Pimobendan

Name

• Pimobendan.

Class of drug

• Positive inotrope.
• Vasodilator.

Uses

Action

• Positive inotrope
  • Phosphodiesterase III inhibition → increased cAMP → promotes calcium entry into myocyte and triggers further release of calcium from sarcoplasmic reticulum.
  • Calcium sensitizing properties affect interaction of calcium with troponin C complex that increases extent of contraction for a given cytosolic concentration of calcium without increasing myocardial oxygen consumption or energy requirement.
• Vasodilator
  • Phosphodiesterase III and V inhibition → increased cAMP in vascular smooth muscle → arterio- and venodilation.
• Effects on cytokines and neurohormones
  • No sign of any activation of neurohormones; some studies have shown a reduction in neurohormonal activation and reductions in the level of pro-inflammatory cytokines.
• Anti-platelet effects
  • May inhibit platelet aggregation thereby reducing the likelihood of thrombosis .

Indications

• Congestive heart failure due to:
  • Dilated cardiomyopathy (DCM). Few studies to date:
    • PITCH study reported improvement in clinical signs in dogs with DCM and CHF.
    • Significant improvement in survival of Dobermanns with DCM and CHF compared to dogs treated with placebo.
    • No significant difference between the survival of pimobendan-treated vs placebo-treated Cocker spaniels (small number of dogs).
    • Studies showed no increase in heart rate or arrhythmias.
  • Degenerative valvular disease (MVD ):
    • QUEST study revealed a longer time to reach endpoint in dogs with MVD and CHF treated with pimobendan plus conventional therapy in comparison to benazepril plus conventional therapy.
    • PITCH study suggested that therapy with ACEI , furosemide and pimobendan led to a greater improvement in clinical signs than therapy with an ACEI alone. 80% of cases had dilated cardiomyopathy, the remainder, acquired valvular disease.
• Pimobendan compared with ramipril in dogs with acquired valvular disease over a 6m period showed a significant reduction in adverse outcomes (eg worsening of heart failure, death) in dogs treated with pimobendan.
• The ACVIM consensus statement recommends treatment of MVD and CHF with furosemide, ACEi and pimobendan. Addition of spironolactone is also recommended as time to reach endpoint is prolonged.

Adverse reactions

Other reported reactions

• Vomiting (approximately 3% of cases treated).
• Moderate tachycardia (in 3 - 5.8% of cases treated).

Treatment

• Reduce dose.