How to manage patient with Non ST elevation Acute coronary syndrome

Transcription

1 How to manage patient with Non ST elevation Acute coronary syndrome Dr.M.Gholipour Assistant proffessor in interventional cardiology Faculty member of guilan university of medical sciences

2 Definitions schemic heart disease may be manifested clinically as either chronic stable angina or an acute coronary syndrome (ACS). Features that help differentiate ACS from stable angina are (1) onset of symptoms at rest (or with minimal exertion) and lasting longer than 10 minutes unless treated promptly (2) severe, oppressive pressure or chest discomfort (2) an accelerating pattern of symptoms that develop more frequently, occur with greater severity, or awaken the patient from sleep

3 Epidemiology n the United States, three recent trends have changed the frequency distribution of the types of ACS: (1) wider use of primary preventive therapies (aspirin, statins, smoking cessation) appears to have resulted in fewer cases of STEM (2) aging of the U.S. population, with higher rates of diabetes and chronic kidney disease (CKD), have increased the incidence of NSTE-ACS (3) the use of more sensitive assays for myocardial necrosis (i.e., cardiacspecific troponin [ctn]) has shifted the classification of NSTE- ACS away from UA toward NSTEM

4 PATHOPHYSOLOGY rupture of unstable atheromatous plaque imbalance between the supply and demand NSTE-ACS coronary arterial vasoconstriction gradual intraluminal narrowing of an epicardial coronary artery

5 Platlet adhesion,activation,aggergation

6 Platelet activation mechanisms and sites of blockade of antiplatelet therapies

7 CLNCAL ASSESSMENT History and Physical Examination NSTE-ACS resulting from atherosclerosis is relatively uncommon in 1) men younger than 40 years and 2) women younger than 50 years, but the incidence rises steadily thereafter The initial symptom is typically described as pressure, heaviness, or frank pain beneath the sternum is usually more intense and lasts longer (>20 minutes). Associated radiation to the ulnar aspect of the proximal part of the left arm, either shoulder, the neck, or the jaw may occur, but symptoms may be present anywhere between the ear and epigastrum

8 Laboratory

9 NSTE-ACS Definite or likely Short term risk management TM SCORE or GRASE SCORE

10 Short-Term Risk of Death or Nonfatal Myocardial schemia in Patients with Unstable Angina HGH RSK 1)Accelerating tempo of ischemic symptoms in preceding 48 hours 2)Prolonged ongoing (>20 min) pain at rest 3) Pulmonary edema, most likely caused by ischemia/new or worsening MR murmur/s 3 or new or worsening rales/hypotension, bradycardia, tachycardia/age >75 yr 4) Angina at rest with transient ST-segment changes > 0.05 mv/undle branch block, new or presumed new/sustained ventricular tachycardia 5) Elevated cardiac Tn, TnT, or CK-M NTERMEDATE RSK 1)Prior M, peripheral or cerebrovascular disease, or CAG; prior ASA use 2) Prolonged (>20 min) rest angina, now resolved, with intermediate or high likelihood of CAD/Rest angina (>20 min) or relieved with rest or sublingual nitroglycerin/nocturnal angina/new-onset or progressive CCS class or V angina in past 2 wk without prolonged (20 min) rest pain, but with intermediate or high likelihood of CAD 3) Age > 70 yr 4)T wave changes/pathologic Q waves or resting STsegment depression < 0.1 mv in multiple lead groups (anterior, inferior, lateral) 5) Slightly elevated cardiac Tn, TnT, or CK-M

11 TM Risk Score for NSTE-ACS The TM risk score is determined by the sum of the presence of 7 variables at admission; 1 point is given for each of the following variables: 65 y of age; 3 risk factors for CAD; prior coronary stenosis 50%; ST deviation on ECG; 2 anginal events in prior 24 h; use of aspirin in prior 7 d; and elevated cardiac biomarkers. TM Score All cause mortality,new or recurrent M,or severe recurrent ischemia,requiring urgent revascularization throgh 14d after randomization

12 GRACE (Global Registry of Acute Coronary Events) risk score was developed to predict death, and death/m, in a cohort of patients with NSTEM enrolled into a multinational observational registry. Nine factors based on the presenting clinical and biomarker characteristics of the patients were identified as independent predictors of death or a combined outcome of death and M both in-hospital and at 6 months: (1) age, (2) heart failure, (3) peripheral vascular disease, (4) admission systolic blood pressure, (5) Killip class, (6) initial serum creatinine concentration, (7) elevated cardiac markers, (8) cardiac arrest on admission, and (9) ST segment deviation.

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14 NSTE-ACS Definite or likely schemia-guided strategy Early invasive strategy Medical treatment

15 schemia-guided Strategy Versus Early nvasive Strategies The early invasive strategy recommendations are stratified by timing: mmediate (within 2 hours): Refractory angina Sign or symptom 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 Sustain VT ot VF

16 Early (within 24 hours): None of the immediate characteristics but new ST-segment depression, a GRACE risk score > 140, or temporal change in troponin Delayed invasive: (25-72hours) None of the above but diabetes mellitus Renal insufficiency (GFR <60 ml/min/1.73 m²) Reduced LV systolic function (EF <0.40) Early postinfarction angina PC within 6 mo Prior CAG GRACE risk score ; TM score 2

17 schemia-guided strategy Ø Low-risk score (e.g., TM [0 or 1], GRACE [<109]) Ø Ø Low-risk Tn-negative female patients Patient or clinician preference in the absence of high-risk features

18 2014 AHA/ACC NSTE-ACS Clinical Practice Guidelines Standard Medical Therapies Oxygen Class 1. Supplemental oxygen should be administered to patients with NSTE-ACS with arterial oxygen saturation less than 90%, respiratory distress, or other high-risk features of hypoxemia. (Level of Evidence: C)

19 Contraindications to nitrate use are hypotension or the use of phosphodiesterase type 5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil, vardenafil) within the previous 24 to 48 hours. PDE-5 inhibitors reduce the breakdown of cyclic guanosine monophosphate (cgmp) and thereby cause an exaggeration and prolongation of the vasodilator effects of nitrates, which can result in severe hypotension, myocardial ischemia, or even death. Nitrates should be used with caution in patients with severe aortic valve stenosis, hypertrophic cardiomyopathy with left ventricular outflow obstruction at rest, right ventricular infarction, or hemodynamically significant pulmonary embolism.

20 2014 AHA/ACC NSTE-ACS Clinical Practice Guidelines Nitrates Administer sublingual NTG every 5 min 3 for continuing ischemic pain and then assess need for V NTG Administer V NTG for persistent ischemia, HF, or hypertension Nitrates are contraindicated with recent use of a phosphodiesterase inhibitors C

21 blockers nitiate oral beta blockers within the first 24 h in the absence of HF, lowoutput state, risk for cardiogenic shock, or other contraindications to beta blockade Use of sustained-release metoprolol succinate, carvedilol, or bisoprolol is recommended for beta-blocker therapy with concomitant NSTE-ACS, stabilized HF, and reduced systolic function Re-evaluate to determine subsequent eligibility in patients with initial contraindications to beta blockers t is reasonable to continue beta-blocker therapy in patients with normal LV function with NSTE-ACS a A C C C

22 eta blockers can be administered to patients with heart failure once their condition has stabilized. f ischemia and/or chest pain persists despite intravenous nitrate therapy, intravenous beta blockers may be used cautiously, followed by oral administration. ntravenous beta blockers should be avoided in patients with acute M and heart failure at initial evaluation. The choice of beta blockers can be individualized by taking into account the drug s pharmacokinetics, physician familiarity, and cost, but beta blockers with intrinsic sympathomimetic activity, such as pindolol, should generally be avoided.

23 CCs(calcium chanel blockers) Administer initial therapy with nondihydropyridine CCs with recurrent ischemia and contraindications to beta blockers in the absence of LV dysfunction, increased risk for cardiogenic shock, PR interval >0.24 s, or second- or third-degree atrioventricular block without a cardiac pacemaker Administer oral nondihydropyridine calcium antagonists with recurrent ischemia after use of beta blocker and nitrates in the absence of contraindications CCs are recommended for ischemic symptoms when beta blockers are notsuccessful, are contraindicated, or cause unacceptable side effects Long-acting CCs and nitrates are recommended for patients with coronary artery spasm mmediate-release nifedipine is contraindicated in the absence of a beta blocker C C C

24 Ranolazine This novel antianginal agent exerts its effects without altering the heart rate or blood pressure. ts predominant mechanism of action is inhibition of the late sodium current in myocardial cells, thereby reducing some of the deleterious effects attributed to the overload of intracellular sodium and calcium during ischemia Ranolazine reduces ischemic episodes and the need for nitroglycerin in patients with chronic stable angina, both as monotherapy and in combination with calcium channel blockers or beta blockers. Ranolazine underwent evaluation in a placebocontrolled trial of 6560 patients with NSTE-ACS who were monitored for an average of almost 1 year. n the overall trial population, ranolazine did not reduce the primary composite outcome of cardiovascular death, M, or recurrent ischemia but did decrease the incidence of recurrent ischemia. The primary outcome, however, was reduced significantly in the subgroups of patients with elevated natriuretic peptides (by 21%) and in those with previous stable angina (by 14%).

25 Angiotensin-converting enzyme (ACE) inhibitors: A slight change in level of recommendation was made. ACE inhibitor is a class recommendation for patients with stable chronic kidney disease (CKD) LVEF < 40%, hypertension (HTN), heart failure, or Diabetes mellitus (DM). n all other patients with cardiac or vascular disease was downgraded from a class a recommendation in prior ACS guidelines to a b recommendation

26 Cholesterol Management Class 1. High-intensity statin therapy should be initiated or continued in all patients with NSTE-ACS and no contraindications to its use (Level of Evidence: A) Class a 1. t is reasonable to obtain a fasting lipid profile in patients with NSTE-ACS, preferably within 24 hours of presentation. (Level of Evidence: C)

27 For early initial oral antiplatelet therapy Clopidogrel loading dose followed by daily maintenance dose in patients unable to take aspirin P2Y12 inhibitor, in addition to aspirin, for up to 12 mo for patients treated initially with either an early invasive or initial ischemia-guided strategy P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) continued for at least 12 mo in post PC patients treated with coronary stents Clopidogrel:300-mg or 600-mg loading dose, then 75 mg/d Ticagrelor:180-mg loading dose, then 90 mg D Ticagrelor in preference to clopidogrel for patients treated with an early invasive or ischemia-guided strategy

28 P2Y12 (Adenosine Diphosphate) nhibitors Management of ACS now routinely includes dual antiplatelet therapy (DAPT), which consists of ASA and a P2Y12 inhibitor.the latter falls into two groups: thienopyridines (ticlopidine, clopidogrel, and prasugrel) and a cyclopentyltriazolopyrimidine (ticagrelor). Thienopyridines act by irreversibly blocking binding of ADP to the platelet surface P2Y12 receptor, thereby interfering with both platelet activation and aggregation by ADP. They are prodrugs that require oxidation by the hepatic cytochrome P-450 (CYP) system to form active metabolites. Thienopyridines also reduce fibrinogen, blood viscosity, and erythrocyte deformability and aggregability through mechanisms that appear to be independent of ADP. n contrast, ticagrelor acts directly as a reversible blocker of the P2Y12 receptor. Drugs that inhibit the CYP system do not affect ticagrelor

29 Glycoprotein b/a nhibitors These drugs block the final common pathway of platelet aggregation, fibrinogen-mediated crosslinkage of plate-lets, caused by a variety of stimuli (e.g., thrombin, ADP, collagen, serotonin. Three agents in this class are available: abciximab, a monoclonal antibody approved only in patients undergoing PC; eptifibatide; and tirofiban (the latter two are reversible small-molecule inhibitors). Each of these agents is adminis-tered as an intravenous bolus followed by continuous infusion. The activity of the small-molecule receptor blockers and the accompanying bleeding risk subside promptly after discontinuation of the infusion. Tirofiban and eptifibatide have short half-lives ( 2 hours), with restoration of platelet function in about 4 hours; thus they should be discontinued 2 to 4 hours before major surgery. Abciximab has prolonged action ( 12 hours) and cannot be reversed rapidly, so major surgery should be deferred until at least 24 hours after administration

30 Parenteral anticoagulant therapy SC enoxaparin for duration of hospitalization or until PC is performed ivalirudin until diagnostic angiography or PC is performed in patients with early invasive strategy only SC fondaparinux for the duration of hospitalization or until PC is performed Administer additional anticoagulant with anti-a activity if PC is performed while patient is on fondaparinux V UFH for 48 h or until PC is performed

31 Direct Thrombin nhibitors These drugs have a potential advantage over indirect thrombin inhibitors such as UFH or LMWH in that they do not require antithrombin and can inhibit clot-bound thrombin. They do not interact with plasma proteins, they provide a very stable level of anticoagulation, and they do not cause thrombocytopenia thus making them an excellent choice for anticoagulation in patients with a history of HT. ivalirudin, the most widely used direct thrombin inhibitor in patients with ACS or undergoing PC, binds reversibly to thrombin and has a half-life of approximately 25 minutes.

32 n patients with NSTE-ACS before angiography, the recommended dose of bivalirudin is a 0.1-mg/kg intravenous bolus followed by an infusion at 0.25 mg/kg/hr. f started during the procedure, a 0.75-mg/ kg bolus dose of bivalirudin should be administered, followed by an infusion at 1.75 mg/kg/hr during PC. t may be discontinued shortly after PC to permit removal of arterial access sheaths. n patients with renal dysfunction, the infusion should be modified as follows: (1) if the creatinine clearance is lower than 30 ml/min and the patient is not being managed with hemodialysis, the infusion rate should be reduced to 1 mg/kg/hr, and (2) in patients undergoing hemodialysis, the infusion rate should be reduced to 0.25 mg/kg/hr.

33 Factor Xa nhibitors Fondaparinux This synthetic pentasaccharide is an indirect Xa inhibitor and requires the presence of antithrombin for its action. n patients undergoing PC, however, fondaparinux was associated with more than a threefold increased risk for catheter-related thrombi. Supplemental UFH at the time of catheterization (85 units/kg if no GP b/ a inhibitor was used; 60 units/kg with a concomitant GP b/a inhibitor) appeared to minimize the risk for this problem with fondaparinux. Thus fondaparinux is an alternative for patients with NSTE-ACS managed noninvasively and, in particular, for patients at higher risk for bleeding. Otamixaban At infusions of and mg/kg/hr, the investigational direct factor Xa inhibitor otamixaban is associated with fewer ischemic complications and similar safety as UFH plus eptifibatide in patients with ACS A large phase trial of otamixaban is under way.

34 Algorithm for Management of Patients With Definite or Likely NSTE-ACS

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36 Risk Stratification efore Discharge for Patients With an schemia- Guided Strategy of NSTE-ACS Class 1. Noninvasive stress testing is recommended in low- and intermediaterisk patients who have been free of ischemia at rest or with low-level activity for a minimum of )12 to 24 hours (Level of Evidence:

37 Myocardial Revascularization: Recommendations Class b 1. A strategy of multivessel PC, in contrast to culprit lesion-only PC, may be reasonable in patients undergoing coronary revascularization as part of treatment for NSTE-ACS (level of evidence )

38 The recommendation for dual antiplatelet therapy (DAPT) remains 12 months (Class recommendation) for both bare metal (MS) and drug-eluting stents (DESs). Consideration can be given (Class b recommendation) for a longer duration of DAPT for patient receiving a DES. Most trials suggesting the potential for shorter durations of therapy have been using specific newer generation stents in all-comers undergoing PC.More information in this area, primarily from observational studies

39 Anticoagulant Therapy in Patients Undergoing PC An anticoagulant should be administered to patients with NSTE-ACS undergoing PC to reduce the risk of intracoronary and catheter thrombus formation. ntravenous UFH is useful in patients with NSTE-ACS undergoing PC ivalirudin is useful as an anticoagulant with or without prior treatment with UFH in patients with NSTE-ACS undergoing PC An additional dose of 0.3 mg/kg V enoxaparin should be administered at the time of PC to patients with NSTE-ACS who have received fewer than 2 therapeutic subcutaneous doses (e.g., 1 mg/kg SC) or received the last subcutaneous enoxaparin dose 8 to 12 hours before PC f PC is performed while the patient is on fondaparinux, an additional 85 U/kg of UFH should be given intravenously immediately before PC because of the risk of catheter thrombosis (60 U/kg V if a GP b/a inhibitor used with UFH dosing based on the targetactivated clotting time n patients with NSTE-ACS, anticoagulant therapy should be discontinued after PC unless there is a compelling reason to continue such therapy. Fondaparinux should not be used as the sole anticoagulant to support PC in patients with NSTEACS due to an increased risk of catheter thrombosis C C C

40 Clarified that in the setting of ACS, aspirin should be continued/administered prior to CAG (and clopidogrel, ticagrelor be discontinued). class n patients referred for urgent CAG, clopidogrel and ticagrelor should be discontinued for at least 24 hours to reduce major bleeding (Level of Evidence: ) n patients referred for CAG, short-acting intravenous GP b/a inhibitors (eptifibatide or tirofiban) should be discontinued for at least 2 to 4 hours before surgery and abciximab for at least 12 hours before to limit blood loss and transfusion (Level of Evidence: )

41 Late Hospital and Posthospital Oral Antiplatelet Therapy Class 1. Aspirin should be continued indefinitely. The maintenance dose should be 81 mg daily in patients treated with ticagrelor and 81 mg to 325 mg daily in all other patients (Level of Evidence: A) 2. n addition to aspirin, a P2Y12 inhibitor (either clopidogrel or ticagrelor) should be continued for up to 12 months in all patients with NSTE-ACS without contraindications who are treated with an ischemia-guided strategy. Options include: Clopidogrel: 75 mg daily (Level of Evidence: ) or Ticagrelor: 90 mg twice daily (Level of Evidence: ) 3. n patients receiving a stent (bare-metal stent or DES) during PC for NSTE-ACS, P2Y12 inhibitor therapy should be given for at least 12 months. Options include: Clopidogrel: 75 mg daily (Level of Evidence: ) or. Prasugrel: 10 mg daily (Level of Evidence: ) or Ticagrelor: 90 mg twice daily (Level of Evidence: ) Class b 1. Continuation of DAPT beyond 12 months may be considered in patients undergoing stent implantation. (Level of Evidence: C)

42 Combined Oral Anticoagulant Therapy and Antiplatelet Therapy in Patients With NSTEACS Class 1. The duration of triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor in patients with NSTE-ACS should be minimized to the extent possible to limit the risk of bleeding. (Level of Evidence: C) 2. Proton pump inhibitors should be prescribed in patients with NSTE-ACS with a history of gastrointestinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist,aspirin, and a P2Y12 receptor inhibitor (Level of Evidence: C) Class a 1. Proton pump inhibitor use is reasonable in patients with NSTE-ACS without a known history of gastrointestinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor (Level of Evidence: C) Class b,targeting oral anticoagulant therapy to a lower international normalized ratio (e.g., 2.0 to 2.5) may be reasonable in patients with NSTE-ACS managed with aspirin and a P2Y12 inhibitor.( Level of Evidence: C)

43 Special Patient Groups: Recommendations Older patient Treat older patients ( 75 y of age) with GDMT, early invasive strategy, and revascularization as appropriate ndividualize pharmacotherapy in older patients, with dose adjusted by weight and/or CrCl to reduce adverse events caused by age-related changes in pharmacokinetics/dynamics, volume of distribution, comorbidity, drug interactions, and increased drug sensitivity Undertake patient-centered management for older patients, considering patient preferences/goals, comorbidities, functional and cognitive status, and life expectancy ivalirudin rather than GP b/a inhibitor plus UFH is reasonable for older patients ( 75 y of age), given similar efficacy but less bleeding risk t is reasonable to choose CAG over PC in older patients, particularly those with DM or multivessel disease, because of the potential for improved survival and reduced CVD events a a A A

44 Special Patient Groups: Recommendations HF and cardiogenic shock Treat patients with a history of HF according to the same risk stratification guidelines and recommendations for patients without HF Select a revascularization strategy based on the extent of CAD, associated cardiac lesions, LV dysfunction, and prior revascularization Recommend early revascularization for cardiogenic shock due to cardiac pump failure DM Recommend medical treatment and decisions for testing and revascularization similar to those for patients without DM A

45 Chronic Kidney Disease Class 1. 1.CrCl should be estimated in patients with NSTE-ACS, and doses of renally cleared medications should be adjusted according to the pharmacokinetic data for specific medications. (Level of Evidence: ) 2. Patients undergoing coronary and LV angiography should receive adequate hydration. (Level of Evidence: C) 3.Calculation of the contrast volume to creatinine clearance ratio is useful to predict the maximum volume of contrast media that can be given without significantly increasing the risk for contrastinduced nephropathy. (Level of evidence:.)(guideline 2012) Class a 1. An invasive strategy is reasonable in patients with mild (stage 2) and moderate (stage 3) CKD (Level of Evidence: )

46 Special Patient Groups: Recommendations Women Women with NSTE-ACS should be managed with the same pharmacological therapy as that for men for acute care and for secondary prevention, with attention to weight and/or renally calculated doses of antiplatelet and anticoagulant agents to reduce bleeding risk Women with NSTE-ACS and high-risk features (e.g., troponin positive) should undergo an early invasive strategy Myocardial revascularization is reasonable in pregnant women with NSTE-ACS if an ischemiaguided strategy is ineffective for management of life-threatening complications Women with NSTE-ACS and low-risk features should not undergo early invasive treatment because of the lack of benefit and the possibility of harm a A C

47 Class 1. All patients with NSTE-ACS should be evaluated for the risk of bleeding. (Level of Evidence: C) 2. Anticoagulant and antiplatelet therapy should be weight-based where appropriate and should be adjusted when necessary for CKD to decrease the risk of bleeding in patients with NSTE-ACS (Level of Evidence: ) Class : No enefit Special Patient Groups: Recommendations Anemia, leeding and transfusion 1. A strategy of routine blood transfusion in hemodynamically stable patients with NSTE-ACS and hemoglobin levels greater than 8 g/dl is not recommended (Level of Evidence: )

48 Special Patient Groups: Recommendations Vasospastic (Prinzmetal) Angina CCs alone or in combination with long-acting nitrates are useful to treat and reduce the frequency of vasospastic angina Treatment with HMG-CoA reductase inhibitor, cessation of tobacco use and additional atherosclerosis risk factor modification are useful in patients with vasospastic angina. Coronary angiography (invasive or noninvasive) is recommended in patients with episodic chest pain accompanied by transient ST elevation to rule out severe obstructive CAD Provocative testing during invasive coronary angiography may be considered in patients with suspected vasospastic angina when clinical criteria and noninvasive testing fail to establish the diagnosis b C