B P5 C39 Non ST Elevation Acute Coronary Syndromes Flashcards
The pathogenesis of NSTE-ACS involves five processes operating singly or in various combinations:
(1) Disruption of an unstable atheromatous plaque
(2) Erosion of an atheromatous plaque
(3) Coronary arterial vasoconstriction
(4) Gradual intraluminal narrowing of an epicardial coronary artery caused by progressive atherosclerosis or restenosis after percutaneous coronary intervention (PCI)
(5) Oxygen supply-demand mismatch
Three mechanisms may lead to plaque disruption:
Most common mechanism of ACS?
Plaque fissure with inflammation
Plaque fissure without inflammation
Plaque erosion
Plaque rupture - most common
Plaque erosion - 40% of ACS cases
_________________ characteristically have large lipid pools with foam cells and a thin fibrous cap.
Plaques that rupture
The key steps in thrombus formation include _____.
(1) Adhesion of platelets to the arterial wall
(2) Platelet activation
(3) Platelet degranulation and further activation
(4) Parallel expression of tissue factor with activation of the coagulation cascade.
Four observations support the central role of coronary artery thrombosis in the pathogenesis of NSTE-ACS:
(1) Autopsy findings of thrombi in the coronary arteries typically localized to a ruptured or eroded atherosclerotic plaque
(2) Visualization by optical coherence tomography (OCT), invasive coronary arteriography, or coronary computed tomographic angiography (CCTA) of plaque ulceration and/or irregularities in the fibrous cap of atherosclerotic plaque, consistent with plaque rupture and thrombus formation;
(3) Elevation of serum markers of platelet activity, thrombin generation, and fibrin formation;
(4) Improvement in clinical outcome with antiplatelet and anticoagulant therapies.
Vasoconstriction causing dynamic obstruction of coronary arterial flow may result from _________________ or from ________________________
Spasm of epicardial coronary arteries (Prinzmetal’s vasospastic angina)
Constriction of small, intramural muscular coronary arteries (vasoconstrictors released by platelets, from endothelial dysfunction)
Atypical manifestations, such as dyspnea without chest discomfort and pain limited to the epigastrium or indigestion, represent “anginal equivalents.”
These atypical findings are more prevalent in _____ and can lead to under recognition, undertreatment, and worse outcomes
Women
Older adults
Diabetes mellitus (DM)
CKD
Dementia
Characteristics of plaque rupture
Lipid rich
Collagen poor, thin fibrous cap
Interstitial collagen breakdown
Abundant inflammation
Smoot muscle cell apoptosis
Macrophage predominance
Less expression of hyaluronidase-2 and hyaluronan-receptor CD 44
Large number of nonculprit plaques and grater panvascular instability
Male predominance
High level of LDL-C
Characteristic of plaque erosion
Lipid poor
PG and GSG rich
Nonfibrillar collagen breakdown
Few inflammatory cells
Endothelial cell apoptosis
Secondary neutrophil involvement
Profound alteration of hyaluronan metabolism resulting in hyaluronan accumulation
Smaller number of nonculprit plaques and less panvascular instability
Female predominance
High level ot TG
The most common abnormalities on the 12-lead ECG are _______________________, which are more likely to be present while the patient is symptomatic.
ST-segment depression and T wave inversion
If possible, comparison with a recent ECG is important because dynamic ST-segment depression as little as 0.05 mV is a sensitive (but not specific) marker for NSTE-ACS. Deep (>0.2 mV) T wave inversions are compatible with, but not necessarily diagnostic of, NSTE-ACS,
Transient ST-segment elevation lasting less than 20 minutes occurs in up to ______ of patients and suggests either UA or coronary vasospasm.
10%
Transient ST-segment elevation lasting less than 20 minutes occurs in up to 10% of patients and suggests either UA or coronary vasospasm.
__________________ are the biomarkers of choice to identify myocardial injury, thus distinguishing between NSTE-ACS and UA.
Cardiacspecific troponins I (cTnI) and T (cTnT)
Role of noninvasive testing in patients with established or suspected NSTE-ACS
(1) establishing the presence (or absence) of significant CAD
(2) diagnosing CAD as the cause of cTn elevation in patients who may have other explanations (see previous section)
(3) evaluating the extent of residual ischemia after initiation of medical therapy to guide management
(4) localizing the territory of ischemia before revascularization in patients with multivessel disease
(5) assessing left ventricular (LV) function.
The safety of early stress testing in patients with NSTE-ACS has been debated, but symptom-limited or pharmacologic stress testing appears to be safe after ______________ of stabilization without symptoms of active ischemia or other signs of hemodynamic or electrical instability.
at least 24 hours
For most patients, electrocardiographic exercise stress testing is recommended if the ECG at rest _______________________
lacks significant baseline abnormalities (e.g., ST depressions, bundle-branch block, electronic pacing)
If significant baseline ECG abnormalities are present, ________________________ should be performed before and immediately after exercise.
Stress perfusion or echocardiographic imaging
High-risk findings on the stress test:
Severe ischemia as reflected by ST-segment depression ≥0.2 mV before stage 3
Hypotension with exercise, ventricular tachyarrhythmia
New or worsening LV dysfunction
Recommended imaging in the ED in patients with chest discomfort and suspected ACS who are at low risk at presentation
CCTA
CCTA in patients with or suspected of having NSTE-ACS can help to (1) recognize or exclude the presence of epicardial CAD, (2) identify which vessel(s) have obstruction, and (3) assist in risk stratification and prognosis
CCTA in patients with or suspected of having NSTE-ACS can help to _____.
(1) recognize or exclude the presence of epicardial CAD
(2) identify which vessel(s) have obstruction
(3) assist in risk stratification and prognosis
_________can provide precise measurements of ventricular volumes and function, detect and assess ventricular wall edema, identify areas of infarcted versus viable hibernating myocardium, establish the presence of myocardial perfusion, quantify wall motion, and identify myocardium at risk in patients with NSTE-ACS
CMR
Addition of high-resolution late gadolinium enhanced imaging can help provide this information when CMR alone is inconclusive.
Features suggesting thrombus include
Lobular intraluminal masses with a rounded or polypoid shape;“haziness” of a lesion
Approximately ______ of patients with a clinical diagnosis of NSTEACS have significant coronary obstruction
% obstructive disease in multiple epicardial arteries
LM with multivessel disease _____
3VD _____
2VD _____
1VD _____
No obstruction _____
90%
LM with multivessel disease 10%
3VD 35%
2VD 25%
1VD 20%
No obstruction 10%
In the clinical setting, __________ are used most commonly to guide coronary stent placement
IVUS or OCT
Risk assessment scores in NSTE ACS
TIMI risk score
GRACE score
TIMI risk score
AAA B CC D
Age ≥65 yr
Prior aspirin
≥2 anginal episodes in prior 24 hr
↑ Cardiac markers
≥3 CAD risk factors
Known CAD (>50% stenosis)
ST deviation ≥0.5 mm of initial ECG
Appropriate indications for CCTA in patients with acute chest pain
Electrocardiogram negative or indeterminate for myocardial ischemia
Low-intermediate pretest likelihood by risk stratification tools
TIMI risk score of 0-2 (low risk) ideal or TIMI score of 3-4 (intermediate) in some cases
HEART score <3
At least 1 negative troponin value, including point-of-care assays
Equivocal or inadequate previous functional testing during index ED or within previous 6 months
Relative contraindications of CCTA in patients with acute chest pain
History of allergic reaction to iodinated contrast
eGFR 30 to <60 mL/min/1.73 m2
Factors likely to lead to nondiagnostic scans; specific will vary with scanner technology and site capabilities
Heart rate greater than site maximum for reliably diagnostic scans after beta blockers (usually 70-80 beats/min)
Contraindications to beta blockers and heart rate not controlled Atrial fibrillation or other markedly irregular rhythm
Body mass index >39 kg/m2
Absolute contraindications of CCTA in patients with acute chest pain
Known acute coronary syndromes
eGFR <30 unless on long-term dialysis
Previous anaphylaxis after iodinated contrast administration
Previous episode of contrast allergy after adequate steroid/antihistamine preparation
Pregnancy or uncertain pregnancy status in premenopausal women
_________________ vasodilators that increase myocardial blood flow and reduce myocardial oxygen requirements by lowering cardiac preload (systemic venodilation) and afterload (systemic arterial dilation), thereby diminishing ventricular wall stress, and they may have a mild antiplatelet effect
Nitrates
_____________ to nitrates may develop within 12 to 24 hours and can be mitigated by nitrate-free intervals or increasing the dose if symptoms persist. A
Tolerance
Important contraindications to nitrates include
Hypotension and use within 24 hours of a phosphodiesterase type 5 (PDE-5) inhibitor, sildenafil or vardenafil, or tadalafil within 48 hours
Relative contraindications to nitrates include hypotension (SBP <90 mm Hg), severe obstruction to LV outflow, large right ventricular infarction, or hemodynamically significant pulmonary embolism.
______________ inhibit the O 2oxygen consumption by lowering heart rate, BP, and myocardial contractility
Beta blockers
Beta blockers should be avoided in patients with
(1) acute or severe HF
(2) low cardiac output
(3) hypotension
(4) contraindications to beta blocker therapy (e.g., high-degree AV block, active bronchospasm)
(5) coronary vasospasm or acute intoxication with cocaine or methamphetamine because unopposed alpha-mediated coronary vasoconstriction may occur, worsening coronary spasm.
Data suggest that coadministration of _____and clopidogrel may blunt the antiplatelet effect of clopidogrel and is associated with an increase short- term risk of ischemic events.
Morphine
Morphine may act as both an analgesic and an anxiolytic; its ____ effects may be beneficial by reducing preload (particularly in patients who have experienced acute pulmonary edema), and _____ by increasing vagal tone.
Venodilator
Mildly reduces heart rate and BP
__________ effective in reducing ischemia in patients with NSTE-ACS and persistent ischemia despite treatment with full-dose nitrates and beta blockers, as well as in patients with contraindications to beta blockers and in patients with hypertension
CCBs
Contraindications to nondihydropyridine CCBs include
Significant LV dysfunction
Increased risk of cardiogenic shock
PR interval longer than 0.24 second
High-degree AV block
The short-acting formulation of the dihydropyridine nifedipine, which accelerates heart rate, can cause harm in patients with ACS when not co-administered with a beta blocker and should be avoided
Clinical effects of new and experimental therapies in NSTE_ACS
Ranolazine
Decreases recurrent ischemia and arrhythmias
Trimetazidine
Decreases short-term mortality
Nicorandil
Decreases arrhythmias and transient ischemia
Activates ATP-sensitive K + channels and dilates arterioles; may have ischemic precondition-like effec
Nicorandil
_________ acetylates platelet c genase 1 (COX-1), thereby blocking the synthesis and release of thromboxane A 2 (TxA2 ), a platelet activator, and reducing platelet aggregation and arterial thrombus formation.
Antiplatelet effects last for the lifetime of the platelets, approximately ____________
ASA
7 to 10 days
It is a cornerstone of antiplatelet therapy in patients with all forms of ACS, as well as those with chronic CAD.
Contraindications to ASA include _____.
Documented allergy (e.g., ASA- induced asthma)
Nasal polyps
Active bleeding
Known platelet disorder
Management of ACS now routinely includes dual-antiplatelet therapy (DAPT) consisting of both ASA and a P2Y12 inhibitor, which blocks the P2Y12 receptor and blocks adenosine diphosphate (ADP) binding to the surface of the platelets. The latter includes the oral thienopyridines _____, which are irreversible blockers, as well as a cyclopentyltriazolopyrimidine _____, which is a reversible P2Y12 inhibitor.
Clopidogrel, prasugrel - irreversible
Ticagrelor - reversible
_______________ the first thienopyridine to be widely studied in patients with CAD, NSTE-ACS, and patients undergoing PCI
Trial in NSTE ACS __________
Clopidogrel
CURE trial
Current guidelines recommend clopidogrel ( _________________ dose) in addition to aspirin in patients with NSTE-ACS who cannot receive ticagrelor or prasugrel (e.g., due to intolerance or very high risk of bleeding due to a prior intracranial hemorrhage or indication for full-dose oral anticoagulation or cost)
600 mg loading dose, 75 mg daily maintenance dose
Use of a 600-mg loading dose achieves a steady-state level of platelet inhibition after ___________
2 hours
Identify 2 treatment strategies of Clopidogrel in NSTE ACS
Preferred?
Two strategies for initiating clopidogrel therapy in patients with NSTE-ACS have evolved:
(1) starting clopidogrel at arrival or hospital admission or
(2) delaying treatment with clopidogrel until after coronary angiography and then administering the drug on the catheterization table if PCI is to be performed.
Initial strategy not preferred no longer recommended in patients in whom the coronary anatomy is not known and an early invasive approach is planned. 1
Formation of the active metabolite of ____________ requires only one step and is generated within 30 minutes of ingestion.
Trial?
Prasugrel
TRITON-TIMI 38 trial
The primary composite of CV death, MI, or stroke was reduced significantly by 19% in the patients randomized to prasugrel through 15 months of follow-up.This benefit was driven by a significant 24% reduction in MI and was particularly striking in patients with diabetes (30% reduction).
In addition, prasugrel markedly reduced the rate of definite or probable stent thrombosis (by 52%), particularly in patients with drug-eluting stents (DESs) (64%); thus prasugrel should be considered in patients who present with stent thrombosis despite compliance with clopidogrel therapy.
Patients with NSTE-ACS (<75 years of age) selected for medical management without revascularization (n = 7,243) were randomized within 10 days of the index event to prasugrel 10 mg daily versus clopidogrel 75 mg daily (patients <60 kg received prasugrel 5 mg daily.) In addition, NSTE-ACS patients ≥75 years of age (n = 2,083) were randomized to prasugrel 5 mg daily versus clopidogrel 75 mg daily.
Among patients with NSTE-ACS selected for medical management without revascularization, the long-term use of prasugrel did not reduce adverse outcomes compared with clopidogrel. Major bleeding was similar between groups; however, major or minor bleeding appeared increased with prasugrel.
TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes)
These results differ from a clear benefit of prasugrel over clopidogrel in reducing cardiovascular events in patients with planned PCI seen in the TRITON-TIMI 38 trial.
This trial sought to study if pretreatment with prasugrel in all patients would be superior to prasugrel given selectively post-angiography in patients undergoing percutaneous coronary intervention (PCI).
Following initial diagnosis of NSTE-ACS, patients received either pretreatment with prasugrel 30 mg, or placebo. If PCI was indicated following coronary angiography, the two arms received a further dose of 30 mg and 60 mg, respectively.
The results of the ACCOAST trial indicate that pretreatment with prasugrel is not associated with superior ischemic outcomes in patients with NSTE-ACS scheduled to undergo an invasive strategy. There is a significantly higher risk of bleeding with pretreatment.
ACCOAST trial (Comparison of Prasugrel at the Time of PCI or as Pretreatment at the Time of Diagnosis in Patients With Non-ST Elevation Myocardial Infarction)
Thus, prasugrel should only be administered following coronary angiography in NSTE-ACS patients undergoing coronary stenting (as was done in the TRITON-TIMI 38 trial)
General recommendations for Prasugrel
Prasugrel (60-mg loading dose, 10-mg daily m nance) in addition to ASA is most suitable in patients with ______________
NSTE-ACS <75 years without a prior stroke or transient ischemic attack who have had coronary angiography and in whom PCI is planned
Prasugrel is not recommended for use in patients with NSTE-ACS before the coronary anatomy is known
Prasugrel is contraindicated in patients with _____ due to evidence of net harm in this group in TRITON-TIMI 3
Prior stroke or transient ischemic attack
It is a reversible inhibitor (hal approximately 12 hours) of the P2Y 12 platelet receptor, in contrast to the thienopyridines, which are irreversible inhibitors. Both the parent drug and its metabolite are active and have similar potency
Trial?
Ticagrelor
PLATO
A broad array of subgroups d strated consistent benefit with ticagrelor over clopidogrel, including patients age ≥75 years, weight <60 kg, with a prior history of stroke or transient ischemic attack, and those managed with a noninvasive strategy
Long-term use of ticagrelor with ASA in patients who had experienced MI 1 to 3 years earlier was evaluated in the _____________
PEGASUS-TIMI 54 trial
the standard maintenance dose of ticagrelor (90 mg twice daily) and a lower dose (60 mg twice daily) reduced the rate of the primary composite endpoint (CV death, MI, or stroke) by 15% and 16%, respectively. Although the rates of TIMI major bleeding were higher with ticagrelor, rates of intracranial and fatal bleeding were not increased. Major bleeding rates were lower and tolerability better with the 60-mg twice-daily dose, 60 which was FDA approved for the prevention of CV death, MI, and stroke in stable patients with a history of MI.
Open-label, multicenter, randomized trial that compared a ticagrelor-based strategy with a prasugrel-based strategy in patients who presented with ACS (59% had NSTE-ACS) in whom an invasive evaluation was planned.
The trial demonstrated a ∼40% relative reduction in patients with NSTE-ACS randomized to prasugrel versus ticagrelor in the primary composite endpoint of death, MI, or stroke at 1 year. Bleeding rates were similar between the treatment arms.
ISAR-REACT 5 trial
Randomized high-risk patients with NSTE-ACS who had received 3 months of ASA + ticagrelor post-PCI to either continued DAPT versus ticagrelor alone in a double-blinded study. The primary bleeding endpoint at 1 year was reduced from 7.6% to 3.6% with ticagrelor monotherapy, while there was no significant difference in the efficacy composite (4.3% vs. 4.4%). T
TWILIGHT trial
These contemporary results provide additional support to shortening DAPT to 3 months in stable patients after NSTE-ACS treated with PCI to reduce the risk of bleeding.
Continuation of DAPT for longer than 12 months may be considered in patients with high ischemic risk
≥65 years
Diabetes
>1 prior spontaneous MIs
Multivessel CAD
CKD
Three common clinical scenarios in which switching between oral P2Y 12 inhibitors may arise include
(1) patients who have recurrent ACS despite DAPT with chronic clopidogrel and ASA
(2) patients who experience intolerance or side effects
(3) excessive cost
In patients on ASA and clopidogrel who experience ACS, switching from clopidogrel to ________________ early after hospital admission, is a Class I recommendation
Ticagrelor at a loading dose of 180 mg followed by 90 mg twice daily
IV direct-acting P2Y 12inhibitor that blocks ADP-ind platelet activation and aggregation with an almost immediate onset of action and short half-life of 3 to 6 minutes
Cangrelor
It has the potential to overcome several practical limitations of oral P2Y 12 inhibitors in patients with NSTE-ACS undergoing PCI.
Because cangrelor is administered intravenously and has a rapid onset and offset of action, it has the potential to overcome several practical limitations of oral P2Y12 inhibitors in patients with NSTE-ACS undergoing PCI. These limitations include _____.
(1) Slower onset action with oral delivery
(2) Delayed absorption of oral agents in patients who have decreased GI perfusion, nausea, or receive opiates
(3) Need to postpone CABG for 5 to 7 days after an oral P2Y12 inhibitor to reduce the risk of bleeding.
Discontinuation of antiplatelet before CABG
Clopidogrel
Prasugrel
Ticagrelor
Clopidogrel - 5 days
Prasugrel - 7 days
Ticagrelor - 5 days
The glycoprotein (GP) IIb/IIIa inhibitors block the final common pathway of platelet aggregation, fibrinogen-mediated cross-linkage of platelets, caused by a variety of stimuli
Types?
Abciximab, a monoclonal antibody approved in patients undergoing PCI
Eptifibatide and Tirofiban, both of which are reversible small-molecule inhibitors approved for use in patients with ACS and in those undergoing PCI
Based on the totality of the evidence, the routine administration of GP IIb/IIIa inhibitors to patients with NSTE-ACS who receive DAPT with ASA and a P2Y 12 inhibitor (i.e., triple-antiplatelet therapy) is not recommended. However, in patients with or at high risk for thrombotic complications during PCI, such as those with diabetes or angiographic evidence of thrombus, and who are at low risk for bleeding, selective use of GP IIb/IIIa inhibitors remains a reasonable option.
____________________ is a mixture of polysaccharide chains of different lengths that prevent coagulation by blocking thrombin (factor IIa) and factor Xa.
Unfractionated heparin (UFH)
A weight-a dose of UFH ( ____________ and ________________)
Target aPTT ____________
60-unit/kg bolus
12-unit/kg/hr infusion
APTT of 50 to 70 seconds or 1.5 to 2.5 times control
Prolonged infusions of UFH increase the risk of an immunogenic heparin-induced thrombocytopenia (HIT), which is an infrequent but serious complication that can cause thrombosis and bleeding and may even be fatal. In patients with HIT, a _____ should be substituted
Direct thrombin inhibitor (e.g., bivalirudin)
To achieve APTT 1.5 to 2.5 times control
OR
Fondaparinux
LMWH has several potential advantages over UFH:
(1) Greater anti–FXa activity (relative to factor IIa) inhibits thrombin generation more effectively
(2) Induces greater release of tissue factor pathway inhibitor than UFH, and it is not neutralized by platelet factor 4
(3) Causes HIT less frequently than UFH
4) High and consistent bioavailability of LMWH allows subcutaneous (SC) administration
(5) Monitoring of the anticoagulation level is not necessary
(6) LMWH binds less avidly to plasma proteins than UFH and therefore has a more consistent anticoagulant effect
Dose of enoxaparin in ACS NSTEMI:
1 mg/kg subcutaneously every 12 hours, with dosing only once daily for patients with a creatinine clearance (CrCl) <30 mL/ min.
Administration of enoxaparin for up to 8 days (or until hospital discharge) was found to be effective in patients with ACS,
1mg of protamine sulfate neutralizes _________ UFH
1 mg= 100 units UFH
The dose of protamine necessary to reverse an infusion of UFH should be based on the total UFH dose administered in the preceding 2 to 3 hours.
Slow IV infusion = prevention of hypotension and bradycardia
Protamine reverses approx 60% of LMWH
t1/2 of heparin: 1-1.5h
A direct thrombin inhibitor, 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. Direct thrombin inhibitors do not interact with plasma proteins, provide a very stable level of anticoagulation, and do not cause thrombocytopenia,
Bilavirudin - binds reversibly to thrombin and has a halflife of approximately 25 minutes
In patients with NSTE-ACS before angiography, the recommended dose of bivalirudin is a 0.10-mg/kg IV bolus followed by an infusion of 0.25 mg/kg/hr. If 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 PCI.
Patients were randomized to fondaparinux (2.5 mg/day, n=10,057) or enoxaparin (1.0 mg/kg twice daily, n=10,021). Other medications including aspirin, clopidogrel, and glycoprotein IIb/IIIa inhibitors were at the investigator’s discretion. Patients who underwent percutaneous coronary intervention (PCI) in the enoxaparin group were to receive unfractioned heparin if the last dose of study medication was received >6 hours prior to PCI. The primary analysis was a test for noninferiority between the treatment groups.
Among patients with non-ST elevation acute coronary syndromes, treatment with fondaparinux was noninferior for the primary composite endpoint of death, MI, or refractory ischemia at day 9 compared with treatment with enoxaparin. Additionally, there was a significant reduction in the safety endpoint of major bleeding at nine days and the secondary endpoint of mortality at six months.
OASIS 5 trial
Thus, fondaparinux is an alternative for patients with NSTE-ACS managed noninvasively, particularly in patients at high risk for bleeding.
Supplemental UFH at cathterization (___________ if no GP IIb/IIIa inhibitor is used; __________ with concomitant GP IIb/IIIa inhibitor) appeared to minimize the risk of this problem with fondaparinux.
85 units/kg
60 units/kg
Default duration of DAPT in ACS NSTEMI with low bleeding risk
DAPT x 12 months
Guidance for managing antithrombotic therapy in patients with AF, ACS, and PCI that allows for tailored approaches depending on the balance between bleeding and ischemic risks have been provided. The major concepts include:
(1) Short initial course of triple therapy with NOAC + P2Y12 inhibitor + aspirin 75 to 100 mg (up to 1 week,18 after which aspirin is discontinued);
(2) Dual therapy with a NOAC + P2Y12 inhibitor until 1 year
(3) NOAC monotherapy after the first year;
(4) Options to shorten the duration and intensity (e.g., use of clopidogrel instead of more potent P2Y12 inhibitors, continuing aspirin in favor of a P2Y12 inhibitor) combination therapy in patients with uncorrectable bleeding risk factors who are at low atherothrombotic risk;
(5) options to increase the duration of intensity combination therapy in patients at high atherothrombotic risk (e.g., due to anatomic complexity of coronary stenting, prior stent thrombosis, multiple recurrent MIs) and low bleeding risk
Severe bleeding is the most common complication of antithrombotic therapy.Efforts to minimize the risk of bleeding include:
(1) Assessment of bleeding (and ischemic) risk using established risk scores18,30-32 to identify and manage modifiable risk factors and to select the most appropriate antithrombotic treatment regimen and duration;
(2) Selection of the anticoagulant and antiplatelet(s) therapies with a lower risk of bleeding;
(3) Appropriate dose adjustment of antithrombotic drugs according to age, body weight, renal function, and use of concomitant medications that increase drug exposure (e.g., verapamil, dronedarone), especially in women and older patients;
(4) Avoidance of other therapies that increase the risk for bleeding (e.g.,NSAIDs)
(5) Radial arterial approach as default vascular access, smaller sheath sizes, timely removal of arterial sheaths, and femoral closure devices
New recommendations from the 2020 European Guidelines include _____.
(1) Performing PCI without interruption of preadmission oral anticoagulant
(2) Not administering UFH in patients on VKAs with an international normalized ratio (INR) >2.5
(3) In patients on NOACs; adding low-dose parenteral anticoagulation (e.g., enoxaparin 0.5 mg/kg intravenously or UFH 60 IU/kg) regardless of the timing of the last administration of the last NOAC dose;
(4) Avoiding routine pretreatment with P2Y12 inhibi- tors
(5) Restricting use of GP IIb/IIIa inhibitors for bailout or periprocedural complications only
In case of major bleeding, the European Society of Cardiology (ESC) provides the following recommendations:
(1) interrupt both anticoagulant and antiplatelet therapies, unless bleeding can be adequately controlled by specific hemostatic measures;
(2) neutralize anticoagulant therapy;
(3) consider platelet transfusion to neutralize antiplatelet agents;
(4) because blood transfusions may have deleterious effects on outcome, transfusions should usually be withheld in hemodynamically stable patients with Hb above 7 g/dL;
(5) erythropoietin is not indicated as a treatment for acute anemia or blood loss, because it may increase the risk of arterial or venous thromboembolism;
(6) minor bleeding should be managed if possible without interruption of antithrombotic therapies.
Three general approaches to cardiac catheterization and revascularization can be used to manage patients with NSTE-ACS:
(1) an early invasive strategy involving routine early (within 48 hours of initial eval- uation) cardiac catheterization, followed by PCI, CABG, or continuing medical therapy, depending on the coronary anatomy;
(2) a delayed invasive approach (coronary angiography >48 hours after presentation);
(3) an ischemia-guided (or selective invasive) approach, with initial medical management and catheterization reserved for patients with hemodynamic instability or recurrent ischemia, either at rest or on a noninvasive stress test, followed by revascularization if the anatomy is suitable
In patients with AF undergoing PCI, default antithrombotic in hospital strategy
1 week TAT (NOAC + DAPT)
OAC: preference for a NOAC over VKA for the default strategy and in all other scenarios if no contraindications.
For both TAT and DAT regimens, the recommended doses for the NOACs are as follows: (1) apixaban 5 mg b.i.d., (2) dabigatran 110 mg or 150 mg b.i.d., (3) edoxaban 60 mg/day, (4) rivaroxaban 15 mg or 20 mg/day.
Three general approaches to cardiac catheterization and revascularization can be used to manage patients with NSTE-ACS:
(1) an early invasive strategy involving routine early (within 48 hours of initial evaluation) cardiac catheterization, followed by PCI, CABG, or continuing medical therapy, depending on the coronary anatomy
(2) a delayed invasive approach (coronary angiography >48 hours after presentation)
(3) an ischemia-guided (or selective invasive) approach, with initial medical management and catheterization reserved for patients with hemodynamic instability or recurrent ischemia, either at rest or on a noninvasive stress test, followed by revascularization if the anatomy is suitable
An early invasive strategy is not recommended in patients with ___________________
Extensive comorbidities in whom the risks of revascularization outweigh the potential benefits
Patients with acute chest pain with low clinical likelihood of ACS and a negative troponin assay
Early invasive strategy is recommended
NSTE-ACS who have ST-segment changes and/or positive troponin assay on admission
Recurrent ischemia
Evidence of congestive HF
NSTE-ACS previously treated with CABG
NSTE-ACS within 6 months of a previous PCI and in whom restenosis may be responsible
Indications for an initial conservative strategy include
Patients with life-threatening comorbid conditions or in lowrisk patients without recurrent symptoms and in whom the risks outweigh the potential benefits
Timing of invasive approach in NSTE ACS
(1) immediate invasive (<2 hours of hospital presentation) in patients at very high risk
(2) early invasive (<24 hours) in patients at high risk
(3) delayed invasive approach (>48 hours) in patients at intermediate risk.
Features to classify patient with NSTE ACS as very high risk
• Hemodynamic instability
• Cardiogenic shock
• Recurrent/refractory chest pain despite medical treatment
• Life-threatening arrhythmias
• Mechanical complications of MI
• Acute heart failure clearly related to NSTE-ACS
• ST-segment depression >1 mm/6 leads plus ST-segment elevation aVr and/or V1
Features to classify patient with NSTE ACS as high risk
• Established NSTEMI diagnosis
• Dynamic new or presumably new contiguous ST/T-segment changes (symptomatic or silent)
• Resuscitated cardiac arrest without ST-segment elevation or cardiogenic shock
• GRACE risk score >140
Factors that favor CABG over PCI in patients with NSTE ACS include
(1) clinical factors such as DM, LVEF <35%, and contraindication to DAPT
(2) anatomic features, such as diffuse instent restenosis, severe coronary calcification, and inability to achieve complete revascularization with PCI
(3) other surgical indications, such as need for valve or aortic surgery
Patients were randomized in a double-blind, 2 x 2 factorial, parallel-group design to either standard lipid lowering with pravastatin (40 mg/day; n=2,063) or aggressive lipid lowering using atorvastatin (80 mg/day; n=2,099).
Among patients hospitalized for an ACS, use of an aggressive lipid-lowering strategy was associated with a reduction in the primary composite endpoint of all-cause mortality, MI, documented unstable angina requiring rehospitalization, revascularization, and stroke at two-year follow-up compared with standard lipid-lowering strategy.
PROVE IT TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction 22)
Intensive statin (atorvastatin, 80 m was even more effective than pravastatin (40 mg)
The U.S. Multisociety Cholesterol 104 and European Dyslipidemia105 Guidelines both support use of a maximally tolerated statin able to achieve _______ reduction in LDL-C in patients with NSTE-ACS. The U.S. Guidelines recommend a target of __________, whereas the European guidelines recommend a goal LDL-C __________
> 50% reduction
US - <70 mg/dL
ESC - <55 mg/dL.
The ______________ demonstrated the added clinical benefit of adding a nonstatin therapy (ezetimibe, a cholesterol absorption inhibitor) to background statin therapy.
IMPROVE-IT trial
______________were developed and have been shown to reduce LDL-C by 40% to 60% regardless of background lipid therapy in a variety of populations with hyperlipidemia
Drugs targeting the proprotein convertase subtilisin kexin type-9 (PCSK9) protein
_____________ trial significantly reduced the risk of adverse CV events by 19% and the key secondary endpoint of CV death, MI, or stroke by 25% compared with placebo after follow-up of 2.2 years
FOURIER trial
The largest experience with PCSK9 inhibition in patients with recent ACS in the _______________ trial that randomized 18,924 with ACS (65% with NSTE-ACS) 1 to 12 months before enrollment to either alirocumab or placebo every 2 weeks added to a high-intensity statin. After a median of 2.8 years the primary endpoint was reduced significantly by 15% with alirocumab.
ODYSSEY OUTCOMES trial
_______________ are recommended in patients with NSTE-ACS at very high risk in whom the LDL-C remains elevated (see earlier) despite maximal tolerated statin and ezetimibe.
PCSK9 inhibitors
True or False
Elderly patients with NSTEACS derive similar or even greater absolute benefits from guideline-directed therapies including DAPT,117 an earlier invasive approach,
True
True or False
Women are more likely to have atypical symptoms and nonatherosclerotic causes of angina, such as microvascular dysfunction and abnormal vascular reactivity
True
Patients with DM have a blunted response to standard antiplatelet regimens, including clopidogrel and ASA.
Subgroup analyses comparing outcomes in patients with and without DM have suggested incrementally greater benefit of some more potent antiplatelet agents, including ________ and ________ in patients with DM.
Prasugrel and GP IIb/IIIa inhibitors
If there is a large territory of myocardial ischemia and severe LV systolic dysfunction, ______________ may be necessary for hemodynamic support peri-PCI.
LV support (e.g., percutaneous ventricular assist devices)
True or False
In NSTEMI, the shock tends to occur later in the hospitalization and in patients with more comorbidities, common extensive CAD, and recurrent ischemia/ infarction
True
Spasm of one or more proximal coronary arteries with resultant transmural ischemia and abnormalities in LV function are the diagnostic hallmarks of
Vasospastic angina
_____ are the diagnostic hallmarks of VA, which may be associated with acute MI, ventricular tachycardia, ventricular fibrillation, and SCD
Spasm of one or more proximal coronary arteries
Resultant transmural ischemia
Abnormalities in LV function
Patients with VA tend to be younger than those with NSTE-ACS attributable to coronary atherosclerosis, and many do not exhibit the classic coronary risk factors, except they are frequently _______________
Heavy cigarette smokers
Angina at rest (in VA) is often extremely severe, tends to cluster between _____, and may be accompanied by syncope related to AV block, asystole, or ventricular tachyarrhythmia.1
Midnight and 8 AM
Approximately ________ of patients with VA also exhibit severe fixed coronary obstruction and may have a combination of exertion induced angina with ST-segment depression and episodes of angina at rest with ST-segment elevation.
1/3
The _____ used to treat migraine head- ache and _____ used to treat depression can precipitate episodes of VA
Ergot derivative
Serotonin antagonists
The key to diagnosis of VA lies in the detection of _____.
Episodic ST- segment elevation
Accompanied by severe chest pain
Usually occurring at rest
Coronary Vasomotion Disorders International Study Group (COVADIS) developed international diagnostic standards for VA. These standards consisted of:
(1) Nitrate-responsibe angina during spontaneous episodes
(2) Transient ischemic ECG changes (ST-segment elevation or depression ≥0.1 mV
(3) Coronary artery spasm, defined as transient coronary artery occlusion “with angina and ECG changes either spontaneously or in response to a provocative stimulus.”
Three provocative tests for coronary spasm can be performed at coronary angiography, _____, although the latter test is no longer available in the United States
Hyperventilation
Acetylcholine (Intracoronary)
Ergonovine (Intracoronary)
Patients with VA should be urged strongly to discontinue __________
Smoking
The mainstay of therapy in VA
Calcium antagonist, alone or preferably in combination with a long-acting nitrate
_____________ agents may actually be detrimental because blockade of beta 2 receptors, which mediate coronary dilation, may allow unopposed alpha receptor–mediated coronary vasoconstriction.
Nonselective beta-blocking agents
In a study of 640 Japanese patients with VA confirmed by acetylcholine provocation testing and no significant coronary stenosis, statin therapy significantly reduced the risk of MACE.
Prevention of plaque formation or progression may explain part of the benefit of statins, but the pleiotropic effects of statins, such as the _____, may also pertain.
Amelioration of endothelial dysfunction
Suppression of inflammation
Inhibition of the Rho A/Rho-kinase pathway
_____ may be indicated in patients with VA associated with discrete, proximal, fixed obstructive lesions, but revascularization is contraindicated in patients with isolated coronary artery spasm without accompanying fixed obstructive disease.
PCI and occasionally CABG
_______________ is contraindicated in patients with isolated coronary artery spasm without accompanying fixed obstructive disease.
Revascularization
Clinical outcomes are excellent in patients with _____________
Isolated coronary spasm and no underlying CAD
Approximately 10% to 25% of patients with UA and 6% to 10% of patients with acute MI may present with nonobstructive (<50% stenosis) epicardial coronary disease, although they may have evidence of myocardial ischemia by electrocardiography or myocardial perfusion imaging. This condition is sometimes still referred to as “_____or MINOCA (Myocardial Infarction with Nonobstructive Coronary Arteries)
Cardiac X syndrome
Amphetamine, or novel psychoactive substance use should be treated similar to those without recent stimulant use, except that patients with signs of acute intoxication (e.g., euphoria, tachycardia, hypertension) should not receive _____________ because of the risk of coronary spasm.
Beta blockers
____________ are preferred agents, in cocaine-induced spasm and benzodiazepines alone or in combination with nitroglycerin may also be used to manage hypertension.
Vasodilators and CCBs
Antithrombotic Therapy in Patients on Chronic Oral Anticoagulation Who Present with an NSTE-ACS
Very-High-Risk Criteria in patients with NSTE-ACS
Hemodynamic instability or cardiogenic shock
Recurrent or ongoing chest discomfort refractory to OMT
Life-threatening arrhythmias or cardiac arrest
Mechanical complications of MI
AHF
Recurrent dynamic ST-T wave changes, particularly with intermittent ST-elevation
High risk criteria in patients with NSTE-ACS
Rise and fall in cTn I compatible with MI
Dynamic or presumably new contiguous ST-T wave changes with or without symptoms (silent) suggesting ongoing ischemia
Transient ST-segment elevation
Elevated TIMI (>4) or GRACE (>140) score
Intermediate risk criteria in patients with NSTE-ACS
DM
Renal insufficiency (EGFR <60)
LVEF <40% or CHF
Early post-MI angina
Prior PCI
Prior CABG
TIMI (2-3) or GRACE (109-140)
Ten performance measures in patients with NSTE-ACS
- Use of aspirin
- Use of an oral P2Y12 inhibitor
- Use of fondaparinux, bivalirudin, unfractionated heparin, or enoxaparin
- Use of beta blocker at discharge for patients with left ventricular dysfunction
- Use of statins
- Use of angiotensin converting enzyme inhibitor I or angiotensin receptor blocker in patients with systolic left ventricular dysfunction or heart failure, hypertension, or diabetes
- Use of early invasive procedures in intermediate- to high-risk patients
- Smoking cessation advice/counseling
- Enrollment in a secondary prevention or cardiac rehabilitation program
- Development of regional and/or national programs to measure performance indicators systematically and provide feedback to individual hospitals
