SCAI chap 18 ACS Flashcards
(127 cards)
1
Q
What is the diagnosis for patients presenting with chest pain without persistent ST-elevation?
A
Patients are typically diagnosed with non-ST-elevation ACS (NSTE-ACS).
2
Q
How are patients with NSTE-ACS classified?
A
They are classified into unstable angina (UA) or NSTEMI based on cardiac biomarkers.
3
Q
What percentage of patients requiring PCI have ACS?
A
More than 80% of patients requiring percutaneous coronary intervention (PCI) have ACS.
4
Q
What has influenced the use of PCI for stable angina?
A
The publication of the COURAGE trial and increasing scrutiny from payers have influenced this.
5
Q
What is the estimated annual incidence of myocardial infarction (MI)?
A
The estimated annual incidence of MI is approximately 805,000.
6
Q
What was the overall MI prevalence in males and females according to the ARIC study?
A
The prevalence was 4.5% in males and 2.1% in females.
7
Q
How do females compare to males in terms of coronary angiography and treatment?
A
Females are less likely to undergo coronary angiography and have lower rates of guideline-directed medical therapy. They are also at higher risk of mortality from myocardial infarction and they have longer door to balloon time.
8
Q
What demographic is more likely to experience late presentation STEMI and cardiogenic shock at a young age?
A
Extremely young patients (under 35 years) are more likely to be white, obese, smokers, or have a family history of CAD.
9
Q
What is the acute in-hospital mortality rate for STEMI and NSTE-ACS?
A
The acute in-hospital mortality for STEMI is 7%, while for NSTE-ACS it is 3%-5%. Mortality equalizes at six months.
10
Q
How does long-term mortality compare between NSTE-ACS and STEMI?
A
Long-term follow-up ( beyond six month) shows that NSTE-ACS has a higher mortality than STEMI.
11
Q
What factors contribute to the higher long-term mortality in NSTE-ACS patients compared to STEMI patients?
A
NSTE-ACS patients tend to be older and have more comorbidities, such as diabetes and renal failure.
12
Q
What is the current understanding of the pathology of ACS?
A
ACS results from coronary artery obstruction causing ischemia and myocardial necrosis.
13
Q
What typically causes acute coronary artery obstruction?
A
It typically results from thrombosis of a ruptured coronary plaque.
14
Q
How is coronary artery disease (CAD) understood in current medical practice?
A
CAD is understood as a stuttering inflammatory process of repeated plaque rupture and healing on top of a lipid core.
15
Q
What are the main reasons why ST elevation acute coronary syndrome rates or declining in North America?
A
Because of reduced rates of smoking and improved medical therapy.
16
Q
What can cause abrupt thrombotic occlusion?
A
Abrupt thrombotic occlusion can occur with plaques that are not obstructive at baseline, although obstructive plaques are more likely to be metabolically active and lead to clinical syndromes.
17
Q
What are the key components involved in coronary thrombosis?
A
Coronary thrombosis involves endothelial dysfunction, platelet activation, and circulating coagulation proteins.
18
Q
What initiates thrombosis at the site of endothelial injury?
A
The platelet is a central actor for thrombosis! Thrombosis begins with rapid adhesion of platelets to the site of injury.
19
Q
What do activated platelets release to stimulate further activation?
A
Activated platelets release adenosine diphosphate (ADP) which stimulates further platelets, activation and thrombin which initiates the coagulation system.
Thromboxane has additional effect on platelet activation. Thromboxane is generated from platelet phospholipase A2.
20
Q
What is the role of glycoprotein IIb/IIIa receptors in thrombosis?
A
Glycoprotein IIb/IIIa receptors on the platelets are EVENTUALLY activated and bind to fibrinogen, cross-linking platelets together, leading to platelet aggregation.
21
Q
What is the final common pathway in platelet aggregation leading to NSTEMI?
A
The platelet GP IIb/IIIa receptor is the final common pathway in platelet aggregation that can lead to NSTEMI.
22
Q
What is the typical result of complete thrombotic occlusion?
A
Complete (100%) thrombotic occlusion typically results in a transmural myocardial infarction (MI) associated with ST-segment elevation.
23
Q
How is NSTEMI diagnosed?
A
NSTEMI is diagnosed when ischemia is sufficient to cause myonecrosis detectable by serum biomarkers.
With the use of high sensitivity troponins, patients who are usually classified as unstable angina are now diagnosed as NSTEMI.
24
Q
What atypical presentations may occur in ACS?
A
Atypical presentations may include dyspnea, epigastric pain, nausea, syncope, or unexplained tachycardia.
25
What is the preferred cardiac biomarker for diagnosing ACS?
The preferred cardiac biomarker is the troponin assay (cTnI or cTnT). It has very high sensitivity above a 95% for myocardial injury. Cardiac markers may not be elevated in the first four hours after onset of symptoms. Serial biomarkers should be drawn at six or eight hour intervals.
26
What does an abnormal troponin level indicate?
Abnormal troponin levels connote an increased risk for major adverse cardiac events and death. The higher is the concentration, the higher is the risk.
Cardiac troponins are usually very specific above 95% when patients have chest pain.
Ultra high sensitivity, troponin assays above 99% sensitivity may reduce further the time to diagnosis.
27
What is the role of B-type natriuretic peptide (BNP) in ACS?
Elevated BNP levels may reflect either acquired or pre-existing left ventricular dysfunction and are associated with an increased risk of complications.
28
What common misapplication occurs in the diagnosis of ACS?
The diagnosis of ACS is commonly misapplied when high sensitivity troponins are elevated in the absence of chest pain or ECG changes, and this is often due to demand ischemia, heart failure, or renal failure.
29
How do CK and CLMB compare to troponin levels in terms of specificity?
Specificity of cardiac troponin for ACS is reported to be very high, above 95%, if patients have chest pain. The test may be frequently abnormal for many other reasons besides ACS, here you may use CK and CKMB, which are less sensitive but more specific markers in a broader patient population. For example, after PCI, troponin assays are extremely sensitive to clinically silent peri procedural necrosis and do not carry the same prognostic value as elevations in CKMB.
30
What is Type 1 Myocardial Infarction (MI)?
Spontaneous MI related to atherosclerotic plaque rupture, ulceration, erosion, or dissection, leading to decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis.
## Footnote
Requires hsTn values above the 99th percentile URL and at least one of the following: symptoms of acute myocardial ischemia, new ischemic ECG changes, development of pathological Q waves, imaging evidence of new loss of viable myocardium, or identification of a coronary thrombus.
31
What is Type 2 Myocardial Infarction (MI)?
MI secondary to an ischemic imbalance due to conditions other than CAD that contribute to an imbalance between myocardial oxygen supply and demand. Example endothelial dysfunction, coronary spasm, coronary embolism, tachycardia, anemia, respiratory failure, hypertension, or hypertension, or left ventricular hypertrophy.
## Footnote
Requires hsTn values above the 99th percentile URL and evidence of an imbalance between myocardial oxygen supply and demand not related to acute coronary atherosclerosis or thrombosis, with at least one of the following: symptoms of acute myocardial ischemia, new ischemic ECG changes, development of pathological Q waves, or imaging evidence of new loss of viable myocardium.
32
What is Type 3 Myocardial Infarction (MI)?
MI resulting in death when biomarker values are unavailable, with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG changes or VF.
## Footnote
Occurs when patients die before blood samples for biomarkers can be obtained or before increases in cardiac biomarkers can be identified.
33
What is Type 4a Myocardial Infarction (MI)?
MI related to Percutaneous Coronary Intervention (PCI) defined by elevation of cardiac biomarker values >5 × 99th percentile URL in patients with normal baseline values ( Baseline values means below 99th percentile URL) . It is also defined as a rise of cTn values above 20% if the baseline values are elevated and are stable or falling.
## Footnote
Requires symptoms suggestive of myocardial ischemia, new ischemic ECG changes or you left bundle branch block, angiographic loss of patency off a major coronary artery or a side, branch or persistent slow flow, or no flow or embolization or imaging evidence of new loss of viable myocardium.
34
What is Type 4b Myocardial Infarction (MI)?
MI associated with stent thrombosis detected by coronary angiography or autopsy in the setting of myocardial ischemia.
## Footnote
Requires a rise and/or fall of cardiac biomarker values with at least one value above the 99th percentile URL.
35
What is Type 4c Myocardial Infarction (MI)?
MI after PCI caused by stent restenosis or restenosis after balloon angioplasty in infarct territory ( no thrombus )
## Footnote
Requires a rise and/or fall of cTn values above the 99th percentile URL, applying the same criteria utilized for type 1 MI.
36
What is Type 5 Myocardial Infarction (MI)?
MI associated with Coronary Artery Bypass Grafting (CABG) defined by elevation of cardiac biomarker values >10 × 99th percentile URL in patients with normal baseline values.
## Footnote
Requires new pathological Q waves or new left bundle branch block, angiographic documented new graft or native coronary artery occlusion, or imaging evidence of new loss of viable myocardium or new wall motion abnormality.
37
What are the changes in concentration of troponin that are most helpful in differentiating acute from chronic causes of myocardial damage?
A rise of 20% typically is used as a criterion for an acute injury specially in patients with renal failure, heart failure, or left ventricular hypertrophy.
38
What are the recommended anti-ischemic therapies in Class I?
1. Bed rest with continuous ECG monitoring
2. Supplemental oxygen in patients with respiratory distress or hypoxemia
3. Nitroglycerin for ischemic symptoms, heart failure, or hypertension
4. Calcium blockers for patients without shock, heart failure, or heart block
5. ACE-inhibitors or angiotensin receptor blockers within 24 h in patients with left ventricular dysfunction
39
What are the recommended anti-ischemic therapies in Class II?
1. Morphine for chest discomfort refractory to nitroglycerin
2. Intravenous ß-blockers for patients without contraindications
40
What is the purpose of anti-ischemic therapies?
Anti-ischemic therapies reduce myocardial oxygen demand or increase myocardial oxygen supply.
41
What nonpharmacologic therapies are included in anti-ischemic therapies?
Bed rest and supplemental oxygen.
42
What is the role of nitroglycerin in anti-ischemic therapy?
Nitroglycerin can cause coronary vasodilatation and increase myocardial blood flow. While beta blockers and calcium channel blockers reduce myocardial demand by reducing heart rate, contractility and afterload.
43
What should be avoided when administering B-blockers?
B-blockers should not be administered for patients with shock, heart failure, or heart block.
44
What tools can be used for risk stratification in UA/NSTEMI?
Risk-stratification models such as the TIMI or GRACE risk score.
45
What is the TIMI risk score used for?
The TIMI risk score is used for identifying patients at high risk for cardiovascular death, recurrent MI, or urgent revascularization. This score in particular is simple but has a less discriminating power.
Patients with Low risk (Timi score below 3 ) are candidates for a conservative approach whereas patients with a moderate or high score or best treated with invasive approach.
46
What are the components of the TIMI risk score?
1. Age >65
2. >3 CAD risk factors
3. Prior coronary stenosis of >50%
4. ST-segment deviation on presentation
5. Two anginal events in prior 24 h
6. Use of aspirin in prior 7 d
7. Elevated serum biomarkers
47
What are the risk levels associated with TIMI scores?
Patients at low risk for cardiac events have a TIMI score <3 and a GRACE score <108.
48
Give the rational behind using morphine and unstable angina or NSTEMI
Morphine is reserved for ANGINA refractory to nitroglycerin. By relieving pain and anxiety this also reduces myocardial oxygen demand.
49
What are the components of Grace score?
1- age.
2- heart rate and pulse.
3- systolic blood pressure.
4- killip class
5- ST segment deviation.
6- cardiac arrest during presentation.
7- creatinine level.
8- positive initial cardiac bio markers.
50
What is recommended for risk stratification of bleeding risks?
Risk stratification of bleeding risks is recommended to guide the choice of pharmacology, strategy, and access site.
51
What is the correlation between major bleeding and adverse outcomes in ACS?
Major bleeding requiring blood transfusion has been strongly correlated with adverse outcomes in ACS, including mortality.
It is likely due to the need to discontinue beneficial, antithrombotic medications when bleeding occurs. Blood transfusions may themselves exhibit immunosuppressant effect leading to complications.
52
What strategies might benefit a high-risk bleeding patient?
A high-risk bleeding patient might benefit from a strategy of bivalirudin or radial access, or a conservative approach with fondaparinux.
53
What scoring systems have been developed for bleeding risk stratification for ACS ?
Multiple bleeding scoring systems have been developed, with common risk factors including female gender, advanced age, renal insufficiency, diabetes, shock, baseline anemia, and extremes of weight. Most of those scoring systems were validated, using femoral access and become less valid when radial access approach is chosen.
54
What do the TIMI and GRACE scores indicate in ACS ?
The TIMI and GRACE scores generally stratify patients adequately, but other conditions not included in the model may place patients at higher risk for cardiac events.
For example, renal insufficiency, diabetes, and left ventricular dysfunction are conditions that would favor invasive strategies over conservative management.
Low risk, patient, for example, women with a negative bio markers, and patients at high risk for bleeding complications probably favor conservative strategy.
Routine invasive approach is usually for patients with moderate to high risk for cardiac complications from acute coronary syndrome. Low risk patient benefit less of invasive strategy.
55
What is the indication for an early invasive approach?
An early invasive approach within the first 24 hours is indicated if hsTn levels are elevated, GRACE score is >140, or if there are new dynamic ST segment changes.
Urgent revascularization is left for hemodynamic instability and significant ischemia.
The above strategies show reduction in complications and better outcomes.
56
What did the meta-analysis of seven trials demonstrate concerning invasive approach in ACS ?
The meta-analysis demonstrated a reduction in all-cause mortality, recurrent MI, and recurrent unstable angina with a routine invasive approach in patients with moderate to high risk of cardiac complications from ACS, compared to a conservative approach.
57
What did the TIMACS trial reveal about early invasive strategies?
The TIMACS trial demonstrated that an early invasive strategy within the first 24 hours was associated with a significant reduction in refractory ischemia and overall better MACE reduction, when compared to delayed invasive strategy above 36 hours, particularly in the high risk patients. So do not delay beyond 24 hours.
Patients with very high risk, including heart, failure, refractory angina, hemodynamic instability should be taken urgently to Cathlab.
58
What is the proportion of ACS patients requiring CABG during hospitalization?
Approximately 10% of ACS patients require CABG during their initial hospitalization, with less than 2% requiring emergency surgery.
In general, we can rely on syntax score to guide whether bypass would be advantageous for the patient.
The benefit of preloading with clopidogrel or Ticagrelor before PCI, for acute coronary syndrome, remains debatable and may be limited only to clopidogrel because of its slower onset of action.
In current clinical practice, only 40% of ACS patients are preloaded prior to PCI, due to concerns of delaying bypass surgery when needed.
P2Y 12 inhibitors should be discontinued for five days prior to urgent bypass.
59
What is the role of aspirin in ACS treatment?
Aspirin irreversibly binds and inhibits platelet COX-1, inhibiting thromboxane A2 formation for the lifetime of the platelet.
60
What is the recommended loading dose of aspirin?
A loading dose of 162 to 325 mg of plain (not enteric-coated) aspirin is recommended to be chewed and swallowed.
Aspirin irreversibly binds and inhibits platelet cyclooxygenase type one, inhibiting thromboxane A2 formation for the lifetime of the platelet, which is seven days.
Platelet inhibition with aspirin is relatively considered weak inhibition.
61
What are ADP receptor antagonists used for?
ADP receptor antagonists inhibit ADP-induced amplification of platelet aggregation. These are ticlopidine, clopidogrel, prasugrel and ticagrelor .
Dual anti therapy with aspirin and ADP receptor antagonist or GP 2B3 inhibitors is recommended for all patients with ACS at medium to high risk in whom an invasive strategy is planned.
62
What are the risks associated with clopidogrel?
Clopidogrel is a prodrug and requires a two-step hepatic conversion to its active metabolite, and its clinical effect on platelet aggregation is variable among patients. This may be due to variations in cytochrome P450 system specially CYP2C 19.
Patients who are poor metabolizers of clopidogrel are at high risk for ischemic events. The use of genetic testing to identify such patients are not yet shown to be effective in reducing thrombotic risk
Its active metabolite, irreversibly binds and inhibits ADP receptor P2Y 12 . 600 mg loading dose have a more rapid onset of action than 300 mg loading dose and it’s in general preferred.
Onset of action is about 2 to 4 hours.
For patient with acute coronary syndrome, it is recommended for up to 12 months.
If patients are allergic to aspirin, then use clopidogrel.
It should be discontinued for five days prior to major surgery like cardiac surgery.
63
What did the CURE trial demonstrate regarding clopidogrel?
The CURE trial demonstrated that clopidogrel 300 mg/75 mg, when added to aspirin, reduced the risk of cardiovascular death, MI, or stroke in patients with NSTE-ACS.
Within this trial, only 20% of patient received PCI, the benefit, however, were more pronounced within the PCI group.
Like all other P2Y12 inhibitors, preloading prior to cath is debatable.
64
What is prasugrel and how does it work?
Prasugrel is a thienopyridine prodrug that irreversibly inhibits the ADP receptor and exhibits a high degree of platelet inhibition.
Onset of action is really quick around 30 minutes perhaps explaining why the ACCCOAST trial demonstrated no benefit to upfront use or preload compared with PRASUGREL administered following PCI.
65
What was the outcome of the TRITON-TIMI 38 trial?
The TRITON-TIMI 38 trial randomized 13,600 patients with acute coronary syndrome including 74% non-ST elevation MI to either PRASUGREL 60/10 or clopidogrel 300/75. For non-ST elevation patients, the drug was given after diagnostic angiography. The study showed that prasugrel was more effective than clopidogrel, in terms of cardiovascular death, stroke, and MI. This was mainly driven by recurrent MI.
The rate of major bleeding was increased, including fatal bleeding,, and CABG related bleeding.
PRASUGREL is contraindicated in patient with history of stroke or TIA, patients older than 75 year and patient with low body weight below 60 KG. These patient tend to have higher risk of bleeding so no net benefit with PRASUGREL over clopidogrel.
66
Is there any randomized trial comparing PCI and CABG ?
No, there are no Randomized trials comparing PCI versus CABG, specifically in patients with ACS.
The same revascularization approach is used in both stable coronary artery disease and acute coronary syndrome, to decide about PCI versus CABG.
67
What is the recommended dose of aspirin for acute coronary syndrome?
162 to 325 mg loading dose followed by daily dose of 75 to 100 mg.
Nonsteroidal inflammatory drugs interfere with antiplatelet effect of aspirin and have been associated with increased cardiovascular risk and should be discontinued on hospital admission.
68
What is the main side effect for ticlopidine ?
Thrombotic thrombocytopenic Pupura.
It is not used anymore. Patient who had allergy to clopidogrel were given this drug but now with the new agents, the drug is not used anymore.
69
What are the main facts about clopidogrel and aspirin and risk of GI bleeds?
Clopidogrel and aspirin increase the risk of G.I. bleeding. Omeprazole may inhibit clopidogrel metabolism, however, in one of the studies called COGENT, omeprazole did not show clinical effects in terms of clopidogrel inhibition. This applies also to all other proton pump inhibitors.
Guidelines still require patients with prior G.I. bleeding to be treated with a non-omeprazole proton pump inhibitor.
70
What are the similarities between prasugrel and clopidogrel?
They are both thienopyridine pro drugs. They both require a two step metabolism but for prasugrel, one step is rapidly mediated by serum esterases. Therefore, PRASUGREL exhibits a high degree of platelet inhibition, regardless of CYP inhibitors or variants. The duration of effect is longer than clopidogrel at 5 to 10 days and it should be discontinued seven days prior to any major surgery.
71
What is Ticagrelor?
Ticagrelor is a newer ADP-receptor antagonist called a cyclopentyl-triazolo-pyrimidine.
72
How does Ticagrelor bind to its receptor?
It binds reversibly to the P2Y12 receptor.
73
What is the half-life of Ticagrelor?
Ticagrelor has a half-life of 12 hours.
74
Does Ticagrelor require metabolism for activity?
No, Ticagrelor requires no metabolism for activity. it has a very rapid onset.
75
What is the onset of action for Ticagrelor?
It exhibits a rapid onset of action.
76
How often must Ticagrelor be administered?
Ticagrelor must be administered twice daily.
77
What is the recommended duration to hold Ticagrelor prior to CABG?
The drug has a fairly shorter half life and reversible inhibition.
Ticagrelor may be held for as little as 1 to 3 days prior to CABG, although 5 days is preferred.
78
What are common side effects of Ticagrelor?
There is up to a 15% rate of dyspnea and an increase in bradycardia. symptoms may be confusing and complicating symptoms following MI.
79
What was the PLATO trial?
The PLATO trial randomized 18,624 patients with ACS to clopidogrel 300/75 or ticagrelor 180/90.
80
What were the results of the PLATO trial regarding major adverse cardiovascular events?
Major adverse cardiovascular events were reduced from 11.7% in the clopidogrel group to 9.8% in the ticagrelor group.
81
What was the overall mortality benefit of Ticagrelor compared to Clopidogrel?
Ticagrelor had an overall mortality benefit of 4.7% vs 9.7%.
More importantly, there was no difference in the rate of major bleeding compared with clopidogrel.
Of equal importance, overall mortality benefit was found with Ticagrelor compared to clopidogrel, and this was driven by reductions in cardiovascular death.
The drug has become the oral anti-platelet agent of choice with a caveat of higher cost, and higher rate of intolerance.
82
What are Glycoprotein IIb/IIIa inhibitors?
They are intravenous agents that inhibit the final pathway of platelet aggregation: binding of platelet to fibrinogen.
83
What are examples of Glycoprotein IIb/IIIa inhibitors?
Examples include abciximab, eptifibatide, and tirofiban.
These agents exhibit, high-level of platelet inhibition more than 90% inhibition, causing reduced ischemic complications, more than 9% relative risk reduction of ischemic complications, however, at the expense of increased risk of bleeding in patients with acute coronary syndrome.
84
What is the risk of thrombocytopenia with GPI use?
The risk of thrombocytopenia is 0.5%-5.6%. This may be specially profound with repeated use of abciximab which is a monoclonal antibody.
85
What is the half-life of eptifibatide and tirofiban?
They have a relatively short half-life of ~2 hours. They are relatively safe for CABG, six hours after administration.
Whereas Abciximab effect is around 48 hours, requires platelet transfusion, in the case of excessive bleeding.
86
What is the prolonged effect of abciximab?
Abciximab has a prolonged effect of 48 hours.
87
When is it reasonable to delay the administration of GPI agents?
It is reasonable to delay until the time of PCI. The upstream treatment is not necessary because it is balanced by increased risk of bleeding so there is no real benefit of upstream use before starting the PCI ( upstream means like preloading, as if u give it way before you start the procedure)
88
What is Cangrelor?
Cangrelor is an intravenous, direct-acting ADP inhibitor. The drug is rapidly acting and rapidly reversible. The plasma half life is around 3 to 5 minutes, and the platelet function normalize within one to two hours after discontinuation.
89
What is the plasma half-life of Cangrelor?
The plasma half-life of cangrelor is 3 to 5 minutes.
90
What were the results of the CHAMPION-PHOENIX trial?
Cangrelor demonstrated a reduction in the primary ischemic endpoint (4.7% vs 5.9%). There was increase in minor bleeding like small hematoma.
The drug was compared against 600 mg loading dose of clopidogrel administered immediately before PCI or after PCI.
91
What is the recommendation regarding the administration of Cangrelor before clopidogrel or prasugrel?
Cangrelor should be discontinued prior to the administration of clopidogrel or prasugrel. The drug inhibits binding of clopidogrel and PRASUGREL metabolites to the P2 Y 12 receptor. Therefore the drug is less helpful in bridging to these oral antiplatelet agents.
The binding of TICAGRELOR is NOT affected by cangrelor.
There was no head to head comparison between the drug and drug pre-treatment with clopidogrel, or against other P2 Y 12 receptor inhibitors or against GPI.
The drug has a very good safety profile and maybe a safer alternative to GPI.
92
What should you understand about major trials for GP 2B3 inhibitors?
Trials were conducted before the availability of clopidogrel, putting their ischemic benefits in question in the current era of dual antiplatelet therapy.
93
What is the primary benefit for using GP2b3a inhibitors?
– Patients treated with invasive approach.
– The highest benefit is in patients with elevated Timi risk score above 4, specially, those with positive troponin assays.
– there is no clear, benefit for use in patients who are managed conservatively with DAPT like aspirin and clopidogrel
94
What are other possible indications for GP 2B3A inhibitors?
The use of GPI has decreased with availability of bivalirudin and more Potent P2 Y12 inhibitors.
However, in some patients who do not receive a loading dose of clopidogrel before PCI, GPI has a class 2a recommendation.
ACS and specially, STEMI patients have high platelet activation level and there is some delay onset for all oral P2 Y 12 inhibitors. This will increase the risk of acute stent thrombosis, PARTICULARLY when bivalirudin is used. GPI here may work as a bridge until oral agents take effect. (Same strategy like Cangrelor ) .
95
What is Unfractionated Heparin (UFH)?
UFH is a mixture of polysaccharide molecules, one-third of which contain the key pentasaccharide sequence that binds to antithrombin.
96
How does UFH work?
UFH binds to antithrombin, which is then activated to inhibit factor Xa and thrombin.
97
What is the goal aPTT for monitoring UFH?
The goal aPTT is 50 to 75 seconds, or 1.5 to 2.5 times the upper limit of normal.
98
What is the goal ACT for PCI when using UFH?
The goal ACT is 250 to 350 seconds, or 200 to 250 seconds if using a GPI.
99
What are typical bolus IV UFH doses in the catheterization laboratory?
Typical bolus doses are 70 to 100 IU/kg, or 50 to 60 IU/kg with GPIs.
100
What is the recommendation for continued anticoagulation after a successful PCI?
Continued anticoagulation is not recommended due to increased bleeding risk without ischemic benefits.
101
What are Low-Molecular-Weight Heparins (LMWH)?
LMWH includes heparin derivatives like enoxaparin, tinzaparin, and dalteparin, with a more consistent dose-response relationship than UFH.
102
How do LMWHs work?
Similar to UFH, LMWH binds to antithrombin, causing inhibition of factor Xa and thrombin.
103
What is the preferred method for monitoring LMWH effects?
The anti-factor Xa assay is preferred, but is not routinely available on a rapid basis.
ACT ( activated clotting time ) however, does not reliably measure low molecular weight heparin.
Monitoring of low molecular weight heparin effect is usually unnecessary except for some extreme cases like severe obesity or patients with renal insufficiency with a creatinine clearance below 30 ML per minute.
104
What is the therapeutic dose of enoxaparin for ACS?
The therapeutic dose is 1 mg/kg SQ every 12 hours, or 0.75 to 1 mg/kg IV for elective PCI, where no other anticoagulant has been administered.
105
What is a recommended booster dose of enoxaparin for PCI?
An additional IV booster dose of 0.3 mg/kg is recommended if PCI is performed 8 to 12 hours after the prior SQ dose ( particularly if fewer than three previous SQ doses have been received by the patient )
Switching from one anticoagulant strategy to another for example from low molecular weight heparin to unfractionated heparin is associated with increased bleeding risk and is discouraged.
106
What was the finding of early studies comparing LMWH to UFH in ACS?
Early studies showed a reduction of MI (10.1% vs 11%) without increases in bleeding. nevertheless, many of these trials were performed without any invasive approach, putting the benefit in question.
107
What did the SYNERGY trial demonstrate regarding enoxaparin and UFH?
The SYNERGY trial of 9978 patients undergoing PCI for non-ST elevation ACS, demonstrated equivalent efficacy between enoxaparin and UFH (14% vs 14.5%) with more TIMI-major bleeding events (9.1% vs 7.6%).
Bleeding events were possibly due to switching of anticoagulation strategies.
108
What are the advantages of LMWH over UFH?
Advantages include lack of monitoring, ease of administration, and lower risk of heparin-induced thrombocytopenia.
The lack of monitoring can be a double edged sword because the inability to assess the adequacy of anticoagulation at the time of PCI may be perceived as a risk.
109
What is fondaparinux?
Fondaparinux is a synthetic pentasaccharide derived from the binding regions of UFH and LMWH . It inhibits factor Xa with antithrombin at high potency.
110
What is the standard dose of fondaparinux?
The standard SQ dose of fondaparinux is 2.5 mg daily.
111
What were the results of the OASIS-5 trial regarding fondaparinux?
Compared with LMWH, Fondaparinux demonstrated noninferiority for ischemic complications and decreased major bleeding from 4.1% to 2.2%. Major bleeding was associated with mortality, which was reduced with Fondaparinux.
112
What is the recommendation for fondaparinux in ACS?
Fondaparinux carries a Class I recommendation for anticoagulation for ACS. But with lower level of evidence, then UFH, LMWH or bivalirudin.
113
Why has fondaparinux not been widely accepted by interventionalists?
It has not been widely accepted due to the small risk of catheter thrombosis.
This can be avoided with a standard bolus of UFH ( 85 IU per KG or 60 IU per KG with GPI ) given at the time of PCI.
It is the preferred agent for patients when a conservative, non-invasive approach is selected.
114
What is Bivalirudin?
Bivalirudin is a direct thrombin inhibitor that does not require antithrombin as a cofactor. It inhibits both free thrombin and fibrin-bound thrombin, which may increase its efficacy in ACS.
The drug generates a predictable anticoagulant effect that can be measured with a PTT and ACT. Repeated measurements are not required.
115
How is Bivalirudin administered?
Bivalirudin is given as an IV bolus of 0.75 mg/kg, with an infusion of 1.75 mg/kg/h. It is excreted by the kidney, and the infusion must be dose-adjusted in renal insufficiency.
116
What was the ACUITY trial?
The ACUITY trial was a randomized, open-label trial of 13,819 patients with ACS planned for an invasive strategy, comparing heparin with GPI, bivalirudin with GPI, or bivalirudin alone. Patients were on aspirin and clopidogrel loading.
117
What were the findings of the ACUITY trial?
There was no difference among all three groups with respect to composite ischemia endpoints . The trial demonstrated a reduction in major bleeding in the bivalirudin alone strategy.
40% of patients within this trial did not have positive biomarkers and did not receive PCI (which lead to ISAR REACT 4 trial ) .
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What is the net clinical outcome in the ACUITY trial?
Bivalirudin alone strategy show a net clinical outcome ( risk of major bleeding added to the risk of major adverse cardiac events) reduced from 11.7% to 10.1% with bivalirudin compared to heparin with GPI.
Crossover from heparin to bivalirudin did not result in excess bleeding and may have had a beneficial effect on ischemia.
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What was the ISAR-REACT 4 trial?
The ISAR-REACT 4 trial tested 1721 patients with NSTEMI receiving PCI, comparing UFH with GPI to bivalirudin alone. The trial used a more rigorous definition of major bleeding, then in the acuity trial.
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What were the results of the ISAR-REACT 4 trial?
The trial demonstrated equivalent ischemic efficacy of bivalirudin compared with UFH + GPI, but with decreased major bleeding (2.6% vs 4.6%, P = .02).
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What was the MATRIX trial?
The MATRIX trial randomized 7213 ACS patients to bivalirudin (with or without an extended infusion) or heparin with selective GPI.
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What were the findings of the MATRIX trial?
There were no significant differences in MACE or net adverse clinical events, between heparin with GPI and bivalirudin alone, including bleeding, but the risk of stent thrombosis was higher with bivalirudin. Continuation of bivalirudin infusion after PCI did not change the results.
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What did the BRIGHT-4 trial demonstrate?
The BRIGHT-4 trial showed that bivalirudin with a bolus and high-dose infusion for 2 to 4 hours, reduced major bleeding and mortality in STEMI patients compared with heparin monotherapy.
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What is the overall conclusion regarding Bivalirudin based on several metaanalysis?
Bivalirudin is equivalent to heparin in terms of ischemic MACE, with a reduction in bleeding risk but an increased risk of acute stent thrombosis.
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What is included in optimal postprocedure care?
Optimal care should include referral for cardiac rehabilitation, smoking cessation assistance, and medical management of heart failure, arrhythmias, and risk factors.
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What is the recommendation for dual antiplatelet therapy after ACS?
Dual antiplatelet therapy should be continued for 12 months after ACS, with prasugrel or ticagrelor preferred.
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What additional antithrombotic treatments are available?
Antithrombotic treatment beyond dual antiplatelet therapy is available for selected high-risk patients, with benefits shown for low-dose rivaroxaban and the PAR-1 antagonist vorapaxar, but with increased bleeding risk.
