Heart Matters

1
Heart MattersAll Things Cardiac

• Barb Bancroft RN, MSN, PNP
• Chicago IL

2
OK, so what are we going to do today?

• Some numbers
• Risk factors for heart disease
• Drugs used to treat cardiovascular conditions
• Lab Tests for cardiac risks and functionlipid
  profile, BNP, Troponin, hs-CRP, blood pressure,
  microalbumin
• The cardiac exam
• The evaluation of the patient with chest pain
• Selected cardiac conditionsacute coronary
  syndromes, hypertension, CHF, AF, valvular heart
  disease, cardiomyopathies

3
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

4
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

5
Risk factors for cardiovascular diseasethe usual
suspects

• In general, cardiovascular disease is
  gender-blindsmoking, hypercholesterolemia,
  diabetes mellitus, hypertension, and the lack of
  exercise are the major controllable risk factors
  for both sexes
• But lets first take a look at the
  NON-controllable risk factorsage, gender, family
  history

6
Your ageand 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

7
Why?

• Estrogen protects our heart even after our
  ovaries diefor about another 10-15
  yearsestrogen 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 womens 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

8
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

9
Things you can changeControllable risk factors

• Smoking
• Hyperlipidemia with LDL cholesterol as the most
  important contributor to CVD
• Diabetes mellitus sugar diabetes
• Hypertension

10
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), ß-blockers (23),or ACE inhibitors
  (23),which have received the bulk of the
  attention in recent years.

11
Smoking and women

• Women who smoke have their first heart attack
  almost 20 years earlier than women who dont
  smoke

12
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

13
How about smoking and clotting with
estrogen-containing products?

• Pills of yesteryear80 to 100 µg per pill
• Could stop an elephant from ovulating
• Pills of 201220-35 µg per pill
• Less clotting risk, greater chance of pregnancy
  if you MISS A PILL
• Its not JUST the pillweight plays a role too

14
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 thats a big BUTTwhen 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)

15
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 warningall 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

16
Comparison of risk of levonorgestrel vs
drospirenone

• Drospirenone rate is 30.8 per 100,000 women-years
• Levonorgestrel rate is 12.5 per 100,000
  women-years
• Another study23.0/100000 w/ drospirenone vs.
  9.1/100,000 with levonorgestrel
• Jick SS and Hernandez RK. BMJ 2011 April 21342
  Parkin L et al. BMJ 2011342

17
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)

18
LDL-cholesterol is the primary problem

• HOWEVER, theres more to it than just a
  cholesterol level
• NEWEST RESEARCH LDL particle size is most
  important
• Subtype/Pattern Alarge, loose LDL molecule
• Subtype/Pattern Bsmall, dense molecules, prone
  to oxidation and penetration of artery walls
  forming fatty plaques

19
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 smallyour
  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

20
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.

21
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.

22
How about patients with Type 1 diabetes?

• 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

23
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 hypertensionnew 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

24
Another important note about hypertension

• Are you a dipper? 10 decline _at_ night
• Or a non-dipper? BP doesnt fall when your head
  hits the pillownon-dippers have a higher risk of
  CV disease, strokes, and end-stage renal disease
• consider night time dosing of anti-hypertensive
  for . non-dippers
• (American Journal of Kidney Diseases
  December 2007)

25
The Deadly duo and Kidney disease

• Hypertension and diabetes increase the risk of
  chronic kidney disease
• Increased pressure in the glomerulusintraglomerul
  ar hypertension
• One of the first manifestations of
  intraglomerular hypertension is microalbuminuria

26
Diabetic/hypertensive nephronhyperglycemia/HTN/h
igh animal protein in the diet

• Afferent arteriole
• ( ? vasodilation by
• ( ? prostaglandinsincreasing GFR)
• Blood entering
• glomerulus
• Glomerulus?filter
• Efferent arteriole
• ( ? vasoconstriction via
• ( ? angiotensin II)
• Intraglomerular hypertension
• and microalbuminuria
• 
  

Microalbuminuria
27
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!

28
What else increases the risk for heart disease?

• Weight gainif a woman gains 44 pounds after high
  school her risk of heart disease increases by 250

29
Weight gain

• But Barb, Ive only gained a pound a year since
  high school!
• And, when, pray tell, did you graduate from high
  school?
• 1960you do the mathits now 2013 or 53 years
  since you graduated from high school
• And youve only gained 1 pound per year?

30
Location, location, location of those extra
poundswaist size

• Are you an apple or are you a pear?

31
Whats going on with belly (visceral) obesity?

• Visceral fat is Insulin resistant
• Visceral fat (now considered endocrine tissuea
  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

32
Throw it all togethermetabolic syndrome

• Central obesitywaist size greater than 40.2
  inches in men, 34.6 inches in women
• High TG (gt150 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)

33
Inflammationhigh sensitivity CRP

• hs-CRP (vascular inflammation) and coronary
  artery disease risk levelbest 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 lt 1 mg/L Average 1-3 mg/L high risk
  gt 3 mg/L
• (Noncardiovascular causes should be considered if
  values are gt 10 mg/L)
• Ridker PM et al. N Engl J of Med 2000
  342836-43 Ridker PM et al. N Engl J of Med
  1997336973-9)

34
What can reduce hs-CRP?

• Exercise
• Loss of abdominal fatwalkin, walkin walkin
• Statins not only reduce LDL but are also potently
  anti-inflammatory
• Aspirin
• Omega-3 fatty acids
• Nuts (especially walnuts)
• The Mediterranean diet

35
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

36
The Cardiologists 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 chokedIm imagining what my casket
  will roll through
• And thats when the proctologist got up and left

37
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
  questionnaireasking about laughinghow 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

38
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

39
Converselysubclinical hyperthyroidism

• Raises the risk for mortality and cardiac events
  as well
• Especially when TSH levels are lt 0.45 mIU/gt and
  even more so when levels were lt0.10 mIU/L
• 29 higher CHD mortality
• 68 higher risk for atrial fibrillation

40
Other risk factors

• PCOS (polycystic ovary syndrome)insulin
  resistance
• Autoimmune diseaseSLE, RA (inflammation)--Risk
  of cardiovascular disease in patients with
  LupusLupus 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 patients3 x gtrisk of hosp.
  w/MI 5x gtrisk of silent MI before dx w/RA
  sudden cardiac death ?feel chest pain
• Atorvastatin and inflammation (RA, SLE,
  MS)(Lancet 2004 June 193632015-21)
• Cocaine and methamphetamine useduhpotent
  vasoconstrictors

41
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

42
Cardiovascular drugs

• 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

43
Drugs to lower LDL-cholesterolThe statins?

• Lovastatin (Mevacor)
• Pravastatin (Pravachol)
• Fluvastatin (Lescol)
• Simvastatin (Zocor)
• Rosuvastatin (Crestor)
• Atorvastatin (Lipitor)
• Pitavastatin (Livalo)

44
The Statin Sisterswhat 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 ruleatorvastatin/Lipitor and
  rosuvastatin/Crestor)

45
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 2004110227-239)

46
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 5083)
• P.S. The bioavailability of simvastatin can
  increase by 700 with grapefruit or grapefruit
  juice

47
LDL guidelines

• Guidelineswith 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 factors100
  mg/dL (lt2.85 mmol/L)
• Unless youre perfect--130 mg/dL (lt3.37 mmol/L)

48
Summary What do the statins do?

• 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

49
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 rhabdomyolysisnever 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

50
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

51
Another drug with a favorable lipid profile

• Cardiovascular benefits
• lowers BP
• decreases LDL-cholesterol
• Lowers blood sugars
• Reduces CV risks in PCOS (primary treatment
  choice for this condition)

52
The ACE inhibitors inhibit angiotensin II

• Captopril (Capoten)(1981)
• Enalapril (Vasotec)(1983)
• Fosinopril (Monopril)
• Lisinopril (Prinivil, Zestril)
• Perindopril (Aceon)
• Moexipril (Univasc)
• Benazepril (Lotensin)
• Quinapril (Accupril)
• Trandolapril (Mavik)
• Ramipril (Altace)

53
What does angie II do?

• She tenses your angiosvasoconstricts your
  arteries--hypertension
• She triggers release of ALaldosterone (from
  the adrenal cortex to save sodium H2O in the
  kidney and excrete potassium and
  magnesium)--hypervolemia
• She increases inflammation in the
  arteries--vasculitis
• Shes prothromboticclots
• Shes 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

54
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

55
How can we inhibit Angie?
ACE --
56
So if you were an ACE inhibitor, what would you
do? Inhibit ACE? Inhibit the formation AT
angiotensin II

• 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-a
  ldosterone)
• Treatment of heart failure by inhibiting
  renin-angiotensin-aldosteroneCHF is a
  HYPER-RENINEMIC state
• Protect the kidney by vasodilating the renal
  efferent arteriole
• Anti-inflammatory
• Decrease growth of tissues or remodelingangiote
  nsin II increases the size of the heart ACE
  inhibitors inhibit this remodeling

57
Side effects, of course

• Hypotensionstart low and go slow
• Hyperkalemia (high potassium) (excreting sodium
  and water and retaining potassium)
• Add a thiazide diuretic to the ACE inhibitor

58
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

59
High K containing foods

• Potatoes
• Prunes
• Raisins
• Apricots
• Bananas
• Halibut
• Canteloupe
• Oranges
• Pasta sauce
• Health.harvard.edu/heartextra for K content of
  1,200 foods

60
Side effects, continued

• Cough (gender differences)
• ACE inhibitors block angiotensin converting
  enzyme but as ACE is inhibited, bradykinin goes
  UPbradykinin is a potent bronchoconstrictor
• Women have more bradykinin to begin with,
  therefore the gender disparity in the cough

61
Side effects, continued

• Life-threatening angioedema (Does my voice sound
  funny to you?)

62
SartansAngiotensin II Receptor Blockers

• Angiotensin receptor blockers (bypass ACE) and
  work by blocking the angiotensin II receptors on
  tissues
• Who are they? The Sartan Sisters
• losartanCozaar
• valsartanDiovan
• candesartanAtacand
• irbesartanAvapro
• telmisartanMicardis
• olmesartanBenicar
• azilsartan -- Edarbi

63
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

64
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
• Creatininea rise of greater than 20-30 is
  considered to be significant smaller rises are
  common and are to be expected in many patients

65
Olols, alols, ilolsBeta 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)

66
Properties of beta blockers

• You dont 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 norepinephrineclinical uses and side
  effects)propranolol is the MOST lipid-soluble
• Water-soluble? Decreased ability to cross blood
  brain barrieratenolol is the least lipid-soluble

67
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 decreasesangina, SVT,
  post-MI to protect the heart from remodeling and
  to reduce heart rate
• atenolol (Tenormin), metoprolol (Lopressor),
  betaxolol (Kerlone) bisoprolol (Zebeta),
  nebivolol (Bystolic)_at_ doses lt10 mg)

68
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

69
Beta blockersother properties

• Water-soluble? (low lipophilicity)
• atenolol (Tenormin), nadolol (Corgard),
  labetalol (Trandate), nebivolol (Bystolic)
• Lipid-soluble? (high lipophilicity--cross the
  blood brain barrier)CNS side effectsanhedonia
  (the Blahs)BUTthe lipid-soluble can also
  calm down the brain
• propranolol (Inderal), timolol (Blocadren),
  metoprolol (Lopressor, Toprol XL), pindolol
• All of the others are moderately lipophilic

70
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 failureuse a beta
  blocker for 2-3 years and longer if tolerated
• Post-MI WITH systolic heart failurecontinue to
  use a beta-blocker indefinitelychoose one that
  improves survivalcarvevdilol, metoprolol ER,
  bisoprolol

71
Calcium Channel Blockers 2 categoriesthe
nondihydropyridines and the dihydropyridines

• Verapamil (Isoptin SR, Verelan and Verelan PM,
  Calan and Calan SR, Covera-HS)block calcium
  channels primarily on the coronary vessels and
  the AV nodeincreasing blood flow to the heart
  and decreasing impulses through the AV nodeused
  to decrease workload of heart and slow the heart
  rate HTN, angina, atrial fib, renoprotective
• Negative inotropic effectavoid in
  patients with CHF
• Calcium channels in bowels (elderly)severe
  constipation

72
2nd drug in the non-dihydropyridine category

• DiltiazemCardizem LA and CD, Dilacor XR,
  Tiazacdilates calcium channels on the coronary
  arteries and peripheral vessel calcium channels
  decreases impulse transmission from atrium to
  ventricle
• Negative inotropic effectsavoid in CHF patients
• Clinical uses
• Atrial fibrillation, Hypertension, Angina,
  Vasospasm, renoprotective
• Less constipation than verapamil

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2nd categorythe Dihydropyridines or the
DIPINESPeripheral 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)

74
Clinical uses of the dipines

• Hypertension
• VasospasmPrinzmetals angina, Raynauds
  phenomenon, cocaine-induced vasospasms
• An added possible benefitmale contraceptive

75
Side effects of CCBs

• Verapamilsignificant constipation lots of drug
  interactions
• Dipinessignificant peripheral vasodilation with
  headaches hypotension, and peripheral edema
  (swollen feetpedal edema (Plendil)
• Diltiazemless significant constipation than
  Verapamil
• All CCBs inhibit calcium-induced contraction of
  the LES, resulting in sphincter relaxation and
  acid reflux

76
Drugs that inhibit platelet function

• ASA81 mg does anyone need more than 81 mg? very
  rarelyhigher 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 mghigher doses decrease
  Brilintas efficacy)
• Clopidogrel and PPIs (especially omeprazole and
  esomeprazole)

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Instead of warfarin/Coumadin

• rivaroxaban/Xareltooral factor Xa inhibitor for
  venous thromboembolism (VTE) no monitoring,
  fewer drug interactions, does not require
  bridging with LMW heparin because of its fast
  onset causes less major bleeding no antidote
  no lab test to monitor compliance, higher cost
• apixaban (Eliquis)a second oral factor Xa
  inhibitor

78
Instead of warfarin/Coumadin

• Dabigatran/Pradaxa direct oral thrombin
  inhibitor relatively short half life of 12-17
  hours doesnt 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.
  20093611139-1151.

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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

80
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? 2.5-3.5
• Study of 100,000 emergency hospitalizations in 58
  hospitalswarfarin bleeding 1 21,000

81
While were 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
• Prescribers Letter, December 2012

82
Parenteral anticoagulants

• HeparinUnfractionated 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
  plateletsanimal derived frequent monitoring and
  dose adjustments also monitor platelet counts
  (Heparin-induced thrombocytopenia/HIT or HITTHIT
  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

83
Parenteral anticoagulants

• Direct thrombin inhibitorsprevent thrombin from
  converting to fibrinogen and fibrin
• Bivalirudin/angiomaxfor PCI (percutaneous
  coronary intervention)
• Argatrobanfor patients with HIT or at risk for
  HIT/HITTS and as an anticoagulant for these
  patients who are undergoing PCI

84
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

85
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 toxicitythe 3rd most common drug that
  brings the elderly to the ER
• Safer, better drugs include diltiazem, verapamil
  (except in elderly), beta-blockers

86
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

87
Diuretics

• Synergistic diuretics that act on the distal
  tubule (thiazides, such as metolazone/Zaroxolyn,
  chlorthalidone/Thalitone or Ksparing agents) are
  often added in those who fail to respond to
  high-dose loop diuretics alone

88
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

89
Nitroglycerincan I blow up with NTG?

• Oral, extended release (Nitro-Bid, Nitroglyn,
  Nitrong, Nitrong SR, Nitro-Time
• Sublingual NTGNitroQuick, Nitrostat
• TranslingualNitrolingual
• IVNitro-Bid IV, Tridil
• TopicalDeponit, Minitran, Nitrodisc, Nitro-Dur,
  Transderm-Nitro
• TransmucosalNitrogard
• Gentleman from Savannah
• USE with afils??

90
The ED drugsthe afils--Cant use with
nitroglycerin

• When was your last dose of Viagra? (sildenafil)
• Cant use Viagra or Levitra (vardenafil) within
  24 hours of receiving NTG Cialis (tadalafil)
  within 36-48 hours
• Side effects
• Hypotension
• Headaches
• GERD
• Blue vision
• Priapism
• A surprise side effect of the afils

91
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

92
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