Management of Hypertension and Hyperlipidemia in Hematopoietic Cell Transplant (HCT) patients

1
Management of Hypertension and Hyperlipidemia in
Hematopoietic Cell Transplant (HCT) patients

• Joseph Bubalo PharmD, BCPS, BCOP
• Oncology Clinical Pharmacy Specialist
• OHSU Hospital Clinics

2
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

3
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.

4
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
• Increased triglycerides (TG)
• Decreased high-density lipoproteins (HDL)
• Hypertension
• Hyperglycemia (fasting)
• Increased waist circumference

Baker KS et al BMT 201247619-25
5
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

Majhail NS, et al BBMT 2009151100-07
6
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 201247619-25
7
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
Baker KS et al BMT 201247619-25
8

• 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
201115521-32
9
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 2007109(4) 1765-72
Tichelli A, et al Haematologica 200893(8)1203-10
10
Special patient groups

• Highest risk patients
• Diabetes
• Abdominal aortic aneurysm
• Carotid stenosis
• Peripheral arterial disease

11
Treating Hypertension

• Hypertension
• Systolic gt 140 and/or diastolic gt 90
• Diabetics systolic gt 130 and/or diastolic gt 80
• Calcineurin inhibitor (CI) -induced hypertension
• Secondary to renal vasoconstriction and sodium
  retention
• Corticosteroids sodium retention
• Other causes

12
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

13
Hypertension in NPO patients

• Intravenous acute care options
• Hydralazine
• Metoprolol
• Topical
• Clonidine

NPO no oral intake
14
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

15
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
16
Treating hyperlipidemia

• Low density lipoproteins (LDL) primary target
  (treat if gt 100)
• HDL and TG secondary (treat lt40 or gt500)
• Lifestyle modifications
• Decreased saturated fats and cholesterol
• Increased plant stanols/sterols and viscous fiber
  to lower LDL
• Weight control and exercise

Circulation 20021063143-3421
17
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

18
Hyperlipidemia Treatment

• LDL predominant
• Statins
• Bile acid binders
• Cholesterol absorption inhibitors
• Hypertriglyceridemia
• Omega 3 fatty acids
• Niacin
• Fibrates

19
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

20
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

21
Cholesterol Absorption Inhibitors

• Ezetimibe
• Decrease LDL15
• 10 mg daily
• Less potent than statins
• Second line agent
• Do not stop but usually not a lot of value to
  starting it

22
Hypertriglyceridemia

• Statins decrease 7-30, helpful in mild disease
  (lt500)
• Niacin - decrease 30-40
• 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

23
Hypertriglyceridemia

• Omega 3 fatty acids - decrease 35-45
• 2-4 gm daily in 2 doses
• Decrease hepatic production of TG
• Impair platelet aggregation
• Doses gt 3 gm/day
• GI upset, diarrhea

24
Hypertriglyceridemia

• Fibrates - decrease 20-50
• Use if gt 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

25
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 2010116(8)1197-1204
26
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

27
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

28
Summary

• Management issues
• Adherence
• Side effects
• Cost
• Monitoring
• Drug interactions
• Success in general population lt30 have both
  hypertension and high cholesterol controlled,
  since ATPIII lt 20 success with dyslipidemia
  control

Egan BM et al Circulation 201312829-41