Tuesday, July 12, 2011

Do Cholesterol-Lowering Drugs Save Lives?

If you read my last post about cholesterol-lowering drugs, then you understand some of the problems that can arise from their use.  Statins can produce some nasty side effects.  But side effects aside, statins save lives right?  I mean, doctors prescribe them to just about everyone, they must be effective.  Not quite... the story is not as simple as it may seem.

When looking at the statin drug clinical trials, it's important to keep a few things in mind.  Firstly, and most importantly... total mortality is more important than heart disease mortality.  If a drug prevents you from dying of heart disease but doesn't affect your chances of dying in general, then that drug is not worth taking.  What's most important is whether or not the drug will extend your life.  Secondly, you must consider that different groups of people may respond differently to the drug.  Women, middle-aged men, the elderly, and those with preexisting heart disease may all respond differently to treatment. 

I'd like to begin by talking about women... both because I like women, and because they don't respond well to statins.  Although many statin studies notoriously neglect to reveal the all-cause death data for women, there are a few studies that do.  Check out the Scandinavian Simvastatin Survivial Study (4S), which was one of the most positive trials to date.  The big pharma folks must have been partying it up when this one came out.  This was a secondary prevention trial, meaning that participants all had pre-existing heart disease (previous heart attack or angina).  For future reference, a primary prevention trial would be an experiment in which the participants did not have pre-existing heart disease.  So, half of them took simvastatin and half of them took a placebo.  The results were great across the board: heart attack numbers were reduced, along with deaths from heart disease and all-cause mortality.  But there was one group that clearly didn't benefit:  women.  Over the duration of the 5.4 years of the trial, 27 (6.6%) of the women taking the statin died, while only 25 (6%) of the women taking the placebo died.  So despite the rest of the data, which was very supportive of statins, there was actually a slight increased risk of death in women from taking the statin.  As you'll soon see, this finding is consistent throughout all of the statin trials, yet it is completely ignored by mainstream medicine.  These drugs simply don't work for women.

Now, men are a bit of a different story.  It's important to split men up into two distinct groups:  those with diagnosed heart disease (previous heart attack or angina), and those without diagnosed heart disease.  In those without heart disease, statins appear to be largely ineffective.  Both the University of British Columbia and Dr. Graham Jackson in the UK have published review articles looking at many of the primary prevention statin trials.  These were both reviews of the existing research, and they did not pick and choose studies that would support one side or the other.  Here's a key statistic from the UBC paper:  "71 primary prevention patients with cardiovascular risk factors have to be treated with a statin for 3 to 5 years to prevent one myocardial infarction or stroke."  And here's one from Dr. Jackson's study:  "Long term use of statins for primary prevention of heart disease produced a 1% greater risk of death over ten years versus placebo when the result of all the big controlled trials reported before 2000 were combined."  Although both studies showed reduction of cardiovascular deaths in those taking statins, overall deaths were either the same or higher.  Oh, and they also found zero effect on cardiovascular deaths in women.  Sounds like statins aren't so effective in those without pre-existing heart disease. 

And I've got more.  In 2005, a study called ASCOT-LLA, which studied Lipitor on high blood pressure patients, was stopped early due to the supposed "massive" reduction in cardiovascular deaths experienced by the Lipitor group.  The researchers considered the benefits so great that it was unethical to continue to deprive the placebo group of proper treatment. This study is considered to be one of those landmark trials that proved once and for all the life-saving benefits of statins.  Well, let's look at the data... you'll have to click to enlarge it.

In that first set of data, I'd like to draw your attention to the "all-cause mortality" graph in the bottom right.  See that vertical line there that I've drawn in?  That's a little trick I learned from Dr. Malcolm Kendrick in his book The Great Cholesterol Con.  The reason that line is drawn in there is because the trial ended at 3.3 years.  The graphs, however, show data until 3.5 years.  If you look closely at the graph, at 3.3 years there is almost no difference between the Lipitor group and the control group, but for the last 0.2 years of the study, the two lines begin to suddenly separate.  WTF mate?  How does one acquire data for a study after the study has ended?  Something seems fishy to me...  tampering of evidence perhaps?  No way to know for sure, but I can say with certainty that there was no reason to shut down this study early.  There's virtually no difference in the all-cause mortality data.  Oh, and that second graph... that's showing the effectiveness of Lipitor on cardiovascular mortality (note: NOT all-cause mortality).  Notice women in this trial had an increased risk of dying from heart disease on the drug.

To sum up the statin drug data, here's a convenient table copied again from Dr. Malcolm Kendrick:

You can see here that the 4S trial, which I discussed earlier, was overall very supportive of statin use.  This trial was purely a secondary prevention trial.  And I must admit that statins do appear to save lives in men with previous heart disease.  But that is the ONLY group for which they save lives.  Purely primary prevention trials, like EXCEL, actually showed in increase in all-cause death on statins.  And then there are trials like WOSCOPS, which was a mix of primary and secondary prevention, and those trials typically yield results somewhere in the middle of the extremes.  Even in the most positive statin data for those with pre-existing heart disease, however, the results are really underwhelming.  You would think that with all the hype surrounding these supposed "life-saving" drugs, the data would be a little stronger.  Even if you do have pre-existing heart disease, and are a man, you can only expect about a 3% reduction in the chance of dying over the next several years.  That is just unimpressive to me.

So despite the relentless pushing of these drugs by big pharmaceutical companies, mainstream doctors, and my Anatomy and Physiology professor, careful examination of the data shows a surprising lack of evidence to support their use.  Statins decrease the risk of dying of heart disease; that's good.  But they don't decrease the risk of dying overall in the majority of the population; that's bad.  So then, if heart disease deaths are decreasing but overall deaths are not, statins must be increasing the risk that you'll die of something other than heart disease.  I'm even going to go as far as to say that they cause these non-cardiovascular-related deaths. Unfortunately, most studies fail to specify exactly what these non-cardiovascular deaths are, but take a look at my previous post for an idea.  If you're a woman, statins won't even reduce your risk for heart disease, and they actually increase your risk of dying overall.  The only population for which statins can save lives is men with pre-existing heart disease, which is less than 5% of the population.  If you're one of those people, take your statin if you're so inclined.  But if you're anyone else, especially a woman, you are barking up the wrong tree.

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