Transcript heartmatters1

Heart Matters—All Things Cardiac
Barb Bancroft RN, MSN, PNP
Chicago IL
OK, so what are we going to do today?
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Some numbers
Risk factors for heart disease
Drugs used to treat cardiovascular conditions
Lab Tests for cardiac risks and function—lipid profile,
BNP, Troponin, hs-CRP, blood pressure, microalbumin
• The cardiac exam
• The evaluation of the patient with chest pain
• Selected cardiac conditions—acute coronary
syndromes, hypertension, CHF, AF, valvular heart
disease, cardiomyopathies
Some numbers?
• Cardiovascular disease costs $273 billion per
year
• Heart disease is the number one cause of death
in the U.S.
• Between 1999 and 2009 the rate of deaths from
CVD declined 32.7 percent. However, it still
accounts for 1 out of 3 deaths per year
• Older adults living a healthy lifestyle are more
likely to delay the onset of cardiovascular
problems by at least seven to 14 years…
Some numbers??
• Meeting 5 of 7 of the following criteria decreases
likelihood of dying from heart disease by 88%
• No smoking
• BMI less than 25
• 150 minutes/week moderate activity; 75 minutes
of strenuous activity
• Healthy diet
• Total cholesterol level less than 200 mg/dL
• BP less than 120/80
• Fasting plasma glucose less than 100 mg/dL
Risk factors for cardiovascular disease—
the usual suspects
• In general, cardiovascular disease is genderblind—smoking, hypercholesterolemia,
diabetes mellitus, hypertension, and the lack
of exercise are the major controllable risk
factors for both sexes
• But let’s first take a look at the NONcontrollable risk factors—age, gender, family
history
Your age…and gender
• Women have the onset of heart disease an
average of 10 years later than men and their
first heart attack 20 years later than men
• Here you are, celebrating your 75th birthday
with all of your GIRLfriends in the nursing
home
Why?
• Estrogen protects our heart even after our ovaries
die…for about another 10-15 years—estrogen is an
anti-oxidant, lowers LDL-C, anti-inflammatory
• HOWEVER, hormone replacement therapy is NOT
cardioprotective
• Prior to menopause, menstrual bleeding decreases
iron stores on a monthly basis; women’s iron stores are
50% less than men until menopause; high iron acts as
an oxidant on LDL-cholesterol
• Oxidation puts LDL-cholesterol into arterial walls
• Once we stop menstruating iron levels creep up and
the CV risk increases
Family history
• Father, mother, brother, or sister who first developed
clinical CAD at age younger than 45-55 for males and
at age younger than 55 to 60 for females;
• An early heart attack (myocardial infarction) or other
cardiovascular event (stroke or peripheral vascular
disease)
• Important to ascertain, but it only modestly adds to
the predictive power of global assessments
Things you can change…
Controllable risk factors
• Smoking
• Hyperlipidemia with LDL cholesterol as the
most important contributor to CVD—
• Diabetes mellitus— “sugar diabetes”
• Hypertension
Stop Smoking
• 36% reduction with smoking cessation
• appears at least as great as other secondary
preventive therapies, such as the use of
statins for lowering cholesterol levels
(29%), aspirin (15%), β-blockers (23%),or ACE
inhibitors (23%),which have received the bulk
of the attention in recent years.
Smoking and women
• Women who smoke have their first heart
attack almost 20 years earlier than women
who don’t smoke
“When should I quit smoking?” How about
NOW?
• If you quit smoking the risk of heart disease
drops substantially in only 2-3 years, reaching
baseline after ten years
• Patients who cut down but continue to smoke
1-4 cigarettes per day continue to have an
elevated risk of heart disease
How about smoking and clotting with
estrogen-containing products?
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Pills of yesteryear—80 to 100 μg per pill
Could stop an elephant from ovulating
Pills of 2012—20-35 μg per pill
Less clotting risk, greater chance of pregnancy
if you MISS A PILL
• It’s not JUST the pill…weight plays a role too…
The Pill, obesity, and clotting risk
• European Active Surveillance study (2000-2006); 59,000
women from seven European countries, looking at heart
health in women using OCs
• For every 100,000 years of pill-taking, 44 women had
blood clots in the placebo group
• For every 100,000 years of pill-taking, 90 women had
blood clots (double the placebo group)
• BUT, and that’s a big BUTT—when the study looked
specifically at women with a BMI over 30, the number
skyrocketed to 230 cases (5x more likely than those in the
placebo group)
Drospirenone in OCs
• April 30, 2012
• FDA Warning about drospirenone in oral
contraceptives
• Yaz, Yasmin, BeYaz, and Safyral, and others may be at a
higher risk for thromboembolism than CHCs containing
other progestins (levonorgestrel, norgestimate, or
norethindrone)
• Controversial warning…all CHCs increase the risk of
venous thromboembolism, whether the progestin
component affects risk continues to be controversial
• And, the risk of clotting during pregnancy is much
higher
Comparison of risk of levonorgestrel vs
drospirenone
• Drospirenone rate is 30.8 per 100,000 womenyears
• Levonorgestrel rate is 12.5 per 100,000
women-years
• Another study—23.0/100000 w/ drospirenone
vs. 9.1/100,000 with levonorgestrel
Jick SS and Hernandez RK. BMJ 2011 April 21;342;
Parkin L et al. BMJ 2011;342
Lowering LDL-cholesterol
• To 70 mg/dL or less (2.0 mmol/L or even lower to
1.8 mmol/L) if you have cardiovascular disease,
diabetes, hypertension or smoke)
• Triglycerides less than 150 mg/dL
• It appears as if the HDLs have fallen out of favor
due to a couple of studies that boosted HDLs for
cardioprotection; the studies found no
differences in CAD with boosting HDLs
(The Lancet, December 8/14, 2012; J Am College of Cardiology,
December 19, 2012)
LDL-cholesterol is the primary problem
• HOWEVER, there’s more to it than just a
“cholesterol” level
• NEWEST RESEARCH: LDL particle size is most
important
• Subtype/Pattern A—large, loose LDL molecule
• Subtype/Pattern B—small, dense molecules,
prone to oxidation and penetration of artery
walls forming fatty plaques
Expanded cholesterol test
• Ratio of small to large LDL molecules
• Test is between $39--$100 and is not covered by
insurance
• One clue that your LDL particles are small—your
triglycerides are high (diabetics have high
triglycerides with higher rates of CV disease)
• The drugs that specifically lower LDL-cholesterol,
the statin drugs, are most effective when the LDL
molecules are small and dense
Type 2 Diabetes Mellitus— “sugar
diabetes”
• Over 28 million type 2 diabetics in the U.S.
• Heart disease and stroke are the No. 1 and 2
causes of death and disability among people
with type 2 diabetes. In fact, at least 65
percent of people with diabetes die from
some form of heart disease or stroke.
Diabetes Mellitus
• Adults with diabetes are two to four times
more likely to have heart disease or a stroke
than adults without diabetes.
• Women with diabetes have a greater risk of
heart disease than men with diabetes
• When patients have both hypertension and
diabetes (the “deadly duo”), which is a
common combination ~70% of the time, the
risk for cardiovascular disease doubles.
How about patients with Type 1
diabetes?
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How long have they had the disease?
Are they smokers? Have hypertension?
How are their kidneys? microalbuminuria?
In T1DM kidney disease rarely occurs within the
first 5 to 10 years of diabetes, with increasing
incidence of nephropathy over the next decade
to a peak at about 15-17 years of having diabetes
• Kidney disease and cardiovascular disease go
hand-in-hand
Hypertension (high blood pressure)
• Hypertension is a risk factor for heart disease in
both men and women
• What is “normal” blood pressure? Less than
120/80
• Diabetes and hypertension—new guidelines (ADA
January 2013, Diabetes Care)—140 /80; old
guidelines of less than 130 systolic showed that
intensive BP control did NOT decrease deaths or
heart attacks and only a slight decrease in strokes
Another important note about
hypertension…
• Are you a dipper? 10% decline @ night
• Or a non-dipper*? BP doesn’t fall when your
head hits the pillow…non-dippers have a
higher risk of CV disease, strokes, and endstage renal disease
*consider night time dosing of anti-hypertensive
for . non-dippers
(American Journal of Kidney Diseases
December 2007)
The Deadly duo and Kidney disease
• Hypertension and diabetes increase the risk of
chronic kidney disease
• Increased pressure in the glomerulus—
intraglomerular hypertension
• One of the first manifestations of
intraglomerular hypertension is
microalbuminuria
Diabetic/hypertensive
nephron…hyperglycemia/HTN/high animal protein in the diet
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Afferent arteriole
( ↑ vasodilation by
( ↑ prostaglandins—increasing GFR)
• Blood entering
glomerulus
• Glomerulus→filter
• Efferent arteriole
( ↑ vasoconstriction via
( ↑ angiotensin II)
• Intraglomerular hypertension
and microalbuminuria
Microalbuminuria
Why is microalbuminuria a “bad” thing?
• The presence of microalbuminuria suggests that
large vessel walls are more permeable to
lipoproteins (causing atherosclerosis) and/or
damage from the local release of growth factors
• There is a 4-fold increase in acute coronary
syndromes in Type 1 DM greater than 35 years
old;
• When microalbuminuria is present the
cardiovascular risk is increased by a factor of 140!
What else increases the risk for heart
disease?
• Weight gain—if a woman gains 44 pounds
after high school her risk of heart disease
increases by 250%
Weight gain
• “But Barb, I’ve only gained a pound a year
since high school!”
• And, when, pray tell, did you graduate from
high school?
• “1960”…you do the math…it’s now 2013 or
53 years since you graduated from high school
• And you’ve only gained 1 pound per year?
Location, location, location of those
extra pounds—waist size
• Are you an apple or are you a pear?
What’s going on with belly (visceral)
obesity?
• Visceral fat is Insulin resistant
• Visceral fat (now considered endocrine
tissue—a NEW organ, yes you have GROWN a
NEW organ) produces adipokines to regulate
glucose transport and boost inflammation
responses
• Inflammatory mediators are produced by
visceral fat--Tumor Necrosis Factor alpha;
Interleukin-6
Throw it all together…metabolic
syndrome
• Central obesity—waist size greater than 40.2
inches in men, 34.6 inches in women
• High TG (>150 mg/dL),
• Low HDL (less than 40 mg/dL in men, less than
50 mg/dL in women)**NEW INFORMATION
• Hypertension (≥ 130/85 mm Hg)
• Fasting glucose ≥ 110 mg/dL
• Metabolic syndrome is present when any 3 of
these risk factors are present
• PCOS (polycystic ovary syndrome is a form of
metabolic syndrome/IRS)
Inflammation—high sensitivity CRP
• hs-CRP (vascular inflammation) and coronary artery
disease risk level—best use in younger individuals
believed to be at intermediate risk for heart disease
• Use of hs-CRP + lipid values together are more
accurate at predicting risk than lipid studies alone
• The bigger the waistline the greater the hs-CRP
low risk < 1 mg/L; Average 1-3 mg/L; high risk > 3
mg/L
(Noncardiovascular causes should be considered if
values are > 10 mg/L)
Ridker PM et al. N Engl J of Med 2000; 342:836-43; Ridker PM et
al. N Engl J of Med 1997;336:973-9)
What can reduce hs-CRP?
• Exercise
• Loss of abdominal fat—walkin’, walkin’ walkin’…
• Statins not only reduce LDL but are also potently
anti-inflammatory
• Aspirin
• Omega-3 fatty acids
• Nuts (especially walnuts)
• The Mediterranean diet
Depression
• Depression is associated with an elevated risk
of fatal CHD in men and women, and it is a
stronger risk factor in women.
• Depression increases the risk of having an AMI
by 400%
• If untreated following an MI or bypass surgery,
the patient is less likely to survive
• Say yes to anti-depressants if necessary
The Cardiologist’s funeral
• A cardiologist died and his funeral was attended by a
multitude of physicians showing their respect
• At the funeral his casket was elevated on the dais and
behind the casket was a huge heart covered in red
roses
• The eulogy was given and as the last words were said,
the massive rose-covered heart opened and the casket
rolled through the open heart of roses
• The gynecologist attending the funeral burst out
laughing and choked…I’m imagining what my casket
will roll through…
• And that’s when the proctologist got up and left…
Didja’ laugh at that joke?
• A study of patients who recently had a heart attack
compared humor responses to matched controls who
did not have a history of heart disease
• They were all given a multiple choice questionnaire—
asking about laughing…how often, how little, how
much ? The highest humor score was 105 and lowest
was 21
• People with a humor score above 50 had the least risk
of heart disease
• The heart patients were least likely to laugh in different
situations and the least likely to use humor in adaptive
situations
Hypothyroidism
• Subclinical hypothyroidism (TSH 5.01-10.0
mIU/L) w/ normal T4 has been associated with
an elevated cardiovascular risks and mortality
in patients under 70 (Arch Internal Med 2012)
• Decreased metabolism decreases the
clearance of lipids from the blood
• Increases the risk for heart disease
• The American College of Endocrinology
suggests age 35 for baseline TSH levels
Conversely…subclinical
hyperthyroidism
• Raises the risk for mortality and cardiac events
as well
• Especially when TSH levels are < 0.45 mIU/>
and even more so when levels were <0.10
mIU/L
• 29% higher CHD mortality
• 68% higher risk for atrial fibrillation
Other risk factors
• PCOS (polycystic ovary syndrome)—insulin resistance
• Autoimmune disease—SLE, RA (inflammation)--Risk of
cardiovascular disease in patients with Lupus—Lupus
patients are 140% more likely to have atherosclerosis;
for patients under 40 the risk is 480% (N Engl J Med,
Dec. 3, 2003);
• CV disease in RA patients—3 x >risk of hosp. w/MI; 5x
>risk of silent MI before dx w/RA; sudden cardiac death
?feel chest pain
• Atorvastatin and inflammation (RA, SLE, MS)(Lancet
2004 June 19;363:2015-21)
• Cocaine and methamphetamine use—duh…potent
vasoconstrictors
Like father, like son?
• For some men, CV disease may be inevitable
• Variant gene on the Y sex chromosome
increases the risk of CV disease by 50%
• The variant gene was found on an area of the
chromosome responsible for the immune
system, suggesting an inflammatory link
• May explain why certain men without
traditional CV risk factors still develop heart
disease
Cardiovascular drugs
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Drugs to lower lipids
Drugs to decrease blood pressure
Drugs to treat heart failure
Drugs to reduce platelet aggregation and
clotting factors
• Drugs that lower blood sugar
• Drugs to reduce arrhythmias
Drugs to lower LDL-cholesterol
The “statins”?
• Lovastatin (Mevacor)
• Pravastatin (Pravachol)
• Fluvastatin (Lescol)
• Simvastatin (Zocor)
• Rosuvastatin (Crestor)
• Atorvastatin (Lipitor)
• Pitavastatin (Livalo)
The “Statin Sisters”…what do they do?
• Inhibit an enzyme in the liver responsible
for the production of the LDL-cholesterol;
works primarily at night to reduce LDL, so
the “statins” work the best when taken
before bedtime (exceptions to the rule—
atorvastatin/Lipitor and
rosuvastatin/Crestor)
LDL-lowering effects
• If so, how low should your LDL go?
• Atorvastatin/Lipitor 10 mg
= 39%
• Fluvastatin/Lescol 40 mg BID
= 36%
• Fluvastatin XL/Lescol 80 mg
= 35%
• Lovastatin /Mevacor 40 mg
= 31%
• Pitavastatin/Livalo 2 mg
= 36%
• Rosuvastatin/Crestor 5 mg
= 45%
• Simvastatin/Zocor 20 mg
= 38%
(Circulation 2004;110:227-239)
Green tea, grapefruit juice, and
simvastatin
• Both green tea and grapefruit juice inhibit the intestinal
enzyme that metabolizes simvastatin. As inhibitors of this
enzyme, both “Gs” have the capability of increasing the
concentration of simvastatin which in turn increases side
effects. The higher the statin dose, the greater the toxicity.
The manufacturer of simvastatin reports that the incidence of
myopathy is 25 times higher with the 80 mg dose of
simvastatin versus the 20 mg dose. (Med Letter 2008
(October 20; 50:83)
• P.S. The bioavailability of simvastatin can increase by 700%
with grapefruit or grapefruit juice
LDL guidelines
• Guidelines—with CAD or a risk equivalent
(PAD, TIA, stroke, abdominal aneurysm), the
LDL should be ~70 mg/dL (2.0 mmol/L or even
lower, perhaps 1.8 mmol/L)
• For the rest of us with other risk factors—100
mg/dL (<2.85 mmol/L)
• Unless you’re perfect…--130 mg/dL (<3.37
mmol/L)
Summary: What do the statins do?
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Decrease total cholesterol
Decrease LDL-cholesterol
Decrease oxidation of LDL-cholesterol
Shrink plaques including plaques in the renal artery and
improve blood flow to vital organs
Stabilize fatty plaques and prevent plaques from
rupturing
Prevent the formation of new plaques in the renal and
other arteries
Decrease mesangial proliferation
Decrease vascular inflammation
SIDE EFFECTS
• Myalgias **(other causes in elderly patients…)
• About 1/20 patients experience muscle pain or weakness
• Myositis; rhabdomyolysis (rare) (ASA is 100x more likely
to cause a fatal side effect than taking a statin)
• Simvastatin at higher doses is the riskiest “statin” for
rhabdomyolysis—never use the 80 mg dose; lots of drug
interactions; do NOT drink green tea or eat grapefruit
or drink grapefruit juice with this statin
• How about adding CoQ10 for muscle aches and pains?
take 50-100 mg/day of CoQ10
• Either switch statins, lower the dose of statins, consider
every other day dosing
How about lowering triglycerides?
• Fenofibrates (Tricor, Triglide)
• Gemfibrozil Lopid)—not to be used with statins
• Niacin? Fallen out of favor… for primary and
secondary prevention especially when LDL levels
are achieved w/ statins (N Engl J Med 2011 Nov 15)
• Fish oil? Lower plasma TG, but recent studies do
not offer any convincing evidence that fish oil
supplements prevent primary or secondary
cardiovascular disease;
• Prescription fish oil, Lovaza 4 grams/day
Another drug with a favorable lipid
profile
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Cardiovascular benefits
lowers BP
decreases LDL-cholesterol
Lowers blood sugars
Reduces CV risks in PCOS (primary treatment
choice for this condition)
The ACE inhibitors inhibit
angiotensin II
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Captopril (Capoten)(1981)
Enalapril (Vasotec)(1983)
Fosinopril (Monopril)
Lisinopril (Prinivil, Zestril)
Perindopril (Aceon)
Moexipril (Univasc)
Benazepril (Lotensin)
Quinapril (Accupril)
Trandolapril (Mavik)
Ramipril (Altace)
What does “angie II” do?
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She “tenses” your “angios”—vasoconstricts
your arteries--hypertension
She triggers release of “AL”—aldosterone
(from the adrenal cortex to save sodium &
H2O in the kidney and excrete potassium
and magnesium)--hypervolemia
She increases inflammation in the arteries-vasculitis
She’s prothrombotic—clots
She’s a potent growth factor and “remodels
tissues”… NOT a good word in various
tissues including the heart and kidneys
(remodeling = enlargement of the heart)
In other words…
A little refresher on the kidney…
• At any given moment, the kidney is “sensing” the
pressure and volume of blood flow
• Low volume or low BP, the kidney will release renin
from a small area (the JGA) just inside the afferent
arteriole
• Renin (the messenger)→(liver) angiotensin I
→angiotensin II→ via Angiotensin Converting
Enzyme (ACE) (primarily in the pulmonary
circulation)
• Angiotensin II triggers the release of “AL”
(aldosterone) from the adrenal cortex
How can we inhibit Angie?
RENIN
ANGIOTENSIN 1
ACE --
ALDOSTERONE
ANGIOTENSIN 2
So if you were an ACE inhibitor, what would you do?
Inhibit ACE? Inhibit the formation AT angiotensin II
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Anti-hypertensive agent via vasodilation (due to inhibiting
angiotensin 2) and inhibition of aldosterone (excrete SODIUM and
H20 BUT you save POTASSIUM)—
(as many as 70% of hypertensive patients in U.S. may have elevated
RAA systems (renin-angiotensin-aldosterone)
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Treatment of heart failure by inhibiting renin-angiotensinaldosterone—CHF is a HYPER-RENINEMIC state
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Protect the kidney by vasodilating the renal efferent arteriole
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Anti-inflammatory
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Decrease growth of tissues or “remodeling”—angiotensin II
increases the size of the heart; ACE inhibitors inhibit this
“remodeling”
Side effects, of course…
• Hypotension—start
low and go slow
• Hyperkalemia (high
potassium) (excreting
sodium and water and
retaining potassium)
• Add a thiazide diuretic
to the ACE inhibitor
What about K+ containing foods?
• May also contribute to hyperkalemia and
cardiac arrhythmias but usually only in
patients with renal insufficiency so or in
patients who are also on K+ sparing
diuretics such as spironolactone (Aldactone)
and eplerenone (Inspra)
• Avoid excessive potassium intake when on
the above drugs or with renal insufficiency
• Advise patients to decrease potassium
intake until they can get their potassium
checked
High K+ containing foods
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Potatoes
Prunes
Raisins
Apricots
Bananas
Halibut
Canteloupe
Oranges
Pasta sauce
Health.harvard.edu/heartextra for K+ content of
1,200 foods
Side effects, continued…
• Cough (gender differences)
• ACE inhibitors block angiotensin converting
enzyme; but as ACE is inhibited, bradykinin
goes UP…bradykinin is a potent
bronchoconstrictor
• Women have more bradykinin to begin with,
therefore the gender disparity in the cough
Side effects, continued…
• Life-threatening angioedema (“Does my voice
sound funny to you?”)
“Sartans”—Angiotensin II Receptor
Blockers
• Angiotensin receptor blockers (bypass ACE) and work
by blocking the angiotensin II receptors on tissues
• Who are they? The “Sartan Sisters”…
• losartan—Cozaar
• valsartan—Diovan
• candesartan—Atacand
• irbesartan—Avapro
• telmisartan—Micardis
• olmesartan—Benicar
• azilsartan -- Edarbi
Two other drug categories that influence the
renin-angiotensin-aldosterone system
• The direct renin inhibitors -- aliskirin (Tekturna)
• The aldosterone antagonists – spironolactone
(Aldactone) and eplerenone (Inspra)—Used for
additional aldosterone inhibition in CHF patients;
be careful with these drugs when used in
combination with ACE inhibitors; potassium and
magnesium levels can increase to dangerous
levels and life-threatening cardiac arrhythmias
can occur
• Keep checking the potassium and magnesium
levels
Monitoring K+ and serum creatinine
If the serum potassium is:
• 5-5.5 recheck in 7 days
• 5.6 to 6.0 stop ACE and check in 7 days
• 6.1-6.5 stop ACE and check immediately
• Greater than 6.5 stop ACE and check urgently (may
need to head to the ER) – do ECG
Creatinine—a rise of greater than 20-30% is considered
to be significant; smaller rises are common and are
to be expected in many patients
“Olols, alols, ilols”—Beta blockers to
the rescue
• atenolol (Tenormin)(may not reduce CV risk in patients
with hypertension)
• betaxolol (Kerlone)
• bisoprolol (Zebeta)*(heart failure choice)
• carvedilol (Coreg) *heart failure choice
• Esmolol (Brevibloc)
• labetalol (Trandate)(Normodyne)—safe during
pregnancy
• metoprolol succinate (Toprol XL, Lopressor)*(heart
failure choice)
• nadolol (Corgard)
• nebivolol (Bystolic)
• propranolol (Inderal)(1968)(nonselective)
• timolol (Blocadren)
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Properties of beta blockers
• You don’t just choose “any ol’ beta blocker”….
• Cardioselective beta blockers only block B1
receptors of heart (SA node and cardiac muscle)
• Non-selective beta blockers blockers block both
beta 1 and beta 2 receptors
• Lipid-soluble? (cross blood brain barrier and
blocker norepinephrine—clinical uses and side
effects)—propranolol is the MOST lipid-soluble
• Water-soluble? Decreased ability to cross blood
brain barrier—atenolol is the least lipid-soluble
Cardioselective beta blockers block the B1
receptors
• Cardioselective beta blockers reduce cardiac
output, heart rate falls (10-15%), blood
pressure falls
• Workload of the heart decreases—angina,
SVT, post-MI to protect the heart from
remodeling and to reduce heart rate
• atenolol (Tenormin), metoprolol (Lopressor),
betaxolol (Kerlone); bisoprolol (Zebeta),
nebivolol (Bystolic)@ doses <10 mg)
Non-selective beta blockers block both
beta-1 and beta-2 receptors
• Blocking beta-2?—decrease skeletal muscle
(tremor), bronchoconstriction (problem w/ COPD
patients and asthmatics); large arteries of the
legs (vasoconstriction)—problem with diabetics
or anyone with PAD
• Non-selective beta blockers-- propranolol
(Inderal), nadolol (Corgard), timolol (Blocadren),
carvedilol (Coreg)
• Use CARDIOSELECTIVE beta blockers for diabetics
and COPD patients
Beta blockers…other properties
• Water-soluble? (low lipophilicity)
atenolol (Tenormin), nadolol (Corgard),
labetalol (Trandate), nebivolol (Bystolic)
• Lipid-soluble? (high lipophilicity--cross the
blood brain barrier)—CNS side effects—
anhedonia (the “Blahs”)—BUT…the lipidsoluble can also “calm down” the brain
• propranolol (Inderal), timolol (Blocadren),
metoprolol (Lopressor, Toprol XL), pindolol
• All of the others are moderately lipophilic
Beta-blockers after an AMI
• Use of a beta blocker is not necessary in a
patients with CAD without prior MI
• Use a beta blocker w/ angina to reduce
symptoms and improve exercise tolerance
• Post-MI WITHOUT systolic heart failure—use a
beta blocker for 2-3 years and longer if tolerated
• Post-MI WITH systolic heart failure—continue to
use a beta-blocker indefinitely—choose one that
improves survival—carvevdilol, metoprolol ER,
bisoprolol
Calcium Channel Blockers; 2 categories…the
nondihydropyridines and the dihydropyridines
1) Verapamil (Isoptin SR, Verelan and
Verelan PM, Calan and Calan SR,
Covera-HS)—block calcium channels
primarily on the coronary vessels and
the AV node—increasing blood flow to
the heart and decreasing impulses
through the AV node—used to decrease
workload of heart and slow the heart
rate; HTN, angina, atrial fib,
renoprotective
Negative inotropic effect—avoid in
patients with CHF
Calcium channels in bowels (elderly)—
severe constipation
2nd drug in the non-dihydropyridine
category
• Diltiazem—Cardizem LA and CD,
Dilacor XR, Tiazac—dilates calcium
channels on the coronary arteries
and peripheral vessel calcium
channels; decreases impulse
transmission from atrium to
ventricle
• Negative inotropic effects—avoid
in CHF patients
Clinical uses—
Atrial fibrillation, Hypertension,
Angina, Vasospasm,
renoprotective
Less constipation than verapamil
2nd category—the Dihydropyridines or the
“DIPINES”—Peripheral vessel calcium channel
blockers
• Amlodipine (Norvasc)
• Felodipine (Plendil)**
• Nifedipine (Procardia XL,
Adalat)
• Nicardipine (Cardene)
• Isradipine (Dynacirc)
• Nisoldipine (Sular)
• Clevidipine (Cleviprex) for IV
use vs. esmolol or IV
nicardipine)
Clinical uses of the “dipines”…
• Hypertension
• Vasospasm—Prinzmetal’s angina,
Raynaud’s phenomenon, cocaineinduced vasospasms
• An added possible benefit…“male
contraceptive”
Side effects of CCBs…
• Verapamil—significant constipation; lots of drug
interactions
• Dipines—significant peripheral vasodilation with
headaches; hypotension, and peripheral edema
(swollen feet—pedal edema; (Plendil)
• Diltiazem—less significant constipation than
Verapamil
• All CCBs inhibit calcium-induced contraction of the
LES, resulting in sphincter relaxation and acid reflux
Drugs that inhibit platelet function
• ASA—81 mg; does anyone need more than 81 mg? very
rarely…higher doses can double the risk of a GI bleed (use
famotidine/Pepcid)
• Use 162 or 325 mg of ASA for FIRST DOSE of an acute MI or
ischemic stroke
• clopidogrel/Plavix for 6 to 12 months after STENT
• pasugrel/Effient
• ticagrelor/Brilinta (if using ASA with ticagrelor only use the
81 mg—higher doses decrease Brilinta’s efficacy)
• Clopidogrel and PPIs (especially omeprazole and
esomeprazole)
Instead of warfarin/Coumadin
• rivaroxaban/Xarelto—oral factor Xa inhibitor
for venous thromboembolism (VTE); no
monitoring, fewer drug interactions, does not
require bridging with LMW heparin because of
it’s fast onset; causes less major bleeding; no
antidote; no lab test to monitor compliance,
higher cost
• apixaban (Eliquis)—a second oral factor Xa
inhibitor
Instead of warfarin/Coumadin…
• Dabigatran/Pradaxa— direct oral thrombin inhibitor;
relatively short half life of 12-17 hours; doesn’t require
monitoring; BID in fixed dose (150 mg)(adjusted with
renal dysfunction); no known food interactions and
minimal interactions with other medications;
• Lower risk of stroke or systemic embolism; lower risk of
hemorrhagic stroke, lower risk of death from any
cause; lower risk of major bleeding (except GI
bleeding)
• Higher risk of MI
• Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus
warfarin in patients with atrial fibrillation. N Engl J Med.
2009;361:1139-1151.
Comparison of intracranial hemorrhage with
new drugs vs.Coumadin
• 2500 patients in my clinic who are taking
warfarin for life, I know that 1 in 300 of them
will have an ICH per year no matter how well
controlled they are," he said. "Now with the
new drugs, this can be reduced to 1 in 500 to
600. That is a big deal.“(Larry B. Goldstein, MD,
professor of neurology at Duke Stroke Center,
Durham, North Carolina)
• No antidote is there IS a bleed…
Warfarin (Coumadin)
• Atrial fibrillation, prevention of DVT and PE
• Inhibits vitamin K-dependent activation of II,
VII, IX, X which are formed in the liver
• When adding or subtracting a drug, check the
INR within 4 days
• Standard therapeutic range for patients on
warfarin is 2-3; mechanical heart valves? 2.53.5
• Study of 100,000 emergency hospitalizations
in 58 hospitals—warfarin bleeding #1; 21,000
While we’re talking about warfarin
• $80 per month (with INR monitoring) vs. newer
rivaroxaban/Xarelto ) ($300+) and apixaban
(Eliquis), dabigatran (Pradaxa)
• Good news? Cheaper
• Bad news? Lots of drug interactions making
warfarin either MORE effective (bleeding) or less
effective (clotting)
• Good news? Vitamin K antidote for warfarin
bleeding; Bad news? No antidote for other
anticoagulants
• Prescriber’s Letter, December 2012
Parenteral anticoagulants
• Heparin—Unfractionated heparin--the old standard
(been around for 100 years)—binds to antithrombin to
prevent both the conversion of fibrinogen to fibrin and
prevent the activation of platelets—animal derived;
frequent monitoring and dose adjustments; also
monitor platelet counts (Heparin-induced
thrombocytopenia/HIT or HITT—HIT w/thrombosis)
• Low-molecular weight heparins (LMWH) such as
fondaparinux (Arixtra) (SQ/qd), enoxaparin (Lovenox)
and dalteparin (Fragmin)—bind to antithrombin
w/more predictable response, no need to monitor
Parenteral anticoagulants
• Direct thrombin inhibitors—prevent thrombin
from converting to fibrinogen and fibrin
• Bivalirudin/angiomax—for PCI (percutaneous
coronary intervention)
• Argatroban—for patients with HIT or at risk
for HIT/HITTS and as an anticoagulant for
these patients who are undergoing PCI
Are we even using DIGOXIN any more?
• One of oldest cardiac drugs and controversial
• Foxglove plant, the witch from Shropshire, and
Dr. William Withering
• New study published in European Heart
Journal found that dig, when used by patients
with atrial fibrillation, increased mortality
rates by 41% from any cause; 35% increase in
deaths from CV causes and a 61 percent
increase in deaths from arrhythmias
Digoxin
• Digoxin – quinidine and verapamil displace dig
and can increase dig levels by 50%• clarithromycin (Biaxin) and digoxin toxicity
(12x more likely to be hospitalized with dig
toxicity)
• Digoxin toxicity—the 3rd most common drug
that brings the elderly to the ER
• Safer, better drugs include diltiazem,
verapamil (except in elderly), beta-blockers
Loop Diuretics
• Indicated for volume overload
• Usually start with furosemide/Lasix 20-40 mg
QD/BID (or 40 mg x serum creatinine)
• Higher doses with significant renal dysfunction
• Titrate up to 600 mg/day; failure of therapy is
often the result of inadequate dosing
• Torsemide (Demadex)—superior absorption and
longer duration of action
• Bumentanide (Bumex)—40 times more potent
mg for mg than furosemide
Diuretics
• Synergistic diuretics that act on the distal
tubule (thiazides, such as
metolazone/Zaroxolyn,
chlorthalidone/Thalitone or K+sparing agents)
are often added in those who fail to respond
to high-dose loop diuretics alone
Chlorthalidone
• For every month a patient takes chlorthalidone
(Hygroton/Thalitone), it extends their life by one
day.
• December 21, 2011 J of Am Med Assoc, enrolled
4700 patients from 1985-1988. ½ took
chlorthalidone, ½ took placebo for 4.5 years
• 22 years later, the # of deaths was identical for Rx
group & placebo, but Rx group lived 158 days
longer than the placebo group before they died
of CV disease and 105 days longer before dying of
other causes
Nitroglycerin—can I blow up with NTG?
• Oral, extended release (Nitro-Bid, Nitroglyn, Nitrong,
Nitrong SR, Nitro-Time
• Sublingual NTG—NitroQuick, Nitrostat
• Translingual—Nitrolingual
• IV—Nitro-Bid IV, Tridil
• Topical—Deponit, Minitran, Nitrodisc, Nitro-Dur,
Transderm-Nitro
• Transmucosal—Nitrogard
• Gentleman from Savannah
• USE with “afils”??
The ED drugs…the “afils”--Can’t use
with nitroglycerin…
• “When was your last dose of Viagra?” (sildenafil)
• Can’t use Viagra or Levitra (vardenafil) within 24
hours of receiving NTG; Cialis (tadalafil) within 3648 hours
• Side effects
•
Hypotension
•
Headaches
•
GERD
•
Blue vision
•
Priapism
• A surprise side effect of the “afils”…
Sexually transmitted diseases have increased by over 300% in
the over 60 crowd since the release of Viagra…
•
•
•
•
•
•
•
More sex
No pregnancy worries
Swingin’ singles
Who cares what the neighbors think?
Swimming pools and golf courses
Can you have a heart attack during sex?
Only if…
Bariatric surgery
• “There is no pharmacologic alternative to weight
loss or diabetes that can produce comparable
results in such a short amount of time…” James
Young, MD, Chairman, Cleveland Clinic
Endocrinology and Metabolism Institute
• Hypertension? 44% prior to surgery; 63% with
significant reduction after surgery; 24% had
diabetes prior to surgery, 73% had improvement
in diabetes symptoms