Heart Matters—All Things Cardiac

Barb Bancroft RN, MSN, PNPChicago IL

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 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 gender-blind—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 NON-controllable 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?

• 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 women-years

• 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?

• 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 end-stage 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

• 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

• 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-cholesterolThe “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?• 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

• 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

• 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? • 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?

ANGIOTENSIN 1

ANGIOTENSIN 2

RENIN

ALDOSTERONE

ACE --

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-aldosterone)

• Treatment of heart failure by inhibiting renin-angiotensin-aldosterone—CHF is a HYPER-RENINEMIC state

• Protect the kidney by vasodilating the renal efferent arteriole• Anti-inflammatory• 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

• 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 ECGCreatinine—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)•

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 lipid-soluble 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, cocaine-induced 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? 2.5-3.5

• 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 36-48 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