New Therapies
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Transcript of New Therapies
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New Therapies
Heather Kertland, PharmD
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• Eplerenone• Ultrafiltration• CRT
Outline
New Agents
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Rales StudyPopulation NYHA Class III and IV heart failure and LVEF≤35%
Comparator spironolactone target dose 50 mg/day vs. placebo
Outcome n = 1,663; mean follow-up = 24 months; mean LVEF 25.6%; mean dose = 26 mg/day;
All-cause mortality: spironolactone was associated with a 30% RRR compared to placebo (34.5% vs. 46%, p<0.001) ARR = 11%; NNT = 9
Safety Hyperkalemia ≥ 6.0 μmol/L: 2% spironolactone vs. 1% placebo (p=0.42)
Gynecomastia in men: 9% spironolactone vs. 1% placebo
New Engl J Med 1999
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Eplerenone (Inspra)• A chemical derivative of spironolactone,
• enhanced selective binding to the mineralocorticoid receptor
• minimizing binding to progesterone and androgen receptors
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Ephesus trialPopulation 3 to 14 days post-MI with either symptoms of HF or diabetes
without HF symptoms; NYHA classes I-IV; LVEF≤40%
Comparator eplerenone target dose 50 mg/day vs. placebo
Outcome n = 6,642; mean follow-up 16 months; mean LVEF 33%; mean dose = 43.5 mg/day;
All-cause mortality: eplerenone demonstrated a 15% RRR compared to placebo (14.4% vs. 16.7%; p=0.008)
ARR = 2.3%; NNT = 43
Composite endpoint of death from CV causes or first hospitalization from a CV event: eplerenone demonstrated a 13% RRR compared to placebo (26.7% vs. 30.0%, p=0.002) ARR = 3.3%; NNT = 30
New Engl J Med 2003;348:
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Ephesus
Safety Hyperkalemia ≥ 6.0 μmol/L:
5.5% eplerenone vs. 3.9% placebo
Gynecomastia in men:
0.5% eplerenone vs. 0.6% placebo
Other DI: substrate for CYP3A4 (concomitant use of strong CYP3A4 inhibitors is contraindicated)
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New Engl J Med 2004;351:542-51
Hyperkalemia
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Rx info• Monitoring K+
– 48 hours post 1st dose– 1,4 and 5 weeks– 1 week after any dose change
• Coverage– Common Drug Review (CDR) – do not cover– ODB
• Exceptional Access - • Experience AMI, have evidence of heart failure and left
ventricular systolic dysfunction (EF <40%) and tried spironolactone but experienced severe symptomatic (painful) gynecomastia.
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Ultrafiltration• Pts not responding to
diuretics• Clinic/inpatient setting• Results 2 – 3 kg greater
weight loss than diuretics, no effect on dyspnea
• No adverse effects on Serum Cr
• Anticoagulation is required
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SMH experienceEndpoint N=8
Age 66.1 yrs
Duration of UF 36 hrs (15 – 65 hrs)
UF rate 50 – 250 mL/hr
Average weight loss 7.5 kg
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SMH Experience
0
50
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baseline Cr Post UF Cr
a
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d
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f
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j
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Summary• UF is an alternative to diuretics for
removing fluid
• Well tolerated with respect to renal function, although can remove fluid too quickly/too much
• No known effects on drug concentrations determined to date
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Resynchronization Therapy (CRT)
• Delayed conduction of electrical signal
• Ventricles do not contract at the same time
• QRS interval > 120 msec on ECG + HF symptoms + reduced EF
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New Engl J Med 2010
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Summary• Indication is heart failure not bradycardia
• Can have pacing capabilities
• Can be combined with ICD
• Impact on drug therapy– Implantation – holding of anticoagulation– Post – improvement in symptoms – decrease
in furosemide