Therapeutics

Stable Ischemic

Heart Disease Dr Sura Al Zoubi

PhD,

MClinPharm

Lecture 5

References

• Pharmacotherapy: A Pathophysiologic Approach, 11e. Chapter 32: Stable Ischemic Heart Disease

• 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease. Circulation.2012; 126: e354-e471.

• 2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease.

• 2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease. (Circulation. 2016;133:000–000.)

Terminology/Definition

• Ischemic heart disease (IHD), also known as coronary artery disease (CAD), is defined as: a lack of oxygen ―ischemia‖ and decreased or no blood flow to the myocardium resulting from coronary artery narrowing or obstruction.

• Ischemic Heart Disease (IHD) may present as:

1. Myocardial ischemia without clinical symptoms,

2. Chronic stable exertional angina pectoris (SA)

3. Coronary artery vasospasm (Variant or Prinzmetal angina)

4. An acute coronary syndrome (ACS)

a) Unstable angina (USA)

b) Non–ST-segment elevation myocardial infarction (NSTEMI)

c) ST-segment elevation myocardial infarction (STEMI)

EPIDEMIOLOGY

• In 2014 an estimated 92.1 million (36.6%) adult Americans had a form of cardiovascular disease (CVD), which includes CAD (16.5 million), HF, stroke, and hypertension (HTN).

• The prevalence of CAD is higher in blacks, men and increases with age.

• Stable angina is the initial manifestation of ischemic heart disease in approximately one-half of all patients who eventually have an MI.

• 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;

1. The extent of atherosclerotic disease,

2. The presence of left ventricular dysfunction,

3. The presence of other comorbidities.

4. The severity of angina symptoms

ETIOLOGY AND

PATHOPHYSIOLOGY

• Angina pectoris is most often the result of an imbalance between myocardial oxygen supply and myocardial oxygen demand (MVO2).

• The pathophysiology of SIHD is driven by an increase in MVO2 in the setting of a fixed decrease in myocardial oxygen supply

• The etiology of the fixed decrease in supply is long-standing, well-developed atherosclerotic plaque

• The process of atherosclerosis begins early in life, with fatty steaks developing in many people in their teenage years or early twenties.

• These plaques grow over decades and start to become pathologic in a person's fifth decade of life and beyond

• In patients with SIHD the plaques are stable, have a reduced lipid core, and a firm calcified covering

• Epicardial conductance vessels (R1) and intramyocardial resistance arterioles (R2).

• Autoregulation

• In atheroslerotic pleaque the vasodilator reserve is limited

• Once the epicardial vessel is narrowed by 70% or more of the luminal diameter, the endocardial vessels must fully dilate in order to maintain normal coronary resistance. These larger plaques are considered ―obstructive

Prinzmetal’s Angina

• Results from transient vasospasm of the coronary vessels

• Patients with this angina may be relatively young and have few or even no cardiac risk factors

• The chest pain is often unpredictable and cyclical in nature, sometimes reverting spontaneously into remission.

• More likely to experience pain at rest and in the early morning hours. Pain is not usually brought on by exertion or emotional stress nor relieved by rest

• the ECG pattern is that of current injury with ST-segment elevation rather than depression.

CLINICAL PRESENTATION

• A thorough patient history is key to the clinical assessment of a patient with SIHD.

• Exertional chest pain is the classic presenting symptom of patients with SIHD.

• The differential diagnosis of ―chest‖ pain is broad. Therefore, it is important to determine if symptoms are due to a cardiac or noncardiac pathology.

• The patient's description of chest pain can be helpful in determining if the pain is more likely SIHD or ACS

• CSA should be distinguished from UA since the latter is associated with a greater risk for MI and death and requires more aggressive treatment.

• Because the pathophysiology of CSA is due primarily to increases in oxygen demand symptoms are typically reproducible.

• Patient will generally experience a similar pattern of discomfort (i.e., same quality, location, and accompanying symptoms) with a similar level of exertion with each angina attack.

• The exception maybe a patient with coronary artery vasospasm, in whom symptoms maybe more variable and unpredictable.

• Patients with CSA will generally be in no acute distress. In patients presenting in acute distress, the clinician should be suspicious of ACS.

• The five components commonly used to characterize chest pain are

1. Quality,

2. Location,

3. Duration of pain;

4. Factors that provoke pain

5. Factors that relieve pain

• Typical pain: sensation of pressure, heaviness, or squeezing in the anterior chest area. (Sharp pain is not a typical symptom of IHD).

• May radiate to the neck, jaw, shoulder, back, or arm.

• May be accompanied by dyspnea, nausea, vomiting, or diaphoresis.

• Chest pain generally lasts from 5 to 20 minutes and it is usually relieved by rest or sublingual nitro-glycerine SL NTG

• Symptoms are often provoked by exertion (e.g., walking, climbing stairs, and doing yard-or housework) or emotional stress and relieved within minutes by rest or sublingual nitroglycerin.

• Other precipitating factors include exposure to cold temperatures and heavy meals.

• Pain that occurs at rest (without provocation) or that is prolonged and unrelieved by sublingual nitroglycerin is indicative of an ACS.

• Some patients, most commonly women and patients with diabetes, may present with atypical symptoms including indigestion, gastric fullness, and shortness of breath.

• Patients with diabetes may experience associated symptoms, such as dyspnea and diaphoresis, without having any of the classic chest pain symptom

• In some cases, ischemia may not produce any symptoms and is termed ―silent ischemia.‖

Differential Diagnosis of Episodic Chest Pain Resembling Angina Pectoris

Diagnostic and Prognostic Testing • A 12-lead ECG recorded during rest is often normal in patients

with chronic stable angina in the absence of active ischemia.

• It should be done within 10 minutes of presentation to the emergency department in patients with symptoms of ischemia.

• Cardiac stress test;

1. Physical exercise (treadmill), Treadmill or bicycle exercise ECG, commonly referred to as a ―stress test,‖ is considered positive for IHD if the ECG shows at least a 1 mm deviation of the ST-segment (depression or elevation).

2. Pharmacologic stress :Dobutamine is commonly used with stress echocardiography, whereas adenosine or dipyridamole are used for nuclear imaging studies. Used in patients who are unable to exercise and is commonly used with echocardiographyto identify stress induced wall motion abnormalities indicative of coronary disease

3. Radionuclides myocardial perfusion imaging (rMPI allows for the identification of multivessel disease and assessment of myocardial viability. An IV radioactive tracer is used to detect areas of the heart that receive less blood after adenosine or dipyridamole infusion, indicating a myocardial perfusion defect and coronary disease

4. Coronary artery calcium scoring via CT, also known as electron beam CT (EBCT) or ―ultra-fast CT,‖ may be performed as a noninvasive means to assess for IHD. Calcium deposits are detected on CT. A calcium score is calculated, and the risk for IHD-related events is estimated.

5. Coronary angiography (invasive) detects the location and degree of coronary atherosclerosis and is used to evaluate the potential benefit from revascularization procedures.

• Stenosis of at least 70% of the diameter of at least one of the major epicardial arteries on coronary angiography is indicative of significant IHD

• Is considered the gold standard for the diagnosis of IHD when:

a) Stress testing results are abnormal

b) Symptoms of angina are poorly controlled.

c) Contrast medium must be used cautiously with adequate hydration in patients with pre-existing renal disease (especially in those with diabetes) to avoid contrast-induced nephropathy

Biomarkers

• Cardiac troponin concentrations are released when there is myocyte death (infarction) and hence are not typically elevated in patients with SIHD

• In a study, 6% of patients with SIHD undergoing treatment PCI had an elevated troponin.

• Patients with an elevated pre-procedure troponin were more likely to have an MI or die in-hospital when compared to patients without an elevated troponin. The differences in these outcomes were still significant 1 year after PCI

TREATMENT

• The treatment of patients with SIHD typically involves two complementary strategies.

1. Slowing the progression of atherosclerosis and preventing complications such as MI, HF, stroke, and death (either sudden cardiac death or progression of underlying CVD). risk-factor modification-Reduce mortality, improve quality of life

2. Reducing the number of ischemic episodes as well as increasing the amount of exertion or exercise a patient can accomplish before chest pain occurs. improve the quality of life through a reduction in symptoms.

Desired Outcomes

1. Reducing the risk of CV events and mortality,

2. A complete, or nearly complete, elimination

of chest pain and return to normal activities

with a functional capacity of CCS class I

angina.

Risk Factor Modification:

ACC/AHA Recommendations

1. Antiplatelet Therapy

• Aspirin almost completely blocks cyclooxygenase-1 (COX-1) activity and subsequent thromboxane A2 production, leading to reduced platelet activation and aggregation for the life of the platelet.

• Nonsteroidal anti-inflammatory drugs (NSAIDs) may interfere with aspirin’s antiplatelet effect when coadministered due to competition for the site of action in the COX-1 enzyme.

• The ACC/AHA guidelines contain the following recommendations for stable IHD: – Aspirin 75 to 162 mg daily should be continued indefinitely in the

absence of contraindications.

– Clopidogrel 75 mg daily is an alternative for patients unable to take aspirin due to allergy or intolerance. (Proton pump inhibitor,mainly omeprazole)

– The combination of aspirin (75–162 mg daily) and clopidogrel 75 mg daily may be reasonable in certain high-risk patients. (patients with established vascular disease)

– Dipyridamole therapy is not recommended.

2. ACEIs and ARBs • In the setting of IHD, angiotensin-converting enzyme (ACE) inhibitors can

1. Stabilize coronary plaque,

2. Restore or improve endothelial function,

3. Inhibit vascular smooth muscle cell growth,

4. Decrease macrophage migration, and

5. Perhaps provide antioxidant activity.

• However, ACE inhibitors have not been shown to improve symptomatic ischemia.

• Two trials demonstrated reductions in cardiovascular death, MI, or stroke compared to placebo in patients at high risk for such events, but a third trial did not show these benefits.

• The ACC/AHA guidelines for stable IHD recommend the following strategies: – Use of ACE inhibitors in patients who also have hypertension, diabetes, left

ventricular dysfunction (ejection fraction 40% or less), or chronic kidney disease, unless contraindicated.

– Angiotensin receptor blockers (ARBs) are recommended for the same populations if patients are intolerant to ACE inhibitors. Combination ACE inhibitor/ARB therapy is not justified.

ACEIs and ARBs

3. Lipid Management

• Class I

1. Lifestyle modifications, including daily physical activity and weight management, are strongly recommended for all patients with SIHD.

2. Dietary therapy for all patients should include reduced intake of saturated fats (to <7% of total calories), trans fatty acids (to <1% of total calories), and cholesterol (to <200 mg/dL [5.17 mmol/L]).

3. In addition to therapeutic lifestyle changes, a high-intensity statin should be prescribed, in the absence of contraindications or documented adverse effects.

4. In patients who are >75 years of age or cannot tolerate high-intensity statin therapy, moderate-intensity statins should be used if tolerated.

5. For patients who cannot tolerate high-intensity statins or do not attain a 50% decrease in LDL-C (or LDL remains >70-100 mg/dL [1.81-2.59 mmol/L]), the addition of ezetimibe first and PCSK-9 inhibitors second is reasonable.

6. Referral to a lipid specialist should be considered.

Intensity of Statin Therapy by Drug

and Dose

4. Blood Pressure Management

• Class I

1. All patients should be counseled about the need for lifestyle modification: weight control; increased physical activity; alcohol moderation; sodium reduction; and emphasis on increased consumption of fresh fruits, vegetables, and low-fat dairy products.

2. In patients with SIHD with BP 130/80 mm Hg or higher, antihypertensive drug therapy should be instituted in addition to or after a trial of lifestyle modifications.

3. The specific medications used for treatment of HTN in SIHD patients should be based on compelling indications (eg, prior MI, angina, HFrEF) and may include beta blockers, ACE inhibitors, or ARBs with addition of other drugs, such as thiazide diuretics, dihydropyridine calcium channel blockers, or aldosterone antagonists, if needed to achieve a goal of BP less than 130/80 mm Hg.

4. For patients with angina and persistent uncontrolled HTN, it is recommended to add dihydropyridine CCBs to beta blockers.

• Class IIa

1. For patients who have had an ACS, it is reasonable to continue beta blockers long-term if needed for treatment of HTN.

5. Diabetes Management

• Class IIa

1. For selected individual patients, such as those with a short duration of diabetes mellitus and a long life expectancy, a goal A1c of 7% (53 mmol/mol Hgb) or less is reasonable.

2. A goal A1c <8% (64 mmol/mol Hgb) is reasonable for certain patients according to age, history of hypoglycemia, the presence of microvascular or macrovascular complications, or presence of coexisting medical conditions.

• Class IIb

1. Initiation of pharmacotherapy interventions to achieve target A1c might be reasonable.

6. Influenza Vaccination

• Class I

• Annual influenza vaccinations are

recommended for patients with SIHD.

7. Physical Activity

• Class I

1. For all patients, the clinician should encourage 30-60 minutes of moderate-intensity aerobic activity, such as brisk walking, at least 5 days and preferably 7 days per week, supplemented by an increase in daily lifestyle activities (eg, walking breaks at work, gardening, household work) to improve cardiorespiratory fitness and move patients out of the least-fit, least-active, high-risk cohort (bottom 20%).

2. For all patients, risk assessment with a physical activity history and/or an exercise test is recommended to guide prognosis and prescription.

3. Medically supervised programs (cardiac rehabilitation) and physician-directed, home-based programs are recommended for at-risk patients at first diagnosis.

• Class IIa

1. It is reasonable for the clinician to recommend complementary resistance training at least 2 days per week.

8. Weight Management

• Class I

1. BMI and/or waist circumference should be assessed at every visit, and the clinician should consistently encourage weight maintenance or reduction through an appropriate balance of lifestyle, physical activity, structured exercise, caloric intake, and formal behavioral programs when indicated to maintain or achieve a BMI between 18.5 and 24.9 kg/m2 and a waist circumference less than 102 cm (40 in.) in men and less than 88 cm (35 in.) in women (less for certain racial groups).

2. The initial goal of weight loss therapy should be to reduce body weight by approximately 5%-10% from baseline. With success, further weight loss can be attempted if indicated.

9. Smoking Cessation Counselling

• Class I

1. Smoking cessation and avoidance of exposure to environmental tobacco smoke at work and home should be encouraged for all patients with SIHD.

• Follow-up, referral to special programs, and pharmacotherapy are recommended along with a systematic strategy for smoking cessation.

10. Management of Psychological

Factors

• Class IIa

1. It is reasonable to consider screening of SIHD patients for depression and to refer or treat when indicated.

• Class IIb

1. Treatment of depression has not been shown to improve cardiovascular disease outcomes but might be reasonable for its other clinical benefits.

11. Alcohol Consumption

• Class IIb

1. In patients with SIHD who use alcohol, it might be reasonable for

• Non-pregnant women to have one drink (4 ounces [~120 mL] of wine, 12 ounces [355 mL] of beer, or 1 ounce [30 mL] of spirits) a day

• Men to have one or two drinks per day,

• Unless alcohol is contraindicated (such as in patients with a history of alcohol abuse or dependence or with liver disease).

12. Avoiding Exposure to Air

Pollution

• Class IIa

1. It is reasonable for patients with SIHD to

avoid exposure to increased air pollution to

reduce the risk of cardiovascular events.

ACC/AHA Class of Recommendations

for Pharmacotherapy to Relieve

Symptoms

Class I

1. β-blockers should be prescribed as initial therapy for relief of symptoms in patients with SIHD (LOE B).

2. Calcium channel blockers or long-acting nitrates should be prescribed for relief of symptoms when β-blockers are contraindicated or cause unacceptable side effects in patients with SIHD (LOE B).

3. Calcium channel blockers or long-acting nitrates, in combination with β-blockers, should be prescribed for relief of symptoms when initial treatment with β-blockers is unsuccessful in patients with SIHD (LOE B).

4. Sublingual nitroglycerin or nitroglycerin spray is recommended for immediate relief of angina in patients with SIHD (LOE B).

Class IIa

1. Treatment with a long-acting nondihydropyridine calcium channel blocker (verapamil or diltiazem) instead of a β-blocker as initial therapy for relief of symptoms is reasonable in patients with SIHD (LOE B).

2. Ranolazine can be useful when prescribed as a substitute for β-blockers for the relief of symptoms in patients with SIHD if initial treatment with β-blockers leads to unacceptable side effects or is ineffective or if initial treatment with β-blockers is contraindicated (LOE B).

3. Ranolazine in combination with β-blockers can be useful when prescribed for relief of symptoms when initial treatment with β-blockers is not successful in patients with SIHD (LOE A).

β-Adrenergic Blockers • 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.

• After MI or acute coronary syndrome, β-blocker therapy should be started and continued for 3 years in patients with normal LV function.

• Only the β-blockers carvedilol, metoprolol succinate, and bisoprolol should be used in patients with LV systolic dysfunction (ejection fraction 40% or less) and heart failure or MI; they should be employed for these IHD patients unless contraindicated.

• 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 chronic obstructive pulmonary disease, peripheral arterial disease (PAD), diabetes, dyslipidemia, and sexual dysfunction. Drugs with combined α1- and β-blockade are effective for IHD, but agents with intrinsic sympathomimetic activity provide little to no reduction in resting HR and are not preferred except perhaps in patients with PAD or dyslipidemia.

• Common adverse effects include bradycardia, hypotension, heart block, impaired glucose metabolism, altered serum lipids (transiently increased triglycerides, decreased HDL-C, and no change in LDL-C), fatigue, depression, insomnia, and malaise.

• β-Blockers are contraindicated in patients with existing bradycardia, hypotension, 2nd- or 3rd-degree atrioventricular (AV) block, asthma, severe PAD, LV dysfunction with unstable fluid status, and diabetes associated with frequent episodes of hypoglycemia.

• If β-blocker therapy needs to be discontinued, doses should be tapered over 2 to 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.

β-Adrenergic Blockers

β-Adrenergic Blockers

Calcium Channel Blockers

• All CCBs reduce MVo2 due to reduced wall tension secondary to decreased arterial pressure and (to a minor extent) depressed contractility.

• Dihydropyridine CCBs primarily affect vascular smooth muscle. Short-acting agents should not be used because of reflex tachycardia. Other side effects of these CCBs include hypotension, headache, gingival hyperplasia, and peripheral edema

• Nondihydropyridine CCBs mostly affect the myocardium. 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

Calcium Channel Blockers

Nitrates

• 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 to 5 minutes prior to activities known to produce angina; protection can last for up to 30 minutes with SL NTG and up to 1 hour with SL isosorbide dinitrate (ISDN).

• Long-acting nitrates (or CCBs) should be prescribed for relief of symptoms 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.

• ISDN is also effective, but the three times daily regimen requires dosing every 4 to 5 hours during the day to provide a nitrate-free interval.

• Chronic nitrate use should incorporate a 10- to 14-hour nitrate-free interval

each day to reduce nitrate tolerance.

• Because this approach places the patient at risk for angina episodes, the

nitrate-free interval is usually provided during the nighttime hours when

the patient has a reduced MVo2 while sleeping.

• The extended-release ISMN products that are dosed twice daily should be

given 7 hours apart (eg, 7:00 am and 2:00 pm).

• An extended-release, once-daily ISMN product is available that provides

12 hours of nitrate exposure followed by a 12-hour nitrate-free interval.

• Transdermal NTG patches are typically prescribed as ―on in the a.m. and

off in the p.m.‖ but patients should be given specific application and

removal times.

Nitrates

• Nitrates should not be used routinely as monotherapy for stable IHD because of the lack of angina coverage during the nitrate-free interval, lack of protection against circadian rhythm (nocturnal) ischemic events, and potential for reflex tachycardia.

• Concomitant β-blocker or diltiazem therapy can prevent rebound ischemia during the nitrate-free interval.

• Common nitrate side effects include headache, flushing, nausea, postural hypotension, and syncope.

• Headache can be treated with acetaminophen and usually resolves after about two 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.

Nitrates

How to use the patches

• Patches can be placed on the chest, shoulder, upper arm or back. Do not place patches on forearm or lower leg.

• Put patch on a different area of skin each day. If patientt uses the same area too much they may get a rash.

• Patches should not be placed on broken skin such as cuts or grazes.

• Advice patients to place the patch on a hairless area of skin. If the area of skin is hairy, advice to clip or shave the hair off.

• The skin should be clean and dry before sticking the patch on. This will make the patch stick properly.

• Patients should not use dusting powder or any greasy substances, eg. ointments or creams, on the skin before applying the patch.

While Patient is using patches • Patches may lower patient’s BP and make them feel dizzy, particularly

when changing position suddenly.

• Advice patient to be especially careful when driving or operating machinery.

• Patients can bathe, shower and swim as normal when wearing a patch.

• If a patch does not stick or falls off, advice patient to use a new patch on a different area of skin and not to re-use a patch once it has been removed from the skin.

• If patient forgot to use the patch;

1. Advice to apply the patch as soon as they remember. However, if it is almost time for their next patch, skip the missed patch. Apply the next patch at the normal time.

2. Never apply extra patches to make up for the missed patch.

Nitrates

Appropriate Use of Sublingual Nitroglycerin

Ranolazine • 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 (Ranexa) 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.

• Because it does not substantially affect HR and BP, it is recommended as add-on therapy 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.

• The initial ranolazine dose is 500 mg twice daily, increased to 1000 mg twice daily within the next 1 to 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.

• Drug-drug interaction:

1. Potent inhibitors of CYP3A4 and P-glycoprotein (ketoconazole, itraconazole, protease inhibitors, clarithromycin, and nefazodone) are contraindicated due to significant increases in ranolazine drug concentrations

2. Potent inducers of CYP3A4 and P-glycoprotein (phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, rifapentine, St. John’s wort) are contraindicated with ranolazine due to significant decreases in ranolazine drug concentrations

3. Moderate CYP3A4 inhibitors (eg, diltiazem, verapamil, erythromycin, and fluconazole) can be used with ranolazine, but the maximum dose should not exceed 500 mg twice daily.

Ranolazine

TREATMENT OF VARIABLE THRESHOLD

ANGINA AND PRINZMETAL ANGINA

• 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. CCBs may be preferred because they are dosed less frequently. Nifedipine, verapamil, and diltiazem are equally effective as single agents for initial management of vasospasm; dose titration is important to maximize the response. Patients unresponsive to CCBs alone may have nitrates added.

• β-blockers are not appropriate therapy for vasospasm because they may induce coronary vasoconstriction and prolong ischemia.

Nonpharmacologic Therapy

(Revascularization)

Nonpharmacologic Therapy

• Surgical revascularization plays an important role in the treatment of SIHD.

• The most common revascularization procedures are

1. Coronary artery bypass grafting (CABG) surgery

2. Percutaneous coronary intervention (PCI) ;

a) Percutaneous transluminal coronary angioplasty (PTCA)

b) Rotational atherectomy

c) Without stent placement

d) With stent placement (90% of cases)

i. Drug eluting stent (DES 82% of cases)

ii. Bare metal stent (BMS).

• PCI vs. CABG

• Decision multifactorial – risk factors, LVF, number of diseased vessels and % of occlusions

• While both of these procedures are highly effective and have advantages in certain groups of patients over pharmacologic approaches, both have limitations.

Revascularization to Improve Survival

Left Main CAD Revascularization

Class I

1.CABG to improve survival is recommended for patients with significant (≥50% diameter stenosis) left

main coronary artery stenosis. (LOE B)

Non-Left Main CAD Revascularization

Class I

1.CABG to improve survival is beneficial in patients with significant (≥70% diameter) stenosis in three

major coronary arteries with or without involvement of the proximal LAD artery or in the proximal LAD

artery plus one other major coronary artery. (LOE B)

2.CABG or PCI to improve survival is beneficial in survivors of sudden cardiac death with presumed

ischemia-mediated ventricular tachycardia caused by significant (≥70% diameter) stenosis in a major

coronary artery. (LOE C)

3.CABG is recommended in preference to PCI to improve survival in patients with multivessel CAD and

diabetes mellitus, particularly if a LIMA graft can be anastomosed to the LAD artery. (LOE B)

Revascularization to Improve Symptoms

Class I

1.CABG or PCI to improve symptoms is beneficial in patients with one or more significant (≥70%

diameter) coronary artery stenosis amenable to revascularization and unacceptable angina despite GDMT.

(LOE A)

Revascularization: ACC/AHA Class I

Recommendations

• All patients without a contraindication should receive aspirin before PCI and thereafter continued for life.

• Patients already on chronic aspirin therapy should take an additional 75 to 325 mg before PCI.

• Aspirin-naive patients should be given a dose of 325 mg at least 2 hours but preferably 24 hours before PCI.

• Chronic treatment with aspirin 81 mg daily is recommended after PCI.

• Patients receiving a stent should also receive a P2Y12 inhibitor (eg, clopidogrel) before PCI.

Pharmacotherapy with PCI

• After elective PCI, DAPT should be continued to reduce the risk of

stent thrombosis

• Patients who receive a BMS, a minimum of one month of DAPT is

sufficient. In patients at high risk of bleeding, a minimum of 2 weeks

can be given

• Patients receiving a DES should receive at least 6 months of DAPT.

In patients with high risk of bleeding or develop significant bleeding

to stop the P2Y12 inhibitor after only 3 months of therapy

• The guidelines state that a longer treatment regimen for both BMS

and DES can be considered in patients who have tolerated therapy,

are not at high risk of bleeding, nor have experienced any bleeding

complications

Pharmacotherapy with PCI

Pharmacotherapy with CABG

• Patients should receive aspirin 100-325 mg daily preoperatively to reduce the risk of graft closure.

• To reduce the risk of CABG-related major bleeding, P2Y12 inhibitors should be discontinued well in advance of an elective CABG surgery (5 days for clopidogrel and ticagrelor; 7 days for prasugrel) and at least 24 hours prior to urgent CABG surgery, if possible.

• Unless contraindicated, β-blockers should be initiated at least 24 hours prior to CABG surgery to reduce the risk of postoperative atrial fibrillation.

• Pharmacotherapy after CABG surgery includes

1. Aspirin; 100 to 325 mg daily should be resumed or initiated within 6 hours of CABG surgery and continued indefinitely, clopidogrel is alternative in case of aspirin allergy

2. Lipid-lowering therapy; High intensity statin,

3. β-blockers; should be initiated after CABG surgery and continued after discharge

4. ACE inhibitors;

a) Patients taking ACE inhibitors or ARBs prior to CABG surgery, these therapies should be resumed following surgery once patients have demonstrated stable hemodynamics and renal function.

b) ACE inhibitor-naïve patients, initiation of an ACE inhibitor should be considered in stable patients with compelling indications (eg, HFrEF, HTN, DM, chronic kidney disease).

5. For symptomatic relief of chest pain episodes, patients need access to SL NTG after surgery.

EVALUATION OF THERAPEUTIC

OUTCOMES • Monitoring for improvements in symptoms related to angina should include

1. Asking the patients about the number of angina episodes and weekly SL NTG

2. Inquiring about exercise capacity or duration of exertion needed to induce angina.

3. Ask the patient about their ability to engage in activities they want to do.

• It is not uncommon for patients to report reduced or no episodes of angina because they have stopped engaging in activities that bring on angina.

• Once patients have received optimal medical therapy, symptoms should improve in 2 to 4 weeks and remain stable until the disease progresses.

• Instruments such as the Seattle Angina Questionnaire and CCS Angina Grading Scale can be used to improve the assessment of symptoms.

• While objective tests such as an exercise tolerance test with or without cardiac imaging can be obtained to assess the adequacy of treatment, they are primarily performed in patients who do not achieve adequate symptom control.

• Following a revascularization procedure, the patients’ symptoms should be assessed every 6 to 12 months.

Thank you