Short-Term Efficacy and Safety of Torasemide and Furosemide in 366 Dogs with Degenerative Mitral Valve Disease: The TEST Study.

BACKGROUND: Furosemide is the only loop diuretic recommended by the ACVIM consensus guidelines for treatment of congestive heart failure (CHF) in dogs related to degenerative mitral valve disease (DMVD). Torasemide is another potent loop diuretic with a longer half-life and a higher bioavailability. OBJECTIVES: (1) To demonstrate that torasemide given once a day (q24h) is noninferior to furosemide given twice a day (q12h) for treating dogs with CHF; (2) and to compare the effect of the 2 drugs on the time to reach a composite cardiac endpoint "spontaneous cardiac death, euthanasia due to heart failure or CHF class worsening." ANIMALS: A total of 366 dogs with CHF attributable to DMVD. METHODS: Analysis of 2 prospective randomized single-blinded reference-controlled trials was performed. Dogs orally received either torasemide q24h (n = 180) or furosemide q12h (n = 186) in addition to standard CHF therapy over 3 months. The primary efficacy criterion was the percentage of dogs with treatment success assessed in each study. The time to reach the composite cardiac endpoint was used as secondary criterion in the overall population. RESULTS: Torasemide was noninferior to furosemide (Ptorasemide  - Pfurosemide  = +7%; 95% CI [-8%; +22%] and Ptorasemide  - Pfurosemide  = +1%; 95% CI [-12%; +14%], respectively, in Study 1 and Study 2). Torasemide (median dose = 0.24 mg/kg/d q24h; range = 0.10-0.69 mg/kg/d) was associated with a 2-fold reduction in the risk of reaching the composite cardiac endpoint (adjusted HR = 0.47; 95% CI = 0.27-0.82; P = 0.0077) as compared with furosemide (median dose = 1.39 mg/kg q12h; range = 0.70-6.30 mg/kg q12h). CONCLUSIONS AND CLINICAL IMPORTANCE: Torasemide q24h is an effective oral diuretic in dogs with CHF.

Heart rate reduction by inhibition of If or by beta-blockade has different effects on postsystolic wall thickening.

BACKGROUND AND PURPOSE: Postsystolic wall thickening (PSWT) is part of thickening that occurs after end-systole and represents wasted effort as it does not contribute to ejection. The effects of antianginal drugs on PSWT remain to be established. We compared the effects on PSWT of two agents that reduce heart rate, the beta-blocker atenolol and the selective inhibitor of If current, ivabradine. EXPERIMENTAL APPROACH: Six dogs were prepared to measure wall thickening by sonomicrometry in the conscious state, at rest and during exercise, after administration of saline, atenolol (1 mg.kg-1) or ivabradine (1 mg.kg-1). KEY RESULTS: Atenolol and ivabradine similarly reduced heart rate vs saline at rest (about 10-20%) and during exercise (about 30%). Atenolol but not ivabradine decreased dP/dtmax. Concomitantly, PSWT increased with atenolol vs saline at rest (0.35+/-0.07 vs 0.21+/-0.03 mm, respectively) and during exercise (0.30+/-0.04 vs 0.15+/-0.04 mm, respectively). In contrast, ivabradine did not alter PSWT. Importantly, atenolol but not ivabradine increased the ratio of postsystolic to systolic wall thickening by 80+/-23%. This enhanced thickening during diastole with atenolol was accompanied by impeded isovolumic relaxation of the left ventricle, as illustrated by the significant correlation between the isovolumic relaxation time constant tau and the postsystolic to systolic wall thickening ratio. None of these effects of atenolol were abolished when heart rate was controlled with atrial pacing. CONCLUSION AND IMPLICATIONS: For a similar heart rate reduction at rest and during exercise, ivabradine, but not atenolol, did not alter PSWT and preserved the part of thickening contributing to ejection.