Cardiotoxicity + Thrombosis Flashcards
What cardiotoxicity do Anthracyclines (Cytotoxic antineoplastics) cause
- Acute cardiomyopathy
- Chronic heart failure years later (irreversible)
MOA of anthracyclines cardiotoxicity (2)
Thought to be due to:
I. Forms free radicals
II. Destroys cardiomyocytes & mitochondria
Risk increases with greater exposure
* Which is why we limit max dose of doxorubicin
How do we manage cardiotoxicity with anthracyclines
Baseline ECG for everyone before starting
- D/C anthracyclines
- Treat as acute cardiac failure
(diuretics, ACE/ARB, Beta blockers)
What anthracycline do you use if you a patient has mild heart disease and really needs an anthracycline
Dexrazoxone
What is the MOA of cardiotoxicity with Trastuzumab (HER2 blocker)
Reversible/irreversible?
NRG1 binds to human epidermal growth factor receptor 4 –> causes heterodimerization of HER-2 (activates it)
- HER-2 plays a role in cardiac growth, survival and response to stress
- blocking prevents this from happening
Reversible
What are risk factors for trastuzumab cardiotoxicity (7)
- Age 60+
- high BMI 25+
- Alcohol
- Low baseline LVEF
- Prior anthracycline use
- HER-2 polymorphisms
- Hypertension meds
What LVEF criteria do we need to stop the HER2 therapy (trastuzumab) (2)
LVEF reduction of 20%+ or LVEF under 50%
How often do we have to monitor cardiac function if being treated for monoclonal AB and previously treated with anthracycline
Every 12 weeks
What cardiotoxicity does VEGF display? MOA?
Hypertension
- Blocking VEGF leads to vasoconstriction (by reducing NO synthesis)
What to do if patient is hypertensive and wanting to start VGEF (not on any anti-hypertensive meds)
What is the step up therapies
- Amlodipine 5mg (CCB) 3-7 days
- Add ACE inhibitor or ARB
- Add indapamide
- Consider increasing dose of 1+ antihypertensive drug
+/- add low dose spironolactone (if normal renal function and K+ < 4.5)
+/- refer to a clinical
What to do if patient starting VGEF has..
QT prolongration
cardiac ischemia/dysfunction
Thrombosis/hemorrhage
cardiac ischemia/dysfunction
- suspend therapy
Thrombosis/hemorrhage
- no real evidence to manage, monitor
What cardiotoxicity do Tyrosine kinase inhibitors especially sunitinib, Pazopanib
Treatment?
When do you hold drug?
QT prolongation
- Baseline ECG, repeats 2-4 weeks and every 3 months
- avoid QTc prolonging drugs
Hold if:
- QTc > 500msec or rise of 60+ msec from baseline
What cardiotoxicity does fluorouracil cause? How does it present
Coronary vasospasm
Presents as angina-like chest pain with possible ECG changes
What is the treatment for coronary vasopasms with fluorouracil?
Rechallenge or d/c?
- Hold causative agent
- Administer nitrates and/or CCB
- ECG monitor
May be able to restart therapy with nitrates/CCBs as secondary prophylaxis
What cardiotoxicity do BTK inhibitors (ibrutinib) cause
Atril fibrillation
Treatment for afib with BTK inhibitors?
Usually use rate control beta blockers
Assess risk using CHADS2-VASc to see if DOACs need to be used
- used cautiously at a reduced dose
When are BTK inhibitors temporarily stopped? (2)
Uncontrolled afib
OR
Bleeding
What other drugs cause QTc prolongation (5)
ALK inhibitors
Ribociclib (CDK 4/6i)
Osimertinib (EGFRi)
Lapatinib (HER1/EGFRi)
Subitinib and Vandetenib (Multi TKIs)
What cardiotoxicity do carfilzomib (proteasome inhibitor) cause
Treatment?
Drop in LVEF
Treatment:
- monitor closely
What do immune checkpoint inhibitors cause?
Treatment?
autoimmune cardiomyopathy
- present as acute cardiac failure
Treatment
- DISCONTINUE causative agent
- Initiate HIGH-DOSE corticosteroids
When does the highest risk of VTE occur during diagnosis
First 3 months
T/F Patients with cancer have a relatively high risk of recurrent VTE despite anticoagulation
True
What are risk factors for cancer-associated VTE
Patient related
- Age, obesity, hypertension
Cancer related
- site of cancer (prostate, colon, breast, ovary, lung, pancreas)
- Advanced (metastatic)
- Initial 3 months
Treatment related
Biological
- elevated platelet pre-chemi
- tumour associated pro-coagulants
What is the MOA of cancer associated thrombosis
- Sometimes damage to endothelium due to surgery or the tumour itself.
- Activation of platelets via interleukins.
When do we consider VTE prophylaxis in cancer outpatients?
Khorana score of 2-3+
- often not used in real world if ambulatory
Which cancer therapy would prompt you to use prophylaxis against VTE? (2)
Drugs to use (2)
IMiD (immunomodulator) therapy + corticosteroid
Lenalidomide + dex
OR
Thalidomide + dex
ASA in lower risk
LMWH in higher risk
What did the AVERT trial tell us about Apixaban 2.5mg BID in VTE risk
Efficacy
Safety
Decreased VTE risk
Doubled chance of major bleed
What did the CASSINI trial tell us about rivaroxaban 10mg daily in VTE risk
Efficacy
safety
No difference in efficacy or bleed risk than placebo
What do we give for primary prevention of VTE in cancer inpatients
Start on a LMWH until discharge or ambulating
- Tinzaparin, Dalteparin
- Make sure no bleeding or other contraindications
What is the current treatment for cancer associated VTE?
Duration?
LMWH for a minimum of 3 months
- associated with less bleeding than UFH and OAC
Consider lifelong anticoagulation for metastatic disease and receiving chemo
For secondary prevention what do trials say about DOACs vs LMWH
Efficacy
Bleeding
Efficacy
- DOACs and LMWH are non-inferior
Bleeding
- All DOACs cause more NON-major bleeding, and GU bleeds compared to LMWH
- Equivalent major bleeds
When is LMWH preferred in secondary prevention (6)
- High risk of bleeding
- GI cancer (or GI malabsorption)
- GUrinary/uterine cancer
- Interaction with DOAC
- Uncontrolled CINV
- Obese, underweight
When would we consider DOACs in secondary prevention
If the patient does not meet LMWH preferred criteria
- Lower risk patients
- Not on a known CYP3A4
- Low incidence of NV
- Strongly dislike injection
