Lecture 9 and 10: Pharmacological Management of Ischemic Heart Disease

Aspirin (preferred) or Clopidogrel

Antiplatelet Agents for Stable Angina

• Beta-blocker (first line)

• Calcium channel blocker

• Long-acting nitrate

• Ranolazine

Anti-anginal medications for Stable Angina

Aspirin

Irreversibly inhibits COX1 = blocks synthesis of thromboxane A2 = diminished platelet aggregation.

Clopidogrel

- Primarily used for MI and stroke prophylaxis

- irreversibly binds to the adenosine diphosphate (ADP) P2Y12 receptor on platelets

- binding prevents activation of the ADP-mediated glycoprotein GPIIb/IIIa complex, which is necessary for platelet aggregation

- action is irreversible for the remainder of the platelet lifespan (7 to 10 days)

Nitrates

for immediate symptom relief of stable ischemic heart disease

-Beta-blockers

-Calcium Channel Blockers

-Long-acting Nitrates

-Ranolazine

agents for angina symptoms in Stable Ischemic Heart Disease

-Anti-hyperlipidemics

-Anti-platelets

-Anti-hypertensives

agents for risk factor modification of Stable Ischemic Heart Disease

-Statin

-Aspirin

risk factor modification for stable angina

• Sublingual nitroglycerin OR

• Nitroglycerin spray

PRN immediate angina relief

Irreversibly inhibits COX-1 and COX-2

MOA of Aspirin

Aspirin

-decreases prostaglandin and thomboxane A2 production

-decreases incidence of CV events and death

-use indefinetely in ischemic heart disease

Aspirin

-CIs: hypersensitivity, active bleeding, or known platelet disorder

-AEs: dyspepsia, heart burn, GI upset, GI bleed/ulceration, bleeding, renal impairement, tinnitus

-other drugs that can cause ototoxicity

-drugs that increase bleeding

-increase levels of methotrexate and lithium

drug interations with aspirin

Beta Blockers

-decrease HR, contractility, and BP

-decrease myocardial O2 demand

-decrease LV wall tension with long term use

-increase coronary perfusion

Beta Blockers

• 1st line for stable angina

• Monotherapy or in combination with CCBs, nitrates, and/or ranolazine

• Combination with nitrates and CCBs shows additive effects on cardiac force

Prinzmetal Angina

you should AVOID Beta blockers in which kind of angina?

-Isradipine

-Amlodipine

-Felodipine

-Nicardipine

(I Am Felo Nic)

Calcium channel blockers for antianginal therapy

Calcium Channel Blockers

-Block voltage-dependent L-type Ca+ channels in vascular smooth muscle

-vasodilation

-decrease PVR and BP

-improves myocardial oxygen supply

Non-DHP Calcium Channel Blockers

-Block voltage-dependent L-type Ca+ channels in the heart

-decrease cardiac contractility

-decrease HR and CO

-reduce myocardial oxygen demand

Calcium Channel Blockers

• Use when BBs are contraindicated or as add on therapy

• Preferred in Prinzmetal angina (due to coronary dilation effect)

Long-acting Nitrates

Indications:

• Angina prophylaxis/treatment

• In combo w/ CCBs for Prinzmetal angina, if needed

Nitrates

Indications:

- chronic anal fissure pain

- congestive heart failure

- perioperative hypertension

- induction and maintenance of intraoperative hypotension.

Nitroglycerin or Glyceryl trinitrate

long acting nitrates

increase cGMP which then causes dephosphorylation of myosin light chain resulting in vascular smooth muscle relaxation

MOA fo long acting nitrates

Long-acting Nitrates

-CIS: Hypotension, Use with PDE-5 Inhibitors, Increased ICP, severe anemia

-AEs: headaches, orthostatic hypotension, tachyphylaxis, reflex tachycardia, dizziness, lightheadedness, flushing, syncope

Long-acting Nitrates

• Not monotherapy

• In combination w/ BBs or CCBs as add on therapy

Inhibits late inward sodium current -----> decrease in intracellular sodium and calcium

MOA of Ranolazine

Ranolazine

-decreases effects of Na and Ca overload in myocardial ischemia

-decreases diastolic wall tesnion and decresaes myocardial oxygen consumption

-little to no effect on HR, contractility, or BP

Ranolazine

-Indications: stable angina (refractory)

-CIs: hepatic cirrhosis and concurrent us of stron CYP3A4 inhibitors/inducers

Ranolazine

-AEs: headache, dizziness, GI upset, may cause QT prolongation

• Use when BBs (or CCBs, long-acting nitrates) are contraindicated or as add on therapy

Nitroglycerin

-quick acting nitrate that can be given sublingual or lingual as a spray

-endogenous vasodilator

vasodilates resulting in decreased LV pressure and decreased preload

MOA of nitroglycerin

Nitroglyerin

-Indications: for acute angina

-CIs: hypotension, concurrent use w/ PDE-5 inhibitors, increased ICP, severe anemia

-AEs: headache, dizziness, lightheadedness, flushing, hypotension, syncope

Nitroglycerin

• Use for immediate (acute) relief of angina

• Take at first sign of chest pain (+ up to 2 more doses Q5 min PRN)

• Take 5-10 min before activity that causes chest pain (prophylactic use)

Nitroglycerin

__________________ should not be used:

- Within 12 hrs of avanafil

- Within 24 hrs of sildenafil or vardenafil

- Within 48 hrs of tadalafil

3 doses in 15 min

what is the max amount of nitroglycerin that you can give a pt?

• Morphine (if severe pain, ischemia, anxiety)

• Oxygen (if arterial sat’ < 90% or respiratory distress)

• Nitroglycerin (SL Q5 min for up to 3 doses PRN or IV)

• Aspirin (ASAP after presentation. Chew dose!)

drugs used for ACS that stabilize the patient and treat pain before or right upon arrival to ED

• GP IIb/IIIa receptor antagonist

• Anticoagulant

• P2Y12 (ADP) inhibitor

• Beta Blocker

• ACE-I

drugs for ACS that decrease myocardial damage and prevent further ischemia

Morphine

-administer IV if ischemia refractory to O2 and SL nitroglycerin

-can be delivered with IV nitroglycerin

stimulates opioid receptors and triggers histamine release

MOA of morphine

Morphine

-causes vasodilation and decreases myocardial oxygen demand

-AEs: hypotension, bradycardia, N/V, sedation, respiratory depression

Naloxone

antidote for morphine

ALL patients

in which pts do you need Continuous oxygen saturation (SaO2) monitoring by pulse oximetry

Oxygen

-used in arterial oxygen desaturation, respiratory distress, and HF

-stabilizes pt and reduces pain

Nitroglycerin

• Immediate relief of ischemia and angina

• IV administration for ongoing ischemia, HTN, or HF

Nitroglycerin

Do not use ___________________:

• If SBP < 90 mm Hg, HR < 50 BPM, or HR > 100 BPM

• Concurrently with PDE-5 inhibitors (eg; Sildenafil)

Clopidogrel

if pt has an aspirin allergy, what should you give them

Chewed

how should pt take their first dose of aspirin

Beta Blockers

-PO within first 24 hours, once stabilized

Beta Blockers

do not administer ____________________ if:

• Signs of HF

• Evidence of low output state

• Increased risk of cardiogenic shock

• Contraindicated otherwise

Metoprolol succinate, Carvedilol, or Bisoprolol

which beta blockers are recommended bc they are proven to reduce mortality in HF?

ACE-I

PO within first 24 hours if HTN, DM, stable CKD, or LVEF ≤ 40%

ARB

what should you prescribe if ACE-I is contraindicated or intolerable?

Beta Blockers

CIs:

- PR interval >0.24 seconds

- Second- or third-degree heart block w/out pacemaker

- Active asthma

- Reactive airway disease

- Acute intoxication from cocaine or methamphetamine

-NSAIDs

-IR DHP CCBs

-IV Fibrinolytic Therapy (unless STEMI)

drugs to be avoided in acute setting (during intial hospitalization)

12 hours

a primary PCI is one that is done within _______________

Reperfusion (PCI or Pharmacological)

what do you want to do ASAP with a STEMI that is within 12 hours of onset?

Fibrinolysis

-pharmacological reperfusion

-administer within 30 min of arrival when anticipated First medical contact device > 120 minutes

-Not used in UA or NSTEMI (due to risk vs. benefit)

• Tenecteplase

• Reteplase

• Alteplase

Fibrinolytics use in STEMI

Before PCI or Fibrinolysis

(to prevent thrombotic complications)

during treatment of a STEMI, when do you administer anticoagulants?

-Unfractionated Heparin (UFH)

-Low Molecular Weight Heparin (LMWH)

-Bivalirudin

-Fondaparinux

anticoagulant options to use in STEMI

Unfractioned Heparin (UFH) or Low Molecular Weight Heparin (LMWH)

preferred anticoagulant option for fibrinolysis or PCI (± GP IIb/IIIa inhibitor in PCI)

Bivalirudin

-preferred anticoagulant in PCI with high bleeding risk

-only consider w/ fibrinolytic therapy if pt develops HIT

Fondaparinux

-preferred anticoagulant option for fibrinolysis

-not used as sole anticoagulant in PCI due to cathetier thrombosis risk

• Clopidogrel

• Prasugrel

• Ticagrelor

ADP (P2Y12) receptor inhibitors

Clopidogreal

ADP (P2Y12) receptor inhibitor preferred with fibrinolysis

Prasugrel

ADP (P2Y12) receptor inhibitor to AVOID if hx of stroke of TIA

ADP (P2Y12) receptor inhibitors

• Loading dose ASAP or at time of reperfusion

• ≥1 year with stent placement (DES or BMS)

• Min of 14 days (> 1 year preferred) with fibrinolytics

• Abciximab

• Eptifibatide

• Tirofiban

GP IIb/IIIa receptor antagonists

GP IIb/IIIa Receptor Antagonists

-antiplatelet agents

-adjunctive use at time of PCI if large thrombus burden or inadequate ADP (P2Y12) receptor antagonist loading

-administer via IV

Bivalirudin

Routine use of GP IIb/IIIa Receptor Antagonists and __________________ are generally not recommended due to increased bleeding risk

Coronary Artery Bypass Graft (CAPG)

-indicated if coronary anatomy not amenable to PCI and ongoing ischemia, cardiogenic shock, severe HF, or other high risks

-Consider if not candidate for PCI or fibronolysis

ADP (P2Y12) receptor and GP IIb/IIIa Inhibitors

what drugs should you discontinue if for Coronary Artery Bypass Graft (CAPG)

• Initial medical therapy + noninvasive CV imaging

• Coronary angiography w/in 25-72 hrs

Ischemia guided (conservative) strategy for NSTEMI

Coronary angiography w/in 24 hrs w/ intent for revascularization (PCI or CABG)

Early invasive strategy for NSTEMI

Early Invasive Strategy

Recommended in:

• Refractory angina

• Clinical evidence of heart failure

• Hemodynamic or electrical instability

• Absence of serious comorbidities

• Absence of contraindications to angiography/PCI

• Patients who are stable but at high risk

-Dual Antiplatelet Therapy

-Initiate Anticoagulant Therapy

For both Early invasive and Ischemia guided (conservative) strategies for NSTEMI, what two other therapies do you need to initiate

Bivalirudin

which anticoagulant should ONLY be used for early invasive strategy in an NSTEMI?

Coronary Artery Bypass Graft (CAPG)

In which early invasive therapy for NSTEMI would you discontinue GP IIb/IIIa inhibitor and ADP (P2Y12) receptor inhibitors?

-Metoprolol succinate

-Carvedilol

-Bisoprolol

Beta blockers preferred for ACS management

Beta Blockers

Initiate PO w/in 24 hrs unless:

• Signs of HF OR

• Evidence of low-output state OR

• ↑ risk for cardiogenic shock OR

• Other BB contraindication present

ACE-Inhibitors

-decreases Angiotensin II

-decreases cardiac remodeling, preload, and afterload

-administer PO within 24 hours, esp if HTN or LVEF <0.4

-can be considered in all pts unless hypotensive or CIs

Aldosteron Antagonist

Recommended in addition to ACE-I and BB if:

• No significant renal dysfunction or hyperkalemia (contraindications)

• Patient has LVEF ≤0.40 and DM or HF

-Eplerenone

-Spironolactone

Aldosterone antagonists

Indefinitely

long term management for ACS:

-Aspirin

> 1 year

long term management for ACS:

-ADP (P2Y12) Inhibitor

PRN

long term management for ACS:

-sublingual nitroglycerin

3+ years

long term management for ACS:

-beta blocker

• Aspirin

• ADP (P2Y12) Inhibitor

• SL Nitroglycerin

• Beta blocker

• ACE-I

• Statin (high intensity)

• Warfarin

• Pain relief (not NSAIDs)

• Lifestyle

components of long term management of ACS