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Thursday, February 25, 2016

Conversion: Beta Blockers



  • Three beta-blockers—carvedilol, bisoprolol, and metoprolol XL—have demonstrated improved survival rates, reduced hospital admissions, and improved New York Heart Failure Association functional class (NYHA FC)
  • both these beta-blockers have convincingly shown improved mortality and morbidity outcomes in HF, and are regarded by international experts and healthcare bodies as mandatory agents to prescribe to all HF patients unless absolute contraindications exist
Bisoprolol
  • Selective beta-1 blocker
  • pharmacokinetic profile allows for once daily dosing and improved patient compliance
  • Cheaper
  • does not require special authority to prescribe
Carvedilol
  • mixed beta- and alpha-blocker
  • more likely to cause hypotension and/or dizziness
  • Carvedilol 25-50mg bid is the most costly of the three agents
Metoprolol XL
  • shown survival benefit in HF (controlled release preparation)
  • is speculated that the controlled release preparations lead to a more pronounced and even beta-blockade over 24 hours in comparison to regular release preparations
Clinical Effectiveness
  • mortality reduction rates were regarded as acceptable for bisoprolol in NYHA FC I-IIIa patients.
  • switching from carvedilol to bisoprolol is a practical and safe method for clinically stable patients with LV dysfunction
  • may provide beneficial effects in regard to prognosis and/or reverse remodeling in patients who experience difficulty with continuation or up-titration of carvedilol because of adverse effects such as dizziness or hypotension
  • no difference regarding impact on renal function between carvedilol and bisoprolol
Patient Selection
  • However, taking into consideration the COPERNICUS study, it was decided that while for the NYHA FC I-III patients, this interchange will be highly encouraged
  • for Class IIIb-IV patients, the physicians may consider leaving the carvedilol unswitched
Caution
  • important to exercise caution in Japan (or equivalent countries) where the recommended maximum doses of β-blockers are less than half of those in Western countries



Dose Conversion:
  • There are 2 conversion table available.
  • One is based on 5:1, which is calculated based on the ratio of optimal dose needed for the mortality outcome.
  • Based on recommended initial starting and target doses of these 2 beta-blockers in the various clinical trials CIBIS II, US Carvedilol Studies,12 and COPERNICUS, and the Clinical Pharmacy Practice Guidelines for HF patients developed by Singapore Ministry of Health, a 5:1 dose conversion (eg, carvedilol 12.5 mg BD to bisoprolol 5 mg OM).

  • Another dosing conversion are commonly seen with British guides and recommendations. This still maintains 5:1 ratio at the optimal dose. But at lower doses, a ratio of 2.5:1 is used.

Dose Titration Guide:
 

Other Beta Blocker Dose Equivalence:
 References:
  1.  PRESCRIBING AND DISPENSING NEWS  No 201 JULY 2009.
  2. Drugs and Therapeutics Newsletter. Sept 2004, volume 11 (3)
  3. http://www.ajpb.com/journals/ajpb/2012/ajpb_mayjun2012/therapeutic-interchange-of-carvedilol-to-bisoprolol-for-chronic-heart-failure-the-singapore-experience
  4. http://www.sciencedirect.com/science/article/pii/S0914508713000579
  5. http://www.globalrph.com/beta_blockers.htm
  6. Advice for Primary Care Regarding Beta-Blockers in Heart Failure and QOF. South East Wales Cardiac Network 2010
  7. Antihypertensive Algorithm for Patients without Diabetes. Updated July 25, 2006

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