The deal comes as the $467 billion e-commerce giant Amazon.com has been quietly exploring ways to expand into the pharmaceutical industry. Jeff Bezos' company has also contributed to the struggles of traditional brick-and-mortar retailers like CVS.

Drugstore operator CVS is in talks to buy health insurer Aetna for a proposed $200 per share or more , sources familiar said. The $66 billion or greater deal would be the largest ever in health insurance history, according to an analysis of Thomson Reuters data.

CVS Health appears willing to pay top dollar for a health insurer in an effort to hold its own against competitors.

"They needed to defend the business from encroachment by Amazon," RBC Capital Markets analyst George Hill told CNBC. "Amazon's ability to impact the business over the near to mid term is low, but the ability to impact the stock is high."

CVS would lose the ability to control its own destiny if it didn't do something, Hill added. "This could be $260 billion in revenue [in 2019]."

The Wall Street Journal first reported that CVS was in talks to buy the health insurer.

CVS has already been trying to establish greater control in its corner of the health care industry. In 2007, the company acquired Caremark pharmacy benefit manager, which has more than 75 million plan members.

Aetna shares closed Thursday 11.5 percent higher at $178.60 a share after The Wall Street Journal posted its report. CVS shares fell about 3 percent Thursday and were down another 0.4 percent in premarket trading Friday.

"The key here is you're going to control the health-care participants in a much greater way," said CFRA senior analyst Joseph Agnese. By acquiring Aetna, CVS could offer customers lower co-pays in the drug stores.

"That will incentivize 23 million people to come to CVS rather than Walgreens," Agnese said. He has a hold recommendation on CVS Health. "I find it very difficult to imagine how Amazon will enter the space without making big acquisitions."

An Amazon spokeswoman told CNBC in a statement the company has a "longstanding practice of not commenting on rumors and speculation."

CNBC reported in May that to develop an internal pharmacy benefits manager for Amazon employees.

However, RBC's Hill expects that, if Amazon were to announce an online pharmacy, it would still take the internet commerce behemoth a decade to get even 10 percent of market share.

In September, Hill had predicted an "inflection point" ahead for CVS should the company transform itself by acquiring a managed care organization like Aetna. Such a move, Hill said at the time, "could transform itself and the space more broadly."

Hill told CNBC on Thursday he was optimistic how it appeared that CVS was now pursuing the right strategy. "A year into this transaction, not only do you have a company with formidable offerings [in health care, but] maybe only United could compete."