The surprised and the desperate cholesterol-guys

The surprised ones

Even those who recommend statin treatment have understood that its benefit is minuscule, in particular for people without previous cardiovascular disease (so-called primary prevention) and they are therefore looking after alternative drugs. Many studies have shown that people with high HDL-cholesterol, the “good” one, live longer than those with low. Therefore, several trials have started testing drugs that are able to increase HDL-cholesterol. One of them is named evacetrapib.

The trial started three years ago and included more than 12,000 patients with various types of cardiovascular diseases, but although it increased HDL-cholesterol by 130 % and decreased the “bad” LDL-cholesterol by 37%, neither heart attacks, strokes, angina or cardiovascular death were prevented and the trials was therefore discontinued in October last year.

Said Steve Nissen, chairman of Cardiovascular Medicine at Cleveland Clinic: “Here we have a paradox. The drug more than doubled HDL and lowered LDL levels by as much as many statins, but had no effect on cardiac events.”

You can read more about that trial in New York Times

But how come that cholesterol-lowering treatment continues? If no difference was seen, and similar results have been achieved in the trials published after the introduction of the new, stricter regulations for drug trials, the content of cholesterol in the blood must be unimportant. In fact, many studies have shown that old people with high cholesterol live the longest. But the leading researchers within this area do not understand the simple facts, or, more likely, they try to maintain the generous economical support from the drug companies.

The desperate ones

At the American College of Cardiology’s recent 65th Annual Scientific Session the results from HOPE-3, a new statin trial were presented. Almost 13,000 individuals without previous cardiovascular disease were given either 10 mg rosuvastatin, or blood-pressure-lowering drugs, or both, or placebo. Some of them were obese, some of them smoked, some of them had hypertension and a few had diabetes, but as mentioned, none of them had cardiovascular disease. According to the abstract of the report, those treated with rosuvastatin had “a significantly lower risk of cardiovascular events” and with minimal side effects after 5,7 years of treatment.

But what is “a significantly lower risk”? Well, although the ”bad” LDL-cholesterol was lowered by about 26%, none of the various cardiovascular events were lowered with statistical significance. However, if you add all of the serious ones together, the risk was lowered by 1.1 per cent and no further improvement was seen in the group, who also took blood-pressure-lowering medicine.

You can also say that you have to treat about one hundred healthy individuals for almost six years to save one of them from a heart attack or a stroke. But please note, you cannot prolong his/her life.

Somebody probably may think that as the treatment with rosuvastatin was without serious side effects, it may be worth trying it. But stop a moment. To be accepted for this treatment the authors used the same method as in most other statin trials; all participants tried the drugs for 4 weeks, and only those who tolerated them were accepted for the trial.

Furthermore, not all side effects were recorded. If you want information about cognitive functions and erectile dysfunction, the authors refer to an appendix, which you have to search for yourself on the web, but in that appendix you cannot find anything about cognitive functions or erectile dysfunction. What you can read is that muscular problems were only recorded if the CK test, a test which reflects the degree of muscular damage, was ten times higher than the upper normal level, and that only those events the investigator thought were associated with either medication, were reported as adverse events. As the male participants were 55 years of age or older and the females 65 years of age or older, I assume that such side effects were seen as a result of their increasing age, not of the treatment.

You can read the full trial reports here:

The rosuvastatin trial
The blood-pressure-lowering trial
The combined trial

PS  Salim Yusuf, the main author of the rosuvastatin-trials, has reported grant support from the Canadian Institutes of Health Research and AstraZeneca during the conduct of the study; grant support from AstraZeneca, Novartis, Bristol-Myers Squibb, and Cadila Pharma, and grant support, personal fees, and non-financial support from Bayer outside the submitted work.

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