Efficacy of Enalapril for Prevention of Congestive Heart Failure in Dogs with Myxomatous Valve Disease and Asymptomatic Mitral Regurgitation

Abstract

We evaluated the long-term effect of early angiotensin-converting enzyme (ACE) inhibition (enalapril maleate) as monotherapy to postpone or prevent congestive heart failure (CHF) in asymptomatic dogs with mitral regurgitation (MR) attributable to myxomatous valvular disease (MVD) in a prospective, randomized, double-blinded, placebo-controlled multicenter trial involving 14 centers in Scandinavia. Two hundred twenty-nine Cavalier King Charles (CKC) Spaniels with MR attributable to MVD but no signs of CHF were randomly allocated to treatment with enalapril 0.25-0.5 mg daily (n ϭ 116) or to placebo groups (n ϭ 113). Each dog was evaluated by physical examination, electrocardiography, and thoracic radiography at entry and every 12 months (Ϯ30 days). The number of dogs developing heart failure was similar in the treatment and placebo groups (n ϭ 50 [43%] and n ϭ 48 [42%], respectively; P ϭ .99). The estimated means, adjusted for censored observations, for the period from initiation of therapy to heart failure were 1,150 Ϯ 50 days for dogs in the treatment group and 1,130 Ϯ 50 days for dogs in the placebo group (P ϭ .85). When absence or presence of cardiomegaly at the entrance of the trial was considered, there were still no differences between the treatment and placebo groups (P ϭ .98 and .51, respectively). Multivariate analysis showed that enalapril had no significant effect on the time from initiation of therapy to heart failure (P ϭ .86). Long-term treatment with enalapril in asymptomatic dogs with MVD and MR did not delay the onset of heart failure regardless of whether or not cardiomegaly was present at initiation of the study.

Effect of Benazepril on Survival and Cardiac Events in Dogs with Asymptomatic Mitral Valve Disease: A Retrospective Study of 141 Cases

“…Although in the latter study MR was not assessed using a Doppler method, we can hypothesize that all the recruited dogs had severe (although compensated) MR, because left atrial enlargement on M‐mode or 2D echocardiography was one of the inclusion criteria 9 . Interestingly, in the SVEP trial, although MR severity was not assessed (because dogs were evaluated at entry only by physical examination, ECG, and thoracic radiographs), CKC with an initial heart murmur of moderate intensity showed a markedly shorter time to CHF than in dogs with low‐intensity murmurs 10 . This may also be related to MR severity because a significant correlation has been demonstrated in the CKC breed between heart murmur grade and MR severity as assessed by ARJ/LAA 36 .…”

“…However, unlike tolerability, conflicting results have been obtained regarding ACEIs efficacy on asymptomatic canine MVD. In the SVEP trial, 10 the number of CKC developing CHF was similar in the treatment and placebo group, and treatment with enalapril did not delay the onset of CHF regardless of whether or not cardiomegaly was present at initiation of the study. Conversely, the follow‐up of dogs recruited from the VETPROOF study (Veterinary Enalapril Trial to Prove Reduction in Onset Of heart Failure) demonstrated that chronic enalapril therapy was effective in delaying the onset of CHF and had a benefit on the combined endpoint of CHF–all‐cause death 9 …”

“…Similarly, another prospective, randomized, double‐blinded, placebo‐controlled multicenter trial (Scandinavian Veterinary Enalapril Prevention, or SVEP, trial), 10 which was conducted over a 4.5‐year period, demonstrated that long‐term treatment with enalapril in asymptomatic Cavalier (CKC) and King Charles Spaniels (KC) with MVD was well tolerated.…”

“…Several prospective, double‐blinded, multicenter, and randomized studies have shown that ACEIs improve quality of life, increase exercise tolerance, and extend life expectancy in dogs with naturally acquired congestive heart failure (CHF) because of degenerative mitral valve disease (MVD) and dilated cardiomyopathy, which are the 2 most common causes of canine CHF 1–6 (see Lefebvre et al 7 for review). However, very few studies have focused on the effects of ACEIs on patients with asymptomatic heart disease 8–12 . One of the most documented and agreed upon aspects of ACEIs obtained from these studies is their short‐ and long‐term tolerability in asymptomatic canine MVD.…”

“…The whole canine population, including dogs from all breeds, was first studied, and then 2 distinct subpopulations were analyzed: (1) a population (CKC‐KC population) including only CKC and KC and (2) a population including dogs from all breeds except CKC and KC (other breed or OB population). The subgroup analysis of CKC and KC dogs was justified from the known faster progression of CHF in these breeds compared with other breeds in addition to the fact that only CKC dogs were studied in the SVEP trial 10 . For each of these 3 populations, the effects of therapy on death from all causes, cardiac death, and cardiac events were studied.…”