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With Aetna Inc. and Humana Inc. pairing off, pressure is mounting on other major health insurers to make their own deals.

Cigna Corp.’s tie-up with Anthem Inc. could be the next one on deck. Cigna rebuffed a bid from Anthem last month, and both were said to have been interested in Humana. But after the acquisition announced Friday, their options just got narrower.

“It paves the way for Cigna and Anthem,” Ana Gupte, an analyst at Leerink Partners in New York, said by phone. “Cigna has fewer choices at this point.”

Aetna struck a $35 billion cash-and-stock deal for Humana, the first in an expected wave of consolidation among the largest companies in the industry. The health-plan providers are under pressure to get bigger after the 2010 U.S. reform known as Obamacare triggered a race for new customers, while reducing margins.

Cigna rejected offers from Anthem for as much as $184 a share in cash and stock, citing concerns about governance and management. Anthem went public on June 20 with its bid, which would create the largest U.S. health insurer with about 53 million members.

Both Anthem and Cigna had held discussions to acquire Humana, people familiar with the matter said last month, asking not to be identified because the information was private.

Now that Humana is no longer an option, an Anthem-Cigna transaction can probably get done at about $190 to $195 a share, Gupte said.

Stock Surge

Kristin Binns, a spokeswoman at Anthem, and Matthew Asensio at Cigna declined to comment. Cigna has climbed 57 percent this year to close at $161.29 on Thursday. Anthem is up 30 percent.

UnitedHealth Group Inc., the largest U.S. health insurer, could also enter the picture. The Minnetonka, Minnesota-based company has weighed buying Aetna or Cigna, the Wall Street Journal reported last month, citing people familiar with the matter. Tyler Mason, a UnitedHealth spokesman, declined to comment.

By acquiring Humana, Aetna gains a large presence in Medicare Advantage, the private health program for the elderly that’s expected to grow rapidly.

Humana on Monday cut its 2015 earnings outlook after more of its Medicare patients got hospital care than expected. Adjusted earnings per share will probably be about $7.75 this year, down from an earlier forecast of $8.75, the insurer said.

Humana shares were up 1.7 percent to $190.60 at 8:48 a.m in New York trading before the market opened, below the $230 a share Aetna has agreed to pay. Aetna shares were down 6 percent to $118.01.

Humana’s updated guidance was consistent with information the company examined during the due diligence process, Aetna Chief Financial Officer Shawn Guertin said on a conference call Monday.

Scale

Anthem’s deal for Cigna would give the companies more scale in commercial coverage, and Anthem has also said that Cigna’s Medicare Advantage business is appealing.

The resolution of a Supreme Court case that had threatened a key piece of the Patient Protection and Affordable Care Act has also paved the way for deals. The court’s 6-3 ruling on June 25 kept subsidies flowing to help more than 6 million people buy health coverage in the markets created by the health-care overhaul.

Antitrust Hurdle

Still, several deals occurring at the same time can make it tougher to win antitrust approval if officials become worried that too much consolidation can limit consumer choice, according to Allen Grunes, a lawyer at Konkurrenz Group in Washington.

Leslie Overton, a deputy assistant attorney general at the Justice Department’s antitrust division, told a conference of health-care lawyers in Washington on June 30 that the department would give insurer mergers a “careful, appropriately thorough analysis” that would consider the evolving marketplace.

“We’re looking forward and we’re predicting what is going to happen,” she said.

Antitrust regulators have become increasingly aggressive, said David Balto, a former attorney at the Federal Trade Commission, which shares antitrust jurisdiction with the Justice Department.

“You need to look at how tough the agencies are getting at merger enforcement,” he said. “This is like swimming with the sharks now.”

Failed Takeovers

Officials at the FTC and Justice Department have stepped up merger enforcement recently, successfully stopping Sysco Corp.’s takeover of US Foods Inc. and Comcast Corp.’s deal for Time Warner Cable Inc. Regulators last week sued to block Electrolux AB’s planned purchase of General Electric Co.’s appliance business.

Competitive concerns are often addressed with divestitures of businesses in individual markets, as occurred when Humana acquired Medicare provider Arcadian Management Services in 2012.

Significant divestitures of Medicare Advantage businesses will likely be required for clearance of the Aetna-Humana deal, possibly in hundreds of counties, Bloomberg Intelligence analyst Jennifer Rie said. The most significant overlaps appear to be in counties in Southern and Midwestern states, including Florida, Texas, Kentucky, Ohio and Missouri, she said.

One smaller health deal is already in the works. Centene Corp. agreed on Thursday to buy Health Net Inc. for about $6.3 billion, creating the biggest private administrator of Medicaid, the U.S. health program for the poor.

Aetna would have to pay Humana a $1 billion breakup fee if the deal falls apart because of regulatory scrutiny, according to Aetna spokeswoman Cynthia Michener. Aetna Chief Financial Officer Shawn Guertin said the companies have examined how their businesses overlap and declined to comment in detail on regulatory scrutiny.

“Obviously it’s something that we think is manageable,” he said on Friday. “At this point, we’re certainly glad that we got this done and that we’re going to be the ones to go through the process first.”

(Updates with Humana forecast in 11th paragraph.)