US Senator John McCain has declared his opposition to the last-ditch effort to repeal and replace “Obamacare”, dealing a likely death blow to the legislation and, perhaps, to the Republican Party’s years of vows to kill the programme.

It was the second time in three months 81-year-old Mr McCain emerged as the destroyer of his party’s signature promise to voters.

“I believe we could do better working together, Republicans and Democrats, and have not yet really tried,” Mr McCain said of the bill, co-written by Lindsey Graham of South Carolina, his best friend in the Senate, and Bill Cassidy of Louisiana.

“Nor could I support it without knowing how much it will cost, how it will affect insurance premiums, and how many people will be helped or hurt by it.”

Mr McCain, who is battling brain cancer in the twilight of a remarkable career, said he could not “in good conscience” vote for the legislation. That all but ensured a major setback for President Donald Trump and Senate Majority Leader Mitch McConnell, and appeared likely to deepen rifts between congressional Republicans and a president who has begun making deals with Democrats out of frustration with his own party’s failure to turn proposals into laws.

During the election campaign, Mr Trump had pledged to quickly kill president Barack Obama’s health care programme – “It will be easy,” he contended – and he has publicly chided Mr McConnell for not winning passage before now.

With the Arizona senator’s defection, there are now two declared Republican “no” votes on the repeal legislation, the other being Rand Paul of Kentucky. With Democrats unanimously opposed, that is the exact number Mr McConnell can afford to lose. But Maine Republican Senator Susan Collins said on Friday she, too, is leaning against the bill, and Lisa Murkowski of Alaska was also a possible “no”, making it highly unlikely that Mr McConnell can prevail.

Mr Trump, speaking at a rally on Friday night in Alabama, called Mr McCain’s opposition “sad” and “a horrible, horrible thing” for the Republican Party.

“This is not going to be easy. Some have gone so far as to announce their opposition already,” he said. “President Trump and I are undeterred.”

Mr Graham, too, vowed in a statement to “press on”, and reaffirmed his friendship with Mr McCain.

Up until Mr McCain’s announcement on Friday, close McConnell allies were still optimistic Mr McCain’s relationship with Mr Graham might make the difference.

Republican leaders hoped to bring the legislation to the Senate floor next week. They face a September 30 deadline, at which point special rules that prevent a Democratic filibuster will expire.