Chronic Treatment of CAD

Question 1

Antiplatelet Drug Benefits

Answer 1

• Significantly reduce vascular events (especially MI) in patients with CAD with or without stents
• Prevent thrombotic complications following stent placements

Question 2

Stent Thrombosis

Answer 2

• Usually occurs in the first month after stent implantation
• Numerous cases of “late” stent thrombosis, especially those treated with DES, occuring months or years after stent
• Stent thrombosis usually catastrophic with life-threatening complications

Question 3

Predictors of Stent Thrombosis

Answer 3

• stenting of small vessels
• stenting multiple lesions
• use of long stents
• use of overlapping stents
• stenting ostial or bifurcation lesions
• suboptimal stent result (underexpansion, malapposition, or residual dissection)
• diabetes mellitus
• low ejection fraction
• advanced age
• acute coronary syndrome
• premature discontinuation of antiplatelet agents
• renal failure

Question 4

BMS + Drug Recommendation

Answer 4

• BMS: Bare-metal stent
• Recommended to place patient on aspirin + P2Y12 inhibitor to reduce stent thrombosis and cardiac events
• Duration of antiplatelet based on anticipated time for stent to be endothelialized
• Longer durations have fewer CV events but more bleeding

Question 5

DES

Answer 5

• Drug-eluting stents
• Shown to have delayed endothelialization
• Used more often in high-risk lesions

Question 6

Aspirin

Answer 6

• EC preparations usually are better tolerated than regular tablets
• No data suggesting 325 mg is better than lower dosages
• Increased risk of GI side effects when 325 mg given daily for chronic prophylaxis
• Monitor for bleeding/bruising GI upset

Question 7

P2Y12 Inhibitors Examples

Answer 7

• Clopidogrel (Plavix)
• Prasugrel (Effient)
• Ticagrelor (Brilinta)

Question 8

Clopidogrel

Answer 8

• Indications: ACS, recent MI/strok/PAD
• Only daily
• Take with 75-325 mg of aspirin daily
• Effected by pharmacogenomic variability
• No C/I
• Possible PPI interaction
• Cheapest option

Question 9

Prasugrel

Answer 9

• Indication: ACS with PCI
• Increased efficacy/bleeding risk than clopidogrel
• Once daily
• Take with 75-325 mg of aspirin per day
• C/I: prior transient ischemic attack or stroke
• Most expensive option

Question 10

Ticagrelor

Answer 10

• Indication: ACS, post-MI
• Increased clinical efficacy/bleeding compared to Clopidogrel
• Twice daily
• Use with =< 100 mg of aspirin per day
• C/I: prior intracranial hemorrhage, severe hepatic impairment

Question 11

Dipyridamole

Answer 11

• Unknown MoA
• Believed to inhibit platelet aggregation through phosphodiesterase inhibition which increases platelet cAMP
• NOT recommended as antiplatelet agent in patients with CAD
• Possible secondary prevention when used with aspirin for stroke

Question 12

Vorapaxar

Answer 12

• Zontivity
• PAR-1 antagonist which irreversibly inhibits thrombin-induced platelet aggregation
• Benefits: reduced the combined endpoint of CV death, MI, stroke, and urgent coronary revascularization in patients with a history of MI/PAD
• Risk: increased moderate-severe bleeding risk and intracranial bleeds
• C/I: history of stroke/TIA or active bleeding
• Expensive (~ the same as Ticagrelor)
• Role in therapy unresolved

Question 13

Clopidogrel + PPI Interaction

Answer 13

• Diminished effect when taken with PPI
• Omeprazole is primarily metabolized by CYP2C19 which is also part of Clopidogrel’s two step metabolization process
• Guidelines still recommend PPIs for those on dual platelet therapy who have prior upper GI bleed history (avoid omeprazole and esomeprazole)
• Use alternative PPI or H2 blocker

Question 14

Genetic Testing

Answer 14

• Not currently recommended under guidelines
• Might be considered in a patient at high risk for poor clinical outcomes to determine if he/she is predisposed to inadequate platelet inhibition with clopidogrel
• If identified to have such a predisposition, an alternative P2Y12 inhibitor MIGHT be considered

Question 15

Nitrates

Answer 15

• No data demonstrating efficacy at reducing cardiac events

- Primarily used to relieve chest discomfort

Question 16

Beta Blockers Benefits

Answer 16

• Reduce reinfarction and mortality when used chronically post-STEMI
• Most evidence of benefit is in STEMI population, but benefits are believed to be achievable in unstable angina/NSTEMI population too (not proven)

Question 17

Beta Blocker Dosing

Answer 17

-Goal HR: 50-60 bpm

Initiating Beta-Blocker:

• HR > 70: begin beta-blocker
• HR 60-69: initiate beta-blocker with caution using low doses
• HR 50-59: typically not recommended; may use very low doses w/close monitoring
• HR < 50: do not initiate beta-blocker

Already on Beta-Blocker:

• HR > 70: increase dosage
• HR 50-69: maintain current dosage
• HR < 50: consider decreasing dosage if symptomatic

-Use cardio-selective beta blockers in those with lung disease

Question 18

ACE-I Benefits

Answer 18

• Decrease progression of heart failure, reinfarction, and mortality
• Limit post-infarction left ventricular dilation and hypertrophy and preserve ventricular pump function
• Patients with left ventricular EF < 40% derive the most benefit
• *If started soon after MI**

-If started later in patients with more stable CAD and preserved LV function, ramipril and perindopril have shown to have benefits

Question 19

ARBs Benefits

Answer 19

• Valsartan shown to be as effective as captopril and telmisartan shown to be effective in preventing major adverse CV events in patients with CAD
• Candesartan shown to reduce composite endpoint of CV death or hospital admission for heart failure patients with heart failure and is a reasonable choice in a patient with LVEF =< 40%
• ACE-I more preferred due to increased evidence and cheaper

Question 20

Aldosterone Antagonists

Answer 20

• Eplerenone has been studied, but not spironolactone
• Eplerenone in addition to optimal therapy shown to reduce mobidity and mortality in patients with acute MI complicated by LV dysfunction and heart failure

Question 21

HMG-CoA Reductase Inhibitors Benefits

Answer 21

• Decrease CV mortality and all-cause mortality in patients with variety of [cholesterol]
• Hypercholesterolemic patients benefit the most
• Goof for primary and secondary prevention of MI
• Pleiotropic effects may be somewhat responsible

Question 22

CCB Benefits

Answer 22

• No beneficial effect on death or nonfatal MI

- Usefulness is controversial and given usually for symptom relief like chest pain

Question 23

Warfarin Benefits

Answer 23

• REduce risk of reinfarction in patients who are unable to take ASA
• Reduce rates of thrombosis and embolism in high-risk patients

Question 24

High-Risk Patients considered for Warfarin

Answer 24

• Large anterior infarcts
• Infarction involving the left ventricular apex
• History of systemic or pulmonary embolism
• Atrial fibrillation

Question 25

Analgesics

Answer 25

• Selective COX-II inhibitors and other nonselective NSAIDs are associated with increased CV risk
• Dose-related increases in risk of death and non-dose dependent trends for rehospitalization for MI for all drugs

Question 26

Ranolazine

Answer 26

• Ranexa
• MoA not determined
• Inhibits the late inward sodium current, reducing intracellular sodium which indirectly leads to calcium overload and increases myocardial wall tension and reduces microvascular perfusion
• No appreciable effect on HR or BP
• Benefits restricted to angina relief
• Expensive
• 500-1000 mg BID
• Prolongs QT interval so only use when others fail
• C/I: use with potent CYP3A inhibitors