A look at the current medication Mackenzie Ames takes for familial hypercholesterolemia, a genetic disorder that inhibits the body from removing LDL cholesterol from the blood, along with photographs of her mother and father, who also suffer from similar conditions, in Raleigh, N.C, June 20, 2018.

Heart disease runs in Mackenzie Ames's family. Her grandfather had a fatal heart attack at age 30 while dancing with her grandmother at the Elks Lodge in Bath, N.Y.

Her mother had a quadruple bypass when she was 42. When Ms. Ames was just 9 years old, her LDL cholesterol level (the bad kind) was 400 mg/dL, about four times higher than it should have been.

Diet and exercise did not help. Ms. Ames tried every cholesterol-lowering drug available, but nothing could get her LDL below 100 mg/dL.

Her problem is a genetic condition, heterozygous familial hypercholesterolemia (F.H.), that leads to high cholesterol levels and heart attacks at a young age. It affects 1.3 million Americans.

In theory, there is a solution — a new class of drugs, called PCSK9 inhibitors, that slash cholesterol levels, reduce the risk of heart attacks and strokes and save the lives of people like Ms. Ames, who lives in Raleigh, N.C.

According to the Food and Drug Administration, patients with F.H. are eligible for the new drugs. But she can't get them. Two insurers have turned her down.

"I have followed every rule, and I still can't get access," Ms. Ames said. "My doctor can't get a straight answer."

Like many similar patients, she has gotten caught in the crossfire of a marketplace battle between insurers, providers of prescription drugs and the makers of these drugs.

Drug companies gave the PCSK9 inhibitors exorbitant price tags — the list figure was as high as $14,600 per year, although payers generally negotiate much lower prices. But insurers balked at the costs and questioned the effectiveness of the new drugs.

Access is beginning to ease now, with some unusual new agreements between the manufacturers, insurers and pharmacy benefit managers who act as intermediaries. Still, these drugs offer a cautionary tale, even as pharmaceutical manufacturers bring to market costly new treatments for common diseases like migraine, nonalcoholic liver disease and severe dermatitis.

Unlike expensive drugs for cancers or rare inherited diseases, the PCSK9 inhibitors were aimed at large numbers of people — as many as 10 million Americans, a number that includes not just people with F.H. but also people with heart disease and stubbornly high cholesterol levels.

For the most part, few of those patients were able to get the medications. In one study, 80 percent of patients who tried to get the powerful cholesterol-lowering drugs were met with initial rejections by insurers; only 50 percent eventually received approval after appealing.

The drugs arrived just after what was called "the hepatitis C debacle" by Jalpa A. Doshi, a health economist at the University of Pennsylvania — the introduction of medications that cured the liver disease but cost $84,000 or more for a course of treatment.

Stunned by those costs, insurers and other payers "were scanning the horizon to see what else was coming on the market," she said. The PCSK9 inhibitors, they learned, could cost the nation anywhere from $21 billion to $113 billion a year.

And unlike hepatitis C medications, the new cholesterol-lowering drugs would be taken for a lifetime.

"The science behind these drugs is astonishing, but the price is also astonishing," said Dr. Steven Miller, chief medical officer at Express Scripts, the largest pharmacy benefit manager in the United States. (It is being acquired by Cigna, the health insurer.)

Until recently, there were no studies showing the drugs did anything except lower cholesterol levels, Dr. Miller added. Payers resisted in part because the manufacturers needed to show that PCSK9 inhibitors also prevented heart attacks and strokes and saved lives.

And given the expense, doctors needed to show that patients really needed these powerful drugs and not cheaper alternatives. "Statins cost around $250 a year," Dr. Miller said.

Dr. Michael Sherman, chief medical officer at Harvard Pilgrim, which provides health insurance plans, echoed those concerns.

"People get very angry when their deductibles go up, or when their premium or cost share goes up," Dr. Sherman said. But the price of expensive drugs "is coming out of somewhere."

The companies that make the drugs, Amgen and Regeneron, note the list price of drugs is always higher than the price insurers agree to pay. Regeneron, the first to market (in cooperation with Sanofi), set its list price to allow for substantial discounting when its competitor, Amgen, got its drug approved, a spokeswoman said.

As for Amgen, whose drug was the second PCSK9 inhibitor to be approved, the drug's price "was set to be competitive within a complex health care system," said Tony Hooper, Amgen's executive vice president.

Both companies say they deplore the subsequent lack of access to their drugs.

Insurers insisted doctors fill out pre-authorization forms describing why their patients needed the drugs, Dr. Doshi said. The practice is not unusual for expensive treatments — but in the case of PCSK9 drugs, the forms tended to be byzantine, inordinately long and complicated.

And while pre-authorization forms for most other drugs require only the doctor's verification of a patient's medical history, the PCSK9 inhibitor forms usually required proof, including long medical records that often had to be faxed.

Skittish insurers have denied patients without clear reason, or asked for additional data that were unavailable, said Dr. Leslie Cho, a cardiologist at the Cleveland Clinic.

Some insurers, for example, "require inordinate testing or documentation," she said. "They might want to know every statin you ever tried, or force you to try statins that make no sense, like trying simvastatin when you have already tried three other statins."

Insurers had asked for documentation of cholesterol levels when the patient was not taking statins. But many had been taking statins for years and had changed doctors several times in the interim. That kind of documentation could be impossible to find.

After a doctor applied for a patient to get the drugs, it could take weeks for insurers to issue a denial, and then the doctor had to resubmit the form to appeal.

Some insurers approved a PCSK9 inhibitor for a patient but then cut off the supply after three months, asking for another pre-authorization request. Doctors often say they have neither the time nor the perseverance to try to get the drugs for their patients.

Insurers would rather not cover such expensive patients, said Ron Howrigon, a former executive at Kaiser Permanente and other health insurers. Patients who need PCSK9 inhibitors are already at high risk for heart attacks and strokes, he noted, and their care can be expensive.

If one insurer puts up enough barriers, patients may switch to another — and even change jobs — to get a drug that they believe might be lifesaving, added Mr. Howrigon, who now heads Fulcrum Strategies, a company that advises doctors on running their practices.

For patients and their doctors, all this marketplace maneuvering is maddening and frustrating. But there are signs that some of the barriers are beginning to fall.

Citing recent data showing Regeneron's PCSK9 inhibitor, Praluent, saves lives, Express Scripts recently made a deal with the drug maker.

Regeneron cut its price to Express Scripts. In return, Express Scripts made Praluent the only PCSK9 inhibitor it will provide to patients whose prescriptions it fills. Express Scripts also said it would greatly simplify its pre-authorization forms for the drug.

Harvard Pilgrim struck a different deal. Amgen is reducing its price to Harvard Pilgrim — and will refund the cost of its drug, Repatha, for any patient taking it who goes on to have a heart attack or stroke. In return, Harvard Pilgrim also simplified its pre-authorization forms.

Amgen has 20 more deals nearing completion like the one Regeneron made with Express Scripts, and officials claim that access for patients with commercial insurance has improved by 33 percent.

Still, many patients and doctors are struggling to lay hands on the drugs. At the Cleveland Clinic, "we had to hire a couple of people to navigate all the paperwork," said Dr. Cho.

They succeed only with extensive documentation of every lab test, every drug, the patient has had. Even in the best circumstances, Dr. Cho said, "it takes four to six weeks to get an approval."

"The problem is that there are certain insurance companies and certain groups that require inordinate testing or documentation," she added. And while her group has had some success with appeals, "once you get denied, it is very hard."

Then there are those patients who finally got the drugs only to see them snatched away.

Rodney Scheidel, a 58-year-old Medicaid beneficiary in New Orleans, has diabetes, severe heart disease and an LDL level of 160 mg/dL. With his condition, the figure should be closer to 70 mg/dL.

He cannot tolerate statins, said Dr. Keith Ferdinand, a cardiologist at Tulane Medical Center. "He meets all the criteria" for a PCSK9 inhibitor, Dr. Ferdinand added.

He managed to get a PCSK9 inhibitor for Mr. Scheidel. After three months, Medicaid cut him off and asked Dr. Ferdinand to reapply for the drug and to document Mr. Scheidel's LDL level to show the drug was working.

"That is crazy," Dr. Ferdinand said. "There is no medical guideline that I know of that says if you had an effective therapy you would stop it and show again that it works."

Now that Mr. Scheidel has stopped taking his drug, his cholesterol level will rise again, which could be interpreted as showing the drug did not work. "It's been an uphill fight all the way," Mr. Scheidel said.

Dr. Ferdinand had the same reaction.

"They make these decisions completely arbitrarily," he said.