[CK] Warfarin reversal addon. FFP 2units vs 4 units <-> preferred PCC (units per INR) + Vitamin K 10mg IV infusion. Recheck INR in 1hour(30minutes for PCC)

RECOMMENDATIONS • Level 1 Fresh Frozen Plasma (FFP) should be used for emergent reversal of elevated INRs. • Level 2 Dosing of phytonadione (Vitamin K) should be based on the patient’s current INR, risk of bleeding, and future need for anticoagulation (Tables 1 & 2). Reversal of warfarin with Vitamin K should be reserved only for the most serious bleeding events or patients who will not be restarted on warfarin. Vitamin K should be administered either orally or intravenously (IV) only. Oral Vitamin K is the safest and most reliable route. IV Vitamin K should be reserved for rapid reversal in serious bleeding events only. Subcutaneous and intramuscular administration of Vitamin K should be avoided. • Level 3 Initial dose of FFP based on risk of bleeding: Low to moderate risk – FFP 2 units High risk or active bleeding – FFP 4 units INR should be rechecked 1 hour after administration of FFP. Prothrombin Complex Concentrate (PCC) should be administered to patients on warfarin with an INR >2 AND evidence of intracranial hemorrhage on CT scan (Table 3). FEIBA NF 1000 units (one vial) IV push over 5 minutes Check INR 30 minutes after administration Vitamin K should not be administered to patients with prosthetic heart valves, only low doses (1mg) should be used if absolutely necessary. The use of recombinant Factor VIIa may be consider

[CK] Cerebral T-waves (TWI deep symmetric in precordial leads) > 5mm and more than 4 contiguous precordial leads.

neurally induced;
 transient T-wave inversion of ≥5 mm depth in ≥4 contiguous precordial leads.

[R] AAD algorithm.

[CK] Vtach management- lidocaine 1.5mg/kg at 20-50mg/min and repeated 5-10minutes + infusion possible. (same as procaineamide 20-50mg/min - continues. max 17mg/kg) cf) amio 150 1 0.5.

• Intravenous lidocaine (1 to 1.5 mg/kg [typically 75 to 100 mg] at a rate of 25 to 50 mg/minute; lower doses of 0.5 to 0.75 mg/kg can be repeated every 5 to 10 minutes as needed), which may be more effective in the setting of acute myocardial ischemia or infarction
• Intravenous procainamide (20 to 50 mg/minute until arrhythmia terminates or a maximum dose of 17 mg/kg is administered)
• Intravenous amiodarone (150 mg IV over 10 minutes, followed by 1 mg/minute for the next six hours; bolus can be repeated if VT recurs)

HF - Amio or Tikosyn - DOC





normal: sotalol, procainacmide, lido+amio
but
<40% : lido + amio. (Tikosyn?

[CK] Anaphylaxis. 0.5mg EPI IV/IM 3 times and infusion + Methylpred 125mg + Albu 5mg in 3mL Neb. + Benadryl. => IVF and CICU.

Diagnosis is made clinically:

The most common signs and symptoms are cutaneous (eg, sudden onset of generalized urticaria, angioedema, flushing, pruritus). However, 10 to 20% of patients have no skin findings.

Danger signs: Rapid progression of symptoms, respiratory distress (eg, stridor, wheezing, dyspnea, increased work of breathing, persistent cough, cyanosis), vomiting, abdominal pain, hypotension, dysrhythmia, chest pain, collapse.

Acute management:

The first and most important treatment in anaphylaxis is epinephrine. There are NO absolute contraindications to epinephrine in the setting of anaphylaxis.

Airway: Immediate intubation if evidence of impending airway obstruction from angioedema. Delay may lead to complete obstruction. Intubation can be difficult and should be performed by the most experienced clinician available. Cricothyrotomy may be necessary.

Promptly and simultaneously, give:

IM epinephrine (1 mg/mL preparation): Give epinephrine 0.3 to 0.5 mg intramuscularly, preferably in the mid-outer thigh. Can repeat every 5 to 15 minutes (or more frequently), as needed. If epinephrine is injected promptly IM, most patients respond to one, two, or at most, three doses. If symptoms are not responding to epinephrine injections, prepare IV epinephrine for infusion.

Place patient in recumbent position, if tolerated, and elevate lower extremities.

Oxygen: Give 8 to 10 L/minute via facemask or up to 100% oxygen, as needed.

Normal saline rapid bolus: Treat hypotension with rapid infusion of 1 to 2 liters IV. Repeat, as needed. Massive fluid shifts with severe loss of intravascular volume can occur.

Albuterol (salbutamol): For bronchospasm resistant to IM epinephrine, give 2.5 to 5 mg in 3 mL saline via nebulizer. Repeat, as needed.

Adjunctive therapies:

H1 antihistamine*: Consider giving diphenhydramine 25 to 50 mg IV (for relief of urticaria and itching only).

H2 antihistamine*: Consider giving ranitidine 50 mg IV.

Glucocorticoid*: Consider giving methylprednisolone 125 mg IV.

Monitoring: Continuous noninvasive hemodynamic monitoring and pulse oximetry monitoring should be performed. Urine output should be monitored in patients receiving IV fluid resuscitation for severe hypotension or shock.

Treatment of refractory symptoms:

Epinephrine infusion¶: For patients with inadequate response to IM epinephrine and IV saline, give epinephrine continuous infusion, beginning at 0.1 mcg/kg/minute by infusion pumpΔ. Titrate the dose continuously according to blood pressure, cardiac rate and function, and oxygenation.

Vasopressors¶: Some patients may require a second vasopressor (in addition to epinephrine). All vasopressors should be given by infusion pump, with the doses titrated continuously according to blood pressure and cardiac rate/function and oxygenation monitored by pulse oximetry.

Glucagon: Patients on beta-blockers may not respond to epinephrine and can be given glucagon 1 to 5 mg IV over 5 minutes, followed by infusion of 5 to 15 mcg/minute. Rapid administration of glucagon can cause vomiting.

[CK] Amiodarone induced liver failure: stop and MUCOMYST ! 150mg/kg for 1 hour! then 50mg/kg 4hr and 100mg/kr for 16hr.

Concern for hyper acute liver injury secondary to amiodarone

Plan to start Mucomyst--N  acetyl cystine-150 mg IV over 1st our and then 50 milligram/kg infused over 4 hr then 100 milligram/kg infused over 16 hr
Will also start pyridoxine 25 mg p.o. Once daily

[CK] Postcardiac surgery Afib: >24hr = 4 weeks .at 4weeks point = reeval(chads, afib or not, etc.)

SUMMARY AND RECOMMENDATIONS

●Atrial fibrillation (AF) and atrial flutter occur frequently after cardiac surgery. Most episodes occur by the third postoperative day. (See 'Incidence and time course' above.)

●Potential adverse outcomes of these atrial arrhythmias include a longer length of stay, stroke, or death. (See 'Adverse outcomes following AF' above.)

●Beta blockers, sotalol, amiodarone, atrial pacing, and antioxidant vitamins lower the risk of the development of AF and atrial flutter after cardiac surgery and may reduce the length of stay and lower the risk of in-hospital stroke. (See 'Prevention of AF and complications' above.)

•We recommend therapy to prevent the development of adverse events associated with the development of postoperative AF and atrial flutter (Grade 1B). (See 'Our approach to prevention' above.)

•We recommend beta blockers rather than amiodarone or sotalol (Grade 1B). Beta blocker therapy should be started prior to surgery and continued at least until the first postoperative visit unless contraindicated. We prefer oral metoprolol 25 mg twice daily. For patients who cannot take beta blockers, either amiodarone or sotalol may be used, with the decision based on patient characteristics and physician familiarity. (See 'Our approach to prevention' above.)  

•We suggest antioxidant therapy in addition to beta blocker therapy (Grade 2C). We start this therapy two days prior to surgery and continue until discharge. We prefer the regimen of vitamin C (1 gram) and vitamin E (400 international units), each given daily. (See 'Our approach to prevention' above.)  

●For hemodynamically stable patients who develop postoperative AF, the optimal ventricular rate range should be determined for each patient. In many patients, this rate will be less than 110 beats per minute.

●For patients who develop well-tolerated postoperative AF and whose rate is well controlled, we suggest not performing cardioversion within the first 24 hours of its development (Grade 2B). Cardioversion may be required within this time frame for those whose AF is poorly tolerated or whose rate is not well controlled. (See 'Rhythm control' above.)

Cardioversion in asymptomatic patients may be reasonable when well-tolerated AF is present near the time of anticipated hospital discharge, or when it does not spontaneously terminate within 24 to 48 hours, so that oral anticoagulation can be avoided.

●For patients with multiple episodes of AF or one episode that lasts more than 24 to 48 hours, and if the perioperative bleeding risks are considered reasonable, we recommend oral anticoagulation (Grade 1B). (See 'Our approach to postoperative anticoagulation' above.)

We suggest anticoagulation with warfarin (international normalized ratio 2 to 3) rather than either a direct thrombin or factor Xa inhibitor (Grade 2C).

For patients in whom anticoagulation is started and irrespective of the rhythm status at the time of discharge from the hospital, we suggest continuation of anticoagulation for at least four weeks, rather than stopping at the time of discharge (Grade 2C).

[CK] Aortic dissection

LONG-TERM MANAGEMENTThere are three main management issues in patients who have survived the initial dissection: ongoing anti-impulse therapy, in the form of blood pressure lowering, to minimize aortic wall shear stress; evaluation for high-risk clinical conditions; serial imaging to detect signs of dissection progression, re-dissection, or aneurysm formation; and reoperation when indicated.

Anti-impulse therapy — Once heart rate control has been achieved and the patient is tolerating an oral diet, intravenous beta blocker (or other antihypertensive) therapy can be switched to an oral route. All patients should be maintained on lifelong therapy to reduce systemic blood pressure and the rate of rise in systolic pressure, both of which will minimize aortic wall stress [6]. Although not evaluated in controlled trials, we suggest a target blood pressure of less than 120/80 mmHg [6]. Combination antihypertensive drug therapy is usually required. => 120/80 and < 70(HR) 

Though unproven, avoidance of strenuous physical activity that would lead to a spike in blood pressure is also recommended as another method to minimize aortic shear stress. (See "Management of Marfan syndrome and related disorders", section on 'Restriction of strenuous activity'.)

Identifying associated genetic conditions — Similarly to thoracic aortic aneurysm, patients with thoracic aortic dissection should be evaluated for possible underlying genetic or familial disorders known to be related, which may increase their individual risk of progression or complications. Screening (transthoracic echocardiography) first-degree family members for aortic aneurysm (or bicuspid valve) should be considered. (See "Clinical features and diagnosis of acute aortic dissection", section on 'Incidence and associated conditions' and "Management of thoracic aortic aneurysm in adults", section on 'Identifying associated genetic conditions'.)

Serial imaging — We generally perform a baseline thoracic magnetic resonance (MR) or computed tomographic (CT) angiography prior to discharge, with follow-up examinations at 3, 6, and 12 months, and annually thereafter, even if the patient remains asymptomatic (and presuming the patient is a candidate for an intervention) [6,36]. (See 'Reintervention for endograft complications' below and 'Reoperation' below.)

The following abnormalities can be detected on serial imaging:

●Extension or recurrence of the dissection

●Aneurysm formation

●Leakage at surgical anastomotic or stent-graft component overlap sites

MR angiography is as accurate as transesophageal echocardiography (TEE), and because it is noninvasive, it is more acceptable for serial studies. MR angiography does not expose patients to iodinated contrast and ionizing radiation, which are important factors for younger patients who will likely have many years of serial monitoring, though due to concerns about long-term retained gadolinium, noncontrast MR angiography is an option that should be considered. CT angiography is an alternative, but it exposes the patient to considerable ionizing radiation and requires iodinated contrast, which may cause nephrotoxicity.

Alternating CT and MR angiography is a reasonable option for patients with good renal function. Noncontrast MR is an alternative for patients with impaired renal function. Transthoracic echocardiography is not considered a monitoring alternative, but it may be necessary to monitor ongoing valvular dysfunction.

[CK] P2Y12 Study - [Q] Clopidogrel - polymorphism(CYP) <- NOT WITH OMEPRAZOLE(Decrease its absorption)

Clopidogrel activation is prevented by CYP2C19 inhibitors such as fluvoxamine, fluoxetine, omeprazole, and carbamazepine. CYP2C19 polymorphisms influence clopidogrel activation; poor metabolizers (CYP2C19*2/*2, *2/*3, or *3/*3) accrue less benefit from clopidogrel therapy.

he antiplatelet drug clopidogrel (Plavix, and others) reduces major cardiovascular events, but can cause bleeding. Proton pump inhibitors (PPIs) are often used with clopidogrel to prevent gastrointestinal bleeding, however, some evidence suggests that PPIs may interfere with the activation of clopidogrel and diminish its antiplatelet effect. FDA-approved labeling recommends avoiding concurrent use of the PPIs omeprazole and esomeprazole with clopidogrel.

=================================================================

Prasugrel’s drug-drug interactions are limited to weak CYP2B6 inhibition; it has clinically significant interactions with narrow therapeutic window CYP2B6 substrates (eg, cyclophosphamide and efavirenz) only.

Ticagrelor is a CYP3A4 and P-glycoprotein substrate and is liable to cumulative bradycardia with other bradycardic medications (eg, beta-blockers and calcium channel blockers). CYP3A4 and P-glycoprotein inhibitors increase ticagrelor levels, inducers do the opposite, and ticagrelor can increase the concentrations of other CYP3A4 substrates. Ticagrelor can both increase digoxin’s concentration and potentiate digoxin toxicity.

Pharmacists are poised to select the best P2Y₁₂ inhibitor based on stenting history, diabetes diagnosis, gastrointestinal or cerebral bleed history, and pharmacokinetics.

Pharmacists can also stress the importance of adherence, bleeding risk, and agent affordability during discharge counseling following a stenting procedure.

===================================================================
Concerns about PPI use and clopidogrel are now out of date, Dr. Brener asserted, due to the availability of alternative antiplatelet therapies and mounting evidence that the association is not real. Clinicians should instead focus on weighing whether patients need to be on PPIs in the first place, he added.

No problem with 

other PPI  - Plavix (possibility but not)

PPI - ticagrelor = no problem at all! 

[CK] Atropine 0.5mg IV Q5MIN(like NTG)

IV, IM: 0.5 mg every 3 to 5 minutes; maximum total dose: 3 mg

HALF LIFE: 3hours. 

it's ok. 

upto 6 TIMES (3mg) 

[CK] Sildenafil for HFpEF exacerbation - WORSE!!! stop it. (for acute phase)

[CK] Sildenafil for HFpEF exacerbation - WORSE!!! stop it. (for acute phase

[CK] more than 3 times = then consider higher - thalassemia.

RBC x 3 = Hb and Hb x 3 = HCT). This is sometimes referred to as "the rule of threes.

https://www.labce.com/spg226471_hematologic_findings_for_various_types_of_beta_tha.aspx

[CK] STEMI 1mm!(2mm for v2 v3)

[CK] Alpha and Beta 1-beta = negative(reject) and really Ho is not true!(No to Not true = 1-beta = power)!

[CK - Read] JVD. normal (6-8)

https://www.ncbi.nlm.nih.gov/books/NBK300/

[CK] NYHA IIIb(more sick than III. h/o resting SOB)

IIIB	NYHA class III patients who are symptomatic with a recent history of dyspnea at rest
Hellgren L, 200242	IIIB	Patients who managed only the lightest of activity without discomfort
Marini C, 200543	IIIB	Advanced heart failure

[CK SAMPLE] Sx. Dx. DDx. Tx. Px.

	Disease basic information/essential(1p/1ds)
Sx
Dx
DDX
Tx
Px

	Disease basic information/essential(1p/1ds)
Sx
Dx
DDX
Tx
Px

[CK] CK on MAR, APR, MAY(ON THIS SEMESTER ASK EVERYTHING)

1. Upload at CONTENTS session(google WORD) = MAYO, GUIDELINE

(1page per group=forever for teaching. mainly contents, number, table and
 algorithm by handmade picture = email and add on.)
1-CAD
2-EP
3-HF
4-Structural
5-Risk: HTN, DM, HLD, Smoking
6-Basic: EKG, ECHO, LHC, RHC, CTA, CMR, CPET, BIOMARKERS
7-
8-
9-IM

2. GUIDELINE in FILE(YAMA -> finish and review to optimize it to 1page group)

3. RESOURCE folder: blogger, PPT, folder(-> review to optimize it to 1page group)
(mainly whole link, picture, algorithm, and so on)

[CK] first episode VT/VF = no need AAD. But if there is no reversible cause, then consider it to use ! (1) Definitely for recurrent one with ICD shock! (2)

Recurrent VF that is not due to a reversible cause can be treated with intravenous (IV) amiodarone. It decreases AV conduction and sinus node function. It also prolongs action potential and refractory period in myocardium and inhibits adrenergic stimulation. Amiodarone can also be used orally on a long-term basis in patients who refuse ICDs, are not candidates for ICDs, or have frequent ventricular arrhythmias.

[CK] STEMI with Anticoagulation(NOAC, Warfarin, already). INR(2) or NOAC = Heparin or Bivalirudin + Plavix to be loaded. (always thinking about bleeding for triple therapy. but AC needed)

Management of STEMI in Patients on NOACs and Undergoing Primary PCI

NOAC = heparin infusion(bivalirudin preferred) + plavix(triple therapy)

Warfarin ant INR <2 = heparin infusion + plavix

-> radial, BMS(new DES) 

No AC = heparin + ticagrelor or prasugrel(CTx: <60kg, >75yo, TIA~Stroke, bleeding)

-> usual. 

Summary:

1) Radial approach preferred to femoral: lower bleeding risk

(Parentral additional anticoagulation)

2) On Warfarin with therapeutic INR 2-3: NO NEED TO ADD HEPARIN INFUSION
    NOAC with? : NEED TO ADD HEPARIN/BIVALIRUDIN INFUSION

    (Esp. <4HRs of NOAC given, START BIVALIRUDIN INFUSION - lower risk of bleeding)

(P2Y12)

3) On Warfarin: Plavix

     On NOAC: Plavix

     Rather than ticagrelor or prasugrel. 

(REF; Management of the patient with an acute coronary syndrome using oral anticoagulationG.J.A. Vos, N. Bennaghmouch, K. Qaderdan, and J.M. ten Berg) 

Triple therapy is associated with an increased risk of major bleeding. Depending on bleeding risk and indication (stable coronary artery disease or ACS), triple therapy should be given for a short duration (1–6 months) followed by dual therapy (clopidogrel 75 mg/day (or alternatively, aspirin 75–100 mg/day) [6] (Level of Evidence: B)

Novel P2Y12 receptor inhibitors (prasugrel and ticagrelor) should not routinely be part of a triple therapy regimen (only in select cases such as stent thrombosis) (Level of Evidence: C)

4) Preferred stent: BMS or new generation DES for Triple therapy(to make it shorter) 

Oct 22, 2015   |  Jaya Reddy Mallidi, MBBS, MHS , FACC; Amir S. Lotfi, MD

Expert Analysis

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Introduction

Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in everyday clinical practice. In 2010, it was estimated that AF affected 5.2 million Americans, and this number is projected to increase to 12.1 million by 2030.¹ With more than 80% of these patients having an indication for oral anticoagulation,² and approximately 35% of these patients having coronary artery disease,³ interventional cardiologists will increasingly encounter patients with ST-segment elevation myocardial infarction (STEMI) who are on oral anticoagulation. Currently, there is a wide variation in clinical practice in management of these patients due to paucity of literature and lack of consensus guidelines.⁴ With the increasing use of new oral anticoagulants (NOACs) – dabigatran, rivaroxaban, apixaban, edoxban – and advent of new antiplatelet agents – prasugrel and ticagrelor – the clinical decision-making in these patients regarding the choice of access site, peri-procedural antithrombotic and antiplatelet agents, and transition to long-term anticoagulation has become even more complex. This review article will address these issues, which arise in acute management of patients with STEMI who having been taking NOACs, and are undergoing primary percutaneous coronary intervention (PCI).

Arterial Access – Radial vs. Femoral

The optimal approach to arterial access in primary PCI in patients with acute coronary syndrome (ACS) remains controversial. In the RadIal Vs femorAL access for coronary intervention (RIVAL) study, both approaches were noted to be equally safe and effective.⁵ However, in a sub-group analysis of STEMI patients, radial approach was associated with a mortality benefit.⁵ Also, in the Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX (MATRIX) trial, a recent multicenter randomized study of 8404 patients radial compared to femoral access in patients with ACS was shown to reduce the net adverse clinical events through a reduction in major bleeding and all-cause mortality.⁶

Patients on NOACs were not included in either of these trials. In the MATRIX trial, only 1.7% of the patients in each of the groups were on warfarin.⁶ However, in both these studies,^5,6 and in other trials,⁷ radial access has consistently been associated with reduced access site vascular complications compared to femoral access. Also, in studies on patients with uninterrupted warfarin therapy undergoing PCI, with mean international normalized ratio (INR) of 2.4, radial access was associated with reduced bleeding and vascular complications.⁸ Extrapolating these data to patients who are on NOACs, the authors of this Expert Analysis article strongly recommend radial over femoral approach whenever feasible.

Peri-procedural Anticoagulation

The most effective peri-procedural anticoagulation regimen to prevent ischemic complications without increasing the bleeding risk in patients with ACS remains to be defined. When patients on NOACs present with STEMI, the situation is even more complex due to the following concerns:

1. Should additional peri-procedural anticoagulation be used?
   In patients on warfarin with INR in the therapeutic range (2.0-3.0), PCI appears to be safe without the need for additional peri-procedural anticoagulation.⁹ It is unknown if this applies to NOACs. In a small randomized study involving 50 patients on dual antiplatelet therapy (DAPT) undergoing elective PCI, use of peri-procedural dabigatran did not provide sufficient anticoagulation during PCI.¹⁰ In contrast, in a similar small study, peri-procedural rivaroxaban given two to four hours prior to elective PCI appeared to provide adequate anticoagulation without increased risk of bleeding.¹¹ Until there are larger studies proving the safety and efficacy of performing PCI on NOACs without additional anticoagulation, it is recommended to give additional heparin or bivalirudin (and avoid glycoprotein [GP] IIb/IIIa inhibitors) regardless of the last NOAC dose, especially in patients presenting with STEMI where the thrombogenic state is exaggerated compared to patients undergoing elective PCI.¹²
2. How to monitor adequate anticoagulation?
   There is no rapid and reliable laboratory assay to monitor the degree of anticoagulation in patients on NOACs. Activated clotting time (ACT) is routinely used to guide heparin administration during PCI, as the dose of heparin has a linear relationship with ACT level.¹³ In contrast, other anticoagulant agents such as bivalirudin increase the ACT level, but do not have a linear correlation with ACT.¹⁴ Similarly, though ACT is prolonged by NOACs, it cannot be used to gauge the anticoagulant activity.¹² NOACs have a very small dose-dependent, or rather flat dose effect on ACT,^15,16 making it unreliable to use in an acute setting. Other coagulation assays are more time consuming and cannot be used practically in the setting of STEMI. Hence, rather than depending on laboratory assays, in patients taking NOACs, the timing of the last dose taken is of paramount importance.¹² All currently available NOACs reach a peak plasma level within one to four hours after ingestion, and reach the trough level between 12-24 hours.¹² Hence, in patients presenting with STEMI who have taken a NOAC within four hours of presentation, the risk of bleeding when giving additional anticoagulants or antiplatelet agents is at least theoretically higher than those who have taken the last dose of NOAC >12 hours before STEMI presentation. If using heparin as the additional peri-procedural anticoagulant, the routine target ACT level (250-300s) can be used for heparin titration, even in patients who are taking NOACs.¹²
3. Which additional anticoagulant agent should be used – heparin vs. bivalirudin?
   The two most commonly used anticoagulation drugs for primary PCI are bivalirudin (direct thrombin inhibitor) and heparin (indirect thrombin inhibitor), with or without GP IIb/IIIa inhibitors. In the most recent randomized trial involving 7,213 patients with ACS, there was no significant difference in major cardiovascular or net adverse clinical events between these two drugs.¹⁷ However, in this trial, and in other multicenter trials, bivalirudin was consistently noted to have reduced risk of major bleeding complications, including non-access site bleeding complications compared to heparin alone or with a combination of heparin and GP IIb/IIIa inhibitors.^17-19 Patients on NOACs were excluded from all these trials. Hence, it is unknown which of these drugs is a better choice in these patients. Given the consistently low rates of bleeding with bivalirudin compared to heparin, it may be prudent to use bivalirudin in patients who have taken the last dose of NOAC within four hours, and in elderly patients with impaired kidney function who are at increased risk of bleeding complications.

Acute and Long-term Antiplatelet Agents

Acute setting

Patients taking NOACs presenting with STEMI should receive a loading dose of aspirin (325 mg) and a P2Y₁₂ inhibitor.¹² In the randomized trials establishing the efficacy of ticagrelor or prasugrel over clopidogrel, patients on NOACs were not included.^20,21The rate of major bleeding was significantly higher with ticagrelor and prasugrel compared to clopidogrel.^20,21 Though the current practice is highly variable in terms of the initial P2Y₁₂ inhibitor used, in patients taking NOACs, a loading dose of clopidogrel (600 mg) is preferable compared to the newer antiplatelet agents given the lower risk of bleeding associated with clopidogrel.

Long-term antiplatelet and anticoagulation regimen

Patients on triple therapy (DAPT plus oral anticoagulant, warfarin, or NOAC) are at increased risk of bleeding.^22,23 The best regimen and duration of therapy to prevent ischemic complications without increasing the risk of bleeding in patients with AF undergoing PCI is unknown. In the recent What is the Optimal antiplatElet & Anticoagulant Therapy in Patients With Oral Anticoagulation and Coronary StenTing (WOEST) randomized trial among patients requiring chronic anticoagulation therapy, the use of clopidogrel and warfarin without aspirin was associated with significant reduction in bleeding without an increase in the rate of thrombotic events.²⁴ It is unknown if these results could be extrapolated to the NOACs. There are no trials to date among patients requiring oral anticoagulation, comparing single antiplatelet agent (SAPT)/DAPT plus NOAC to SAPT/DAPT plus warfarin in post-ACS patients. Ongoing trials are evaluating various combinations of NOACs and antiplatelet agents in patients with AF undergoing PCI (A Study Exploring Two Strategies of Rivaroxaban (JNJ39039039; BAY-59-7939) and One of Oral Vitamin K Antagonist in Patients With Atrial Fibrillation Who Undergo Percutaneous Coronary Intervention (PIONEER AF PCI) and Evaluation of Dual Therapy With Dabigatran vs. Triple Therapy With Warfarin in Patients With AF That Undergo a PCI With Stenting (RE-DUAL PCI) study). However, until more data are available, the authors of this Expert Analysis article advocate use of triple therapy with warfarin (INR 2.0-2.5) rather than NOACs for the shortest duration possible, depending on the type of stent and individual bleeding risk. Use of bare metal stents or newer generation drug-eluting stents is preferred so as to minimize the duration of triple therapy. However, the latest updated European Heart Rhythm Association (EHRA) guidelines on use of NOACs recommend restarting the same NOAC in combination with SAPT or DAPT after discontinuation of parenteral anticoagulation in patients with ACS, based on expert opinion rather than currently available evidence.¹² It is recommended to reduce the doses of NOACs when combining with DAPT (dabigatran 110 mg twice-daily, apixaban 2.5 mg twice-daily, and rivaroxaban 15 mg once-daily or edoxaban 30 mg once-daily).¹²

In summary, patients with STEMI undergoing primary PCI on NOACs pose a challenging clinical situation to interventional cardiologists. The current literature is limited to guide in the management of these patients in terms of choosing the appropriate antiplatelet and anticoagulation regimens to balance the risk of ischemic events and bleeding. Until further data are available, the authors of this Expert Analysis article recommend use of radial access, loading dose of aspirin and clopidogrel, and additional peri-procedural anticoagulation with heparin or bivalirudin in the acute setting for these patients. Post-ACS, for patients at high risk of embolic events, triple therapy (DAPT plus warfarin or reduced-dose of NOAC) is recommended for as short a duration as possible.

References

1. Colilla S, Crow A, Petkun W, Singer DE, Simon T, Liu X. Estimates of current and future incidence and prevalence of atrial fibrillation in the U.S. adult population. Am J Cardiol. 2013;112:1142-7.
2. Lip GY, Laroche C, Dan GA, et al. A prospective survey in European Society of Cardiology member countries of atrial fibrillation management: baseline results of EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot General Registry. Europace. 2014;16:308-19.
3. Kralev S, Schneider K, Lang S, Süselbeck T, Borggrefe M.. Incidence and severity of coronary artery disease in patients with atrial fibrillation undergoing first-time coronary angiography. PLoS One. 2011;6:e24964.
4. Potpara TS, Lip GY, Dagres N, et al. Management of acute coronary syndrome in patients with non-valvular atrial fibrillation: results of the European Heart Rhythm Association Survey. Europace. 2014;16:293-8.
5. Jolly SS, Yusuf S, Cairns J, et al. Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial. Lancet. 2011;377:1409-20.
6. Valgimigli M, Gagnor A, Calabró P, et al. Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial. Lancet. 2015;385:2465-76.
7. Jolly SS, Amlani S, Hamon M, Yusuf S, Mehta SR. Radial versus femoral access for coronary angiography or intervention and the impact on major bleeding and ischemic events: a systematic review and meta-analysis of randomized trials. Am Heart J. 2009;157:132-40.
8. Baker NC, O'Connell EW, Htun WW, et al. Safety of coronary angiography and percutaneous coronary intervention via the radial versus femoral route in patients on uninterrupted oral anticoagulation with warfarin. Am Heart J. 2014;168:537-44.
9. Karjalainen PP, Vikman S, Niemelä M, et al. Safety of percutaneous coronary intervention during uninterrupted oral anticoagulant treatment. Eur Heart J. 2008;29:1001-10.
10. Vranckx P, Verheugt FW, de Maat MP, et al. A randomised study of dabigatran in elective percutaneous coronary intervention in stable coronary artery disease patients. EuroIntervention. 2013;8:1052-60.
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