recommended to eat fish vs. those not
 29% ↓ in total mortality in fish group

Front 11

O3 FAs in lowering TGs

Back 11

 Data for TG lowering – wellestablished!
– ~ 4 gm/day = 25-30% TG reduction
– Lovaza™ (omega-3-acid ethyl esters) is FDA approved to treat ↑ TG’s
 Dose: 4 gm/day (either all together or divided BID)

Front 12

O3 FAs dose

Back 12

 Dose
– Typically 1-4 gm/day
– For cardiac/all-cause mortality prevention: 0.5 -
1.8 gm/day (usually ~ 1 gm/day)
– For TG lowering, 3-4 gm/day

Front 13

O3 FAs Products

Back 13

 Products
– Lovaza™ (prescription only)
– Various OTC (i.e. Puritan’s Pride Omega-3 Fish
Oil)
– Fatty fish (i.e. salmon, herring, halibut)
 Be mindful of mercury content…

Front 14

O3 FAs side effects

Back 14

 Side effects:
– GI upset
– Fishy aftertaste, fishy burp
 Typically occurs with OTC products – can put
in freezer to reduce incidence
– Or use enteric coated product
DO NOT FREEZE LOVAZA CAPSULES!
– Potential for increased bleeding
 Especially with high doses (>3 gm/day) or in
combination with anti-platelet and/or antithrombotic
therapy
*as increase dose, increase risk of SEs See table in notes

Front 15

O3 FAs drug interactions

Back 15

 Interactions:
– Anti-coagulant/anti-platelet drugs
– Anti-hypertensive drugs
– Oral contraceptives
– Orlistat (Xenical®, Alli®)

Front 16

O3 FAs caution/contraindications

Back 16

 Cautions/contraindications:
– Can paradoxically ↑ LDL
– Large doses can affect platelet function
– Large amts of dietary fish oil – mercury, PCB’s,
other toxins…
– Safety in pregnancy unknown…

Front 17

How do you know how much O3 FA is in a capsule?

Back 17

When recommending OTC
products – look at EPA +
DHA amounts on product
label!
Ex: a 1200 mg capsule contains only about 324 mg O3 FA per capsule

Front 18

what is coenzyme Q10?
(Q10)

Back 18

Ubiquinol” – found in most foods

Front 19

Q10 potential mechanisms

Back 19

– Oxidative metabolism facilitation (antioxidant)
– Membrane stabilization
– Cofactor  production of ATP

Front 20

Q10 potential uses

Back 20

Potential uses: HF, HTN, angina, counteract statin-associated myalgias

Front 21

Q10 data in heart failure

Back 21

some studies show benefit, some show no difference
– Benefits seen: clinical improvement in signs/symptoms, improvements in LVEF,
SV, and functional status

Front 22

Q10 data in angina

Back 22

improved exercise
tolerance

Front 23

Q10 data in HTN

Back 23

↓ in SBP/DBP, but results
inconsistent

Front 24

Q10 data in statin associated myopathy

Back 24

– CoQ10 is the end-product of mevalonate
pathway
 Statins block HMG-CoA  mevalonate
– Statins ↓ CoQ10, but significance is
uncertain
– CoQ10 supplementation in statin-induced
myopathies produces conflicting results…

Front 25

Q10 doses

Back 25

– HF: up to 100mg/day, divided
– Angina: 50mg TID
– HTN: 120-200mg/day, divided
– Statin-associated myopathy: 100-200mg/day

Front 26

Q10 products

Back 26

 Products
– Many OTC products available
– Look for reputable brand or USP symbol (or
certification of product by ConsumerLab.com)
– Watch out for combo products!

Front 27

Q10 side effects

Back 27

 Side effects
–Well-tolerated!
– GI upset in <1% of patients
 Incidence decreased when doses
>100mg/day are divided
– Rash

Front 28

Q10 interactions

Back 28

 Interactions:
– Anti-hypertensives
– Chemo (doxorubicin) – possible…
–Warfarin
– Vitamin K

Front 29

Q10 cautions/precautions

Back 29

– None; however, beware of drug-drug
and/or drug-herb interactions

Front 30

is Q10 more or less effective with food?

Back 30

take with a fat containing
meal to maximize
absorption

Front 31

what is hawthorn?

Back 31

Member of the rose – rosaceae – family
– Flavanoids are active components

Front 32

potential mechanisms hawthorn

Back 32

Potential mechanisms:
– Cardiac: ↑ force of contraction and refractory
period
– ↑ cAMP
– Anti-arrhythmic properties

Front 33

potential uses Hawthorhn

Back 33

HF, coronary
circulation dysfunction, angina,
arrhythmias

Front 34

Hawthorn HF data

Back 34

 Evidence in HF is contradictory
 SPICE (unpublished data):
– Extract WS1442 vs. placebo
– 6-month data looked promising…
– No difference between groups @ 24 months
 HERB CHF:
– Extract WS1442 vs. placebo
– No difference between groups @ 6 months
 Previous studies have shown improvement in
exercise tolerance and HF symptoms
– Too short duration?
– Only modest improvements?
– Severity of HF in study population?
– Appropriate background therapy?

Front 35

hawthorn dose

Back 35

Dose
– Standardized extract: 160-1800 mg/day
(divided) for HF

Front 36

Hawthorn products

Back 36

 Products
– Look for standardized preparation
– Crategutt® in Europe – preparation of WS1442 (used in SPICE and HERB CHF
trials)

Front 37

hawthorn side effects

Back 37

– Vertigo, dizziness
– Hypotension
– GI upset
– Fatigue
– Sweating
– Palpitations
– Sleeplessness, agitation

Front 38

Hawthorn drug interactions

Back 38

– MAJOR:
 Beta-blockers
 Calcium channel blockers
 Digoxin
 Nitrates
 PDE-5 inhibitors
***do NOT use hawthorn with these meds

Front 39

hawthorn cautions/contraindications

Back 39

– Natural Medicine’s Database recommends NOT
using in HF due to data from the HERB CHF study (extract shown to ↑ the early risk of HF progression)

Front 40

hawthorn vs digoxin

Back 40

– In Europe, often used in place of digoxin
– Has digoxin-like properties, but contains no cardiac glycosides
– No benefit to adding it to digoxin
– If a pt has HF symptoms despite therapy with hawthorn, the pt should be switched to digoxin (as appropriate)

Front 41

What part of Garlic is used medicinally?

Back 41

Applicable part is the bulb
(and allicin)

Front 42

potential mechasnisms of garlic?

Back 42

– May act as an HMG-CoA reductase inhibitor
– ↓ oxidative stress & LDL oxidation
– Anti-thrombotic
– Promotes smooth muscle relaxation and
vasodilation

Front 43

potential uses of garlic?

Back 43

HTN, dyslipidemia, CHD,
atherosclerosis

Front 44

garlic data in CVD risk reduction

Back 44

– For
 Meta-analysis showed beneffiit in ↓ TG and
platelet aggregation (thought to improve CVD)
– Against
 Small RCT using garlic powder showed no
anti-inflammatory or lipid-lowering effects in
high-risk primary prevention pts

Front 45

darlic data for HTN

Back 45

–Mixed
– Pre-clinical studies have shown garlic to modulate NO and endothelin-1
– Meta-analysis (2001) of 30 studies showed mixed/modest ↓ in BP (range: 2- 7%)
– Meta-analysis (2008) of 11 studies showed garlic ↓ SBP in HTN pts
 Did not see difference in normotensive pts

Front 46

garlic data for dyslipidemia

Back 46

– Again, data is mixed
– Meta-analysis (2001) showed modest, short-term lipid reduction
 Pooled data: ↓ TC by 7.2 mg/dl @ 4-6 weeks and 17.1% at 8-12 weeks (CI 0.03-0.34 and 0.32-0.57)
 Average reductions @ 20-24 weeks not significant
– Meta-analysis (2009) of 13 trials showed no statistically significant ↓ in lipids
– NCCAM-funded study
 Adults with LDL 130-190 mg/dl included
 Randomized to 1 of 3 garlic preps or placebo
 Results: no statistically nor clinically significant effects of any of the garlic preps on LDL

Front 47

garlic dose

Back 47

– Range for dyslipidemia and HTN is 600 to 2400 mg/day (standardized 0.5 to 1.3% allicin content)

Front 48

garlic products

Back 48

– OTC vs. actual garlic
– Controversy: OTC products vary greatly; “odorless” products may not contain any active ingredient (allicin)
– FYI: Garlique® promotes its allicin component

Front 49

garlic side effects

Back 49

– Breath/body odor
– GI upset
– ↑ risk of bleeding
– Allergic reaction
 Pts with pollen allergy predisposed to true IgE-mediated allergy

Front 50

garlic interactions

Back 50

– Anti-coagulant/anti-platelet drugs
– OCP’s
– Cyclosporine
– MAJOR: isoniazid, NNRTI’s, saquinavir

Front 51

garlic cautions/contraindications

Back 51

– P450 effects
– Caution with multiple anti-coagulant and/or antiplatelet
drugs and herbs
– Pregnancy – though not published, garlic thought to have abortifacient properties

Front 52

what is red yeast rice (RYR)?

Back 52

Product of rice fermented with
Monascu purpureus yeast (yeast grown on rice)

Front 53

RYR potential mechanisms

Back 53

– Contains monacolins -> monacolin K ->
mevinolin ->lovastatin!
– HMG-CoA reductase properties

Front 54

RYR uses

Back 54

dyslipidemia

Front 55

RYR data for dyslipidemia

Back 55

– Study of 86 patients compared red yeast
rice plus diet changes vs. diet changes
alone
 RYR group: 30 mg/dl ↓ in LDL @ 12 weeks
 Placebo group: 5 mg/dl ↓ in LDL @ 12 weeks

Front 56

RYR side effects in red yeast
rice plus diet changes vs. diet changes alone study

Back 56

 RYR group: 1 pt admitted with
musculoskeletal CP
 Placebo group: 1 rash, 1 HA, 1 pneumonia
 No LFT abnormalities in either group

Front 57

RYR dyslipidemia study in China

Back 57

– Study of 79 patients in China compared
RYR vs. placebo
 RYR group: 27.7% ↓ in LDL @ 8 weeks
 Placebo group: 1.5% ↓ in LDL @ 8 weeks
– Side Effects
 RYR group: 21 patients
 Placebo group: 28 patients
 No cases of rhabdomyolysis or anaphylaxis
 CPK elevations observed, but none >3x ULN

Front 58

RYR dose

Back 58

For dyslipidemia, range 600mg BID to 1800mg BID

Front 59

RYR products

Back 59

– Used in clinical trials: Cholestin,
Xuezhikang, Zhibituo, and “Red Yeast
Rice”
– Cholestin (not available in the US)
contains 9.6mg lovastatin/2400mg dose

Front 60

RYR Side Effects

Back 60

– Similar to statins!
 GI upset
 Elevated liver enzymes
 Myopathy (potential for
rhabdomyolysis)
 Anaphylaxis

Front 61

RYR interactions

Back 61

similar to statins
– Coenzyme Q10
– 3A4 inhibitors, i.e. clarithromycin, ketoconazole,
cimetidine, protease inhibitors
– Hepatically

Front 62

RYR cautions/contraindications

Back 62

– RYR is a statin – avoid use in combination with other statins (i.e. atorvastatin, simvastatin)
– Avoid in patients with significant liver dysfunction
– Do not use in pregnancy (statins = category X)

Front 63

Clinical Pearls of RYR

Back 63

– Should be considered as an HMG-CoA reductase inhibitor with regard to MOA, side effects, interactions, and cautions
– Depending on the product, OTC Red Yeast Rice has been found to contain as
much as 5 mg lovastatin/tab (typical dose for lovastatin is 10-40 mg/day)

Front 64

Herbs likely ineffective in CVD

Back 64

 Beta-carotene
– No evidence for primary or secondary prevention
– Study of male smokers s/p MI showed ↑ risk of death
 Vitamin E (α-tocopherol)
– Clinical trials show no benefit; epidemiologic
data do
– Caution: ↑ doses (≥ 400 IU/day) may ↑ side effects and all-cause mortality in some patients

Front 65

Herbs to AVOID in CVD

Back 65

 Ma Huang (ephedrine)
– Can cause HTN, MI, stroke
 Bitter orange
– Stimulant effect can cause MI, stroke, other cardiotoxicity (i.e. arrhythmia)
 Licorice
– Large doses ->HTN
 Belladonna
– Can cause tachycardia and exacerbate HF
 Yohimbe/yohimbine
– Contraindicated in angina/CVD; can cause HTN
or hypotension

Front 66

What are the available CAM products?

Back 66

– Omega-3 Fatty Acids
– Coenzyme Q10
– Hawthorn
– Garlic
– Red Yeast Rice