Twice a month, Cynthia Barnes turns over the functions of her liver to a cabinet-size machine on a constant spin cycle, filtering cholesterol from her blood in a three-hour process that would be dull if it weren’t a lifesaver.
When the machine stops, Barnes’ cholesterol numbers start going bad again. The fit 56-year-old has a rare genetic trait that gives her a cholesterol count in the 400 range, when 240 is high-risk. She tried statin drugs, but they couldn’t lower the count without crippling side effects.
“Don’t get me wrong,” said Barnes, who works in loss prevention for an insurance group. “I’m happy. Every year I’ve used either statins or this treatment, I’ve bought time. But more people would rather take a pill than do what I’m doing.”
Doctors and patients alike are excited to find themselves at a busy crossroads in heart health. The filtering process called LDL apheresis offers relief to hard cases like Barnes’, but on the horizon, a new drug tantalizes experts with the prospect of raising HDL, or “good” cholesterol, while lowering “bad” LDL.
Statins go mainstream
Meanwhile, the remarkably effective statins gradually go generic, lowering costs significantly.
Since their introduction in 1987, statin drugs such as Zocor, Lipitor and Crestor have helped reduce deaths from heart disease, which remains the nation’s No.1 killer. Experts credit the drug class for contributing to a better than 36 percent decline in deaths from coronary heart disease between 1996 and 2006.
Basically, statins work by blocking an enzyme in the liver that manufactures cholesterol.
Statins’ success has prompted some advocates to compare them to antibiotics in terms of impact — and half-jokingly suggest statins, like fluoride, should be added to the drinking water.
With patents on mainstays like Zocor already expired and Lipitor expiring soon, generics are bringing prices down. “Lipid regulators” only last year dropped to No.2 in annual drug revenue to antipsychotics, and more generic options promise even more cost savings.
“I think the ‘statin era’ will never end,” said Dr. Gregory Schwartz, chief of cardiology at Denver VA Medical Center. “They’re an amazing class of drugs. They reduce cardiovascular risk by about 30 percent if you take all the data in composite. It’s that 70 percent of risk that remains that we try to whittle down, step by step, with additional treatments.”
New drug amazes doctors
Meanwhile, results from early clinical trials of a drug called anacetrapib (ana-SET-tra-pib) have wowed health care professionals who think it might be the next big thing for cholesterol management.
Dr. Robert Eckel, director of the Lipid Clinic at the University of Colorado Hospital, was among the many doctors astounded by the drug’s ability not only to markedly raise HDL — an elusive goal so far — but also to lower LDL on par with many statins.
Eckel’s first reaction to the anacetrapib news was to see it as “a rocket sent to the moon ending up on Jupiter.” He could see the drug lowering LDL by 10 percent or 15 percent, but the trial showed an average 40 percent reduction while raising HDL by 138 percent.
Another drug in the same class — called “CETP inhibitors” — that initially seemed promising ultimately failed miserably. Torcetrapib turned out to be an $800 million fiasco for drugmaker Pfizer when an inordinate number of deaths in the treatment group forced a halt to its development in 2006.
Anacetrapib, developed by Merck, revived prospects for CETP inhibitors when it showed none of those problems that plagued its predecessor.
“It’s the best shot on goal we’ve got right now,” said Dr. Steven Nissen, a Cleveland Clinic heart specialist involved in numerous drug trials. “No other therapy that I see out there has that potential out-of-the-park home run.”
Another drug in the same class called dalcetrapib has had milder effects on cholesterol levels but is further along in clinical testing than anacetrapib, whose upcoming trial could take at least six years.
“Both could work, neither could work or one could work,” said the VA’s Schwartz, who’s leading the current dalcetrapib study. “Bottom line here is, once you have established heart disease, the risk of having more problems remains substantial. I don’t have a horse in this race except I want one of the horses to win, so that we can improve the care we give our patients.”
Statins certainly set the bar high.
They have “clearly, unequivocally” reduced risk for another heart attack or stroke in patients with heart disease and appear to have had similar effects as a preventive measure among high-risk patients, Eckel said.
Statins, along with careful monitoring of diet, exercise and medical regimen, are a key part of a Kaiser Permanente cardiac care service in Colorado covering 13,000 patients with heart-related illnesses.
Kari Olson, a doctor of pharmacy who helps oversee follow-up care for those patients, advocates making statins available over the counter, alongside Tylenol or Rolaids.
“I suspect the overall rate of heart events would go down,” Olson said.
Casual patients can prove as unreliable with the drugs, though, as they are with a tough diet regimen.
Without the kind of nursing and pharmacist follow-up Kaiser provides in its cardiac section, said researcher Thomas Delate, more than half of less risky patients prescribed a statin without follow-up will stop taking it within a year. Medicines that are meant to prevent a negative — put off a heart attack, for example — are notoriously difficult to sustain among users who feel relatively healthy.
Critics of the pharmaceutical-friendly culture in U.S. medicine say the billions of dollars spent on statins each year distract the health care industry from other heart health options. But the drugs are cheap compared with heart incidents, Delate notes, often less than $10 a month for generics. Combined with intensive follow-up programs, statins arguably save the health care system billions.
A Kaiser Colorado study comparing its closely monitored cardiac patients with a group who received traditional, more hands-off care, found the monitored patients had an 89 percent reduction in deaths and each cost the Kaiser system $22,000 less a year by reducing additional heart problems.
Not all on pill bandwagon
Put that way, the numbers sound good. But Dr. John Abramson, a former family practitioner who now writes about the drug industry and lectures at Harvard’s medical school, notes that even for patients who already have had a heart incident, studies show statins prevent a second stroke or heart attack for one person out of every 22 taking the drug.
By contrast, positive lifestyle changes in diet and exercise would help far more people, Abramson said — but advocates of that approach don’t shape and target their messages nearly as effectively as the drug industry markets pills.
The evidence for drugs helping those who haven’t yet had any incidents is even thinner, he added.
“If you give 250 diabetics a statin, you’ll save a life a year. And that’s definitely a good thing to do,” Abramson said. Many diabetics also have high heart risks. “If you get 250 diabetics exercising, you’ll save five lives a year, and that’s five times more important.”
The growing fear among health advocates is that a generation of unprecedented success with statins will be reversed by the American weight problem. Increasing obesity rates are already starting to play havoc with mortality rates improved by statins, diet and exercise.
“The obesity and diabetes epidemic is hugely frightening to those of us who follow these trends,” said the Cleveland Clinic’s Nissen. “Unless we can get to our kids, we’re going to lose some ground.”
And while prescriptions written for statins continue to rise — and may do so for years to come as more generics take hold — there’s no mistaking that now, all eyes are looking forward to the upcoming clinical trial for anacetrapib, which will involve 30,000 patients in several countries.
Dr. Carlin Long, chief of cardiology at Denver Health Medical Center, counts himself among those eagerly anticipating the large-scale trial. But he also notes that, even if the drug delivers, the price will be critical.
“If these drugs work out in the next five years to be real lifesaver medications, then we have a dilemma,” he said. “If, as when most new drugs come out, it costs you $3 to $5 a day, you’re pricing lower-income people completely out of that market, unless we subsidize that in some manner.”
At Kaiser Permanente, Olson said she’s still waiting for “another tool in the toolbox.”
“Even with all we can do, there’s still a significant portion of patients who have recurrent events,” she said. “With some people, we still can’t do enough.”
Ken, a 70-year-old patient of Eckel’s who did not want his full name used, said he suffered a minor heart attack in 2000 and went on statins — including high doses of Lipitor — for more than three years. He’s convinced that the drug not only dramatically changed his cholesterol and triglyceride levels but also gave his heart time to repair itself.
“I was lucky on that,” he said, “but very unlucky in the long term.”
The side effects, he said, were literally killing him. That’s when he connected with Eckel and found a non-statin drug combination.
When Ken stumbled onto news of the clinical trials for anacetrapib, the first thing he thought was: “Wow.” But with even a best-case scenario still years away, he also realizes that there’s no telling whether he’ll be able to take advantage of it.
“I’m frustrated; I wish it had been there in 2000,” he said. “I wish it was there in ’58, so it could have saved my dad and mom. But it wasn’t. And you learn at this age to play the hand that you’re dealt as best you’re able.”
