Intensive atorvastatin effective in CKD patients and also reduces second and third cardiovascular events
Istanbul, Turkey - Analyses from two large "lower-is-better" cholesterol studies have provided additional support for intensive lipid lowering with high-dose
atorvastatin (Lipitor, Pfizer). One analysis showed that aggressive statin therapy reduced the risk of cardiovascular events in coronary heart disease patients with chronic kidney disease and diabetes, while another showed that high-dose statin therapy reduced not only first events but second and third cardiovascular events as well.
These are the findings from two post hoc analyses of the Incremental Decrease in Events Through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) studies, both presented this week here at the 77th European Atherosclerosis Society (EAS) Congress.
"Individuals in TNT who had existing vascular disease, diabetes, and chronic kidney disease brought a lot of pathology into this study," said TNT investigator Dr James Shepherd (University of Glasgow Medical School, Scotland). "These individuals, when they were given treatment to reduce their risk, got major benefit, a 35% reduction in risk. . . . None of the benefits from the aggressive intervention with statins were associated with serious side-effect problems that would influence decisions in clinical practice."
TNT and IDEAL helped forge the "lower-is-better" movement
The updated US guidelines issued by the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III suggest that LDL-cholesterol levels be reduced below 100 mg/dL, to as low as 70 mg/dL, in patients at high risk for coronary heart disease. TNT, previously reported by heartwire, was conducted in stable coronary heart disease patients to determine whether they, too, should be treated to the lower LDL-cholesterol levels.
In the TNT study, intensive lipid lowering with atorvastatin 80 mg daily provided greater protection from major cardiovascular events compared with low-dose atorvastatin in stable CHD patients. High-dose atorvastatin reduced the primary composite end point of death from CHD, nonfatal MI, resuscitation after cardiac arrest, and fatal or nonfatal stroke 22% compared with patients treated with atorvastatin 10 mg, a finding previously reported by heartwire.
In TNT, explained Shepherd, approximately 1500 of the patients had diabetes mellitus, and of these, 546 subjects had chronic kidney disease, defined as estimated glomerular filtration rate (eGFR) <50 mL/min per 1.73m2. As noted, these patients had significantly more hypertension, CABG surgery, peripheral vascular disease, congestive heart failure, and cerebrovascular accidents than those with normal eGFR.
Investigators showed that among nondiabetic patients, those with chronic kidney disease had a significant 30% greater risk of major cardiovascular events than those with normal eGFR. In addition, among the diabetic patients, those with chronic kidney disease had a similarly significant 32% greater risk of cardiovascular events than patients with normal kidney function. In terms of treatment effects, atorvastatin 80 mg significantly reduced the risk of time to first major cardiovascular events in patients with diabetes and chronic kidney disease, by 35%.
Shepherd said that intensive treatment with the high-dose statin was safe and well tolerated, with just 1.1% of diabetes and chronic kidney disease patients reporting treatment-related myalgias. A small number of patients, 1.5%, had elevated liver enzymes, a common side effect that occurs as physicians push the dose higher. He reiterated, however, that these increases should not concern clinicians looking to aggressively treat stable coronary patients with existing diabetes or with diabetes and chronic kidney disease.
Time to second and third events
In a second presentation at the EAS meeting, Dr Matti Tikkanen (University of Helsinki, Finland) presented a seldom-seen end point in another post hoc analysis from the IDEAL trial, a comparison of high-dose atorvastatin vs usual-dose simvastatin (Zocor, Merck) in patients with a previous MI. Investigators evaluated the effect of intensive statin therapy with atorvastatin on cardiovascular events beyond the first event during the course of the five-year study.
In IDEAL, the primary end point was missed, a composite of coronary death, nonfatal MI, or cardiac arrest with resuscitation, but investigators pointed to reductions in secondary end points. Based on the other "lower-is-better" trials and the reduction in secondary end points, investigators reported that aggressively lowering LDL cholesterol in patients with a previous MI can provide a benefit without an associated increase in noncardiovascular mortality or other adverse events.
In this new analysis, investigators showed that atorvastatin 80 mg significantly reduced the risk of a second cardiovascular event, one that occurred after the first event was documented, by 24%, and reduced the risk of a third event by 19%.
"Patients who have had multiple cardiovascular events continue to benefit from long-term intensive statin therapy," said Tikkanen. "Physicians treating such patients should ensure that they adhere to sufficiently high-dose statins."
| The news from the street . . . |
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Despite the EAS news and atorvastatin still being the best-selling prescription drug in the world, a report in the Wall Street Journal suggests Pfizer's "competitive position has declined because of efforts by health plans to promote the use of cheaper, generic cholesterol drugs."
In terms of the bleak news, the Journal notes that Lipitor's Dr Robert Jarvik commercials have been taken off the air amid complaints they were misleading and that the drug loses patent protection in early 2010. In addition, sales are down 2% from last year.
However, the company could benefit from the ENHANCE backlash, although not nearly as much as it would like. Generic simvastatin, say forecasters, is likely to receive the bulk of prescriptions when physicians take some patients off ezetimibe (Zetia, Merck/Schering-Plough Pharmaceuticals). Pfizer continues to apply to the US patent office for an extension to its patent, one that would extend protection to June 2011.
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Pfizer sponsored the TNT and IDEAL studies.
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| April 30, 2008 08:24 PM (EDT) |
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absolute risk
What was the absolute risk in the high dose arms???? |
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| May 01, 2008 12:12 AM (EDT) |
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35% risk reduction?
Is that good enough? I usually think of a 35% as an F-, even where I went to school. |
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| May 01, 2008 07:11 AM (EDT) |
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Depends
William,
If depends. Reminds me of my first physics test at the University of Kentucky. The high score was a 52% and was achieved by a gentleman who taught physics in the Navy but had come into Civilian life in pursuit of becoming a PA. I made a 48% and hired him on the spot to be my tutor. He got the only A, and the few of us who hired him got the only B's. WE were offered the opportunity to re-take the class for free because there were so many complaints to the academic ombudsman. I took my "B" and ran with it, happy to get it over with.
My rambling point? Some risk reduction is certainly better than NO risk reduction especially if the majority of patients who NEED risk reduction won't take the "best" therapy.
Second best is better than nothing and when NOT combined with diet and exercise, second best isn't as good as it should be.
Melissa |
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| May 01, 2008 08:25 AM (EDT) |
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35%
Yes but the comparator drugs and doses in the control group have each been proven to reduce risk by 35-45% themselves, so that is an additional reduction on top of 35%. To me this really pushes high dose statins to the top of the agenda. They are the single most effective intervention we can do for patients (other than smoking cessation, which can be very difficult to implement). |
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| May 01, 2008 10:28 AM (EDT) |
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What about other options?
Ok, so high dose statins alone are better than low dose statins alone on a population basis.
Are high dose statins better than low dose statin plus omega-3 fatty acids, or low dose statin plus niacin, or low dose statin plus Vit D-3? What about a combination of low dose statin (or high dose statin), zeteia, niacin, omega-3 and vit D-3? Perhaps coronary disease would diasppear which is nearly what I am experiencing in my "outside the box" practice. We don't know because the studies don't exist.
We have suspected a benefit from Omega-3 fatty acids since Sinclair made the observation in 1956; yet still no great studies or clearly defined role. I hope that Abbott gives us some quality outcomes DATA from Simcor soon (unlike what Merck has done for Zetia) but seriously folks, Niacin has been available for a while.
Medical research, as it turns out, is probably not best done in a pure entrepreneurial environment. If we looked at quality of outcomes rather than profit potential, I can only imagine how differently we would be preventing heart attacks today. The value of atherosclerotic imaging would be understood by everyone, possibly even Steve Nissen.
When the marketing departments and persons with financial interests control what studies are done, the losers are us and our patients. Whatever happened to the NIH?
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| May 01, 2008 12:44 PM (EDT) |
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you mention vit-D3
I did a comprehensive literature search looking for RCTs on vit-D3. The women's health study, which enrolled 40,000 patients, enrolled to vit D or placebo with no difference in stroke or MI rates. A recent analysis in BMJ which was randomized suggested INCREASED rates of MI and CV death. So no, I do not prescribe vit D3 for cardiovascular prophylaxis and I doubt you will find a single supportive randomized shred of evidence.
And no there are no trials comparing high dose statin to low dose statin + D3 or omega,etc. We have to work with the evidence we have. In JELIS in the Japanese population, omega-3 conferred benefit on top of statin alone, so yes there seems to be additive benefits. On the other hand we now have 3 meta-analyses and 7 hard outcomes based RCTS of intensive vs moderate statin strategies showing benefit. So I will stick to what works. Airy fairy otherwise. |
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| May 01, 2008 08:35 PM (EDT) |
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Vit D
As I recall, the study you reference used 200 IU twice daily. I am not sure if they used D-3 or D-2. Did they check levels and see if there was any change in 1,25 OH D levels? If levels were not checked, I have trouble taking much out of this study at all; kind of a waste of a potentially important study.
There are other small studies using higher doses of vit D-3 which show improvement. Other studies relate low blood levels of vit D with higher incidence of CAD. A recent study demonstrated decreased coronary and all cause mortality with IV Vit D in CRF patients. Although these other studies are underpowered with number of enrollees, the women's health study is underpowered with inadequate dosing or documentation of a change in levels.
As a modest dose of D-3 has no potential for detriment, costs 5 cents a day, and helps improve bone density, I am willing to take the risk that it does good until better DATA comes along (which probably won't happen). The studies showing decrease in cancer rates just increase the intrigue.
Don't get me wrong, I don't use vit D-3 instead of statins but recommend it to patients as part of good nutrition to make up for the fact that we don't run around outside naked nearly as much as we probably should.
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| May 01, 2008 09:15 PM (EDT) |
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it was 200 mg BID of Vit D-3 plus CaCO3
Baseline dietary intake was another 400 IU in both groups. Blood samples were collected in 100% of patients and randomly assayed in 6%. |
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| May 01, 2008 09:39 PM (EDT) |
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Vit-D, RRR, etc.
Any absorbed calcium in CKD population, especially stage 5, throws off a myriad number of parameters. Vit-D may not abe statin,.. yes. But not entirely without data to support use in some.
Best tutorial on RRR I ever heard was the 'tear a sheet of paper in half' demo. 1st, tear off a third,.. that`s 33% RRR. Tear a third of that piece off, again 33%. But the total RRR from baseline is 33% + [33% X 33%]= 33% + 11% = 44%. that is not 66%,.. and the ARR is quite small. Dr. Superko really puts that in perspective. The % still having events in placebo vs % in the treatment arm,.. lifetime risk of an eent vs. 3-5 years in RCT. Long way to go after 'correcting' ApoB components.
RRR in diabetics in the CDP was 54%,.. 2-3 g/d nacin mono-therapy.
Industry plays with us. What % of diabetics, un-corrected/un-treated have tot-HDL`s in the mid-50`s ? So,.. that sub-group can expect the benefit seen in that statin RCT. What about the other 90+ % who have low HDL ? Received the indication anyway.
The Devil,... she/he/it is assuredly in the details.
Things that make you go Hmmmm,...?
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| May 01, 2008 10:02 PM (EDT) |
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Vit-D, RRR, etc.
Any absorbed calcium in CKD population, especially stage 5, throws off a myriad number of parameters. Vit-D may not abe statin,.. yes. But not entirely without data to support use in some.
Best tutorial on RRR I ever heard was the 'tear a sheet of paper in half' demo. 1st, tear off a third,.. that`s 33% RRR. Tear a third of that piece off, again 33%. But the total RRR from baseline is 33% + [33% X 33%]= 33% + 11% = 44%. that is not 66%,.. and the ARR is quite small. Dr. Superko really puts that in perspective. The % still having events in placebo vs % in the treatment arm,.. lifetime risk of an eent vs. 3-5 years in RCT. Long way to go after 'correcting' ApoB components.
RRR in diabetics in the CDP was 54%,.. 2-3 g/d nacin mono-therapy.
Industry plays with us. What % of diabetics, un-corrected/un-treated have tot-HDL`s in the mid-50`s ? So,.. that sub-group can expect the benefit seen in that statin RCT. What about the other 90+ % who have low HDL ? Received the indication anyway.
The Devil,... she/he/it is most assuredly in the details.
Things that make you go Hmmmm,...?
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| May 01, 2008 10:15 PM (EDT) |
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CTT, 90,000 patient meta
Meta-Analysis of statin RCT`s.
> 70% of treatment arm had an event vs. placebo. I think it is unrealistic to rely on statin mono-therapy as the 'end-all'. Crude analogy,.. but, how many drugs does it take to really get BP to goals ? And that is just surrogates. We live by surrogates and thus,.. ezetimibe approved with no outcomes.
I think that also holds us back. Niacin works, and has outcomes. But an isolated HDL outcomes trial,.? That`s nearly impossible. No drug yet designed,... ONLY moves HDL. based on surrogates,.. the benefit of naicin could be , 50%, if only HDL is analyzed.
statins have many effects,.. and many not routinely measured. it is obviously NOT just LDL. dr. Shaw was quite eloquent at a ACC presentation. Who cares if it is/isn`t the HDL ? Niacin works.
As far as recent criticism of B. Greg Brown`s FATS, FATS f/u & HATS,... a statistician would not argue that the N was too small. 90% with a very low P value says it all, with regression via QCA and several trials uncovering much the same: NO industry funding. SCOR, CLAS-I, CLAS-II, AFREGS, etc.
Statins are GREAT, yes. But will we ever see a 75% RRR in a large trial,... ? Just bein` a provocateur here. Fire away,.. fire @ will,...
TC/HDL |
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| May 02, 2008 07:10 AM (EDT) |
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yep
GREACE study showed 50% reduction with atorvastatin mean dose 24 mg.
TNT showed an additional benefit of 25% with top dose of atorvastatin 80 mg/d vs conventional low dose monotherapy.
So yes, I think that high dose statins do reduce events compared with placebo by about half or so.
The ARR vs RRR scenario you paint is overly grim. In clinical practice, patients are at higher risk of events than those seen in trials. Therefore baseline risk and commensurately ARR are higher than in trials. Only about 15% of patients we routinely encounter in clinically care would be eligible, approached, screened, and randomized after run-in (lower in some trials). These highly compliant, comorbidity-free, healthier patients have lower event rates and therefore the ARR is artificially too low to generalize to clinical practice. Thus your scenario of ARR vs RRR misses a big point - one that most clinicians miss when they harp on about the ARR being miniscule. |
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| May 02, 2008 07:39 AM (EDT) |
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benefit
Actually the one group that seemed to show benefit in WHI from vit D were patients already on statins at baseline (P=0.04 for interaction effect of statins by vitamin D). The hazard ratio of 0.54 in patients on statins for vit D and 1.00 for those not on statins.
The authors write: "women with self-reported hypercholesterolemia and those who used statins were at lower risk for stroke if assigned to active calcium/vitamin D (P=0.04 for interaction for both)."
However, this needs to be prospectively concerned. |
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| May 02, 2008 08:43 AM (EDT) |
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Self reporting
Self reporting is well............self reporting.
Melissa |
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| May 03, 2008 11:52 PM (EDT) |
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Dan, Brad
Dan, I think this secondary analysis -as you have stated in the past- is not conclusive as it is secondary (IDEAL) did not meet the primary with atorva vs. simva and (ASPEN) as we have discussed in the past didn't meet any endpoints.
Also your comments that ARR and RRR don't apply to our clinical populations with regard to risk. I don't know about that the 5 yr MACE risk in 4S was over 25% and HPS was 20% and over 40%-30% in the DM groups. 5 yr MACE in VAHIT and HHS was also really high. I think these lipid primary and secondary prevention studies reflect ARR and RRR very well in practice. These studies are very high risk people even the primary prevention studies are high risk when you look at the number of events over that specificed time period.
Even when you look at PROactive and STENO2 short and long term studies and TNT and PROVEITTIMI, etc...
People make big commentary about the BP reduction in UKPDS in less than 10 years, but recall the event rate for MACE was over 40% with BP of 144 and 50% with BP of 154 - yes 25% event reduction but still really high events (which led to the risk calculations in ACCORD people with DM and CAD below)
One thing we were excited about was the low number of events in the DM ACCORD study which was stopped due to safety concerns with events of 1.1% mort/year on conventional glucose control and 1.4% mort/yr on intensive control this was a NNH for death of 300/year (the same as prasugrel the antiplatelet drug by the way) but MUCH less than the expected 5% mort/yr that was expected. We are excited to see such low event and mort rates with advanced medical care of the 21st century.
Brad, (hope you are well)
The NNT for pts in high dose vs. low dose statin studies to prevent MACE has run around 45 people, the NNH for AE's (of any kind) runs around 50 with the higher doses in these studies.
I would be hard pressed to draw conclusions from any post hoc analysis such as these prevented or even the new tg data posthoc reported this week.
Mike |
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| May 04, 2008 07:45 AM (EDT) |
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and on and on it goes...
TNT, atorvastatin 80 mg vs 10 mg. If you are going to quote NNT, then quote it for all cardiovascular events.
33.5% event rate in atorvastatin 10 mg group for first cardiovascular event. 28.1% in atorvastatin 80 mg group. A clear dose-response effect seen here, with an ARR of 7.4% and NNT of 13. Given that the comparison was to a drug that was highly effective in preventing events at lower dosing in GREACE, CARDS, ASCOT-LLA, etc, I suspect that atorvastatin 80 mg/d in chronic CAD is one of the most effective interventions you can use for preventing ANY cardiovascular event.
I agree that those event rates are very high.
Disclosures: None |
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| May 04, 2008 01:06 PM (EDT) |
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does it really....
I know the exchange rate between the US and Canada has dropped a lot but last time I checked that was a 5.4% change and NNT of 18.2 (28.1-33.5, and in a secondary endpoint at that) What I think is most impressive about this is that even on 80 mg of atorva 80, nearly 30% of these stable CAD pts will had any CV event. that's amazing to me. In the true primary which is the big consequence still nearly 9% had an event on high dose and 11% on low dose, what would placebo had been ??? 13-16%??? If that were the case the high dose would have reduced events 40-45% or 1%/1% as we know statins will do and perhaps the placebo all cv event rate would have been 40% (speculation but probably realistic) - again a VERY high risk population.
And there you go again quoting secondary endpoints (thats ok, i like to look at the seondaries also). The primary endpoint was total major CHD events 10.9 vs. 8.7% with NNT just under 50. No total mort benefit, not death chd benefit. If you look at 2ndary endpoints any CV endoint were as you describe and and coronary event was 21.6% and 26.5% ARR 5% with NNT of 20. HOWEVER, for the primary the NNT was just under 50 and AE's related to treatment were 5.8% and 8.1% treatment related AE's resulting in DC of drug were 5.3% and 7.2% with NNH of just over 50.
The big points for me were:
1. these people still have a lot of events
2. atorva 80 reduces events more than atorva 10 and appears to be related to further reduction of LDL, thus goals for high to very high risk pts is reasonable at 70 or lower.
3. for the primary endoint low high dose atorva vs. low dose atorva NNT is 50
4. for secondary endpoints of any cv event, etc. the NNT is 20 and holds value
5. for AE's which resulted in enough harm to force stopping atorva 80 the NNH was 50.
6. There was no all cause mortality nor CHD mortality benefit of atorva 80 over atorva 10 mg.
There is currently no study which has proven that any 'statin' which reduces ldl/nhdl/apob/ratios in a similar mg/mg reduction is better than any other and thus the NCEP and other guidelines rec. reaching the lipoprotein goals for each individula pt based on their risk and medical history. I know you have found lipitor to complement your practice (many of us have found that) and for the simple reason that is lowers ldl quite effectively.
Always fun to share ideas and studies and numbers with you and of course take care of patients in our practices. |
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| May 04, 2008 01:11 PM (EDT) |
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does it really....
(Post with multiple typo corrections - wow it's early on sunday, may need some coffee - numbers are correct in both)
I know the exchange rate between the US and Canada has dropped a lot but last time I checked that was a 5.4% change and NNT of 18.2 (28.1-33.5, and in a secondary endpoint at that) What I think is most impressive about this is that even on 80 mg of atorva, nearly 30% of these stable CAD pts still had any CV event. that's amazing to me. In the true primary which is the big consequence still nearly 9% had an event on high dose and 11% on low dose, what would placebo had been ??? 13-16%??? If that were the case the high dose would have reduced events 40-50% or 1%/1% as we know statins will do and perhaps the placebo all cv event rate would have been 40% (speculation but probably realistic) - again a VERY high risk population.
And there you go again quoting secondary endpoints (thats ok, i like to look at the seondaries also). The primary endpoint was total major CHD events 10.9 vs. 8.7% with NNT just under 50. No total mort benefit, no death chd benefit. If you look at 2ndary endpoints any CV endoint were as you describe and and coronary event was 21.6% and 26.5% ARR 5% with NNT of 20. HOWEVER, for the primary the NNT was just under 50 and AE's related to treatment were 5.8% and 8.1%. Treatment related AE's resulting in DC of drug were 5.3% and 7.2% with NNH of just over 50.
The big points for me were:
1. these people still have a lot of events
2. atorva 80 reduces events more than atorva 10 and appears to be related to further reduction of LDL, thus goals for high to very high risk pts is reasonable at 70 mg/dl or lower.
3. for the primary endoint high dose atorva vs. low dose atorva NNT is 50
4. for secondary endpoints of any cv event, etc. the NNT is 20 and holds value
5. for AE's which resulted in enough harm to force stopping atorva 80 the NNH was 50.
6. There was no all cause mortality nor CHD mortality benefit of atorva 80 over atorva 10 mg.
There is currently no study which has proven that any 'statin' which reduces ldl/nhdl/apob/ratios in a similar mg/mg reduction is better than any other and thus the NCEP and other guidelines rec. reaching the lipoprotein goals for each individual pt based on their risk and medical history. I know you have found lipitor to complement your practice (many of us have found that) and for the simple reason that is lowers ldl quite effectively.
Always fun to share ideas and studies and numbers with you and of course take care of patients in our practices. |
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| May 04, 2008 04:53 PM (EDT) |
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my bad math, but worse statistical considerations
You keep saying there was no reduction in death in TNT. But the HR was:
1.01 (0.85-1.19); p=0.92
What this means with 95% certainty is that there could have been as much as a 15% reduction in death or a 19% increase. The trial was clearly not powered for death, which occurred in <6% of patients. It was powered on the primary endpoint. You would need a larger trial to show any certainty about what is happening with death. Therefore, don't say there was no reduction in death. Say we are uncertain about death.
Furthermore, as you know in the ASCOT-LLA extension study, there was a significant reduction in mortality with atorvastatin 10 mg/d in a lower risk population. Likely then 80 mg/d in these stable CAD patients reduces death (by inference). |
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| May 05, 2008 10:09 AM (EDT) |
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okay
So, what you are saying is that I would need to enroll 10,000 patients in my practice for 4.9 years to show a 0.01 chance of mortality change 15% reduction of death or 19% increase of death with a 95% certainty. That is perfectly correct like TNT. 'Therefore', there was no reduction in death and we are certain what this particular study with this particular design in this demographic over 5 years did show 'no statistical reduction in death.' This is not a criticism of atorvastatin, perhaps if this were a 10 year study design, we would see a dramatic reduction as in WOSCOPS 10 yr extension.
ASCOT-LLA 'inferences' - 'furthermore' at 3.3 years this study showed wonderful event reductions in 20,000 pts with htn and lipid abnl. 10,000 of the 20,000 were enrolled in the lipid arm with BP 164/95 and dual tx of bp and the lipid arm with atorva above placebo resulted in morbidity reduction. Wonderful news again showing statins benefit patients at low, moderate and high risk.
LLA 3.3 years stopped early
(again these people had bp and lipids treated and these were the benefits of lipid tx above placebo)
All mortality 0.87 0.72-1.06 ns
CV mort 0.84 0.62-1.14 ns
LLA extension extra 2.2 years
All mort 0.83 0.69-1.01 ns
CV mort 0.84 0.60-1.17 ns
Followed to final visit analysis
All mort 0.85 0.74-0.98
CV mort 0.84 0.67-1.05 ns
One could infer that over the 3.3-5.5 or very end of study one could treat this population and for every 200/130/80 people we would see all cause mortality reduction of one person per each above. For CV mortality one would need treat 500/500/200 NS over the above time periods to prevent one death.
My intention is not to minimize the use of statins, nor to minimize atorvas contribution to evidence based medicine. It is merely to point out again - getting to bp goal as directed by patient risk and med hx, getting to all lipid goals as defined by ncep/aha/acc/ada, glucose goals. You point out a lot of atorva studies, maybe we should go back and analyse all of the prava, simva, lova, fluva, gemfib, nicotinic acid, resin studies, etc... I have no problem agreeing with you.
extension and observation studies are what they are. |
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| May 05, 2008 11:50 AM (EDT) |
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going back and analyzing all of the prava, simva, lova, fluva etc
Yes I'd like that. While we're at it, can we also analyze all those positive hard endpoint driven crestor and ezetimibe studies at the same time? Given that these are probably the #2 and #3 most prescribed lipid lowering agents in North America and Europe (see recent analysis of ezetimibe trends by Jackevicius et al in NEJM).
Then we can really be practicing evidence-based medicine.
But wait ... I'm not sure any such studies already exist! (tongue-in-cheek remarks) |
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| May 05, 2008 04:28 PM (EDT) |
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dan, i give up
actually lipitor number one followed by all generics then followed by all others. i think crestor market share less than 10% and vytorin who knows.
I'm going to have a drink of whiskey and have nothing further to add.
I think steno 2 8.8 years and 13 year data are a nice example of using ebm in dm2 pts with uma (covering bp, lipid, glucose, platelet tx) but still showed very high event rates, but most importantly showed over 60% micro reduction and over 50% macro reduction and most impt mort reduction with the ext study. that's evidence, another shot of whiskey.
have I offended you in any way, which has resulted in this diaglogue?
i think asking for hard endpoint data for products that have been on the market less than 5 years while reasonable is hard to be expected. atorva showed no endpoint data for nearly 7 years. now rosuva (jupiter announced pending publication)) has it - even the atrova reps say it means nothing based on their company position. |
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| May 06, 2008 11:13 AM (EDT) |
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good discussion with no offense taken or implied
Michael, I know you practice outstanding preventive cardiology and lipidology. I was simply playing "Devil's Advocate". No offense meant and no offense taken.
(Coming off two weeks of call with 36 inpatients under my belt can't help!) |
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