OK, the move begins tomorrow. Apologies for the several non answered emails, I'll get to them when we're a bit unpacked and have got net access up and running in Bearsden!
Peter
Monday, July 20, 2009
Tuesday, July 07, 2009
May 2009: ASTEROID destroys lipid hypothesis!
Here's a nice quote from this paper:
"Atheroma regression occurred in most patients and was not linked to the LDL cholesterol achieved"
Read that line very carefully. Now read it again. That's it, the rest of the post is just rambling on my part.
But is the lipid hypothesis dead? To quote Malcolm Kendrick from 2005 on a different study:
"The great ship Cholesterol-Lowering has ripped its guts out on the harsh rocks of evidence, but still it does not sink"
ASTEROID was a mini version of the J-LIT study (see below) with three modifications. First it was only 501 patients, so there was never any possibility of looking at clinical outcomes, good or bad. Second was it was only run for two years, which repeats point one but with underlining. Third is that they used a crippling dose of statin, sufficient to drop the mean LDL cholesterol level to 60mg/dl.
Luckily there were minimal adverse reactions to this, if you believe Nissen, which I don't:
"Adverse events were infrequent and similar to other statin trials"
Anyway, they went looking for adverse reactions by level of LDL cholesterol, much as did J-LIT. As might be expected there was no graduation of adverse reactions by cholesterol level because, as Nissen might say, there weren't any!
"Adverse events occurred infrequently during the trial, and no pattern appeared relating the frequency of any adverse event to the achieved LDL cholesterol"
Dying of cancer is difficult in 2 years in the USA. Try five years in Japan, or 10 years in Japan, and use over a 40,000 rather than 500 patients. The excess deaths in the lowest LDL groups will be there, just don't expect them to show in 500 patients.
Final quote:
"Similarly, the on-treatment atheroma volume, change in atheroma volume, and high percentage of subjects with atheroma regression did not differ by the achieved LDL cholesterol"
This is a classic. If the lowering of LDL does not correlate with atheroma volume decrease, why do people believe that lowering LDL is what shrinks atheroma? And if the statin per se is causing atheroma shrinkage, which it certainly is, how come long term large studies of the same design show an increasing body count from cardiac causes when statinating to very low levels of LDL? That's what happened in J-LIT and it's what will happen in ASTEROID if they keep going, except 500 people is far to small to separate the occasional death from chance. Is statin induced atheroma shrinkage beneficial? J-LIT suggests not and ASTEROID is too miniscule to look at clinical outcomes. They will be bad.
Executive summary: lower LDL cholesterol has no linkage to shrinkage of plaque.
Peter
"Atheroma regression occurred in most patients and was not linked to the LDL cholesterol achieved"
Read that line very carefully. Now read it again. That's it, the rest of the post is just rambling on my part.
But is the lipid hypothesis dead? To quote Malcolm Kendrick from 2005 on a different study:
"The great ship Cholesterol-Lowering has ripped its guts out on the harsh rocks of evidence, but still it does not sink"
ASTEROID was a mini version of the J-LIT study (see below) with three modifications. First it was only 501 patients, so there was never any possibility of looking at clinical outcomes, good or bad. Second was it was only run for two years, which repeats point one but with underlining. Third is that they used a crippling dose of statin, sufficient to drop the mean LDL cholesterol level to 60mg/dl.
Luckily there were minimal adverse reactions to this, if you believe Nissen, which I don't:
"Adverse events were infrequent and similar to other statin trials"
Anyway, they went looking for adverse reactions by level of LDL cholesterol, much as did J-LIT. As might be expected there was no graduation of adverse reactions by cholesterol level because, as Nissen might say, there weren't any!
"Adverse events occurred infrequently during the trial, and no pattern appeared relating the frequency of any adverse event to the achieved LDL cholesterol"
Dying of cancer is difficult in 2 years in the USA. Try five years in Japan, or 10 years in Japan, and use over a 40,000 rather than 500 patients. The excess deaths in the lowest LDL groups will be there, just don't expect them to show in 500 patients.
Final quote:
"Similarly, the on-treatment atheroma volume, change in atheroma volume, and high percentage of subjects with atheroma regression did not differ by the achieved LDL cholesterol"
This is a classic. If the lowering of LDL does not correlate with atheroma volume decrease, why do people believe that lowering LDL is what shrinks atheroma? And if the statin per se is causing atheroma shrinkage, which it certainly is, how come long term large studies of the same design show an increasing body count from cardiac causes when statinating to very low levels of LDL? That's what happened in J-LIT and it's what will happen in ASTEROID if they keep going, except 500 people is far to small to separate the occasional death from chance. Is statin induced atheroma shrinkage beneficial? J-LIT suggests not and ASTEROID is too miniscule to look at clinical outcomes. They will be bad.
Executive summary: lower LDL cholesterol has no linkage to shrinkage of plaque.
Peter
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