The power of Donald Trump’s endorsement will be put to its latest test on Saturday, when Louisiana holds primary elections in which the US senator Bill Cassidy, who voted to impeach the president following the January 6 insurrection, then tried to make amends by casting the pivotal vote to confirm Robert F Kennedy Jr as health secretary, stands a chance of losing his party’s nomination.

An incumbent Republican running for a third term representing a deeply Republican state, Cassidy would normally be a shoo-in for re-election. But in January, Trump abruptly said that the US representative Julia Letlow should run against Cassidy and offered his endorsement, underscoring his continued willingness to seek revenge against anyone in the Republican party who has crossed him.

The president’s campaign to oust a senator of his own party – the sort of thing that was unheard of in previous administrations, but not under Trump – may have achieved the desired effect. Letlow promptly jumped into the Republican Senate primary, as did state treasurer and former representative John Fleming. An Emerson College poll released last month showed Cassidy in third place among likely Republican voters, with Fleming and Letlow neck and neck for the lead.

“This is a primary that is mostly about Trump,” said Robert Hogan, a Louisiana State University political science professor, adding that the president’s spurning of Cassidy was probably the “death knell” for his time in the Senate.

Should he indeed lose re-election this year, Cassidy would join a growing list of Republicans whose political careers have ended at Trump’s hands. Earlier this month, five of the seven Republican Indiana state senators who halted a Trump-backed effort to gerrymander the state in Republicans’ favor lost their primaries. In North Carolina, Republicans are in a high-stakes battle to keep hold of one of their Senate seats because Thom Tillis has opted to retire, after breaking with Trump last year over his top domestic policy bill.

A gastroenterologist who co-founded a clinic serving uninsured patients in Baton Rouge, Cassidy served in the House of Representatives before beating the Democratic senator Mary Landrieu in 2014. During Trump’s first term, he was an architect of the failed Republican effort to repeal the Affordable Care Act.

His relationship with the president soured following the assault on the Capitol by the president’s supporters, after which Cassidy and six other Republicans voted to convict Trump in the Senate, but the effort came up short. Cassidy later supported a fruitless attempt to establish an independent commission investigating the insurrection, and called on Trump to end his 2024 re-election bid after his indictment for allegedly possessing classified material.

Louisiana’s Republican party censured Cassidy in 2021 for his vote in Trump’s trial, and the senator’s political peril intensified when Trump returned to the White House last year.

Cassidy cast the deciding vote to advance vaccine skeptic Kennedy’s nomination to lead the Department of Health and Human Services out of the Senate health committee, which he chairs. The decision flew in the face of the senator’s training as a physician and his stated support for immunizations, and was widely seen as an attempt to smooth things over with the president.

Trump’s endorsement of Letlow made clear the senator’s effort was insufficient. Cassidy has meanwhile criticized some of Kennedy’s policies as secretary, and opposed Trump’s attempt to have the wellness influencer Casey Means confirmed as US surgeon general, leading Trump to blame the senator for having to withdraw her nomination.

In Louisiana, changes to the primary system probably worsened the prospects for Cassidy’s political career. In 2024, the Republican governor, Jeff Landry, a prominent Trump supporter, worked with the legislature to change the rules of the state’s US Senate primaries so that candidates are nominated only by party members and unaffiliated voters. Ron Faucheux, a veteran political strategist in Louisiana, said he suspected the changes were intended to ensure that Republicans like Cassidy who fall out of favor with Trump have no avenue to remain in office.

“The new primary system is geared to help staunch, conservative, pro-Trump candidates get elected, because it’s geared to nominate them on the Republican side and putting them in the runoffs against Democrats, [who] nobody thinks can win,” he said.

Cassidy’s campaign has acknowledged the difficulty of this year’s re-election campaign, and said their goal is for the senator to finish in the top two of the primary, and advance to a runoff election scheduled for next month.

“The mission is pretty simple. It’s to go out, get as many votes as we can on Saturday and position ourselves well for the runoff election to come in June,” campaign consultant Mark Harris told reporters this week.

Both of Cassidy’s challengers have sought to convince voters they are the president’s choice, with Letlow noting her endorsements from both Trump and Landry, and Fleming’s campaign distributing photos of him posing with the president.

Cassidy has meanwhile focused on criticizing Letlow, saying that the race was hers to lose. Dubbing her “Lib Letlow”, his campaign has seized on comments she made in support of campus diversity programs while interviewing to lead the University of Louisiana at Monroe. Letlow has since publicly repudiated those initiatives.

If there’s a saving grace for Cassidy, it could be unaffiliated voters, whose views have not been captured in polls, Faucheux said. But even if Cassidy makes it to a runoff, the president’s opposition will present a significant headwind.

“My guess is that a runoff would be tough for Cassidy, because even though there’s a lot of personal animosity between Letlow and Fleming in the campaign, I think a lot of their voters would tend to be pretty strongly pro-Trump voters,” he said.