Wednesday, September 12, 2012

Rabbits from the Hat by David Healy

The power that prompting concern in us about some measure of our apparent health can have in the development of new drug markets is demonstrated dramatically in the cholesterol story.

For fifty years it has been known that very high cholesterol levels and especially familial hypercholesterolemia, an uncommon genetic disorder that leads to high cholesterol levels, can be risk factors for heart attacks. These are the people whose cholesterol levels really do count but these could often be picked up without a blood test by the old style clinical glaze alone – in people with this illness there are cholesterol deposits around the eyes.

In the early 1950s, the Framingham study, which followed 5,209 men and women from Framingham, Massachusetts, in an attempt to pinpoint the risk factors for heart attacks and strokes, identified the risks as obesity, a history of heart attacks or other cardiovascular events, smoking, and a sedentary lifestyle. Raised cholesterol was also a risk factor, but of much less importance; moreover, it was only a risk factor when one or more of these serious risks were also present. The most important things, then, for people who have not already had a heart attack, are to reduce weight, get fit, and stop smoking rather than to measure cholesterol levels.

In fact most Western countries saw a 30 percent drop in cardiovascular mortality between 1970, when increased attention to smoking, diet and fitness began, and the 1990s when the statin group of drugs became widely used to lower cholesterol levels. And aside from the selected use of statins after cardiovascular events, raw study data ( as distinguished from ‘study reports’ given out by the pharmaceutical companies) suggest that, if anything, there is an increase risk in mortality in people using statins who are not otherwise at risk of a cardiovascular event.

While, therefore, there are some people, primarily in hospital care, who have already had a heart attack or stroke, who may be helped by cholesterol screening, widespread and indiscriminate cholesterol testing in society in general with consequent treatment with statins that slightly elevated cholesterol readings almost inevitably lead to, may in fact lead to as much harm as good.

While cholesterol-lower statins grew to become a $30 billion a year market in the late 1990as, it was also becoming clear that simply lowering cholesterol did not provide a person much benefit. Indeed, the drugs could be risky in their own right, and cholesterol itself, scientists were finding, was not without benefits. This however did not put a brake on statin sales – the numbers were ‘refined’. Popular articles and medical reports began to distinguish between high and low density cholesterol and their ratio to each other, as well as triglycerides and fatty acids (which are further lipids found in the blood) Where we all might have had and average overall cholesterol level before, it was becoming increasingly unlikely that any of us would be absolutely “normal” on all these measures and could walk out of a doctor’s office without being proffered a drug to match our numbers, even though the attention that cholesterol and other lipids now receive in medical encounters is out of all proportion to their clinical usefulness.

Extrapolation from studies that demonstrated a benefit in men already ill to the rest of us has led to claims that ‘balancing” out lipids will reduce our future risk. This is a completely mythical balancing, rather like remedying a supposed imbalance of neurotransmitters with antidepressants. Several studies have suggested there may be as much if not more benefit to be gained from adopting a Mediterranean diet, which is more likely to increase than reduce cholesterol levels. For women in particular, the data suggests that attempting to reduce cholesterol levels may increase mortality. Alarmingly, women without coronary artery disease now constitute almost a quarter of those taking statins with almost 10 percent of women over the age of seventy being on statins [which may cause muscle pain and weakness!). More generally 40 percent of people taking statins have no history of coronary artery disease.

These developments have been driven by a series of studies designed to map out norms for cholesterol and lipid levels, the achievement of which would supposedly lead to minimal or no risk of cardiovascular events. There is a set of cholesterol levels that is linked to almost no cardiovascular events – levels found in teenagers or people in their twenties. But these levels are linked to no cardiovascular events because cardiovascular events almost never happen at this age. There is thus no particular reason to believe that cholesterol levels at this range protect against strokes. Nevertheless, it is just these values that have been set as the normal range for adults of every age. According to norms like these, 94 percent of New Zealand’s population has elevations of their lipid levels that carry some risk.

It is a clear contradiction to set up as a normative standard a level to which 94 percent of a population are abnormal. These may be optimal cholesterol levels but they are not normal levels. This is akin to what happened with the advent of drugs like Viagra, when impotence was reconfigured as erectile dysfunction. Impotence had been a disorder of men who were completely or close to completely unable to function. But marketers have progressively redefined the target so that now even twenty-year-olds, who from time to time have an erection that falls any way short of full rigidity, are invited to think of themselves as having a condition that could benefit from treatment and are encouraged to see a pill as a way out of anxiety.

In the case of cholesterol, the context in which any discussion of cholesterol levels made sense – where patients had a history of heart attacks in their family, smoked, were obese, and were also hypertensive – was progressively stripped away, so that the clinical gaze now focuses on the numbers themselves and their deviations from the norms, partly because here is an area where a drug can be prescribed and a doctor can document that something has been done.

Just being constantly reminded of our own numbers on a scale of cholesterol norms can seduce. Even someone like me who knows better, who knows that cholesterol levels are for the most part meaningless in terms of overall health, when faced with his own lipid numbers, if these are thought to be even marginally too high, is likely to be unnerved or perhaps challenged. “I know there’s no real need to get this marginally elevated level down, but hey, let’s see what I can do.” Faced with an apparent deviation of our numbers from the norm, some of us can ‘feel’ our arteries clog up on the spot and would find it almost impossible to do nothing.

Just as Sanjeebit Jachuk found his patients began suffering after a diagnosis of hypertension where they had been fine before, so also many readers of this book would likely start start to suffer from effects they imagine excessive cholesterol brings if faced with their lipid levels [ e.g. chest pains, nausea, incidents of short breath, tiredness which simply arise in the normal courses of life]. Once we only visited a doctor when we were suffering and we hoped to leave in a happier frame of mind about relief in the offering, often later grateful for an encouragement that we did not know at the time defied the numbers. Now we are much more likely to start suffering [in terms of anxiety and fear as well] when some nonessential blood test, health program, or ad prompts us to visit a doctor, who is unlikely to counsel us to leave well enough alone.

At the epicenter of this are companies who have cholesterol- lowering drugs to market. This market is worth $35 billion per year, with the best seller, Pfizer’s Lipitor, making over $12 billion worth of sales in 2008. At the heart of the marketing of Lipitor has been a series of ads that have pulled no punches. One shows the soles of the feet of a corpse in the morgue, with a name tag on its left big toe, and a strap line on the side – Which would you rather have, a cholesterol test or a final exam? Another shows an open heart with its traceries of blood levels and a strap line – Lipitor reduces risks of heart attacks by 36 percent. Behind claims like this, there is typically a study in which 3 percent of older men with a history of heart problems and other risk factors have a heart attack on placebo compared to 2% taking Lipitor or whichever drug – this is a 50 percent reduction in what is called relative risk in contrast to absolute risk. But even for consumers alert to this piece of trickery, there is nothing in the ad to let women or men with no history of heart problems know that these figures of risk reduction do not apply to them.

Pressure like this makes the idea of taking something or going on some diet that might lower lipids very seductive. So much so that even though using pills to lower cholesterol appears to increase mortality, the pill becomes a solution to the problem that attention to cholesterol levels has created. This follows the standard recipe for pulling a rabbit out of a hat –first put rabbit in hat. . .

The new focus on blood lipids, blood sugars, bone density, peak flow and the like has transformed encounters between doctors and patients. But the change has not come simply from blood tests and other obvious measurements. It has also come from the use made of scales developed to measure aspects of behavior. These rating scales were needed in trials of antidepressants, tranquilizers, analgesics, hypnotics, drugs for sexual dysfunction, and other drugs used to modify behavior , for the same reasons as cholesterol levels are needed in statin trials and DXA scans in bisphosphonate trials. In lieu of evidence that patients get up from their beds and walk, feel better again, and return to work, these rating scales produce numbers that go in the right direction on treatment and can be held up as evidence that the treatments are working. The rating scale scores thus developed all too often translate into treatment, without further thought. As a result, for example, anti-depressants have moved in less then ten years from rarely being used prenatally to being among the commonest drugs given in pregnancy –despite convincing evidence that they double the rate of birth defects and miscarriages.

David Healy is a professor of Psychiatry at Cardiff University and former Secretary of the British Association for Psychopharmacology

1 comment:

  1. In pharmacology the promise of evidence based medicine based on randomized, controlled clinical trials has been subverted by the inaccessibility of the raw data produced by these experiments, now largely conducted by companies who only release summary reports and time and time again have been caught manipulating their studies to eliminate or reduce reported incidents of adverse effects and to make their products seem more effective then they really are. If the National Institute of Health or any other agency of government conducts a study the law requires that all the raw data ( exactly what happened to every patient in the study) be made available to the private pharmaceutical companies but the companies are not required to hand-over data to the government except in the context of a lawsuit.

    In the absence of full disclosure it cannot be imagined that the conduct of the pharmaceutical companies is science and the results are plainly seen in the continuing rise in health care costs and the declining heath and longevity of the American people : Pharmageddon

    The revenues that pharmaceutical companies glean from patent protections are used primarily for marketing purposes rather than the development of life-saving drugs. At any rate, all the original and fundamental researches upon which the drug companies found the development of their new products since the 1960s were publicly funded or provided gratis by private individuals with humanitarian rather than mercenary purposes.