Upon arrival patient’s chest pain had resolved with SL NTG, morphine, and metoprolol 5mg IV. Presentation and findings were consistent with a NSTEMI
Given patient’s prior cardiac history and presence of other risk factors, she was scheduled for a cardiac catheterization in the AM once her INR is reversed to < 1.8
Patient underwent an uncomplicated cardiac catheterization and received DES to her mid-LAD and proximal circumflex. She was loaded with clopidogrel and continued on her aspirin.
She was restarted on her warfarin and bridged with UF heparin until her INR ≥ 2
The day prior to discharge the patient was started oral antibiotics for a positive UA concerning for UTI that was consistent with the patients complaint of dysuria and self-reported history of UTIs
Medication changes/additions at discharge
Added clopidogrel 75mg daily
Increased metoprolol XL to 50mg daily
Increased enalapril to 15mg twice daily
Increased atorvastatin to 80mg qpm
Added Bactrim DS 1 tablet BID x 7 days
Five days post-discharge the patient presents to her anticoagulation clinic for routine follow up and is referred to the ER due to an INR of 9.8 with no overt signs or symptoms of hemorrhage with the exception of increased bruising on her bilateral upper and lower extremities, but can remember injuring herself.
What are the clinical issues that need to be addressed in this case?
Clopidogrel (Plavix®) – duration of therapy?
Dual antiplatelet therapy + anticoagulation with warfarin, is it really necessary? Which can I stop?
Does the patient have to stay in the hospital until her INR is at goal?
Dealing with drug-drug interactions before they impact the patient
Supratherapeutic INRs – when to watch, when to reverse and how to reverse
What if this patient had presented with a STEMI rather than NSTEMI or unstable angina?
Clopidogrel and duration of therapy
Rx: Clopidogrel 75mg po daily, #30, PRN refills for anyone with a new DES stent
Due to the risk of late in-stent thrombosis with DES, current clinical practice and most guidelines recommend a minimum of one year following stent placement
Dual antiplatelet therapy + anticoagulation with warfarin, are all three necessary?
If indicated, yes. It is necessary especially in patients with an indication for anticoagulation with CAD recently having a stent placed within the last 12 months
Clinical decision of risk vs. benefit in others
Low Molecular Weight Heparins
Agents: Enoxaparin, Dalteparin, Tinzaparin
Fairly consistent level of anticoagulation if dosed appropriately
Allows for decreased length of stay
Calculate CrCl, don’t just look at the SCr (especially in pts ≥ 75yrs of age)
$$$ - without Rx insurance coverage (and sometimes with)
Monitoring (anti-Xa levels) – not readily available at all clinical labs
Limited data in certain cardiac disease states (e.g. mechanical heart valves)
What if this patient had a listed heparin allergy?
What are the alternatives for anticoagulation?
Factor Xa inhibitor (synthetic pentasaccharide)
Once daily SQ injection, renal clearance, 17 hr half-life
NO REVERSAL AGENT
Direct Thrombin Inhibitors (DTIs)
Bivalirudin, Argatroban, Lepirudin
NO REVERSAL AGENT
Variable half-life depending on agent
All interfere with INR lab assay (falsely ↑ INR)
Check dosing, then recheck dosing – also important consideration for how the drug is cleared
Drug-Drug Interactions with Warfarin
Assume that 30% to 40% of all drugs you’ll be prescribing over the course of the next 2 to 3 years, and beyond may potentially interact with warfarin
Antibiotics – most either via inhibition of metabolism or alteration in gut flora
**Amiodarone, propafenone, flecainide, quinidine, diltiazem and verapamil
Antidepressants – fluoxetine, fluvoxamine
Statins – simvastatin, lovastatin, fluvastatin and rosuvastatin
Utilizing Vitamin K to Reverse INRs INR Clinical Setting Therapeutic Options < 5 No bleeding Hold warfarin until INR in therapeutic range ± vitamin K 2.5mg po Rapid reversal required Hold warfarin and give vitamin K 1mg IV infusion or 2.5mg po 5 – 8.9 No bleeding Hold warfarin until INR in therapeutic range ± vitamin K 2.5mg po Rapid reversal required Hold warfarin and give vitamin K 1-2mg IV infusion or 2.5mg po ≥ 9 No bleeding Hold warfarin until INR in the therapeutic range and give vitamin K 2.5-5mg po or 1-2mg IV infusion and repeat q24h PRN Rapid reversal required Hold warfarin and give vitamin K 1-10mg IV and may repeat q6-24h PRN Any INR Serious or life threatening bleeding Hold warfarin and give vitamin K 10mg IV infusion and supplement with FFP or PPC or recombinant factor VIIa and repeat as necessary guided by INR
How would your management of this patient differed if she presented with an STEMI?
Immediate treatment is the same as NSTEMI
MONA, UF Heparin or LMWH, clopidogrel
PCI: door-to-balloon within 90 minutes
GP IIb/IIIa therapy post-PCI at discretion of interventionalist – what do you need to know?
Fibrinolytic therapy: door-to-needle w/in 30 minutes of arrival if PCI not available
Streptokinase, Alteplase, Reteplase, Tenecteplase
Consideration for time from onset of chest pain and time of patient presentation (risk vs. benefit)
Presentation > 24 hrs from onset of chest pain – likely no benefit
What you need to know
All patients receiving fibrinolytic therapy
Aspirin 162 to 325mg
UF Heparin 60 units/kg bolus (max 4000 units) followed by continuous infusion of 12 units/kg/hr (max 1000 units/hr) adjusted to goal aPTT of 50-70 seconds
Dosing differs for each agent
1.5 MU IV over 60 minutes
15 mg IV bolus, then 0.75 mg/kg IV over 30 min (max 50 mg), then 0.5 mg/kg (max 35 mg) over 60 minutes (max total dose = 100mg)
10 units IV x 2, 30 minutes apart
< 60 kg = 30 mg IV bolus
60 to 69.9 kg = 35 mg IV bolus
70 to 79.9 kg = 40 mg IV bolus
80 to 89.9 kg = 45 mg IV bolus
≥ 90 kg = 50 mg IV bolus
Active internal bleeding (not including menses)
Previous intracranial hemorrhage at any time
Ischemic stroke within past 3 months
Known intracranial neoplasm
AVM or aneursym, or suspected aortic dissection
Severe, uncontrolled HTN (> 180/110 mmHg)
h/o ischemic stroke > 3 months
Concurrent use of anticoagulants
Known bleeding diathesis
Traumatic or prolonged CPR (> 10 minutes) or major surgery (< 3 weeks), recent internal bleeding (< 4 weeks)
Active peptic ulcer disease
History of severe, chronic poorly controlled hypertension
Heart Failure Case
81yo male is admitted to the Cardiology service for increased SOB, fatigue and malaise over the past 2 to 3 weeks. Of note his weight has increased 12 kg during this time. The patient reports he had been in his usual state of health, with the exception of a recent gout attack a few weeks ago, his pain was well controlled with colchicine and ibuprofen.
Pertinent Labs : K + 4.6, BUN 45, SCr 2.3, Hct 8.2, Hct 25 (↓ 31), INR 5.2, Digoxin 1.0
Vitals: BP 122/74 , HR 118, SaO2
ECG : atrial fibrillation, QTc = 452 msec
Hospital course: Patient was aggressively diuresed with IV diuretics, warfarin was held until INR within goal range, TEE-guided cardioversion failed, amiodarone was initiated and the patient remained in AF but achieved adequate rate control, patient’s HF symptoms improved significantly following 15-liter net negative diuresis and he was discharged home with clinic follow up in 2 weeks
Medication changes at d/c : ↑ torsemide to 80 daily, amiodarone 400mg daily
Therapeutic Issues to Consider
Drug-disease state interactions
Optimizing diuretic therapy
When to consider using intravenous vasodilators or inotropes in ADHF
HF Drug-Disease State Interactions
Non-steroidal anti-inflammatory agents (NSAIDs)
Inhibition of prostaglandin synthesis - ↓ renal blood flow, compensatory Na+ and fluid retention, blunts diuretic response, and ↑ SVR
Na+ and fluid retention
Often anti-inflammatory of choice in HF pts, secondary to lack of prostaglandin effects
Fluid retention. Contraindication in NYHA Class III and IV
Increased anaerobic glucose metabolism and subsequent elevated lactate levels
Decreased renal function and pulmonary edema-induced hypoxia increased this risk
HF Drug-Disease State Interactions
Class I agents – contraindicated in HF patients
Negative inotropic effect and risk of proarrhythmia
Class III agents – use with caution*
*Amiodarone has been well studied in this population
Others including sotalol and dofetilide use with caution
When do you consider utilizing intravenous agents such as vasodilators and inotropes in heart failure patients?
How do I know which agent to use?
Hemodynamic Profile Assessment Reference: Stevenson LW. Eur J Heart Fail. 1999;1:251. Congestion at Rest Low Perfusion at Rest No No Yes Yes Warm & Dry Warm & Wet Cold & Wet Cold & Dry
Possible evidence of low perfusion
Narrow pulse pressure
Low serum sodium
Hypotension with ACE inhibitor
Renal dysfunction (one cause)
Patient Selection and Treatment Reference: Stevenson LW. Eur J Heart Fail. 1999;1:251. Congestion at Rest Yes No Warm & Dry PCWP normal CI normal (compensated) Cold & Wet PCWP elevated CI decreased Cold & Dry PCWP low/normal CI decreased Vasodilators Nitroprusside Nitroglycerin Inotropic Drugs Dobutamine Milrinone Normal SVR High SVR Low Perfusion at Rest No Yes Warm & Wet PCWP elevated CI normal Natriuretic Peptide Nesiritide or
Intravenous Agents for Heart Failure increase; decrease; + effect (number of and qualitatively associated with degree of effect); 0 no effect Reference: Adapted from Young JB. Rev Cardiovasc Med .2001;2(suppl 2):S19. Therapy CO PCWP BP HR Arrhythmia Shorter Onset Longer Offset Dopamine (ng/kg/min) Low (<3) Mod (3 –7) High (7–15) +++ +++ +++ 0 0 0 Dobutamine +++ 0 Milrinone + ++ Nitroglycerin +++ 0 Nesiritide ++ ++ Nitroprusside ++++ 0
HV is a 37 yr old female admitted to the Cardiology service secondary to chest palpitations, SOB and lethargy which have been progressive for the past 4 to 5 days
ECG: atrial fibrillation with RVR (130 bpm)
Patient was initially given 5mg IV metoprolol x 2 without adequate rate control, then received diltiazem 25mg IV x1 followed by a continuous infusion at 5mg/min with adequate rate control. She was also initiated on heparin via continuous infusion.
The following morning the patient underwent TEE-guided cardioversion, which was unsuccessful as a LAA thrombus could not be ruled out, so cardioversion was cancelled.
The patient was converted from IV to oral diltiazem and later discharged home still in atrial fibrillation but with adequate rate control
Clinical Decision Points
Rate vs. rhythm control vs. DCC vs. pharmacologic cardioversion
If you chose rate control which agent would be the most appropriate for this particular patient?
If you chose rhythm control which agent would be the most appropriate for this particular patient?
This case doesn’t mention warfarin, does this patient require anticoagulation?
Approach to treating atrial fibrillation/flutter
How symptomatic is the patient and is there sequela (ischemia, acute pulmonary edema)
Risk vs. benefit of immediate cardioversion
Symptoms uncomfortable but immediately tolerable
Initial therapy should be based on drugs that slow conduction and increase refractoriness of the AV node
Consider etiology of atrial fibrillation/flutter
Precipitated by high states of adrenergic tone (e.g. thyrotoxicosis
So which antiarrhythmic do I choose? Depends – what is the goal of therapy? Rate or rhythm control? Depends – what type of patient are we talking about – age, cardiac history, acuity? † - denotes predominate ion channel interaction, most agents have a multitude of effects responsible for their antiarrhythmic potential Class Specific Antiarrhythmic Agents Mechanism of Action† Role Class I IA IB IC Disopyramide, Procainamide, Quinidine Lidocaine, Mexilitine Propafenone, Flecainide, Moricizine Na+ channel blockade Intermediate Fast on/off Slow on/off A/V V A Class II Metoprolol, Esmolol, etc. Beta-adrenergic blockade A/V Class III Amiodarone, Sotalol, Dofetilide, Ibutilide Dronedarone (pending FDA approval) Potassium channel blockade A/V Class IV Diltiazem, Verapamil Ca++ channel blockade A Misc. Adenosine, Digoxin, Magnesium Agent specific A/V
Considerations for immediate rate control
LVSD (EF < 40%) – use caution, may exacerbate HF
Long-term consideration for rate control
Class Specific Antiarrhythmic Agents Mechanism of Action† Class II Metoprolol, Esmolol, etc. Beta-adrenergic blockade Class IV Diltiazem, Verapamil Ca++ channel blockade Misc. Adenosine (SVT), Digoxin (AF. AFL) Agent specific
Considerations in atrial fibrillation/flutter
Select agents with proven role in atrial arrhythmias
Significant considerations for side-effects and tolerability
Concurrent disease states
Class Specific Antiarrhythmic Agents Mechanism of Action† Role Class I IA IB IC Disopyramide, Procainamide, Quinidine Lidocaine, Mexilitine Propafenone, Flecainide, Moricizine Na+ channel blockade Intermediate Fast on/off Slow on/off A/V V A Class III Amiodarone, Sotalol, Dofetilide, Ibutilide Dronedarone (pending FDA approval) Potassium channel blockade A/V
Via process of elimination
5 remaining agents
Structural heart disease present?
Excludes class I agents (3 remaining agents)
Other patient characteristics
Consideration for drug-drug side-effects
Class Specific Antiarrhythmic Agents Mechanism of Action† Role Class I IA IB IC Side effects preclude long-term use No efficacy in atrial arrhythmias Propafenone, Flecainide Na+ channel blockade Intermediate Fast on/off Slow on/off A/V V A Class III Amiodarone, Sotalol, Dofetilide Dronedarone (pending FDA approval) Potassium channel blockade A/V
Intravenous Antiarrhythmic Dosing Drug Clinical Situation Dose Amiodarone Recurrent VT/VF Cardiac Arrest 150 mg IVPB x 1 over 10 minutes, then 1 mg/min x 6 hrs, then 0.5 mg/min infusion x 18+ hours 150-300mg IV bolus repeated PRN Diltiazem PSVT; rate control AF 0.25 mg/kg IV bolus (may repeat x 1 with 0.35 mg/kg bolus) then 5-15 mg/hr infusion Ibutilide Termination AF 1 mg/10min IVPB, may repeat x 1 Lidocaine VT/VF 100 mg IV push (may repeat x 2), then 2-4 mg/min infusion (1-2 mg/min in HF or liver disease) Magnesium Torsades, VT/VF 1-2 grams in 10ml NS IV push (MR x 2) Procainamide AF (WPW), VT 15-18 mg/kg at 20-50 mg/min IV load, then 1-6 mg/min infusion Verapamil PSVT; rate control AF 5mg IV push (may repeat up to 20mg), then 5-15 mg/hr infusion
4) Nitrates – PDE inhibitors (e.g. Viagra) Synergistic reduction in venous tone resulting in significant hypotension. Avoid combination 5) Warfarin - Rifampin Induces warfarin metabolism – often requires significant increases in warfarin doses by 50-100% within 7-14 days
Top 10 Drug-Drug Interactions in Cardiology Drugs Consequence/Suggested Action 6) Amiodarone – Beta-blockers Potential for bradycardia (and arrhythmias) especially on initiation, monitor for bradycardia 7) Amiodarone – Diltiazem/Verapamil Additive reduction in heart rate and myocardial contraction – monitor for bradycardia or signs of CO 8) Diltiazem/Verapamil - Statins Similar to amiodarone-statin interaction, try to avoid simvastatin, and lovastatin 9) Spironolactone – ACE Inhibitors/ARBs & KCl supplements Clinically indication concomitant therapy in HF, but carries high risk for hyperkalemia, especially with SCr – monitor closely, within 3 to 5 days of initiation or dose escalation 10) Propafenone - Warfarin Increased warfarin effect due to inhibition of metabolism – monitor INRs more closely x 2 weeks, dose reduce PRN