New Cure for Cholesterol
CHOLESTEROL. It's a slimy subtance your body makes and also absorbs from fatty foods to toughen cell walls and create essential hormones. It can also kill you. A precursor of heart attacks and strokes, cholesterol buildup is as seductive - and deadly - as a jelly donut. Or a hamburger with fries. We North Americans take in way too much in daily diets rich in saturated and trans fats, and once it's in, cholesterol has been likened to a cockroach - cunning and hard to kill.
Changing your diet - cutting way back on red meats, dairy products and fast foods, and scarfing down plateloads of fruit and veggies - can help reduce the amount of cholesterol in your blood. So can exercise, which reduces stress. But not everyone is game for these challenges, and so medical science has developed its own antidote: anti-cholesterol agents called statins, which do a better job anyway of lowering cholesterol, and which, some admirers say, are the closest thing today to a miracle drug. For the past five years they have been the fastest-growing prescription medication in Canada, part of a $28-billion-a-year global market. As many as four million Canadians pop a statin each night before they go to bed.
Statins are one of the reasons Canada's mortality rate from heart disease has been declining even as the population ages, and that heart attacks aren't the death sentence they used to be - U.S. Vice-President Dick Cheney has had four. What's more, in the last year alone a new wave of studies has confirmed that these cholesterol pills not only reduce the risk of heart attacks but also stroke, in some cases, by a third or more. Adding to the mystique, they also appear to show benefits for a long list of other ailments: diabetes, multiple sclerosis, HIV, Alzheimer's disease, rheumatoid arthritis, colorectal cancer, macular degeneration and glaucoma. Hence the "miracle" designation.
Some of these studies are admittedly pretty small: only 63 participants, for example, in the Alzheimer's pilot; 27 for multiple sclerosis. But on the cholesterol-lowering front, the study groups have been massive - as many as 20,000 participants over five-year periods. And what they've brought about is nothing short of a revolution in cardiac care. Physicians are now aiming to reduce the so-called bad cholesterol - the low-density lipoproteins (LDL) that clog the coronary arteries and those to the brain, blocking blood flow - to much, much lower levels than was previously thought safe. This is especially true for those considered at high risk of heart attack or stroke - generally those who've had one already, diabetics, or people with chronically high blood pressure or cholesterol. New groups being targeted include the elderly, post-menopausal women whose weight or blood pressure isn't what it should be, and the dietarily challenged. This more aggressive approach is quickly spreading to encompass those once considered at much lower risk, such as the sedentary but otherwise healthy fortysomething, with maybe some family history of HEART DISEASE, who doesn't want to give up his afternoon cruller. And that raises the question: who exactly should be on statins? Everyone over 40?
"Virtually every study with statins has shown that if you lower the blood level of cholesterol, you lower the risk of heart disease," observes Dr. Lawrence Leiter of Toronto's St. Michael's Hospital, one of Canada's foremost lipid experts. "Will statin therapy work on lower-risk people? I have absolutely no doubt it will. The question is: can we afford it?"
It's a good question. But given that cardiovascular disease is still the country's No. 1 killer, of an almost equal number of men and women, and that, by most counts, the majority of Canadians over 40 and virtually all over 50 have some cholesterol-induced obstruction in their arteries, can we afford not to? Indeed, a running joke among cardiologists is that the statins have now proven themselves so effective and so safe - only about one in a million die from their use and then only if not properly monitored - they should be added to the drinking water like fluoride. Some aren't joking.
In the U.S., medical authorities were so impressed by the new research data - five huge clinical trials published in the past three years - they issued far-reaching, new cholesterol guidelines for physicians this summer. In the process they leapfrogged Canada's - until then thought to be the most aggressive in the world - at least when it came to very high-risk individuals. The British went one better. In July, after much public debate, health officials authorized the low-dose sale of Zocor, an early statin with a long track record, over the counter at pharmacies. Like multivitamins.
If you're a paunchy British male in your late 40s, or a woman in your late 50s and maybe a smoker, you can pop down to your local chemist, fill out a form to ensure you're not a high-risk candidate who really should be seeing a doctor, and walk away with a month's supply of Zocor to cut the odds. It's the first shot in what may well be a consumer revolution in preventive cardiac care, and the advertising campaign is just now kicking into high gear.
Not everyone, mind you, is enamoured with widespread statin dependency. Leiter, a cautious believer, nonetheless warns that high cholesterol is only one of the factors doctors consider in assessing the risk of heart attack: family history for heart disease at a young age, blood pressure, excessive weight and smoking status are just as important.
More stringent critics include the Center for Science in the Public Interest, a U.S. consumer group. It wants the new U.S. guidelines rolled back, mostly on the grounds that many of the scientific authorities had, in the past, received research contracts from the statin-making drug companies. And James Wright, a medical researcher at the University of British Columbia, has been leading a campaign to restrict statins primarily to those who have already had some kind of major heart incident. Basing his assessment on the same research as everyone else, he argues the drugs may do as much harm as good for those who are generally healthy.
Wright's is a minority take, but even Ottawa cardiologist Dr. Andreas Wielgosz, a spokesman for the Heart and Stroke Foundation of Canada, says the British evidence for selling it over the counter "is not strong," and the studies behind it didn't really examine the effects on women, who tend to have naturally higher blood cholesterol levels than men. "I think far more can be achieved with lifestyle changes," he says. "I recognize that is difficult for many people, but that doesn't mean we throw in the towel and go after the drugs."
Statins work by reducing the activity of an enzyme in the liver that controls cholesterol production. They have been shown to reduce bad cholesterol by as much as 50 to 60 per cent while also boosting the good stuff, the high-density cholesterol that helps scour the arteries. But they are not without problems. Statins don't interact well with at least two known antibiotics, and they can cause birth defects, so they can't be taken by pregnant women. Some patients have complained of headaches, nausea and a drop-off in sexual libido. And some researchers claim statins inhibit the development of a key enzyme in the heart. But the biggest concern seems to be muscle weakness.
About one in 1,000 people on statins exhibited significant muscle pain and weakness, U.S. regulators reported. In extreme cases this can lead to something called rhabdomyolysis, a muscle-tissue breakdown that brings on kidney failure. One high-dose statin, Bayer's Baycol, was removed from the market in 2001 after 31 people died of rhabdomyolysis. More recently, Health Canada, following regulators in Europe and the U.S., issued a warning in June that a statin called Crestor, from British drug maker AstraZeneca, should be monitored for this disease. Since February 2003, when Crestor was approved here, there have been eight known cases of rhabdomyolysis among Canadians taking the medication.
Perhaps because of these concerns, Canadian drug companies aren't rushing to direct sales. But perhaps that's because things are going pretty well as is. Both Montreal-based Pfizer Canada Inc., and its New York parent, Pfizer Inc., say they have no plans to lobby for over-the-counter status. Why should they? Their statin, Lipitor, is currently the bestselling drug on the planet, with yearly revenues of over US$9 billion.
However, at least two of Pfizer's competitors are reportedly planning to reapply for non-prescription status in the U.S - so the marketing gloves are likely to come off soon. Adding to the momentum, the British decision was based on the projection that selling low-dose cholesterol drugs directly to consumers could save 10,000 lives a year. The very rough Canadian translation, based on population, would be 5,000 lives, a significant number when you consider that 79,000 Canadians die of heart disease annually.
So should Canada follow suit? Become a statin nation? "It's a tough call," says cardiologist Dr. Robert Myers, director of the congestive heart failure clinic at Toronto's Sunnybrook and Women's College Health Sciences Centre. "But I would say no. This isn't cough medicine. Or a vitamin that you pee out if there is too much in your system. This is still a drug."
Myers's main concern, like that of most other Canadian doctors surveyed, is that the British plan doesn't require a cholesterol test before or after people pick up their Zocor. Self-treaters might well be deluding themselves if what they really need is a much higher dose to bring their LDL numbers down. What's more, they won't necessarily be monitored for the rare but possibly serious side effects.
Many of these concerns could be addressed were Canada to authorize over-the-counter sales. Cholesterol testing is becoming vastly more simplified, and a Toronto company is planning to bring out portable testing devices for home use and pharmacies. As well, self-medicators could be bombarded with the kind of warning messages you get on cigarette packages. But for many physicians, what the cholesterol debate really revolves around is getting the right statin dose to the people who are otherwise falling through the cracks. And for that, University of Alberta pharmacist Ross Tsuyuki has a suggestion.
From 1998 to 2000, Tsuyuki and one of his students ran a trial with over 600 patients and 54 community pharmacies in Alberta and Saskatchewan. Using their own personal knowledge of their customers and their computer records, the pharmacists brought forward a list of those who might be considered at risk for heart attacks or strokes and invited them to participate in the study. About half were handed a brochure about heart disease; the rest were given a detailed questionnaire, some face-to-face counselling and a quickie cholesterol test. A brief analysis of the results was then faxed to each individual's family doctor, and an impressive number, 57 per cent - much more than the brochure group - ended up on a statin, or further monitoring. "The idea was not to take family physicians out of the loop," says Tsuyuki, "but to get them some help. When it comes to cholesterol reduction, family doctors are just drowning in patients."
That drowning is part of the new argument for over-the-counter treatment. It assumes that while some high-risk individuals might slip through, thousands of others will benefit from the scattershot approach. Diets alone don't do the job - generally they reduce cholesterol levels by about five to 10 per cent, most doctors say - and the ensuing cost of increased statin prescriptions would swamp any pharmacare system Ottawa and the provinces might come up with.
But though statins are the fastest-growing class of prescription drugs in Canada, there is a view among many doctors that they are not getting to enough people who need them before they've had a heart attack or stroke. The best estimates are that between three and four million Canadians are taking statins, but that's less than half of those who could benefit, says Dr. Ruth McPherson, director of the lipid clinic at the University of Ottawa Heart Institute. As well, she adds, 20 to 30 per cent aren't getting the appropriate dose, especially given the newer, more aggressive treatment guidelines, because Canadian doctors tend to undertreat. Both of these assessments open the doors wide for greater long-term savings in the health care system and, admittedly, drug company profits. But they also assume people will stay with their drug regimes - and that's not necessarily the case.
"If you look at adherence rates," says Muhammad Mamdani, a scientist with Ontario's Institute for Clinical Evaluative Sciences, "they are terrible. We are estimating that more than half the patients started on these drugs stop them within about two years." That could be due to concern about side effects, or possibly because people don't feel any obvious benefit. And some of the biggest dropouts are, perversely, the elderly, those most at risk of heart attack or stroke. ICES estimates that of the approximately $150 million Ontario's drug plan spends on statins for the elderly, about a third is wasted because people drop the drug too early to benefit fully. "It's the biggest issue facing statins all over the world," says Mamdani, "getting people to stay on them."
The Cholesterol Pill
Prescription growth in Canada of statin medications in retails sales
Annual sales ($ in billions)
Source: IMS Health Canada
Maclean's October 25, 2004