Ischemic Heart Disease PDF - Al-Zaytoonah University of Jordan

Cardiovascular Diseases Dr. Alaa Hammad Dr. Ameerah Ibrahim Al-Zaytoonah University of Jordan 2 CONTENTS Introduction Pathophysiology Major Risk Factors Sign and symptoms Treatment Ischemic Heart Diseases (IHDs) Coronary Artery Diseases (CADs) Coronary heart Diseases (CHD) ▪ They are a group...

Cardiovascular Diseases Dr. Alaa Hammad Dr. Ameerah Ibrahim Al-Zaytoonah University of Jordan 2 CONTENTS Introduction Pathophysiology Major Risk Factors Sign and symptoms Treatment Ischemic Heart Diseases (IHDs) Coronary Artery Diseases (CADs) Coronary heart Diseases (CHD) ▪ They are a group of diseases characterized by shortage of blood (oxygen) supply to the heart muscle. ▪ The main cause of this shortage is complete or partial obstruction to the blood flow in one or more of the coronary arteries or their branches. They may be clinically presented as: • Myocardial infarction (complete deprivation of blood supply to part of the myocardium) • Angina pectoris (partial and transient deprivation of blood supply to part of the myocardium) • Ischemic arrhythmias • Silent ischemia Determinants of myocardial oxygen supply & demand Angina pectoris ▪ Angina of exercise (exertional angina, stable angina): The patient gets the anginal pain attack after exercise or emotion. The stress threshold that induces the attack is constant. ▪ Unstable angina (preinfarction angina): It is referred to angina of recent onset (within 2 months) or begins to intensify within the previous 2 months (starts to occur at rest or with lower exercise threshold). Thrombosis may be added to atherosclerosis as the mechanism of pathogenesis. This condition may proceed to infarction. ▪ Variant angina (Prinzmetal's angina): It is characterized by rest pain. Coronary vasospasm contributes largely to the pathogenesis. Acute Coronary syndrome • ACSs are ischemic heart diseases result primarily from diminished myocardial blood flow secondary to an occlusive or partially occlusive coronary artery thrombus • ACSs are classified according to electrocardiographic (ECG) changes into: • ST-segment-elevation ACS (STE ACS or STEMI) and • non–ST-segment-elevation ACS (NSTE ACS), which includes: • non–ST-segment elevation myocardial infarction (NSTE MI) and • unstable angina (UA). Pathophysiology • The most common cause of CAD is atherosclerosis. • Atherosclerosise is a slowly progressive disease of large to medium-sized muscular arteries (the coronary arteries are commonly involved) • Atherosclerosis starts by a lesion called fatty streaks (collection of lipid-laden macrophages and smooth muscles), then develops into intimal atheromatous plaques (superficial fibrous capsule, cellular zone and necrotic center with lipid). The plaque may be complicated by calcification, fissuring, rupture and ulceration. • Fissuring, rupture and ulceration predispose to thrombosis that completes the obstruction of the artery and trigger ACS (unstable angina or myocardial infarction). • MI first 6-12 hours changes starts by pale, then cyanotic then well-defined, yellow and soften infracted area. In survived patient, fibrous tissue replaces the infracted area in 6 weeks. Atherosclerosis progression Pathophysiology ❑ Panel A depicts the cross-section of a normal coronary artery. ❑ Panel B depicts the cross-section of a coronary artery with a stable atherosclerotic plaque. ❑ Note that the lipid core is relatively small in size and the fibrous cap is made up of several layers of smooth muscle cells. Platelet adhesion in response to the fissured plaque Meshlike occlusion in the coronary lumen Unstable atherosclerotic plaque Occlusive thrombus Complications of myocardial infarction • Arrhythmia • CHF • Cardiogenic shock • Pericarditis • Mural thrombosis • Ventricular rupture • Ventricular aneurysm Major risk factors of IHDs • Age • Male gender • Family history • Hypertension • Diabetes mellitus • Cigarette smoking • Hyperlipidemia • Low physical activity Diagnostic tests • A 12-lead ECG recorded during rest is often normal in patients with chronic stable angina in the absence of active ischemia. – should be done within 10 minutes of presentation to the emergency department in patients with symptoms of ischemia. • Cardiac stress test – Physical exercise (treadmill), – Pharmacologic stress :Dobutamine is commonly used with stress echocardiography, whereas adenosine or dipyridamole are used for nuclear imaging studies • 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). • Pharmacologic stress test: Dobutamine (beta1 agonist) is a pharmacologic stressor used in patients who are unable to exercise and is commonly used with echocardiography→ to identify stress- induced wall motion abnormalities indicative of coronary disease. Diagnostic tests (cont’d) • 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: – stress testing results are abnormal – or symptoms of angina are poorly controlled. – 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 • Cardiac catheterization and coronary angiography used in patients with suspected CAD to document the presence and severity of disease as well as for prognostic purposes. • Interventional catheterization used for thrombolytic therapy in patients with acute MI and for managing patients with significant CAD to relieve obstruction through percutaneous transluminal coronary angioplasty (PTCA), atherectomy, laser treatment, or stent placement. Cardiac Catheterization Cardiac catheterization is used to study the various functions of the heart. Using different techniques, the coronary arteries can be viewed by injecting dye or opened using balloon angioplasty. The oxygen concentration can be measured across the valves and walls (septa) of the heart and pressures within each chamber of the heart and across the valves can be measured. The technique can even be performed in small, newborn infants. Coronary Angiography A.Coronary arteriogram. Images were obtained from the left lateral projection with contrast injection into the left main coronary artery. The left anterior descending (L), left circumflex (CX), and first obtuse marginal (O) branches are visualized. Severe stenosis is seen in the midportion of the left anterior descending artery (arrow ) in this patient, who had unstable angina pectoris. B.Coronary arteriogram, same projection and patient as in A, obtained 1 day later. The stenosis in the left anterior descending coronary artery (arrow) has been reduced after percutaneous balloon angioplasty. Clinical picture and diagnosis of an attack of IHDs 1. Symptoms and signs 2. ECG changes 3. Myocardial injury enzyme markers Signs and symptoms • Retrosternal pain may radiate to the left shoulder, left arm, back, neck, epigastrium. This may be the only symptom in angina pectoris. • Other symptoms that may be associated with ACS are tachycardia or bradycardia, low grade fever, rapid respiration, hypotension. • Prodromal symptoms preceding the retrosternal pain consisting of chest vague discomfort, fatigue, nausea, vomiting, and sweating. • Syncope may herald the onset of acute myocardial infarction • Silent myocardial infarction may occur and more common in: ❖ 1. Women with preexisting hypertension ❖ 2. Diabetic patients ❖ 3. Elderly ECG changes • In addition to the patient’s history and presentation, the diagnosis of ACS is based on the electrocardiogram (ECG) and laboratory results from a cardiac injury profile. • A 12-lead ECG should be obtained within 10 minutes of presenting to the emergency department (ED). The ECG is an indispensable tool in the diagnosis of ACS and has become the key point in the decision pathway. Key findings on ECG consist of ST segment elevation, ST segment depression, or T-wave inversion. – By definition, STEMI consists of ST segment elevation in two or more contiguous leads and either exceeding 0.2 mV (2 mm) in leads V1, V2, and V3 or 0.1 mV (1 mm) or greater in other leads. – NSTE-ACS consists of ST segment depression exceeding 0.1 mV (1 mm) in two or more contiguous leads or T-wave inversions exceeding 0.1 mV (1 mm). Myocardial injury enzyme markers • a. Creatinine kinase-MB mass detected in 3-6 hrs • b. maximal in 10-24 hours and return normal in 3-4 days. • c. Troponin I detected in 4-6 hours, maximal in 24 hours, and return to normal in 3-10 days • Measurements taken over the 1st 12 to 24 hrs • Troponin is the preferred biomarker for assessment of myocardial damage owing to its high cardiac specificity and sensitivity (90.7% and 90.2%, respectively) as well as the development of newer sensitive troponin assays. • MI diagnosis: • one troponin value greater than MI decision limit set by lab • or • 2 CK MB values greater than MI decision limit set by lab Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* (Updated August 2015) TABLE 1 Applying Class of Recommendation and Level of Evidence to Clinical Strategies, Interventions, Treatments, or Diagnostic Testing in Patient Care* (Updated August 2015) Treatment of ACS’sDesired outcomes • Short-term desired outcomes in a patient with ACS are: 1. Early restoration of blood flow to the infarct-related artery to prevent infarct expansion (in the case of MI) or prevent complete occlusion and MI (in unstable angina) 2. Prevention of death and other complications 3. Prevention of coronary artery reocclusion 4. Relief of ischemic chest discomfort 5. Resolution of ST-segment and T-wave changes on ECG • Long-term desired outcomes are: 1. control of risk factors, 2. prevention of additional cardiovascular events, including reinfarction, stroke, and HF. 3. improvement in quality of life. 32 Non-pharmacological treatment: Treatment of ACS-initial interventions • Admission to the intensive care unit with close monitoring of the patient, heart and blood pressure. • Complete rest • Oxygen therapy Pharmacologic treatment: Treatment of ACS-initial interventions • Immediately upon presentation, one SL NTG tablet should be administered every 5 minutes for up to three doses to relieve chest pain and myocardial ischemia. • Intravenous NTG should be initiated in all patients with an ACS who do not have a contraindication and who have persistent ischemic symptoms, heart failure, or uncontrolled high BP. (No use PDEI) • The usual dose is 5 to 10 mcg/min by continuous infusion, titrated up to 200 mcg/min until relief of symptoms or limiting side effects (e.g., headache or hypotension). Treatment should be continued for approximately 24 hours after ischemia is relieved. • Aspirin: 162-325 mg • Opioid analgesic (2-4 mg by IV push q 5-15 minutes up to 10 mg of morphine i.v.) with anti-emetic e.g. prochlorperazine or cyclizine Treatment of ACS-initial interventions • Start 80 mg of atorvastatin as early as possible, and preferably before PCI, in patients not on statin. • Give beta blocker (eg, metoprolol 25 mg orally) IF no signs of heart failure (or high risk for heart failure), hemodynamic compromise, bradycardia, or severe reactive airway disease. If hypertensive, may initiate beta blocker IV instead (eg, metoprolol 5 mg intravenous every 5 minutes times three doses as tolerated). Acute Management STEMI 1 Select reperfusion strategy (PCI vs. fibrinolytics) 2 Give antiplatelet therapy +ASA 3 Give anticoagulant therapy to all patients • Reperfusion therapy is indicated in patients with STE ACS presenting within 12 hours of the onset of chest discomfort who have at least 1 mm of STE in two or more contiguous ECG leads or a new left bundle-branch block. Reperfusion Therapy • It should also be considered in patients with those findings and persistent symptoms of ischemia who present within 12 to 24 hours of symptom onset. • Fibrinolysis is preferred over primary PCI in patients presenting within 3 hours of symptom onset (delay, if PCI is not available). • Primary PCI is preferred over fibrinolysis in patients with contraindication for fibrinolytic agents Initial pharmacotherapy for ST-segment elevation myocardial infarction • aOptions after coronary angiography also include medical management alone or CABG surgery. • bClopidogrel preferred P2Y12 when fibrinolytic therapy is utilized. No loading dose recommended if age older than 75 years. • cGiven for up to 48 hours or until revascularization. • dGiven for the duration of hospitalization, up to 8 days or until revascularization. • eIf pretreated with UFH, stop UFH infusion for 30 minutes prior to administration of bivalirudin (bolus plus infusion). • fIn patients with STEMI receiving a fibrinolytic or who do not receive reperfusion therapy, administer clopidogrel for at least 14 days and ideally up to 1 year. (ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; ASA, aspirin; CI, contraindication; FMC, first medical contact; GPI, glycoprotein IIb/IIIa inhibitor; IV, intravenous; MI, myocardial infarction; NTG, nitroglycerin; PCI, percutaneous coronary intervention; SC, subcutaneous; SL, sublingual; UFH, unfractionated heparin.) STEMI-PCI *The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily. 2013 ACCF/AHA STEACS Circulation. 2013;127:529-555 Antiplatelet therapy Aspirin • All patients suspecting of having acute myocardial infarction should receive low dose aspirin (162 mg) irrespective of thrombolytic therapy and to be continued indefinitely. • For patients undergoing PCI and receiving stents, the recommended dose is 325 once daily for at least 30 days with bare metal stents, for 3 months with a sirolimus-eluting stent, and for 6 months with a paclitaxel-eluting stent, followed by 75 to 162 mg once daily thereafter (81 preferred) 2013 ACCF/AHA STEACS Circulation. 2013;127:529-555 Uptodate 10/2013 Antiplatelet therapy P2Y12 inhibitors • Clopidogrel is recommended for patients with an aspirin allergy. • A 300- to 600-mg on the first hospital day, followed by a maintenance dose of 75 mg/d indefinitely. • For patients treated with fibrinolytics and in those receiving no revascularization therapy, clopidogrel either 75 or 300 mg on day 1 followed by 75 mg/d for at least 14-28 days with aspirin. • For patients undergoing primary PCI, clopidogrel is given as a loading dose followed by a 75 mg/d, in combination with aspirin 325 mg once daily, to prevent subacute stent thrombosis and long-term cardiovascular events. Dual antiplatelet therapy is recommended for at least 1 month after placement of a bare-metal stent and for at least 1 year (or possibly indefinitely) after placement of a drug-eluting stent. • Abciximab is a first-line GP IIb/IIIa inhibitor for patients undergoing primary PCI who have not received fibrinolytics. It should not be administered to STE ACS patients who will not be undergoing PCI. †Balloon angioplasty without stent placement may be used in selected patients. It might be reasonable to provide P2Y12 inhibitor therapy to patients with STEMI undergoing balloon angioplasty alone according to the recommendations listed for BMS. (LOE: C) 2013 ACCF/AHA STEACS Circulation. 2013;127:529-555 Treatment Algorithm for Duration of P2Y12 Inhibitor Therapy in Patient With Recent ACS (NSTE-ACS or STEMI) 2013 ACCF/AHA STEACS Circulation. 2013;127:529-555 Anticoagulant treatment • UFH is a first-line anticoagulant for STE ACS, both for medical therapy and PCI. • UFH should be initiated in the emergency department and continued for at least 48 hours in patients who will receive chronic warfarin after acute MI. • If a patient undergoes PCI, UFH is discontinued immediately after the procedure. • Warfarin is used for • Secondary prevention when aspirin is contraindicated • Patient has chronic atrial fibrillation • Patient with left ventricular thrombus • Extensive wall motion abnormalities and impaired ejection 2013 ACCF/AHA STEACS Circulation. 2013;127:529-555 Beta blockers • Beta-blockers intravenously (in conjunction with thrombolytic treatment) followed by oral administration are beneficial as they • Has anti-arrhythmic effect • Improve subendocardial perfusion • Redistribution of coronary blood flow • Reduce the infarct size • Decrease mortality • Reduce re-infarction • Decrease intracranial bleeding due to thrombolytic therapy • In patient with contraindication for beta-blockers, low dose esmolol intravenously may be used. • Verapamil and diltiazem (CCB) may be used when beta-blockers can not be used. They may reduce the size of the infarct. Angiotensin Converting enzyme Inhibitors • ACE inhibitors should be initiated in all patients after MI to reduce mortality, decrease reinfarction, and prevent the development of heart failure. • Data suggest that most patients with CAD (not just those with ACS or heart failure) benefit from an ACE inhibitor. • The dose should be low initially and titrated to the dose used in clinical trials if tolerated. • ARBs are substitute to ACEIs (due to intolerance, cough, or angioedema) Aldosterone Antagonists • Either eplerenone or spironolactone should be considered within the first 2 weeks after MI to reduce mortality in all patients already receiving an ACE inhibitor who have LVEF ≤40% and either heart failure symptoms or a diagnosis of diabetes mellitus. • The drugs are continued indefinitely. • Example oral doses include the following: • Eplerenone: 25 mg initially; target dose 50 mg once daily. • Spironolactone: 12.5 mg initially; target dose 25 to 50 mg once daily. Magnesium and potassium • Magnesium and potassium are reserved to patients with hypomagnesemia or hypokalemia • Antiarrhythmics are associated with increased mortality and arrhythmias and are only recommended in preexisting arrhythmia. • Benzodiazepine • Stool softener Anti-hyperlipidemics • All patients with CAD should receive dietary counseling and pharmacotherapy in order to reach a low-density lipoprotein (LDL) cholesterol concentration <100 mg/dL. Newer recommendations from the National Cholesterol Education Program give an optional LDL goal of <70 mg/dL in selected patients.—New recommendations • Statins are the preferred agents for lowering LDL cholesterol and should be prescribed at or near discharge in most patients. • A fibrate derivative or niacin should be considered in selected patients with a low high-density lipoprotein (HDL) cholesterol (<40 mg/dL) and/ or a high triglyceride level (>200 mg/dL). STEMI-fibrinolytics Self-reading Uptodate® 10/2013 Self-reading Contraindications of fibrinolytic drugs • Absolute contraindications • (1) active internal bleeding; • (2) previous ICH at any time; • (3) ischemic stroke within 3 months; • (4) known intracranial neoplasm; • (5) known structural vascular lesion; • (6) suspected aortic dissection; and • (7) significant closed head or facial trauma within 3 months • Relative contraindications • (1) severe, uncontrolled hypertension (> 180/110 mm Hg); • (2) history of prior ischemic stroke longer than 3 months prior, dementia, or known intracranial tumor • (3) current anticoagulant use; • (4) known bleeding diathesis; • (5) traumatic or prolonged CPR or major surgery within 3 weeks; • (6) noncompressible vascular puncture; • (7) recent (within 2 to 4 weeks) internal bleeding; • (8) pregnancy; • (9) active peptic ulcer; • (10) history of severe, chronic poorly controlled hypertension; and • (11) for streptokinase, prior administration (>5 days) or prior allergic reactions. Coronary artery bypass graft (CABG) • Infrequently performed in patients with STEMI. • The main indications – Emergent or urgent CABG related to • Failure of fibrinolysis or PCI, or • hemodynamically important mechanical complications (ACE, angiotensin-converting enzyme; ACS, acute coronary syndrome; ARB, angiotensin receptor blocker; CABG, coronary artery bypass graft surgery; IV, intravenous; NTG, nitroglycerin; PCI, percutaneous coronary intervention; SC, subcutaneous; SL, sublingual; UFH, unfractionated heparin.) aAlthough recommended by the 2004 American College of Cardiology and American Heart Association practice guidelines, no dose recommendation is given. 64 bSee Table 18–4 for dosing and specific types of patients who should not receive enoxaparin or IV NTG.) NSTEMI Early Pharmacotherapy for NSTE ACS • In general, early pharmacotherapy for NSTE ACS is similar to that for STE ACS with three exceptions: 1.Fibrinolytic therapy is not administered. 2.GP IIb/IIIa receptor blockers are administered to high-risk patients. NON–ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROME • According to ACC/AHA practice guidelines, early pharmacotherapy should include: • Intranasal oxygen (if oxygen saturation is <90%); • SL NTG (IV therapy for selected patients); • Aspirin • An oral β-blocker (IV therapy optional); and • An anticoagulant (UFH, LMWH [enoxaparin], fondaparinux, or bivalirudin). • Morphine is also administered to patients with refractory angina, as described previously. These agents should be administered early, while the patient is still in the emergency department. Risk Stratification • NST ACS patients stratified based on clinical presentation, lab findings • Risk categories • high • medium • low • TIMI: Thrombolysis In Myocardial Infarction • Treatment based on TIMI score TIMI RISK SCORE for UA/NSTEMIA HISTORICAL • Age  65 •  3 CAD risk factors (FHx, HTN,  chol, DM, active smoker) • Known CAD (stenosis  50%) • ASA use in past 7 days PRESENTATION • Recent (24H) severe angina • Cardiac markers • ST deviation  0.5 mm Antman et al JAMA 2000; 284: 835 - 842 • 0-2 is low risk, 3-4 is intermediate risk, and 5-7 is high risk . 68 NSTEMI management • Patients with NSTE ACS who are considered to be at low risk (based on TIMI risk score) should have serial biochemical markers obtained. If they are negative, the patient may be admitted to a general medical floor with ECG telemetry monitoring, undergo a noninvasive stress test, or may be discharged. • Moderate-risk patients with negative biochemical markers may initially undergo a noninvasive stress test, with only those having a positive test proceeding to angiography. • Moderate-risk patients with positive biochemical markers typically also undergo angiography and revascularization, if indicated. • High-risk NSTE ACS patients should undergo early coronary angiography (within 24 to 48 hours) and revascularization if a significant coronary artery stenosis is found. Revascularization (PCI or CABG) • Factors that influence the choice of revascularization procedure include: • the extent and complexity of CAD; • short-term risk and long-term durability of PCI; • operative mortality (which can be estimated by the Society of Thoracic Surgeons “STS” score); • diabetes mellitus; • CKD; • completeness of revascularization; • LV systolic dysfunction; • previous CABG; and the ability of the patient to tolerate and comply with DAPT. • In general, the greater the extent and complexity of the multivessel disease, the more compelling the choice of CABG over multivessel PCI. 71 Initial pharmacotherapy for non–ST-segment elevation (NSTE) ACS aReasonable to choose ticagrelor over clopidogrel for maintenance P2Y12 for NSTE-ACS patients treated with an early invasive or ischemia-guided strategy. bReasonable to choose prasugrel over clopidogrel for maintenance P2Y12 for NSTE-ACS patients undergoing PCI who are not at high risk for bleeding. Do not use if prior history of stroke/transient ischemic attack (TIA), age older than 75 years, or body weight less than or equal to 60 kg (132 lb). cMay require IV supplemental dose of enoxaparin; dNot to be used as the sole anticoagulant during PCI. Give additional 85 units/kg IV without GPI and 60 Units/kg IV with GPI. eIf pretreated with UFH, stop UFH infusion for 30 minutes prior to administration of bivalirudin bolus plus infusion. (ACE, angiotensin-converting enzyme; ACS, acute coronary syndrome; ARB, angiotensin receptor blocker; ASA, aspirin; CABG, coronary artery bypass graft; CI, contraindication; DES, drug-eluting stent; GPI, glycoprotein IIb/IIIa inhibitor; IV, intravenous; NTG, nitroglycerin; PCI, percutaneous coronary intervention; SC, subcutaneous; SL, sublingual; UFH, unfractionated heparin). Algorithm for Management of Patients With Definite or Likely NSTE-ACS NSTE-ACS: Definite or Likely Ischemia-Guided Strategy Early Invasive Strategy Initiate DAPT and Anticoagulant Therapy 1. ASA (Class I; LOE: A) Initiate DAPT and Anticoagulant Therapy 1. ASA (Class I; LOE: A) 2. P2Y12 inhibitor (in addition to ASA) (Class I; LOE: B) : • Clopidogrel or • Ticagrelor 2. P2Y12 inhibitor (in addition to ASA) (Class I; LOE: B): • Clopidogrel or • Ticagrelor 3. Anticoagulant: • UFH (Class I; LOE: B) or • Enoxaparin (Class I; LOE: A) or • Fondaparinux (Class I; LOE: B) 3. Anticoagulant: • UFH (Class I; LOE: B) or • Enoxaparin (Class I; LOE: A) or • Fondaparinux† (Class I; LOE: B) or • Bivalirudin (Class I; LOE: B) Can consider GPI in addition to ASA and P2Y12 inhibitor in high-risk (e.g., troponin positive) pts (Class IIb; LOE: B) • Eptifibatide • Tirofiban Medical therapy chosen based on cath findings Therapy Effective Therapy Ineffective Therapy Effective Therapy Ineffective PCI With Stenting Initiate/continue antiplatelet and anticoagulant therapy 1. ASA (Class I; LOE: B) CABG Initiate/continue ASA therapy and discontinue P2Y12 and/or GPI therapy 1. ASA (Class I; LOE: B) 2. P2Y12 Inhibitor (in addition to ASA): • Clopidogrel (Class I; LOE: B) or • Prasugrel (Class I; LOE: B) or • Ticagrelor (Class I; LOE: B) 2. Discontinue clopidogrel/ticagrelor 5 d before, and prasugrel at least 7 d before elective CABG 3. GPI (if not treated with bivalirudin at time of PCI) • High-risk features, not adequately pretreated with clopidogrel (Class I; LOE: A) • High-risk features adequately pretreated with clopidogrel (Class IIa; LOE: B) 4. Anticoagulant: • Enoxaparin (Class I; LOE: A) or • Bivalirudin (Class I; LOE: B) or • Fondaparinux† as the sole anticoagulant (Class III: Harm; LOE: B) or • UFH (Class I; LOE: B) 3. Discontinue clopidogrel/ticagrelor up to 24 h before urgent CABG (Class I; LOE: B). May perform urgent CABG <5 d after clopidogrel/ticagrelor and <7 d after prasugrel discontinued 4. Discontinue eptifibatide/tirofiban at least 2-4 h before, and abciximab ≥12 h before CABG (Class I; LOE: B) Late Hospital/Posthospital Care 1. ASA indefinitely (Class I; LOE: A) 2. P2Y12 inhibitor (clopidogrel or ticagrelor), in addition to ASA, up to 12 mo if medically treated (Class I; LOE: B) 3. P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), in addition to ASA, at least 12 mo if treated with coronary stenting (Class I; LOE: B) †In patients who have been treated with fondaparinux (as upfront therapy) who are undergoing PCI, an additional anticoagulant with anti-IIa activity should be administered at the time of PCI because of the risk of catheter thrombosis. Factors Associated With Appropriate Selection of Early Invasive Strategy or Ischemia-Guided Strategy in Patients With NSTE-ACS Immediate invasive (within 2 h) Refractory angina Signs or symptoms of HF or new or worsening mitral regurgitation Hemodynamic instability Recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapy Sustained VT or VF IschemiaLow-risk score (e.g., TIMI [0 or 1], GRACE [<109]) guided Low-risk Tn-negative female patients strategy Patient or clinician preference in the absence of high-risk features Early None of the above, but GRACE risk score >140 invasive Temporal change in Tn (Section 3.4) (within 24 h) New or presumably new ST depression Delayed None of the above but diabetes mellitus invasive Renal insufficiency (GFR <60 mL/min/1.73 m²) (within Reduced LV systolic function (EF <0.40) 25−72 h) Early postinfarction angina PCI within 6 mo Prior CABG GRACE risk score 109–140; TIMI score ≥2 Angina Pectoris—Stable angina Factors determine O2 consumption • The goal in pharmacotherapy of angina pectoris is to restore the balance between oxygen supply and need. This can be achieved by pharmacologically manipulating the main determinant factors of myocardial oxygen consumption as follow - Preload :- The volume of blood returns to the heart is a determinant of stroke volume. - Any increase in stroke volume is accompanied by an increase in heart work and consequently oxygen consumption. Angina Pectoris - Afterload :- It is largely determined by peripheral resistance. The increase in the diastolic blood pressure carries a load on the heart, which necessitate more cardiac work and more oxygen demand. - Heart rate :- It is an important determinant of myocardial oxygen demand. Many antianginal drugs act by decreasing heart rate, while drugs that cause tachycardia may aggravate the condition or precipitate anginal attack. Treatment of angina pectoris Treatment strategies • Pharmacotherapy of angina pectoris aims at correcting the imbalance between the oxygen myocardial need and supply. This can be achieved by: oDecreasing the preload on the heart oDecreasing the afterload on the heart oReducing heart rate oIncreasing blood supply to the myocardium by dilating coronary arteries Treatment of angina pectoris • Pharmacotherapy usually is enough to alleviate the condition and return most of the patients to normal life. • However, some patients and physicians chose mechanical intervention to revascularize the ischemic myocardium by coronary artery bypass surgery or angioplasty. Treatment of angina pectoris General management 1. Halting provocative exercise 2. Reduction of risk factors such as hyperlipidemia, diabetes mellitus etc. 3. Aggravating factors should be treated. These conditions include aortic stenosis, sever anemia, thyrotoxicosis, hypertension, tachyarrhythmias, drugs (corticosteroids, NSAIDs, etc). 4. Ideal weight should be attained and maintained. 5. Cessation of smoking. 6. Estrogen replacement therapy in postmenopausal women showed to lower the risk of ischemic heart diseases. Treatment of angina pectoris Pharmacotherapy: • Three main groups of drugs are used singly or in combinations. These are • organic nitrates • beta-blockers • calcium antagonists. Treatment of angina pectoris Organic nitrates • Mechanism of action: They dilate veins and to a lesser extend arteries reducing preload and afterload and dilate the main coronary arteries. The most commonly used nitrates are nitroglycerin and isosorbide dinitrate in different pharmaceutical formulation. Treatment of angina pectoris Nitroglycerin Onset of action Duration of action Recommended dose Sublingual 1-3 min 30-60 min 0.3-0.9 mg during the attach Oral 40 min 3-6 hr 2.5-9 mg tid Transdermal 40-60 min 4-8 hr 2.5-15 mg/24hr Intravenous 1-2 min 3-5 min 5 µg/min Formulation Treatment of angina pectoris • Sublingual nitroglycerin is used during the attack or as a prophylaxis when the attack is expected. • During the attack, sublingual nitroglycerin halts symptoms within 3 minutes in 75% of patients. Another 15% become pain free in 5-15 minutes. • Nitroglycerin aerosol is an alternative to sublingual nitroglycerin. It is sprayed in the mouth to be absorbed from the oral cavity. • Transdermal nitroglycerin (ointment or skin patch) is used for chronic continuous treatment. It is contraindicated when worsening of ischemia occurs on withdrawal of the effect. Treatment of angina pectoris Isosorbide dinitrate Formulation Onset of action Duration of Usual recommende action d dose Oral 20-40 min 4-6 hr 20-60 mg/day Sublingual 2-5 min 1-2 hr 2.5-5 mg during the attack Treatment of angina pectoris • Oral isosorbide dinitrate is used for continuous chronic treatment. • Other available organic nitrates are erythritol tetranitrate, pentaerythritol tetranitrate, and isosorbide mononitrate. Treatment of angina pectoris Beta-adrenoceptor blocking drugs • They act by reducing myocardial contractility and slowing the heart rate. They produce objective and subjective improvements in 80% of patients with chronic exertional stable angina. • The main factors that affect the choice of beta-blockers are • Selectivity • Partial agonistic activity • Lipid solubility. • Selective β1-blockers act selectively on the heart and can be used (in low doses) when non-selective β-blockers are not recommended Treatment of angina pectoris • Partial agonists have minimal effect on heart rate. They have low efficacy, and usually not recommended in the treatment of angina pectoris. • Less lipid-soluble β-blockers penetrate poorly into the CNS. They have less central side effects. They have long action that can improve patient compliance. • The guideline for the safe and effective dose of β-blockers is heart rate. Resting heart rate should not be less than 50-60 per minute. The maximal heart rate during exercise is about 100 per minute or less. Beta blockers Drug Beta 1 selectivity Intrinsic activity More soluble in T½ Dose / day Recommended in Acebutolol + + Water 3-4h 400-1200 once or divided in 2 doses Hypertension Atenolol + - Water 6-9h 25-200mg Hypertension, angina Betaxolol + - Water 14-22h 10mg- Hypertension, glaucoma Beta blockers Drug Beta 1 selectivity Intrinsic activity More soluble in T½ Dose / day Recommended in Carteolol - + Water 6h 2.5mg Hypertension, glaucoma Esmolol + - Water 10min 500ug/kg/min for 1 min then 50200ug/kg/min Arrhythmia, hypertensive crisis, MI, unstable angina Labetalol - + Lipid 5h 1-2mg/min infusion (Maximal 2400mg). Bolus dose of 20 mg/10min (maximal 300mg). 2001200mg PO bid Hypertensive crisis, hypertension note: it has alpha1 blocking effect Beta blockers Drug Beta 1 selectivity Intrinsic activity More soluble in T½ Dose / day Recommended in Metoprolol + - Lipid 3-4h 25-100mg bid Hypertension, angina Nadolol - - Water 14-24h 20-240mg Hypertension, angina Oxprenolol - + Lipid 60-480mg in 3 divided doses Hypertension 1-2 h Beta blockers Drug Beta 1 selectivity Intrinsic activity More soluble in T½ Dose / day Recommended in Penbutolol - + Lipid 5h 20mg- hypertension Pindolol - + Lipid 3-4h 5-30mg bid hypertension Propranol ol - - Lipid 3.5-6h 40-480mg in 3 divided doses Hypertension, angina, arrhythmia Beta blockers Drug Beta 1 selectivity Intrinsic activity More soluble in T½ Dose / day Recommended in Sotalol - - Water 12h 80-320mg bid Arrhythmia Timolol - - Lipid 4-5h 10-30mg bid Hypertension, glaucoma Carvidolol - (α1 blocker) - Lipid 7-10h 6.5-50mg in 2 divided doses Hypertension, CHF Bisoprolol + - Moderate lipid solubility 9-12 h 5-10 mg Hypertension, CHF Treatment of angina pectoris Some of the commonly used β-blockers in angina pectoris include: - Propranolol is given in a dose of 40-480mg/day in 3 divided doses. It is nonselective, lipid soluble βblocker. - Atenolol is given in a dose of 25-200mg once a day. It is selective, water soluble β-blocker. Treatment of angina pectoris - Metoprolol is given in a dose of 50-200 mg/day in two divided doses. It is selective, and lipid soluble. Verapamil elevates the plasma level of metoprolol. - Nadolol is given in a dose of 20-60mg once a day. It is nonselective, and water soluble. - Discontinuation of β-blockers should be gradual. Abrupt discontinuation may lead to unstable angina, myocardial infarction or sudden death. Treatment of angina pectoris Calcium channel blocking drugs • They act by one or more of the following mechanisms. • They reduce myocardial contractility • Dilate the coronary arteries • Reduce afterload. Treatment of angina pectoris • They are alternative to β-blockers, especially in: • Coronary artery spasm • Myocardial insufficiency • Bronchospam. • Different calcium antagonists of different chemical groups have been recommended to be used in angina pectoris. Nifedipine and nicardipine of the dihydropyridine group, verapamil, diltiazem and bepridil. These drugs differ in the extent of their effect on the heart and blood vessels. These differences have been shown in the below table. Treatment of angina pectoris / Calcium channel blockers Drug Dose mg/day AV Vasodilatati conduction on Nifedipine 30-180 - + 0 or increase Nicardipine 20-60 - ++ Decrease Diltiazem 120-360 + Verapamil 120-480 ++ Bepridil 200-400 + Heart rate Decrease ++ Decrease Decrease Treatment of angina pectoris • Data in conduction and vasodilatation columns is comparative between these 2 characters. • Nifedipine for oral absorption is no longer used as has It has rapid onset of action (5-20 minutes) and It may produce reflex tachycardia due to vasodilatation and hypotension that may result in worsening of angina. • Nifedipine metabolism is polymorphic. • Nicardipine is similar to nifedipine but has no negative inotropic effect. Treatment of angina pectoris Treatment of stable angina • The initial treatment is by organic nitrates. • Sublingual nitroglycerin may be enough if the patient gets one attack every few days. • Chronic prophylactic nitrate treatment may be started if the attacks are more than once daily. Treatment of angina pectoris • Beta-blockers may be instituted. They may be advantageous in some patient by being: • Cardioprotective • Antiarrhythmic • Antihypertensive • Lack of tolerance. • Calcium channel blockers are as effective as β-blockers and can substitute them. (long-acting) • Combination of calcium channel blocker and β-blocker is possible. However, attention should be paid to the cardiac function. Treatment of angina pectoris Treatment of variant angina • For the acute attack sublingual nitroglycerin is used. • Long-acting organic nitrates decrease the frequency of the acute attacks. • Calcium channel blockers may be more effective and some consider them as the drugs of choice and nitrates may be added. • Combination of nifedipine-diltiazem or nifedipine-verapamil may be used if single drug is not effective. • Beta-blockers have no role in the treatment of variant angina.