SIHD& ACS.pptx

Introduction
2
 Ischemic heart disease (IHD) is defined as lack of oxygen
and decreased or no blood flow to the myocardium resulting
from coronary artery narrowing or obstruction.
 CAD is the leading cause of ischemic heart disease and is
typically the result of atherosclerotic plaques in the
epicardial vessels.
 SIHD typically manifest as either chronic stable exertional
angina or ischemia without clinical symptoms (silent
ischemia).
 Less common causes of SIHD include microvascular angina.

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 Coronary vasospasm represents a form of angina that results
from an increase in coronary vascular tone that can occur in
either normal or diseased vessels.
 Inappropriate, insufficient, or untreated SIHD cannot only
lead to MI and cardiac death, but also the development of
heart failure (HF), arrhythmias, and valvular disease.

Epidemiology
4
 According to AHA statistics, in 2014 an estimated 92.1
million (36.6%) adult Americans had at least one form of
cardiovascular disease (CVD),
 Which includes CAD, HF, stroke, and hypertension (HTN).
 Among patients with CVD, approximately 16.5 million adult
Americans had CAD,
 Corresponding to an estimated prevalence of 6.3%.
 Among patients with CAD, the total number of patients with
SIHD is difficult to determine.

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 The mortality and costs associated with CAD are enormous.
 In 2015, CVD was the number one cause of death in the
United States with CAD being the most common cause of
CVD death,
 Accounting for almost 400,000 deaths—44% of all CVD-
related mortality.
 The prognosis of patients with SIHD is related to
 The extent of atherosclerotic disease, the presence of LV
dysfunction, and the presence of other comorbidities.
 In addition to mortality, SIHD leads to significant morbidity.

Etiology and Pathophysiology
6
 Angina pectoris usually results from increased myocardial
oxygen demand (MVo2 ) in the setting of a fixed decrease in
myocardial oxygen supply because of atherosclerotic plaque.
 The etiology of the fixed decrease in supply is long-standing,
well-developed atherosclerotic plaque.
 These plaques grow over several decades.
 The extent and rate of growth are related to risk factors such as
smoking, dyslipidemia, HTN, DM, and genetics.
 Major determinants of MVo2 are heart rate (HR), myocardial
contractility, and intramyocardial wall tension during systole.

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 A doubling in any of these individual parameters requires a 50%
increase in coronary flow to maintain myocardial supply.
 Coronary atherosclerotic plaques typically develop in larger
epicardial (R1 or conductance) vessels, which normally offer
little resistance to myocardial flow.
 As plaques grow and narrow the lumen, the affected vessel
begins to provide considerable resistance to blood flow.
 Smaller endocardial (R2 or resistance) vessels
 Provide most resistance to flow in normal coronary arteries and
 Can contract and dilate to maintain blood flow based on
metabolic demands of the myocardium.

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 As a result, coronary plaques that occupy less than 50%–70%
of the vessel luminal diameter rarely produce ischemia or
angina.
 When the luminal diameter of epicardial vessels is reduced by
70% or more,
o Endocardial vessels are maximally dilated, much of the
coronary flow reserve has been used, and minimal physical
exertion may result in a flow deficit with myocardial ischemia
and often angina.
 When epicardial stenosis exceeds 90%, endocardial flow
reserve is exhausted (referred to as critical stenosis).

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 When coronary stenosis exceeds 70%,
o Ischemic episodes lead to production of vascular endothelial
growth factor and basic fibroblast growth factor which,
o Combined with endogenous vasodilators (eg, nitrous oxide,
prostacyclin), cause native collateral vessels to increase in
diameter (arteriogenesis) to maintain perfusion.
 Inflammation also plays a role in IHD;
o Macrophages and T-lymphocytes produce cytokines,
chemokines, and growth factors that activate endothelial cells,
increase vasoreactivity, and cause proliferation of vascular
smooth muscle cells.

The coronary circulation with
R1and R2
10

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 CRP may be elevated and correlates with adverse cardiovascular events.
 Some patients have plaque that causes a fixed decrease in supply but also
have reduced myocardial oxygen supply transiently due to vasospasm at
the site of the plaque.
 Vasospasm is typically caused by endothelial damage induced by the
plaque.
 Ischemic episodes may be more common in the morning hours and be
precipitated by cold exposure and emotional or mental stress.
 Patients with variant (Prinzmetal) angina usually do not have a coronary
flow obstructing plaque but instead have significant reduction in
myocardial oxygen supply due to vasospasm in epicardial vessels.

Clinical presentation
12
 Patients typically complain of chest pain precipitated by
exertion or activities of daily living that is described as
squeezing, crushing, heaviness, or chest tightness.
 It can also be more vague and described as a numbness or
burning in the chest.
 The location is often substernal and may radiate to the right or
left shoulder or arm (left more commonly), neck, back, or
abdomen.
 Ischemic symptoms may be associated with diaphoresis,
nausea, vomiting, and dyspnea.
 Chest pain generally lasts from 5 to 20 minutes and is usually
relieved by rest or sublingual nitroglycerin (SL NTG).

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 Some patients present with atypical chest pain,
characterized by mid epigastric discomfort, effort
intolerance, dyspnea, and excessive fatigue.
 Patients with diabetes mellitus may have decreased pain
sensation due to neuropathy.
 Patients with variant (Prinzmetal) angina are
o Typically younger and may present with chest pain at rest,
often early in the morning, and
o May have transient ST-segment elevation on the ECG.

Diagnosis
14
 Obtain the medical history to identify the quality and
severity of chest pain, precipitating factors, location,
duration, pain radiation, and response to nitroglycerin or
rest.
 Ischemic chest pain may resemble pain from non cardiac
sources, and diagnosis of anginal pain may be difficult
based on history alone.
 Assess non modifiable risk factors for CAD
 Identify the presence of modifiable CAD risk factors:
hypertension, diabetes mellitus,……

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 Physical exam findings are usually nonspecific, but patients
having an ischemic episode may present with
 Tachycardia, diaphoresis, shortness of breath, nausea, vomiting,
and lightheadedness.
 Other positive findings may include pulmonary crackles,
displaced point of maximal impulse, and a third heart sound in
patients HFrEF.
 Markers of inflammation,, may be elevated.
 Cardiac troponin concentrations are not typically elevated in
stable IHD.

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 Resting ECG is normal in at least half of patients with
angina who are not experiencing acute ischemia.
 Coronary angiography is the most accurate test for
confirming CAD but is invasive and requires arterial
access.
 Myocardial perfusion imaging, cardiac magnetic resonance,
coronary artery calcium scoring, and CT angiography can
also be used to detect CAD.

Treatment
17
Goals of Treatment:
 A primary goal of therapy is
 Complete (or nearly complete) elimination of anginal
chest pain and return to normal activities.
 Long-term goals are
 To slow progression of atherosclerosis and
 Prevent complications such as MI, heart failure, stroke, and
death.

Nonpharmacologic therapy
18
 Risk factor modification is the primary nondrug approach
for primary and secondary prevention of CAD events.
 Lifestyle modifications include
 Daily physical activity, weight management,
 Dietary therapy (reduced intake of saturated fats, trans-fatty
acids, and cholesterol), smoking cessation,
 Psychological interventions (eg, screening and treatment for
depression if appropriate),
 Limitation of alcohol intake, and avoiding exposure to air
pollution.

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 Surgical revascularization options for select patients
include
 Coronary artery bypass grafting (CABG) or
 Percutaneous coronary intervention (PCI) with or
without stent placement.

Pharmacologic therapy
20
 GDMT reduces the rates of death and MI similar to
revascularization therapy.
 Approaches to risk factor modification include the following
recommendations:
 Dyslipidemia: Use moderate- or high-dose statin therapy in
the absence of contraindications or adverse effects, in
addition to lifestyle changes.
 Blood pressure: If BP is ≥130/80 mm Hg, institute drug
therapy in addition to or after a trial of lifestyle
modifications.

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 Diabetes mellitus: Pharmacotherapy to achieve a target
A1C of ≤7% (53 mmol/ mol Hb) is reasonable for select
patients
 (eg, short duration of diabetes and long life expectancy).
 Annual influenza vaccinations are recommended.

Algorithm for treatment of SIHD
22

Antiplatelet Therapy
23
 Aspirin irreversibly blocks cyclooxygenase-1 (COX-1)
activity and subsequent thromboxane A2 production,
leading to reduced platelet activation and aggregation.
 A small percentage of patients are nonresponsive to
aspirin’s antiplatelet effects.
 Antiinflammatory drugs (NSAIDs) may interfere with
aspirin’s antiplatelet effect when coadministered by
competing for the site of action in the COX-1 enzyme.
 The ACC/ AHA guidelines contain the following
recommendations for stable IHD:

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 Aspirin: 75–162 mg daily should be continued indefinitely in the
absence of contraindications.
 Clopidogrel: 75 mg daily is an appropriate alternative when
aspirin is contraindicated.
 Patient responsiveness to clopidogrel is highly variable, with
estimates of nonresponsiveness ranging from 5% to 44% of
patients.
 DAPT with aspirin plus a P2Y12 inhibitor is beneficial after PCI
with coronary stent placement and after treatment for ACS. Its
benefits in other situations are less clear.
 The combination of aspirin (75–162 mg daily) and clopidogrel 75
mg daily may be reasonable in certain high-risk patients.

ACE Inhibitors and ARBs
25
 In the setting of IHD, ACE inhibitors
 Stabilize coronary plaque, restore or improve endothelial
function, inhibit vascular smooth muscle cell growth,
 Decrease macrophage migration, and possibly prevent oxidative
stress.
 However, ACE inhibitors have not been shown to improve
symptomatic ischemia or reduce chest pain episodes.
 Clinical trials of the role of ACE inhibitors or ARBs in reducing
cardiovascular events (eg, cardiovascular death, MI, stroke) in
high-risk patients have produced conflicting results.

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 The ACC/AHA guidelines for stable IHD recommend the
following strategies:
 Use ACE inhibitors in patients who also have hypertension,
diabetes, HFrEF, or chronic kidney disease, unless
contraindicated.
 ARBs are recommended for the same populations if patients are
intolerant to ACE inhibitors.
 Combination ACE inhibitor/ARB therapy should be avoided
due to the lack of additional benefit and a higher risk of adverse
events (eg, hypotension, syncope, renal dysfunction).

β-Adrenergic Blockers
27
 β-Blockers competitively inhibit the effects of neuronally
released and circulating catecholamines on β-adrenoceptors.
 Blockade of β1 -receptors in the heart and kidney reduces
HR, contractility, and BP, thereby decreasing MVo2 .
 β-Blockers are recommended over calcium channel blockers
(CCBs) for initial control of angina episodes in patients with
stable IHD.
 The target is to lower the resting HR to 50–60 beats/min and
the exercise HR to <100 beats/min.

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 β-Blockers may be combined with CCBs or long-acting nitrates
when initial treatment with β-blockers alone is unsuccessful.
 Only the β-blockers carvedilol, metoprolol succinate, and
bisoprolol should be used in patients with HFrEF, starting with
low doses and titrating upward slowly.
 Selection of a particular agent depends on the presence of
comorbid states, preferred dosing frequency, and cost.
 β1 -Selective agents are preferred in patients with
o Chronic obstructive pulmonary disease, peripheral arterial
disease (PAD),
o Diabetes, dyslipidemia, and sexual dysfunction.

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 β-Blockers are contraindicated in patients with
o preexisting bradycardia, hypotension, 2nd- or 3rd-degree
atrioventricular (AV) block, uncontrolled asthma, severe PAD,
o hypotension, HFrEF with unstable fluid status, and diabetes
associated with frequent episodes of hypoglycemia.
 If β-blocker therapy must be discontinued, doses should be tapered
over 2–3 weeks to prevent abrupt withdrawal,
 Which can significantly increase in MVo2 and induce ischemia
and even MI because of up-regulation of β-receptors in the
myocardium.

Calcium Channel Blockers
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 CCBs modulate calcium entry into the myocardium, vascular
smooth muscle, and other tissues.
 All CCBs reduce MVo2 by reducing wall tension via
 lowering arterial BP and (to a minor extent) depressing
contractility.
 CCBs also provide some increase in supply by inducing
coronary vasodilation and preventing vasospasm.
 CCBs or long-acting nitrates should be prescribed for relief of
symptoms when β-blockers are contraindicated or cause
unacceptable side effects.

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 Dihydropyridine CCBs (eg, nifedipine, amlodipine, isradipine,
and felodipine)
 Primarily affect vascular smooth muscle with little effect on the
myocardium.
 These drugs produce
 Minimal reduction in contractility and either no change or
increased HR due to reflex tachycardia from direct arterial
dilation.
 Nifedipine produces more impairment of LV function than
amlodipine and felodipine.
 Short-acting agents should not be used.

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 Nondihydropyridine CCBs (verapamil and diltiazem) mostly
affect the myocardium with minimal effects on vascular
smooth muscle;
 They reduce HR, contractility, and MVo2,
 Initial therapy for relief of symptoms with a long-acting
nondihydropyridine CCB instead of a β-blocker is a
reasonable approach.
 Common side effects of these CCBs include bradycardia,
hypotension, AV block, and symptoms of LV depression.

Nitrates
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 Nitrates increase concentrations of cyclic guanosine
monophosphate in vascular endothelium, leading to reduced
cytoplasmic calcium and vasodilation.
 Most vasodilation occurs on the venous side, leading to
reduced preload, myocardial wall tension, and MVo2 .
 Arterial vasodilation increases as doses are escalated, which
can produce reflex tachycardia that can negate some of the
antianginal benefits.
 This effect can be mitigated with concomitant β-blocker
therapy.

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 Nitrates also produce vasodilation of stenotic epicardial vessels
and intracoronary collateral vessels, increasing oxygen supply
to the ischemic myocardium.
 All patients should have access to sublingual (SL) NTG 0.3 or
0.4 mg tablets or spray to treat acute angina episodes.
 Relief typically occurs within 5 minutes of administration.
 SL nitrates can also be used to prevent acute episodes if given
2–5 minutes before activities known to produce angina;
 Protection can last for up to 30 minutes with SL NTG and up to
1 hour with SL ISDN.

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 Long-acting nitrates (or CCBs) should be prescribed for relief
of symptoms
o when β-blockers are contraindicated or cause unacceptable
side effects.
 Various nitrate formulations are available for acute and chronic
use.
 Transdermal patches and isosorbide mononitrate (ISMN) are
most commonly prescribed for long-term prevention of angina
episodes.
 Chronic nitrate use should incorporate a 10- to 14-hour nitrate
free interval each day to reduce nitrate tolerance.

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 Transdermal NTG patches are typically prescribed as “on in
the am and off in the pm”
 but patients should be given specific application and
removal times (eg, apply at 8:00 am and remove at 8:00
pm).
 Nitrates should not be used routinely as monotherapy
for stable IHD.
 Concomitant β-blocker or diltiazem therapy can prevent
rebound ischemia during the nitrate-free interval.

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 Common nitrate side effects include
 Headache, flushing, nausea, postural hypotension, and
syncope.
 Headache can be treated with acetaminophen and usually
resolves after about 2 weeks of continued therapy.
 Transdermal NTG may cause skin erythema and
inflammation.
 Initiating therapy with smaller doses and/or rotating the
application site can minimize transdermal nitroglycerin side
effects.

Ranolazine
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 Ranolazine reduces ischemic episodes by selective inhibition of
late sodium current (INa),
 which reduces intracellular sodium concentration and
improves myocardial function and perfusion.
 It does not impact HR, BP, the inotropic state, or increase
coronary blood flow.
 Ranolazine is effective as monotherapy for relief of angina
symptoms but should only be used
 If patients cannot tolerate traditional agents due to
hemodynamic or other adverse effects.

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 Because it does not substantially affect HR and BP,
 It is recommended as add-on therapy to traditional antianginal
agents
 for patients who achieve goal HR and BP and still have
exertional angina symptoms,
 patients who cannot achieve these hemodynamic goals due
to adverse effects, and
 patients who reach maximum doses of traditional agents
but still have angina symptoms.

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 The initial ranolazine dose is 500 mg twice daily,
increased to 1000 mg twice daily within the next 1–2
weeks if tolerated.
 It can be combined with a β-blocker when initial treatment
with β-blockers alone is unsuccessful.
 Adverse effects include constipation, nausea, dizziness,
and headache.
 Ranolazine can prolong the QTc interval and should be
used with caution in patients receiving concomitant QTc-
prolonging agents.

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 Potent inhibitors of CYP3A4 and P-glycoprotein
(ketoconazole, itraconazole, protease inhibitors,
clarithromycin, and nefazodone) or
 Potent inducers of CYP3A4 and P-glycoprotein (phenytoin,
phenobarbital, carbamazepine, rifampin, rifabutin, rifapentine,
St. John’s wort)
 are contraindicated with ranolazine due to significant
increases and decreases in ranolazine drug concentrations,
respectively.

Drugs and Regimens for Stable Ischemic Heart
Disease
42

Treatment of variable threshold angina
and prinzmetal angina
44
 Patients with variable threshold angina require pharmacotherapy
for vasospasm.
 Most patients respond well to SL NTG for acute attacks.
 Both CCBs and nitrates are effective for chronic therapy.
 Nifedipine, verapamil, and diltiazem are equally effective as
single agents for initial management of coronary vasospasm;
dose titration is important to maximize the response.
 Patients unresponsive to CCBs alone may have nitrates added.
 β-Blockers are not useful for vasospasm because they may
induce coronary vasoconstriction and prolong ischemia

Evaluation of therapeutic outcomes
45
 Assess for symptom improvement by number of angina
episodes, weekly SL NTG use, and increased exercise
capacity or duration of exertion needed to induce angina.
 Use statins for dyslipidemia, strive to achieve BP and A1C
goals, and implement the lifestyle modifications of dietary
modification, smoking cessation, weight loss, and regular
exercise.
 Once patients have been optimized on medical therapy,
symptoms should improve over 2–4 weeks and remain
stable until the disease progresses.

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 Patients may require evaluation every 1–2 months until target
endpoints are achieved; follow-up every 6–12 months
thereafter is appropriate If the patient is doing well, no other
assessment may be necessary.
 Although followup exercise tolerance testing with or without
cardiac imaging can be performed to objectively assess
control of ischemic episodes, this is rarely done if patients are
doing well because of the expense involved.
 Monitor for adverse drug effects such as headache and
dizziness with nitrates; fatigue and lassitude with β-blockers;
and peripheral edema, constipation, and dizziness with CCBs.

Introduction
48
 Acute coronary syndrome (ACS) is an acute manifestation of
CAD and, for many patients, is the first indication they have
CAD.
 Patients with ACS typically experience an acute reduction in
coronary blood flow most often due to a ruptured
atherosclerotic plaque and subsequent formation of an
intracoronary thrombus.
 The reduction in coronary blood flow produces myocardial
ischemia and, if left untreated,
 may lead to myocardial infarction (MI).

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 The spectrum of ACS includes
 ST-segment elevation myocardial infarction
(STEMI),
 Non-ST segment elevation myocardial infarction
(NSTEMI), and
Unstable angina (UA).

Etiology
50
 Endothelial dysfunction, inflammation, and the formation of
fatty streaks contribute to the formation of atherosclerotic
coronary artery plaques, the underlying cause of CAD.
 The predominant cause of ACS in more than 90% of
patients is
 The acute rupture, fissure, or erosion of an unstable
atherosclerotic plaque followed by
 Subsequent thrombus formation that impairs distal blood
flow resulting in acute myocardial ischemia and
potentially infarction.

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 Atherosclerotic plaques that rupture typically have thin fibrous
caps and tend to be nonobstructive, occluding <70% of the luminal
diameter;
 Thus, patients may not experience angina prior to plaque rupture
due to
 adequate autoregulation that maintains blood flow and oxygen
supply during increased myocardial oxygen demand.
 Increased catecholamine release during physical or emotional
stress may enhance the likelihood of rupture of a thinning fibrous
cap.

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 Plaque rupture breaches the barrier between the necrotic
plaque core and blood components; circulating platelets are
attracted and adhere to the area of injury.
 Platelet adhesion occurs via
 Platelet glycoprotein (GP) VI receptors binding to collagen
within the damaged fibrotic cap, as well as platelet GP Ib-IX
receptors and von Willebrand factor.
 Platelets are then activated by collagen, thrombin,
thromboxane A2 , adenosine diphosphate (ADP),
epinephrine, and serotonin.

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 Binding of these activators to their specific receptors on the
platelet surface results in
 increased platelet surface area and release of further platelet
activators from granules within platelets.
 Assembly of tenase and prothrombinase complexes within
activated platelets produces most of the activated factor Xa and
IIa (thrombin) in the coagulation cascade.
 A change in the conformation of the GP IIb/IIIa surface
receptors of platelets cross-links platelets to each other through
fibrinogen bridges, resulting in platelet aggregation and
formation of a platelet plug in the area of plaque rupture.

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 Activation of the clotting cascade forms a fibrin meshwork
(thrombus) around the platelet plug
 That traps cellular components such as red blood cells and
causes abrupt reduction in myocardial blood flow and
oxygen supply.
 If ischemia is left untreated, myocyte necrosis and cell death
may ensue.
 After MI, acute and chronic adaptations occur to prevent
hemodynamic collapse but may also lead to ventricular
remodeling and post-MI complications.

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 Stimulation of the sympathetic nervous system (SNS) and
RAAS compensates for decreased cardiac output.
 However, chronic hyper activation of these systems can lead
to ventricular hypertrophy and further impairment of
contractility and cardiac output.
 Release of inflammatory mediators and collagen deposition
contribute to myocardial fibrosis or scarring,
 which can lead to thinning of the left ventricular (LV) wall
and eventual development of dilated cardiomyopathy.

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 Complications of MI include
o Ventricular arrhythmias, bradyarrhythmias, heart block,
o Heart failure (HF), cardiogenic shock, LV free-wall or septal
rupture,
o Thromboembolism (including stroke secondary to LV
thrombus embolization),
o Aneurysm formation, and pericarditis.
 Many patients with ACS develop depression during the
convalescent period.

Clinical presentation
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 The patient is typically in acute distress and may present with
or develop hypertensive crisis, acute HF, cardiogenic shock,
or cardiac arrest.
 The classic symptom of ACS is abrupt-onset substernal chest
pain or discomfort often described as
 A squeezing, heaviness, or tightness that persists for 10
minutes or longer.
 Symptoms may radiate to the arms and shoulders (especially
on the left side), back, abdomen, or jaw.

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 Nausea, vomiting, diaphoresis, or shortness of breath may
also be present.
 Many patients have atypical symptoms without chest pain,
such as
 Epigastric pain, indigestion, pleuritic chest pain, and
increasing exertional dyspnea.
 Older adults, women, and patients with diabetes mellitus
(DM), impaired renal function, and dementia are more likely
to present with atypical features.

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 No physical examination findings are specific for ACS.
 Nonspecific findings include S4 or paradoxical splitting of
S2 heart sounds on auscultation.
 Signs of acute decompensated HF include jugular venous
distention, pulmonary edema, and an S3 on auscultation.
 Patients may also present with arrhythmias, heart block,
hypertension (HTN), hypotension, or shock.

Diagnosis
60
 Obtain 12-lead ECG within 10 minutes of presentation.
Changes suggestive of acute ischemia include STE, ST-
segment depression, and T-wave inversion.
 Presence of a new LBBB in patients with suspected ACS is
strongly suggestive of acute MI.
 Some patients with ACS have no ECG changes, so
appropriate evaluation and risk stratification must carefully
assess
 Medical history, presenting symptoms, and cardiac
biomarkers.

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 Cardiac troponin (either T or I) is measured at the time of
presentation and repeated 3–6 hours later to detect myocardial
injury;
 Elevated blood levels occur within 2–4 hours of myocyte injury
or necrosis and may remain elevated as long as 2 weeks.
 Elevated levels in a patient with ACS symptoms, ischemic
changes on ECG, or other evidence of ischemia confirm the
diagnosis of MI.
 Additional troponin levels should be obtained beyond 6 hours
after symptom onset in patients with intermediate- to high-risk
features of ACS but normal troponin levels during serial
measurements.

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 Elevated dynamic cardiac troponin levels with ST-segment
elevation of at least 1 mm in two contiguous leads or new
LBBB on the presenting ECG confirms the diagnosis of
STEMI.
 In contrast, the diagnosis of NSTEMI is appropriate for patients
with symptoms of ACS and elevated troponin levels without at
least 1 mm ST-segment elevation on the ECG at presentation.
 Patients with symptoms consistent with ACS but in whom
troponin is not elevated may have UA or an alternative
diagnosis.

Treatment
63
Goals of Treatment:
 Short-term goals includes:
o (1) early restoration of blood flow to the affected artery to
prevent infarct expansion (in the case of MI) or prevent
complete occlusion and MI (in UA),
o (2) prevention of death and other complications,
o (3) prevention of coronary artery reocclusion, and
o (4) relief of ischemic chest discomfort.
 Long-term goals include control of CV risk factors, prevention
of additional CV events, and improvement in quality of life.

General approach to treatment of
ACS
64
 The clinical presentation, past medical history, ECG, and
biomarkers are used to stratify patients as
 Low, medium, or high risk and determine which patients may
benefit from reperfusion therapy, an early invasive approach, or
medical management.
 Treatment decisions are based on the initial and ongoing risk
stratification.
 Because STEMI has the highest short-term risk of death, these
patients should be emergently referred for primary PCI;
confirmation of elevated troponin should not delay treatment.

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 General measures include
 hospital admission,
 oxygen administration if saturation is <90% (0.90)
 bed rest with continuous multilead ST-segment monitoring
for arrhythmias and ischemia,
 frequent measurement of vital signs, ischemic pain relief,
and
 prompt initiation of antithrombotic therapy.

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 Assess kidney function to identify patients who may need
dosing adjustments and those at high risk of morbidity and
mortality.
 Measure serum potassium and magnesium levels, which
may affect heart rhythm.
 Obtain complete blood cell count (CBC), fasting lipid panel,
and coagulation tests because most patients will receive
antithrombotic therapy

Acute supportive care for ACS
67
 Aspirin is recommended for all ACS patients without
contraindications, regardless of the type of ACS or
management strategy.
 The initial dose is 162–325 mg (non-enteric coated) given as
soon as possible and chewed and swallowed to speed
dissolution and onset of platelet inhibition (<30 minutes).
 After the initial dose, aspirin 81 mg daily is continued
indefinitely.
 In CI to aspirin, clopidogrel with a loading dose followed by
a maintenance dose should be used as an alternative.

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 Nitroglycerin (NTG) is indicated for relief of anginal
symptoms, uncontrolled HTN, and acute HF.
 The sublingual (SL) dose is 0.3–0.4 mg every 5 minutes for
up to 3 doses as needed for angina.
 Consider intravenous (IV) NTG for persistent angina despite
SL NTG at an initial dose of 10 mcg/min titrated to symptom
relief and desired blood pressure (BP).
 Continue IV NTG until symptoms have resolved, BP is
controlled, and HF symptoms have subsided.
 Gradually taper the infusion upon discontinuation.

69
 Oxygen administration (2–4 L/min) should be reserved for
select patients,
 particularly those with oxygen saturation <90% (0.90).
 Morphine is an analgesic, anxiolytic, and venodilator that
reduces oxygen demand,
 but its role in ACS is uncertain because some studies have
shown adverse outcomes.
 Current guidelines recommend IV morphine for pain relief in
patients with STEMI.

70
 Recommended doses are 4–8 mg IV × 1 (lower dose in elderly),
then 2–8 mg IV every 5–15 minutes as needed.
 In NSTE-ACS, IV morphine use is recommended only in patients
refractory to treatment with other anti-ischemic medications;
 doses between 1 and 5 mg every 5–30 minutes are
recommended.
 β-Blockers should be administered to all patients without
contraindications
o because they reduce angina and the risk of MI and arrhythmias,
even though their mortality benefit in the reperfusion era is
uncertain.

71
 Current guidelines recommend initiation of an oral β-
blocker within the first 24 hours of ACS presentation and
continuation for at least 3 years in patients with normal LV
ejection fraction (LVEF).
 Recommended doses include:
 Carvedilol: 6.25 mg orally twice daily; target dose is 25 mg
twice daily as tolerated.
 Metoprolol: 25–50 mg orally every 6–12 hours for 2–3
days, then once daily (metoprolol succinate) or twice daily
(metoprolol tartrate); target dose is 200 mg daily.

72
 CCBs have anti-ischemic effects but may not have
beneficial effects on mortality, MI, or recurrent MI.
 Guidelines recommend nondihydropyridine CCBs for
angina symptoms in patients with ACS who have
o A contraindication, have intolerance, or are refractory to β-
blockers
 Long-acting CCBs are recommended for patients with ACS
with known or suspected vasospasm.

73
 Recommended doses include:
✓ Diltiazem: 120–360 mg/day orally
✓ Verapamil: 240–480 mg/day orally
✓ Amlodipine: 5–10 mg orally once daily
✓ Nicardipine: 60–120 mg/day orally
✓ Nifedipine extended-release (ER): 30–120 mg orally
once daily.

74
Treatment strategies in STEMI

Primary PCI
75
 Mechanical reperfusion with PCI using intracoronary
balloons, stents, or other devices within 90 minutes of first
medical contact is the reperfusion treatment of choice.
 Compared to reperfusion with fibrinolysis, primary PCI
 Improves survival, establishes consistent revascularization to
the infarct-related artery,
 Reduces the risk of stroke and intracranial hemorrhage
(ICH), and
 Reduces reinfarction and recurrent ischemia.

Fibrinolysis
76
 Administer fibrinolysis to patients with STEMI when PCI
cannot be performed within 120 minutes of first medical
contact, provided no contraindications exist.
 Limit use of fibrinolytics between 12 and 24 hours after
symptom onset to patients with clinical and/or ECG evidence
of ongoing ischemia.
 Absolute contraindications to fibrinolytic therapy include
 any prior hemorrhagic stroke, ischemic stroke within 3 months,
 intracranial neoplasm or AV malformation,
 active internal bleeding, aortic dissection,

77
 considerable facial or closed head trauma in the past 3
months, intracranial or intraspinal surgery within 2 months,
 severe uncontrolled HTN, and
 for streptokinase treatment within previous 6 months (if
considering streptokinase again).
 Primary PCI is preferred in these situations.
 A fibrin-specific agent is preferred over the non–fibrin-
specific agent streptokinase because of greater reperfusion
success and less systemic bleeding.

78
 Fibrinolytic therapy is associated with a slight but
statistically significant risk for stroke, largely attributed to
ICH (0.9%–1.0% of patients).
 Administer antithrombotic therapy with antiplatelet agents
and parenteral anticoagulation concomitantly with both
primary PCI and fibrinolysis to improve vessel patency
and prevent reocclusion.

79
Treatment strategies in NSTE-ACS

Early Invasive Approach
80
 Patients presenting with NSTE-ACS typically have a partially
occluded coronary artery with some residual perfusion;
 therefore, the need for and urgency to perform PCI is not as
critical.
 With an early invasive approach, diagnostic angiography is
typically performed within the first 24 hours with the intent to
perform revascularization if appropriate.
 Guidelines recommend this strategy in patients with
intermediate to high risk for death, MI, refractory angina,
acute HF, cardiogenic shock, or arrhythmias.

Ischemia-Guided Approach (Medical
Management)
81
 If an early invasive strategy using PCI is not considered
appropriate, select low-risk patients may receive more
conservative ischemia-guided medical management,
o where antiplatelet and anticoagulants are administered and
PCI is not initially planned.
 Patients are evaluated for signs and symptoms of recurrent
ischemia or hemodynamic instability (eg, with noninvasive
stress testing) and taken for coronary angiography and
possible PCI only if symptoms recur.

Antithrombotic therapy for ACS
82
 Both antiplatelet and anticoagulant therapy are necessary in
the acute treatment phase of ACS because
 platelets dominate the pathophysiologic processes in arterial
thrombosis, and
 thrombin is involved in both platelet activation and
coagulation.
 After hospital discharge, most patients are continued on
long-term antiplatelet therapy only, although long-term
anticoagulant therapy may benefit some high-risk
individuals.

Antiplatelet Therapy
83
 Aspirin: A dose of 81 mg daily is continued indefinitely
(after the initial 162–325 mg dose) in patients with either
STEMI or NSTE-ACS,
 regardless of the management strategy employed.
 Patients undergoing PCI for STEMI or NSTE-ACS already
receiving chronic aspirin 81 mg daily should be given an
additional dose of 81–325 mg before the procedure.
 P2Y12 Inhibitors: An oral agent is typically given with
aspirin as dual antiplatelet therapy (DAPT) to prevent stent
thrombosis and thrombotic CV events.

84
 Any of the four agents may be given with primary PCI, but
only clopidogrel has been evaluated in large clinical trials in
patients with STEMI receiving reperfusion with fibrinolysis.
 Recommended doses are as follows:
 Clopidogrel: 600-mg oral loading dose before primary PCI for
STEMI or NSTEACS.
 Give a 300-mg oral loading dose to patients receiving a
fibrinolytic or who do not receive reperfusion therapy.
 Avoid a loading dose in patients age ≥75 years.
 The maintenance dose is 75 mg daily.

85
 Withhold clopidogrel and ticagrelor for at least 5 days and
prasugrel for 7 days before elective surgery (eg, CABG
surgery).

Anticoagulants
86
 Although patients with ACS are typically on at least two
antiplatelet agents for a year or more,
 a single anticoagulant is usually given for a short time (the
initial few days of hospitalization).
 Current evidence in the acute management of ACS is with
injectable anticoagulants.
 Unfractionated heparin (UFH) has been widely used in ACS
management for several decades.
 Based on experience, UFH can be used across the spectrum of
ACS and regardless of the management strategy.

87
 Because of significant interpatient variability in anticoagulant
response, therapy must be monitored with the activated partial
thromboplastin time.
 Platelet counts should also be monitored daily or every other day
to detect HIT.
 If HIT is suspected, discontinue UFH and provide anticoagulation
with an IV direct thrombin inhibitor.
 LMWHs provide a predicable anticoagulant dose response with
no need for routine therapeutic monitoring.
 Anti-Xa level monitoring may be helpful in obese patients (>190
kg) and patients with severe renal insufficiency.

88
 Fondaparinux provides a predicable anticoagulant dose
response with no need for therapeutic monitoring (similar to
LMWH).
 In patients with STEMI receiving fibrinolytics,
fondaparinux had efficacy and safety similar to UFH.
 However, fondaparinux is rarely used in patients with
STEMI based on the lack of superiority to UFH and the
benefit shown with enoxaparin over UFH in this population.

Anticoagulant Drug Use and Dosing for
Treatment of Acute Coronary Syndrome
89

Secondary prevention of
ischemic events
91
 After a diagnosis of ACS, patients are considered to have
ASCVD and should be treated aggressively because they are at
the highest risk of recurrent major adverse cardiovascular events
(MACE).
 Aggressive risk factor modification strategies should be
initiated and continued indefinitely (eg, increased physical
activity, dietary modification, weight loss, BP modification, and
smoking cessation).
 Pharmacotherapy proven to decrease mortality, HF, reinfarction,
stroke, and stent thrombosis should be initiated prior to hospital
discharge in all patients without contraindications.

92
 This includes anti-ischemic, antiplatelet, lipid-lowering, and
antihypertensive therapies.
 Medication reconciliation at discharge should include assessment for the
medication classes listed below as appropriate unless a contraindication
exists.
 Aspirin: Treat with aspirin 81 mg once daily indefinitely.
 P2Y12 inhibitor: Because the ischemic risk following ACS is high,
DAPT with aspirin plus a P2Y12 receptor inhibitor is indicated for most
patients for at least 12 months regardless of the management strategy
employed.
 Continuation of DAPT beyond 12 months may be reasonable for patients
at higher ischemic risk if they also have a low bleeding risk.

93
 β-Blocker: Continue therapy for at least 3 years and
indefinitely in patients with concomitant HFrEF.
 Statin: Initiate high-intensity statin therapy during the index
hospitalization once the patient has been stabilized and
continue treatment indefinitely.
 All patients should receive the highest dose of maximally
tolerated statin.
 Reassess a lipid panel 4–6 weeks after initiation of therapy
with the goal of a 50% reduction in LDL-C from baseline.

94
 Non-statin cholesterol-lowering medications: For patients
with very high risk ASCVD (eg, post-ACS) and LDL-C >70
mg/dL on maximally tolerated statin therapy.
 ACE inhibitor: Early administration (within 48 hours of
presentation) is associated with lower mortality within the first
month of therapy with additional benefit observed during over
longer treatment durations.
 Aldosterone antagonist: To reduce mortality, consider
administration within the first 14 days after MI in patients
treated with both an ACE inhibitor (or ARB) and β-blocker with
LV dysfunction (LVEF ≤40% and either HF symptoms or DM.

95
 Nitroglycerin: All patients not taking PDE-5 inhibitors
should be prescribed and instructed on appropriate use of
short-acting NTG, either
 SL tablets (0.3–0.4 mg SL every 5 minutes, up to 3 doses)
or
 lingual spray to relieve acute anginal symptoms on an as-
needed basis.

Evaluation of therapeutic outcomes
96
 Evaluation of short-term efficacy focuses on restoration or
preservation of coronary blood flow, symptom relief, and
prevention of MACE.
 Determine restoration of blood flow and relief of ischemia by
resolution of ischemic ECG changes on presentation, which
should occur soon after revascularization.
 Although troponin levels may remain elevated for several days,
levels in patients with MI should peak within 12–24 hours and
then decline steadily once ischemia is relieved.
 Monitor for development of ACS complications (eg, HF,
arrhythmias) frequently.

97
 Prior to hospital discharge, perform echocardiogram or
equivalent modality to identify patients with LV dysfunction
who are at high risk of death and candidates for guideline-
directed medical therapy and device therapy.
 Assure that evidence-based therapies shown to reduce the risk
of MACE following ACS have been initiated.
 Long-term outcome evaluation is directed at maintaining
functional capacity, quality of life, and continued focus on risk
reduction.
 Monitor patients at every healthcare encounter for
development of adverse effects from ACS pharmacotherapy.

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