Enalapril in asymptomatic mitral valve disease (stage B): does early treatment delay heart failure? — POSSIBLE (the treatment made no difference)

In dogs with myxomatous mitral valve disease but no heart failure (stage B), does enalapril vs placebo delay the onset of congestive heart failure?

Shelf #208 · gate-verified and displayed under the developer's blinded-trial rule

POSSIBLE (the treatment made no difference): Starting enalapril in dogs with asymptomatic myxomatous mitral valve disease did not significantly delay the onset of congestive heart failure in either of the two blinded, placebo-controlled trials that tested it. In SVEP — 229 Cavalier King Charles Spaniels followed in 14 Scandinavian centers — 43% of enalapril dogs and 42% of placebo dogs developed heart failure (P = .99), with adjusted mean time to heart failure of 1,150 vs 1,130 days (P = .85). In VETPROOF — 124 dogs with moderate-to-severe compensated mitral regurgitation — the primary endpoint, CHF-free survival, was likewise not significantly improved; secondary measures (CHF-free days, dogs free of CHF at day 500 and at study end, and time to CHF-or-all-cause death, a 317-day benefit) favoured enalapril, and the authors called the delay modest. Positive secondary endpoints after a null primary do not overturn the primary verdict: on the question asked, early enalapril made no demonstrated difference. Drafted Nov 10, 2026 (VetMed build, topic #208); all figures from abstracts fetched and verified at drafting.

Kvart 2002 (SVEP): heart failure in 43% on enalapril vs 42% on placebo (P = .99) — no delay

Prospective, randomized, double-blinded, placebo-controlled multicenter trial (record's own abstract wording; indexed as Randomized Controlled Trial)

Who: Dogs: 229 Cavalier King Charles Spaniels with mitral regurgitation attributable to myxomatous valvular disease but no signs of congestive heart failure, in a multicenter trial involving 14 centers in Scandinavia. Dogs were randomly allocated to enalapril 0.25–0.5 mg daily (n = 116) or placebo (n = 113) as monotherapy, and evaluated by physical examination, electrocardiography, and thoracic radiography at entry and every 12 months.

Result: The number of dogs developing heart failure was similar in the treatment and placebo groups (n = 50 [43%] and n = 48 [42%], respectively; P = .99). The estimated means, adjusted for censored observations, for the period from initiation of therapy to heart failure were 1,150 ± 50 days for the treatment group and 1,130 ± 50 days for the placebo group (P = .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 = .98 and .51, respectively). Multivariate analysis showed that enalapril had no significant effect on the time from initiation of therapy to heart failure (P = .86). The authors concluded that long-term enalapril in asymptomatic dogs with myxomatous valve disease and mitral regurgitation did not delay the onset of heart failure, whether or not cardiomegaly was present at the start.

Watch out: One breed only: every dog was a Cavalier King Charles Spaniel, the breed with early-onset hereditary MMVD — the cleanest test population, but generalisation to other breeds is by extrapolation. Enalapril was tested as monotherapy at 0.25–0.5 mg daily; the trial says nothing about ACE inhibition combined with other preclinical-stage treatment.

Kvart C, Häggström J, Pedersen HD et al. Efficacy of enalapril for prevention of congestive heart failure in dogs with myxomatous valve disease and asymptomatic mitral regurgitation. J Vet Intern Med. 2002;16(1):80-8. PMID: 11822810. Registry ID: none in the record. MeSH: Angiotensin-Converting Enzyme Inhibitors · Animals · Disease-Free Survival · Dog Diseases · Dogs · Dose-Response Relationship, Drug · Double-Blind Method · Electrocardiography · Enalapril · Female · Heart Failure · Heart Valve Diseases · Male · Mitral Valve Insufficiency · Multivariate Analysis · Physical Examination · Prospective Studies · Radiography · Scandinavian and Nordic Countries · Severity of Illness Index · Treatment Outcome

Atkins 2007 (VETPROOF): primary endpoint (CHF-free survival) not significant; secondary endpoints favoured enalapril

Placebo-controlled, double-blind, multicenter, randomized trial (record's own design wording; indexed as Randomized Controlled Trial)

Who: Dogs: 124 dogs with compensated, naturally occurring (moderate to severe) mitral valve regurgitation, in a multicenter trial. Dogs randomly assigned to receive enalapril or placebo were monitored for the primary endpoint of onset of congestive heart failure for up to 58 months. Secondary endpoints included time from study entry to the combined endpoint of CHF–all-cause death; number of dogs free of CHF at 500, 1,000, and 1,500 days; and mean number of CHF-free days.

Result: Kaplan-Meier estimates of the effect of enalapril on the primary endpoint did not reveal a significant treatment benefit. Chronic enalapril administration did have a significant benefit on the combined endpoint of CHF–all-cause death (benefit was 317 days [10.6 months]). Dogs receiving enalapril remained free of CHF for a significantly longer time than those receiving placebo (by CHF-free days) and were significantly more likely to be free of CHF at day 500 and at study end. The authors concluded that results suggest enalapril modestly delays the onset of CHF in dogs with moderate to severe mitral regurgitation, while improvement in the primary endpoint, CHF-free survival, was not significant.

Watch out: The headline-positive findings are all secondary endpoints; the pre-specified primary endpoint (onset of CHF / CHF-free survival) was not significant, so the trial cannot carry a claim that enalapril delays heart failure. The 317-day figure belongs to the combined CHF–all-cause-death secondary endpoint, not to time-to-CHF alone. Dogs had moderate-to-severe regurgitation — a later preclinical population than SVEP's all-comers.

Atkins CE, Keene BW, Brown WA et al. Results of the veterinary enalapril trial to prove reduction in onset of heart failure in dogs chronically treated with enalapril alone for compensated, naturally occurring mitral valve insufficiency. J Am Vet Med Assoc. 2007;231(7):1061-9. PMID: 17916031. Registry ID: none in the record. MeSH: Angiotensin-Converting Enzyme Inhibitors · Animals · Antihypertensive Agents · Death, Sudden, Cardiac · Disease Progression · Disease-Free Survival · Dog Diseases · Dogs · Double-Blind Method · Enalapril · Female · Heart Failure · Kaplan-Meier Estimate · Male · Mitral Valve Insufficiency · Severity of Illness Index · Time Factors · Treatment Outcome

Synthesis: two blinded trials, two null primary endpoints — early enalapril does not demonstrably delay CHF

Synthesis

Who: Synthesis of the two cards above: Kvart et al. 2002 (SVEP; 229 asymptomatic Cavalier King Charles Spaniels with MMVD mitral regurgitation, Scandinavia) and Atkins et al. 2007 (VETPROOF; 124 dogs with compensated moderate-to-severe mitral regurgitation, multicenter).

Result: Across 353 randomised dogs in two double-blind, placebo-controlled trials, enalapril started before heart failure did not significantly delay CHF onset on either trial's primary analysis: SVEP was flatly null (43% vs 42% developing heart failure; time to failure essentially identical), and VETPROOF's primary endpoint was not significant, with its encouraging results confined to secondary endpoints the authors themselves summed up as a modest delay. The honest shelf verdict is that the treatment made no demonstrated difference on the question asked — which is why this pack carries the no-difference stamp even though VETPROOF's secondary signals keep the door open for later-stage (moderate-to-severe) dogs.

Watch out: Neither trial tested enalapril in dogs that already had heart failure — the symptomatic-stage ACE-inhibitor question is a different shelf (benazepril BENCH, topic #204) with a different, positive answer. Do not read this null across to treatment of CHF itself.

Synthesis of Kvart C et al. PMID: 11822810 and Atkins CE et al. PMID: 17916031. Registry IDs as on the individual cards.

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