Statins Keep Working After You Don’t Take Them?
14 CommentsBy Ed Silverman // October 10th, 2007 // 5:24 pm
That’s the conclusion of a new study that says the cholesterol-lowering meds help prevent heart attacks for at least a decade after people stop taking them. And this is the first long-term study of the world’s top-selling type of medication, by the way, the Associated Press reports. The research is a follow-up to a study in Scotland showing that men taking Pravachol for five years substantially lowered their risk of heart attack and death from heart disease.
They were followed for another 10 years after most stopped taking the drug. That group was compared with a group of men who were given dummy pills during the five-year study, the AP writes. There was a 25 percent lower risk of heart attack or death from heart disease among those in the statin group, when compared with the placebo group. The study participants were middle-aged men who had never had a heart attack but who had a very high average level of LDL, or bad cholesterol - 192.
While the study found protection lasted after statin use stopped, the drugs usually are prescribed indefinitely, especially for people with known heart disease. Federal guidelines say these drugs are very safe and may be used by people with LDL levels as low as 130, or even 100 if they are at very high risk of heart attack, the AP writes. The new results, based on medical records from more than 90 percent of the men in the original experiment, appear in the latest issue of The New England Journal of Medicine (subscription may be required).
The researchers concluded that the statin’s protective effect was probably because existing plaque was stabilized and the progression of coronary artery disease was slowed. “Continuing treatment after five years may be beneficial,” they wrote. Pravachol is sold by Bristol-Myers Squibb, which provided some funding for the study, as did Daiichi Sankyo, which makes WelChol. All but one of the researchers reported receiving consulting fees, lecture fees or research grants from a total of five other drugmakers, four of which sell statins.
[UPDATE: An astute reader points out that the study also indicated a higher rate of prostate cancer among Pravachol patients than those given placebo].
After the original study ended in 1995, participants returned to their own doctor’s care and decided whether to continue or start taking statins. Five years later, about 39 percent of the original statin patients were still taking the drugs, and 35 percent of the placebo takers were using statins. Over the 15-year period, 619 of the original statin takers and 674 of the placebo takers died, the AP writes.
Mike Domanski of the National Heart, Lung, and Blood Institute says the study’s biggest weakness is the fact that after the study ended, more of the original statin patients took the drugs than those in the placebo group. The researchers argued that that difference couldn’t explain the overall long-term protection demonstrated in the study.
Domanski wrote in an editorial that the study clearly shows the benefit of statin use “is durable over the long term” and that there now can be no doubt reducing levels of LDL cholesterol has a role in preventing and treating heart disease. Still uncertain, he adds, is how early people with high cholesterol should start using statins and how low one’s LDL should be for the most benefit.
Currently, the National Cholesterol Education Program, a federally funded advisory group, and leading heart doctor groups recommend cutting the LDL level to below 70 for patients at very high risk of a heart attack, below 100 for high-risk patients and below 130 for moderate-risk patients.
Doug Bremner
Safe?! Did they mention the meta-analysis that shows that high dose statins cause cancer? Or muscle damage? Or the fact that the West of Scotland Pravachol Study (WOSCOPS) did not show that Pravachol had any effect on mortality, which is what people care about? If you know anyone from Scotland, they also have terrible diet and other risk factors for heart disease, like smoking, etc. Not your typical person.
LOR
WelChol is a bile acid sequestrant, not a statin.
Doug Bremner
I read the paper, and although they did find a statistically significant reduction in all cause mortality, I don’t think that in their press release they highlighted the statistically significant 51% increase in prostate cancer that they found, much greater than the 25% reduction in combined heart attacks and cardiac mortality, their primary endpoint. I did a detailed review on my blog.
www.topbloodpressureadvice.info » Statins Keep Working After You Don’t Take Them?
[...] Ed Silverman wrote a fantastic post today on “Statins Keep Working After You Don’t Take Them?”Here’s ONLY a quick extractThe research is a follow-up to a study in Scotland showing that men taking Pravachol for five years substantially lowered their risk of heart attack and death from heart disease. They were followed for another 10 years after most … [...]
www.topcholesteroladvice.info » Statins Keep Working After You Don’t Take Them?
[...] Ed Silverman wrote a fantastic post today on “Statins Keep Working After You Don’t Take Them?”Here’s ONLY a quick extractThat’s the conclusion of a new study that says the cholesterol-lowering meds help prevent heart attacks for at least a decade after people stop taking them. And this is the first long-term study of the world’s top-selling type of … [...]
Reality
Doug,
This is actually somewhat analogous to what we were talking about in the Gardasil post. Given what we know about the natural histories of the diseases, the overall effect on mortality by the 25% decrease in CV mortality almost certainly outweighs the effect by a 51% increase in prostate cancer incidence. This supported, at least in part, by the similar rates in non-CV mortality, including cancer mortality, both of which have HRs close to 1, and pretty narrow CIs. What would’ve been helpful would be a mortality rate for prostate cancer alone.
I think you give short shrift to the authors’ discussion of the increased incidence. They go well beyond merely saying it’s probably due to chance–they spend a decent portion of 3 paragraphs discussing it and reviewing earlier studies showing no increased incidence with statins.
And I wouldn’t dismiss out-of-hand the issue of multiplicity–it’s a legitimate statistical concern.
I do think, however, that such a large increase is worthy of further investigation.
Doug Bremner
But there has already been a meta-analysis showing an increase in cancer with high dose statins. The reference and a link to the paper is on my blog. The PROSPER trial also showed a statistically significant increase of 25% of cancer. The worrisome thing about this study is the cancer rates keep increasing over time. I will say that the current study did show a decrease in total mortality, which most of the primary prevention studies previously did not show.
Doug Bremner
Alsheikh-Ali AA, Maddukuri PV, Han H, Karas RH. Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer: Insights from large randomized statin trials. Journal of the American Academy of Cardiology. 2007;50(5):409-418.
Reality
That’s awfully magnanimous of you to admit that the study showed a decrease in mortality.
Your post on your blog implies that I’m somehow dodging you, which is preposterous. You can post all the meta-analyses about statin safety you want. That was never the point, and it was something I acknowledged, and I think my posts bear that out. The points were that:
1. You make an overly simplistic 1-to-1 comparison of a 25% percentage decrease in coronary events to a 51% increase in prostate cancer as thought they’re on an equal scale. If one of your medical students or residents made this type of comparison, I’m sure you’d point out that it is a false comparison.
If a new drug has been shown to decrease the incidence of prostate cancer by 51%, but it has this tiny AE of 20% increased mortality. How do you feel about Pharma Co. X getting FDA approval for this new drug?
Let’s take it a little further: I am not a statistician by any stretch of the imagination, but as I calculate it, the NNT for the combined endpoint is 27, and 55 for all-cause mortality. The NNH for prostate cancer incidence is 111. Given that I’m much more likely to die from CVD than prostate cancer (and we’re not even talking about death from prostate CA, just incidence), I’ll take my chances with a statin.
2. You grossly mischaracterized the authors’ treatment of the incidence of prostate cancer, which you still haven’t acknowledged.
Reality
Doug,
And just to be complete, here’s how you summarized the authors’ take on prostate cancer:
“The authors stated that the increase was “probably due to
chance and not causally related. A similar ruse was given for the finding from PROSPER of a 25% increase in cancer, where the authors said that it was due to “the play of chance”.”
I included the second sentence to show how you injected your own clear bias.
For people who actually care, here’s what the authors ACTUALLY wrote in the discussion:
“The only cancer outcome that occurred with significantly greater frequency in the pravastatin group than in the placebo group was prostate cancer. Taking into account the multiple statistical tests performed, it is arguable that this result was due to chance rather than to a causal relationship. In the meta-analysis of statin trials,(17) data were not reported for prostate cancer as a separate site of cancer. However, there was no excess in the number of genitourinary cancers in that analysis, and the results of an observational case–control study suggest a possible reduction in prostate cancer (18) with statin use. A meta-analysis of the incidence (19) of cancer in statin trials showed no significant difference in the incidence of prostate cancer between the statin and control groups in trials involving a total of 20,063 participants. However, reports on these other studies did not include data on long-term follow-up, and some cancers may have a long latency period.
“Our results should be compared with those observed in the long-term follow-up of the Scandinavian Simvastatin Survival Study (5) and the LIPID trial.(7) Both were secondary prevention studies, and in both studies most participants were treated with open-label cholesterol-lowering drugs at the start of the post-trial follow-up period (84% in the Scandinavian study and 90% in the LIPID study). The Scandinavian group reported on an extended 5-year follow-up of deaths and incident cancers (5). They found no ongoing benefit with respect to a reduction in the rate of death from any cause or from cardiovascular disease in the follow-up period and no evidence of an increase in the incidence of cancer. There were more cases of prostate cancer in the placebo group than in the statin group. The LIPID Study Group reported results (7) for a 2-year extension. During this period, there was ongoing evidence of a benefit with respect to a reduction in deaths from coronary cause and deaths from any cause. There was no evidence of an excess incidence of cancers of the prostate and testes combined in the group randomly assigned to receive pravastatin. There is no obvious explanation for the apparent disparity between the two studies with respect to the extended benefit achieved. It is possible that the extended benefit of a period of treatment with a statin will depend on the severity of coronary disease at baseline. In that respect, our study population would rank as having the least severe coronary disease at baseline, and the Scandinavian population as having the most severe disease. Hence, it is not clear that the results achieved
during long-term follow-up in our study can be extrapolated to the treatment of patients with established coronary heart disease. In addition, all study participants were middle-aged men, which means that our findings cannot necessarily be extrapolated to any other group.”
When you give the whole context, it kind of takes away from your “gotcha” moment, don’t you think? It’s worth noting, too, that this is about 1/4 of the discussion by eyeballing it. And this is NEJM, where space is at a premium.
I hope that folks like John Mack see fit to either amend or correct their posts regarding Doug’s assertion, selective quotation, and misleading information.
I’ll close statement from your post:
“…I think it is time for these researchers to start playing by the rules of statistics, i.e. don’t use statistics only when it goes in your favor.”
Noted without comment.
Doug Bremner
‘Arguably due to chance’ sounds pretty similar to ‘probably due to chance’. And since the PR machines are already trumpeting the beneficial long term effects of statins, I don’t need to add to that, and I have already acknowledged the long term reduction in mortality. You complain that I don’t tell folks that they should be glad to take a drug that will save them from heart attack or cardiac mortality in 1 case out of 100, while causing prostate cancer in 2 cases out of 100? If you are male you would know that many men would rather die from the impotence that comes with prostate surgery, while if you are a woman you should know that statins have no beneficial effect for women without heart disease.
Walsh JM, Pignone M. Drug treatment of hyperlipidemia in women. J.A.M.A. 2004;291:2243-2252.
And the meta-analysis I cited is the best way to look at a question like whether statins cause cancer, since it puts all the studies together, and therefore has more power.
If I disagree with the points above, does that mean I am in denial of Reality?
Reality
Doug,
I’m not saying you’re in denial about the power of meta-analyses or the overall hazards of statins. And I’m also not saying people shouldn’t be warned about the potential hazards. What I am saying is you are completely off-base in terms of the relative risk-benefit ratio as concerns the study at hand if you really think these are equivalent endpoints on a percentage-to-percentage basis.
And you’ve got to be kidding me if think you accurately represented the entirety of the safety discussion with that little blurb.
How men would rather die? What? True or not, the irrelevance of the point is staggering, and makes clear to me that any further serious discussion of this study and your (mis)representation of it is a colossal waste of my time.
Green Apple Agent
Nice post! I think we have a lot to worry about with the threat of heart attacks. Check out this informative article I found where you can learn more about preventing heart attacks
Concerned Citizen
Look no further for anecdotal evidence of statin overindulgence. We have your neuropathy, your neurodegenerative diseases, rhabdomyolysis, your transient global amnesia, severe memory loss, hormonal imbalances and their associated effects — and that’s just for starters. And there’s certainly enough to go around for every age and sex. These underreported major sides are the dirty little secrets of a multi-billion dollar global drug industry and a mostly broken Medwatch reporting system.
http://www.spacedoc.net/board