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“ High”dralazine -Does D osage Matter In Heart Failure?

“ High”dralazine -Does D osage Matter In Heart Failure? . Manish Khullar, BSc Pharm Interior Health Pharmacy Resident Cardiology Rotation January 23, 2014. Learning Objectives. Describe the pathophysiology of heart failure (HF) List the therapeutic alternatives for HF

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“ High”dralazine -Does D osage Matter In Heart Failure?

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  1. “High”dralazine-Does Dosage Matter In Heart Failure? Manish Khullar, BSc Pharm Interior Health Pharmacy Resident Cardiology Rotation January 23, 2014

  2. Learning Objectives • Describe the pathophysiology of heart failure (HF) • List the therapeutic alternatives for HF • To be able to explain the evidence of the different doses of hydralazine used in patients with HF

  3. Our Patient

  4. Our Patient

  5. Our Patient

  6. Review of Systems

  7. Investigations • Diagnostics: • Chest x-ray (upon admission) • Enlarged heart • Bilateral pleural effusions • Pulmonary edema • ECHO (2012) • EF: 15-20%

  8. Current Problems and Medications

  9. Current Problems and Medications

  10. Course in Hospital • Furosemide poIV on admission • Hydralazine TID QID (200mg/day) • Nitroglycerin patch 0.4mg  0.6mg

  11. List of DTPs • RS is at risk of mortality, MI, strokeand further exacerbations of HF secondary to uncontrolled hypertension • RS is at risk of mortality, exacerbations of HF, hospitalizations, and worsening kidney function secondary to not being on an ACEI/ARB • RS is at risk of mortality, exacerbations, and hospitalizations secondary to not being on an optimal dose of carvedilol • RS is at risk of mortality, exacerbations, and hospitalizations secondary to not being on an optimal dose of spironolactone • RS is at risk of mortality, exacerbations, and hospitalizations secondary to not being on an optimal dose of hydralazine

  12. List of DTPs • At risk of arrhythmias secondary to hypokalemia due to furosemide • RS is at risk of death and reinfarction secondary to not being on a statin for secondary prevention of MI 8) RS is at risk of recurrent gout attacks secondary to not being on prophylaxis therapy 9) RS is at risk of C. difficile infection, pneumonia and vitamin B12 deficiency secondary to being on twice daily PPI

  13. DTP Focus RS is at risk of mortality, HF exacerbations and hospitalizations secondary to not being on an optimal dose of hydralazine

  14. Goals of Therapy • Prolong survival • Reduce morbidity • Exacerbations • Hospitalizations • Minimize symptoms • Prevent adverse events • Improve QOL

  15. Background: Pathophysiology

  16. Treatment Approach in HF Can J Cardiol 2006; 22:23-45

  17. Background: • Hydralazine: • Vasodilation of arterioles with little effect on veins ↓ systemic vascular resistance ↓ afterload • Nitroglycerin: • Relaxation of both arteries and veins↓ preload and afterload↓ myocardial oxygen demand

  18. Background: Classification of HF • New York Heart Association: • NYHA I: No symptoms with normal activites • NYHA II: Symptoms with ordinary activity (symptoms if walk more than 1 set of stairs or hurrying on the level) • NYHA III: Symptoms with less than ordinary activity (<100m or 1 flight of stairs) • NYHA IV: Symptoms at rest or minimal activity

  19. AHA Guidelines • “A combination of hydralazine and isosorbidedinitrate can be useful to reduce morbidity or mortalityin patients with current or prior symptomatic HF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency, unless contraindicated…” • Recommended target dose: 300mg daily in divided doses AHA 2013

  20. Canadian Guidelines • A combination of ISDN and hydralazine may be considered for heart failure patients unable to tolerate other recommended standard therapy • Recommended target dose: 225mg daily in divided doses Can J Cardiol 2006; 22:23-45

  21. Clinical Question • In a patient with NYHA III heart failure, is a total daily dose of 225mg of hydralazine as compared to 300mg daily as effective at reducing mortality, number of exacerbations, hospitalizations and symptoms?

  22. Literature Search

  23. VHeFT N Engl J Med 1986; 314:1547-1552

  24. VHeFTResults: Efficacy N Engl J Med 1986; 314:1547-1552

  25. N Engl J Med 1986; 314:1547-1552

  26. VHeFT Results: Safety N Engl J Med 1986; 314:1547-1552

  27. Limitations of VHeFT • Small sample size • Patients were not on modern background therapy • Only 55% reached target dose at 6 months • Younger patient population • Men only • Limited generalizability

  28. A HeFT $

  29. Scoring System New Engl J Med 2004;351:2049-2057

  30. Results: Efficacy New Engl J Med 2004;351:2049-2057

  31. Results: Safety New Engl J Med 2004;351:2049-2057

  32. Limitations of AHeFT • No power calculation defined • Examined a population where efficacy is more likely to be established • Only 68% percent reached target dose • Younger population • Generalizability • African Americans, ACEIs/ARBs, digoxin, excluded uncontrolled hypertension

  33. Bottom Line of AHeFT • “The addition of a fixed dose ISDN + hydralazine to standard therapy for HF is efficacious and increases survival among black patients with advanced heart failure”

  34. Bottom Line of Hydralazine 225mg daily vs. 300mg daily… • No head-to-head comparison • Unknown which is more effective • Guideline recommendations are based on underpowered trials or trials with limited generalizability!

  35. Patient Specific Factors • Patient’s comorbidities • Tolerability • Cost

  36. Our Options • Add ACEIs/ARB • Increase beta blockers • Hydralazine 225mg daily divided TID • Hydralazine 300mg daily divided QID • Increase nitropatch dose to 0.8mg/hr • Increase spironolactone dose to 25mg daily

  37. Therapeutic Recommendation • Hydralazine 75mg po QID (300mg/day) • Spironolactone 25mg po daily • Nitropatch 0.8mg/hour • Continue carvedilol 12.5mg po BID • Continue furosemide 80mg po daily

  38. Other Recommendations • Initiated potassium chloride 40mEq po BID x 1 day • Initiated allopurinol 100mg po daily • Changed pantoprazole 40mg to once daily

  39. Monitoring Plan

  40. Follow-up • Janurary 14th: • Repeat chest x-ray: • pulmonary edema and pleural effusions improved significantly • Cardiomegaly improved slightly but still persists • January 15th: • Patient improved clinically and no longer symptomatic • Discharged on Jan 16th: • Medications were reconciled • Counselled the patient on adherence and medication changes • Patient discharged

  41. Questions… ? (Logged a personal best of 21 DTPs for this patient!!!!)

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