Do Statins Reduce Overall Mortality

[ofonorow]

The meta analysis that caught my attention more than 10 years ago at Oxford found that Lp(a) (a form of LDL) increases the risk of heart attack/CVD by 70% The Framingham study was also reevaluated and came to a similar result. Lp(a) and not LDL is the primary risk factor, and if a particular study doesn't consider the Lp(a) fraction, then the finding could very well be associated with Lp(a) - as Pauling/Rath assert.

This doesn't seem to be the same reference, but it is similar
http://www.clinchem.org/cgi/content/abstract/44/11/2301
http://www.ncbi.nlm.nih.gov/pubmed/1534 ... d_RVDocSum
Lipoprotein(a) Is Associated Differentially With Carotid Stenosis, Occlusion, and Total Plaque Area
http://atvb.ahajournals.org.proxy.cc.ui ... 28/10/1851
Lipoprotein(a) Levels and Risk of Future Coronary Heart Disease
http://archinte.ama-assn.org.proxy.cc.u ... /168/6/598

Conclusions There are independent, continuous associations between Lp(a) levels and risk of future CHD in a broad range of individuals. Levels of Lp(a) are highly stable within individuals across many years and are only weakly correlated with known risk factors. Further assessment of their possible role in CHD prevention is warranted.

We know through several large clinical trials that statins reduce all-cause mortality. A meta-analysis conducted by the Cholesterol Treatment Trialist's (CTT) group in 2005 demonstrates that statins reduce the risk of all-cause mortality and mortality from coronary heart disease, proportional to the reduction in LDL-cholesterol. A 1 mmol/L reduction in LDL, for instance, reduced both mortality as well as the incidence of major vascular events in the treatment arm.

I can point to a similar study that showed a more striking effect of low serum vitamin C levels and the increased mortality of an elderly population in the United Kingdom.
http://www.ncbi.nlm.nih.gov/pubmed/1459 ... t=Abstract

But to your point, it would be a highly surprising result if statin drugs really reduce all-cause mortality, especially given the large number of studies where no such effect has been seen. If you can give me a better pointer to the study you are citing, I will take the time to read it.

note. After putting all the responses in the same topic, I decided to try putting each issue into its own separate topic..?

[godsilove]

The meta analysis that caught my attention more than 10 years ago at Oxford found that Lp(a) (a form of LDL) increases the risk of heart attack/CVD by 70% The Framingham study was also reevaluated and came to a similar result. Lp(a) and not LDL is the primary risk factor, and if a particular study doesn't consider the Lp(a) fraction, then the finding could very well be associated with Lp(a) - as Pauling/Rath assert.

This doesn't seem to be the same reference, but it is similar
http://www.clinchem.org/cgi/content/abstract/44/11/2301
http://www.ncbi.nlm.nih.gov/pubmed/1534 ... d_RVDocSum
Lipoprotein(a) Is Associated Differentially With Carotid Stenosis, Occlusion, and Total Plaque Area
http://atvb.ahajournals.org.proxy.cc.ui ... 28/10/1851
Lipoprotein(a) Levels and Risk of Future Coronary Heart Disease
http://archinte.ama-assn.org.proxy.cc.u ... /168/6/598

Conclusions There are independent, continuous associations between Lp(a) levels and risk of future CHD in a broad range of individuals. Levels of Lp(a) are highly stable within individuals across many years and are only weakly correlated with known risk factors. Further assessment of their possible role in CHD prevention is warranted.

There are multiple risk factors for CVD. Lp(a) may well be an independent risk factor for CVD, but that does not preclude LDL-C from being a risk factor either.

But to your point, it would be a highly surprising result if statin drugs really reduce all-cause mortality, especially given the large number of studies where no such effect has been seen. If you can give me a better pointer to the study you are citing, I will take the time to read it.

The CTT meta-analysis showed that there was a reduction in all-cause mortality proportional to a reduction in LDL-C.(Link)

There are probably other studies addressing all-cause mortality, but to my knowledge this is the most comprehensive meta-analysis.

[ofonorow]

Thank you for that link, I only read the abstract, but I wonder about the raw numbers and your claim that statins reduce overall mortality from these numbers, something like 7% of the study population died, 13% had major vascular events and 4.5% contracted cancer.

Obviously these were very ill patients. And I happen to know that generally cardiovascular patients are advised against taking vitamin C.

So on the basis of these numbers they cite a 12% reduction in mortality for the group on statins. (On the surface this sounds impressive, but from my personal observations over the past decade, I would predict that medicine could have achieved about a 90% decrease in overall mortality, all they had to do was provide the study group with the Linus Pauling specified levels of vitamin C ( 5-6 g).)

I'll admit, the abstract has intrigued me to read the entire paper.

One of my first questions is why they limited their study to these 14 trials, when there have been hundreds and hundreds of trials.

A prospective meta-analysis of data from 90,056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol. FINDINGS: During a mean of 5 years, there were 8186 deaths, 14,348 individuals had major vascular events, and 5103 developed cancer. Mean LDL cholesterol differences at 1 year ranged from 0.35 mmol/L to 1.77 mmol/L (mean 1.09) in these trials. There was a 12% proportional reduction in all-cause mortality per mmol/L reduction in LDL cholesterol (rate ratio [RR] 0.88, 95% CI 0.84-0.91; p<0.0001). This reflected a 19% reduction in coronary mortality (0.81, 0.76-0.85; p<0.0001), and non-significant reductions in non-coronary vascular mortality (0.93, 0.83-1.03; p=0.2) and non-vascular mortality (0.95, 0.90-1.01; p=0.1). There were corresponding reductions in myocardial infarction or coronary death (0.77, 0.74-0.80; p<0.0001), in the need for coronary revascularisation (0.76, 0.73-0.80; p<0.0001), in fatal or non-fatal stroke (0.83, 0.78-0.88; p<0.0001), and, combining these, of 21% in any such major vascular event (0.79, 0.77-0.81; p<0.0001).

By the way, what are "weighted estimate of outcomes?"

[ofonorow]

[godsilove]

Thank you for that link, I only read the abstract, but I wonder about the raw numbers and your claim that statins reduce overall mortality from these numbers, something like 7% of the study population died, 13% had major vascular events and 4.5% contracted cancer.

Obviously these were very ill patients.

"Very ill"? What makes you say that?

And I happen to know that generally cardiovascular patients are advised against taking vitamin C.

This is news to me. How do you know this?

Even IF that were the case, it would still apply to the controls who were on a placebo.

So on the basis of these numbers they cite a 12% reduction in mortality for the group on statins. (On the surface this sounds impressive, but from my personal observations over the past decade, I would predict that medicine could have achieved about a 90% decrease in overall mortality, all they had to do was provide the study group with the Linus Pauling specified levels of vitamin C ( 5-6 g).)

Perhaps statins are not as effective as vitamin C. But where's the evidence?

One of my first questions is why they limited their study to these 14 trials, when there have been hundreds and hundreds of trials.

The CTT group published the protocol for which studies would be eligible in 1995 - I believe most of the 14 trials were already planned or underway.

There may be several small trials of statins, but not all of them are placebo-controlled.

By the way, what are "weighted estimate of outcomes?"[/color]

An example of a weighted estimate would be a weighted mean (means, medians, etc are all "estimates" in statistics).

Say you have have two groups, A and B consisting of 10 people and 90 people, respectively. Both groups are randomly sampled from the same population, and you want to know what the average height of the population is. Say the average height in group A is 5.0 feet, and the average height in group B is 6.0 feet. You could calculate an unweighted mean simply by adding the two means and diving by two, hence getting 5.5 ft. However, since the sample in group A is relatively small, there is a higher chance of sampling error and the average could be lower simply by chance. A weighted mean would account for the different sample sizes, i.e. (5.0*0.1) + (6.0*0.9) = 5.9 feet.

The same thing is done in metanalyses which draw data from multiple studies with varying sample sizes.

[godsilove]

[ofonorow]

90,056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol. FINDINGS: During a mean of 5 years, there were 8186 deaths

8186 deaths out of 90056 individuals in five years implies to me that these patients were very ill. (I remember the Harvard Rimm study had something like 657 events (not deaths, just cardiovascular episodes) in something like 60,000 nurses).

I still do not understand "with all that work" you describe, how it could require on average five years to get these results analyzed, especially if these results were so good for the drugs companies. A year, maybe, two years on the outside. Something else is going on, and I suspect the results didn't come out the way they had hoped, and I know from reading the Brown studies, that after reevaluating, they admitted dropping various subjects from the study.

[godsilove]

90,056 individuals in 14 randomised trials of statins was done. Weighted estimates were obtained of effects on different clinical outcomes per 1.0 mmol/L reduction in LDL cholesterol. FINDINGS: During a mean of 5 years, there were 8186 deaths

8186 deaths out of 90056 individuals in five years implies to me that these patients were very ill. (I remember the Harvard Rimm study had something like 657 events (not deaths, just cardiovascular episodes) in something like 60,000 nurses).

I guess I was just thrown off by your use of the word "very". A number of patients included in this meta-analysis were on statins for secondary prevention, i.e. they had already had a previous vascular event such as a heart attack. I would imagine that those on it for primary prevention also had also at least one CV risk factor. They weren't a normal, healthy population - but I guess I misunderstood what you meant by "very ill".

I still do not understand "with all that work" you describe, how it could require on average five years to get these results analyzed, especially if these results were so good for the drugs companies. A year, maybe, two years on the outside. Something else is going on, and I suspect the results didn't come out the way they had hoped, and I know from reading the Brown studies, that after reevaluating, they admitted dropping various subjects from the study.

It's actually fairly normal for clinical trials to be published 2-3 years after publication - and most clinical trials don't involve thousands of patients. I think the size of these trials needs to be factored in.

[malcolan]

Statin drugs obviously lower cholesterol, but I'm in the camp that thinks your cholesterol number is not a good indicator/predictor of cardiovascular disease.

Maybe I'm just simple minded, but to me, if your cholesterol is high, then what you have is an inflammation problem...not a heart problem.

Also, I don't believe for a second that statins reduce overall mortality....and neither does Byron Richards, who wrote an article about it last summer.

Here's a link, if anyone cares to read it.

http://www.naturalnews.com/024001.html

That's my 2 cents...keep the change.

[BaronZemo]

I have two uncles one had a stroke and was permantly disabled , I believe he was on statins at the time and still had a stroke, maybe bp pills a s well. Another was on statins, tryglyceride meds, bp meds and stints . two years in on all the meds, he had two stints that were blocked. Was operated on, cleared up. I believe now he is taking fish oil. At any rate, he has had no problems in three years. There father died of HA at the age of 50 back in the days before medicine was developed to treat cholesterol. So there seems to be some benefite to satins.

My belief is that to get real benefit from C etc is to take it at an early age, so these problems never get a real foothold, I don't stains are without benefit, just costly and with potential bad effects on body, but I believe this is true with most medications , find a natural alternative if possible, otherwise go the western medicine route as last resort.

[godsilove]

Here's a link, if anyone cares to read it.

http://www.naturalnews.com/024001.html

That's my 2 cents...keep the change.

That article doesn't actually address the issue of statins reducing overall mortality, which has been demonstrated in meta-analyses of RCTs involving statins, albeit the reduction is small.

The paper in the Canadian Medical Association Journal found a V-shaped relationship between LDL-cholesterol and cholesterol in type II diabetic patients not receiving statins. Cancer risk was increased at very low LDL levels, but given that this was an observational study one cannot presume that low LDL has a causative role. What we do know is that these patients did not have lowered cholesterol due to statin use, since they weren't using them.

[Ralph Lotz]