Henderson added that the “significant markers” on the blood test had come down since last Thursday but still indicate that the horse has not fully recovered from the illness.

He also said that they would not add further stress to the horse in order to ensure his improvement.

“This is very sad for all of us but it is in everybody’s best interests that we have a fit and healthy Constitution Hill to win back his crown next year,” the statement continued.

AP McCoy called Constitution Hill “the horse of a generation” after last year’s win but he has only raced once this season.

That came in the Christmas Hurdle at Kempton on Boxing Day where he won easily under jockey Nico de Boinville, but he missed last month’s Cheltenham Trials Day over fitness concerns.

Another favourite has been ruled out of the Cheltenham Festival, which starts on Tuesday 12 March.

Trainer Barry Connell said Marine Nationale will miss the Arkle Chase with a leg injury.

Analysis – ‘There will be other days’

Frank Keogh, BBC racing reporter

Racing’s big will-he, won’t-he wait is over and it’s bad news for fans of the sport that Constitution Hill will miss its showpiece meeting next week.

After pulverising the opposition last year, his defence of the Champion Hurdle was keenly awaited, particularly as he has only raced twice since.

It will inevitably take some of the gloss off the meeting’s opening day next Tuesday, and now last year’s runner-up State Man is odds-on favourite to triumph for dominant Irish trainer Willie Mullins.

Constitution Hill’s trainer Nicky Henderson has put the welfare of his horse first and kept punters well briefed on the situation.

There will be other days for this exceptional equine star.