Transcript Chemotherapy Review 2002

Management of Hypertension and
Hyperlipidemia in Hematopoietic
Cell Transplant (HCT) patients
Joseph Bubalo PharmD, BCPS, BCOP
Oncology Clinical Pharmacy Specialist
OHSU Hospital & Clinics
Objectives
• Discuss the unique needs of blood pressure
and lipid management in the HCT
population
• Review selection and individualization of
the different therapeutic options available
for managing hypertension and
hyperlipidemia
Patient Case
• AA is a 27 year old male s/p a sibling donor
HCT for his AML. He is currently day
+125 and doing well. His recent
cyclosporine taper was interrupted due to
GVHD of the skin and bowel which have
responded to treatment with prednisone and
continuation of his cyclosporine at
therapeutic levels.
• His blood pressure has been slowly
creeping up and today is 155/91.
Prevalence of Cardiac Risk
• Autologous and allogeneic HCT experience
higher mortality rates and 2.3 x the risk of
cardiovascular (CV) death in adults
– Similar reports for pediatrics
• Higher rates of CV risk factors
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Increased triglycerides (TG)
Decreased high-density lipoproteins (HDL)
Hypertension
Hyperglycemia (fasting)
Increased waist circumference
Baker KS et al BMT 2012;47:619-25
Hypertension
• Reported in 21-63% of patients
• Solid organ transplant reports 65-100%
incidence
• Calcineurin inhibitors most likely cause
– Cyclosporine (CSA) worse than tacrolimus (FK)
– Sirolimus and mycophenolate less likely to cause
hypertension
– Corticosteroids mixed effects
• At 2 years post transplant hypertension resolved
in 2/3 of patient in one report
Metabolic Syndrome
• Insulin resistance – Primary driver
– Also central obesity, glucose intolerance,
dyslipidemia, hypertension,
– Common among HCT survivors
– Lead to Type II diabetes mellitus (DM) &
atherosclerotic CV disease
• Contribution of HCT related procedures
and complications still unclear
– TBI, high dose chemotherapy, calcineurin
inhibitors, corticosteroids, GVHD, etc
Baker KS et al BMT 2012;47:619-25
Screening
Screen (condition)
Interval/test
Blood pressure (hypertension)
Measure at every healthcare episode
Fasting Lipids (dyslipidemia)
Every 2 years if hypertension or
hypercholesterolemia, every 5 years if
not
EKG/echocardiogram (cardiomyopathy) 2 years after completing therapy then
every 1-5 years depending on treatment
exposures
Fasting glucose (impaired glucose
tolerance/diabetes)
Every 2 years
• Given the well documented increased
cardiovascular risks of people post-HCT the
next steps in the evolution of care is to
identify those at risk early and to implement
interventions to modify those risks or
disease defining events
Chow EJ et al Annals Internal Medicine 2011;155:21-32
Issues/Risk factors
• Older age and cardiovascular disease, esp.
arterial
• Co-morbidities at time of HCT
– Traditional risk factors (obesity, inactivity,
smoking, etc) do not change
• Allogeneic increased hypertension over
autologous
Baker KS et al Blood 2007;109(4): 1765-72
Tichelli A, et al Haematologica 2008;93(8):1203-10
Special patient groups
• Highest risk patients
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Diabetes
Abdominal aortic aneurysm
Carotid stenosis
Peripheral arterial disease
Treating Hypertension
• Hypertension
– Systolic > 140 and/or diastolic > 90
– Diabetics: systolic > 130 and/or diastolic > 80
• Calcineurin inhibitor (CI) -induced
hypertension
– Secondary to renal vasoconstriction and sodium
retention
• Corticosteroids – sodium retention
• Other causes
Treating Hypertension
• Dihydropyridine calcium channel blockers
– Amlodipine, nifedipine (XL only), felodipine,
NO nicardipine
– Verapamil, diltiazem not preferred but may be
useful for cardiac arrhythmias
• Reverses acute vasoconstriction, may limit
CI nephrotoxicity through preferential
dilatation of afferent arteriole
• Rare cases of increased CSA levels
Hypertension in NPO patients
• Intravenous acute care options
– Hydralazine
– Metoprolol
• Topical
– Clonidine
NPO – no oral intake
Alternate Antihypertensives
• Beta blockers – for patients with prior CV
history, monitor heart rate
• Angiotensin converting enzyme inhibitors
(ACE) inhibitors – drug of choice in diabetics,
increased risk for nephrotoxicity, hyperkalemia
• Angiotensin receptor blockers (ARB) – alternate
to ACE inhibitors. Less nephrotoxic?
• Diuretics
• May be preferred depending on co-morbidities
Antihypertensive Dosing
Drug
Starting dose
Maximum
Amlodipine
2.5-5 mg daily
10 mg daily
Felodipine
2.5-5 mg daily
20 mg daily
Nifedipine XL
30 mg daily
180 mg daily
Hydralazine IV
5-10 mg Q 4-6 hours
20 mg q 6 hours
Metoprolol IV
2.5-5 mg Q 6-8 hours
10 mg Q 6 hours
Clonidine (topical)
0.1 mg daily
0.3 mg daily
Treating hyperlipidemia
• Low density lipoproteins (LDL) primary
target (treat if > 100)
– HDL and TG secondary (treat <40 or >500)
• Lifestyle modifications
– Decreased saturated fats and cholesterol
– Increased plant stanols/sterols and viscous fiber
to lower LDL
– Weight control and exercise
Circulation 2002;106:3143-3421
Drug causes of hyperlipidemia
• Glucocorticoids
– affect metabolic pathways increasing weight,
blood glucose, lipids
• Cyclosporine
– Inhibit bile acid synthesis, block LDL receptor
• Tacrolimus
– Less lipid effects than CSA
• Sirolimus, everolimus
– Increase triglycerides and lipids
Hyperlipidemia Treatment
• LDL predominant
– Statins
– Bile acid binders
– Cholesterol absorption inhibitors
• Hypertriglyceridemia
– Omega 3 fatty acids
– Niacin
– Fibrates
Statins
• Not 3A4 metabolized
Preferred
– Fluvastatin 20-80 mg
– Pravastatin 10-80 mg
– Rosuvastatin 5-40 mg
• 3A4 metabolized
– Atorvastatin 10-80 mg
– Lovastatin 20-80 mg
– Simvastatin 20-80 mg
• Avoid use if on azole
• Decrease LDL and TG, Increase HDL
• Monitor transaminases, myositis, rhabdomyolysis
Bile Acid Binders
• Decrease LDL 15-30%
• Colesevelam 3750 mg daily – preferred
– Can dose as once or twice daily
– Dose several hours away from other drugs
– Monitor drug levels (CSA, FK)
• Less absorption issues vs. colestipol or
cholestyramine
• Do not use if high TG
Cholesterol Absorption Inhibitors
• Ezetimibe
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Decrease LDL~15%
10
mg daily
Less potent than statins
Second line agent
• Do not stop but usually not a lot of value to
starting it
Hypertriglyceridemia
• Statins – decrease 7-30%, helpful in mild
disease (<500)
• Niacin - decrease 30-40%
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Use ER dose forms to improve tolerance
Good choice if LDL high as well
No drug interactions
AE: flushing, GI intolerance, increase glucose,
uric acid
Hypertriglyceridemia
• Omega 3 fatty acids - decrease 35-45%
– 2-4 gm daily in 2 doses
– Decrease hepatic production of TG
– Impair platelet aggregation
• Doses > 3 gm/day
– GI upset, diarrhea
Hypertriglyceridemia
• Fibrates - decrease 20-50%
• Use if > 500 mg/dl
– Gemfibrozil 600-1200 mg daily, in 2 doses
– Fenofibrate 45-200 mg daily – preferred
• AE: cholelithiasis, GI upset, myopathy –
increased with statins
• Caution in renal impairment
Monitoring
• Obtain fasting lipid profile pre-transplant
– Start therapy if indicated
• Post HSCT
– Repeat fasting lipid profile 4-8 weeks post
transplant then every 3 months if on
immunosuppression
• Stable patient at goal, check every 6-12
months
• Patient without dyslipidemia every 1-2
years
Griffiths ML et al Blood 2010;116(8):1197-1204
Monitoring
• Challenging in acute care setting post
HSCT
– Effects of TPN
• Intermittent lipids can give false results
– GI chemo toxicity or GVHD may affect med
selection and efficacy/absorption
– Increased drug interaction issues
• Long term follow up clinic more predictable
results
Patient Case AA
• Antihypertensive?
• Fasting lipid panel, then follow up
• Diet intervention vs. medication if indicated
• Individual patient issues that need to be
considered
• Availability for follow-up
Summary
• Management issues
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Adherence
Side effects:
Cost
Monitoring
• Drug interactions
• Success – in general population <30% have
both hypertension and high cholesterol
controlled, since ATPIII < 20% success
with dyslipidemia control
Egan BM et al Circulation 2013;128:29-41