LEFT VENTRICULAR HYPERTROPHY IN DIALYSIS

Choice of Beta Blocker

Objectives

Gain an appreciation and understanding of the management of Left Ventricular Hypertrophy in hemodialysis patients

Review the evidence supporting selection of a beta-blocker in hemodialysis patients

Mr. TC

58 yoa male admitted on 4 Dec ID ht: 172 cm wt: 52 kg BMI: 17.6 CC: cough/SOB, leg swelling HPI: was in Victoria visiting son,

progressively weak over 2 days Previous admission – NRGH Oct 2011

for LLL pneumonia - ICU

Mr. TC

PMH: DM, diabetic retinopathy, hypertension, dyslipidemia, chronic kidney disease - diabetic nephroslcerosis with protinuria, hypokalemia

Surgeries: Bilateral cataract extractions, left finger amputation – saw injury

Allergies: none Compliance: supported by daughter who

helps to organize medications in dosette. No issues

Mr. TC

Social History: Lives at home with spouse and 5

children Chauffeur Born in China and emigrated to Canada

at age 16 Non smoker, non drinker No illicit drug use

Medications PTACondition Medication

Hypertension ramipril 5 mg dailyamlodipine 2.5 mg daily

CKD epoeitin 4000 Units twice weeklyferrous gluconate 300 mg TID

furosemide 20 mg QAM and 40 mg lunch

calcium carbonate 1250 mg TID ACRanitidine 150 mg daily

Medications PTACondition Medication

Diabetes Insulin glargine 6 units HS aspart via sliding scale

Hyperlipidemia Rosuvastatin 10 mg HS

New Diagnoses

Severe CAD – CABG x 3 15 Dec Acute renal insufficiency – start HD

18 Dec for volume control Recurrent bradycardia – code blue X

3 DDDR pacemaker

Left Ventricular Hypertrophy EF 40% prior to CABG, improved to 50%

by 28 Dec

Discharge Medications – 12 Dec

Condition Medication

Hypertension ramipril 5 mg daily

ERSD acetaminophen 325-650 mg Q6H prnepoeitin 6000 Units three times/weekferrous gluconate 125 mg IV Q 2 weekscalcium carbonate 500 mg TID ACpantoprazole 40 mg dailyreplavite 1 tablet dailydousate sodium 100 mg BIDlactulose 15-30 ml BID PRNsennosides 1-2 tabs daily PRNfurosemide 80 mg BID

Discharge MedicationsCondition Medication

Diabetes insulin regular 30 %/NPH 70% 10 units QAM and 12 units QPM

Hyperlipidemia rosuvastatin 10 mg HS

Post CABG ASA 81 mg dailymetoprolol 25 mg BID

Labs 11 Jan

Hg 72 HCT 0.22 MCV 89 Retic 60 Iron 7 Fe Sat 0.18 Ferritin 764 Na 133, K 5.1 Cl 103 CO2 24 Scr 208, EGFR 29 70% Urea

Reduction TSH 2.65 Alb 31 Ca 2.17 PO4 2.07 PTH 6.9

DRPs

Patient is at risk of morbidity and mortality due to left ventricular hypertrophy (LVH)

Patient is anemic and at risk of morbidity and worsening LVH

Patient is hyperphosphatemic and at risk of mineral bone disease

Primary Goals of Therapy

Health Care Team Reduce morbidity and mortality

associated with dialysis and cardiovascular disease

Regress left ventricular hypertrophy Achieve targets for diabetes control

Patient Wishes to be off dialysis Return to work

Left Ventricular Hypertrophy

Occurs in up to 80 % of dialysis patients Major risk factor for mortality

2/3 die from heart failure or sudden death Worsening LVH

Strong predictor of sudden death and arrhythmias

Associated prolonged QT interval and dispersion

Major risk factors Increasing age, hypertension, volume overload

and anemia

LVH Management

Control blood pressure Conerstone is volume control Antihypertensive medications

Correct anemia Maintenance of calcium and

phosphate mineral balance Vascular calcification

Antihypertensive medications

PICO

Patient: Post CABG dialysis patient with left ventricular hypertrophy

Intervention: metoprolol

Comparator: other beta blockers

Outcome: mortality, regression of left ventricular hypertrophy

Literature Search

Search terms Dialysis or hemodialysis, beta blockers

Databases Medline, IPA, CDSR, ACP Journal Club

Limits Humans, English

Results 2 RCTs – 1 retrospective cohort study

.

Cice, G., Ferrara, L., Di Benedetto, a, Russo, P. E., Marinelli, G., Pavese, F., & Iacono, a. (2001). Dilated cardiomyopathy in dialysis patients--beneficial effects of carvedilol: a double-blind, placebo-controlled trial. Journal of the American College of Cardiology, 37(2), 407-11.

Cice 2001

P: N=114, hemodialysis with symptomatic heart failure (NYHA II-III), EF<0.35

I: carvedilol highest tolerated dose to 25 mg BID

C: placebo O: changes in LV end-systolic and end-

diastolic volumes, LVEF and heart failure symptoms after 12 months

ResultsCarvedilol Metoprolol

Basal 12 months

Basal 12 months

LVEDV ml/m2

100 ± 9 94 ± 4 97 ± 8 98 ± 6 P<0.05

LVESV ml/m2

74 ± 8 62 ± 8 72 ± 9 72 ± 8 P<0.05

LVEF % 26 ± 8 36 ± 11 26 ± 8 26 ± 8 P<0.05

Limitations

small numbers, short duration open label no intention to treat excluded recent MI or CABG in past 3

months

Cice, G., Ferrara, L., D’Andrea, A., D’Isa, S., Di Benedetto, A., Cittadini, A., Russo, P. E., et al. (2003). Carvedilol increases two-year survival in dialysis patients with dilated cardiomyopathy. Journal of the American College of Cardiology, 41(9), 1438-1444.

Cice 2003

P: as per 2001 study - continuation I: carvedilol highest tolerated dose to

25 mg BID C: placebo O: primary - as per 2001,

secondary - all-cause mortality, all-cause hospital admission, cardiovascular mortality, acute non-fatal MI and composite

ResultsCarvedilol Metoprolol

Basal 12 month

s

24 month

s

Basal 12 month

s

24 month

s

LVEDV ml/m2

100 ± 9

94 ± 4 94 ± 5 97 ± 8 98 ± 6 100 ± 5

P<0.05

LVESV ml/m2

74 ± 8 62 ± 8 64 ± 6 72 ± 9 72 ± 8 74 ± 3 P<0.05

LVEF % 26 ± 8 36 ± 11

37 ± 10

26 ± 8 26 ± 8 24 ± 10

P<0.05

Results

Limitations

small numbers, short duration open label No intention to treat Excluded recent MI or CABG in past 3

months

Abbott, K. C., Trespalacios, F. C., Agodoa, L. Y., Taylor, A. J., & Bakris, G. L. (2004). β-Blocker Use in Long-term Dialysis Patients: Association With Hospitalized Heart Failure and Mortality. Archives of internal medicine, 164(22), 2465. Am Med Assoc.

Abbott 2004

P: N=2550, peritoneal and hemodialsysis from, DMMS Wave 2, with and without LVH

I/C: risk associations of medication classes used to outcome Chart review – medications at start of study Beta blockers analyzed with subdivision

Cardioselective vs non-cardioselective

O: admission for HF, cardiovascular related death, or death from any cause Medicare claims over 4 years

Demographics

Results

Limitations

Retrospective cohort analysis Hypothesis generating

small numbers, underpowered Did not follow medication changes Did not report on outcome of death

alone Carvedilol not included in study

FDA approved 1997

Recommendation

recommend continue metoprolol follow up echo in 3 months to assess

LVD

Monitoring Plan

What Who When

Blood pressure RN Ongoing

Anemia – by AMP RN, Pharmacist monthly

Signs/Sx heart failure RN, MD, Pharmacist

Ongoing

Metoprolol adverse effects (dizziness, headache, depression, puritis, diaahea, bradycardia, cold extremities)

RN, MD, Pharmacist

Ongoing

QUESTIONS?

References

1. Up to Date

2. Kidney Disease Outcomes Quality Initiative (KDOQI) Guidelines, 2002 The National Kidney Foundation

3. Cice, G., Ferrara, L., Di Benedetto, a, Russo, P. E., Marinelli, G., Pavese, F., & Iacono, a. (2001). Dilated cardiomyopathy in dialysis patients--beneficial effects of carvedilol: a double-blind, placebo-controlled trial. Journal of the American College of Cardiology, 37(2), 407-11.

4. Cice, G., Ferrara, L., D’Andrea, A., D’Isa, S., Di Benedetto, A., Cittadini, A., Russo, P. E., et al. (2003). Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy. Journal of the American College of Cardiology, 41(9), 1438-1444.

5. Abbott, K. C., Trespalacios, F. C., Agodoa, L. Y., Taylor, A. J., & Bakris, G. L. (2004). Β-Blocker Use in Long-term Dialysis Patients: Association With Hospitalized Heart Failure and Mortality. Archives of internal medicine, 164(22), 2465. Am Med Assoc.