Inner Circle Forums
Portions of the Undoctored Inner Circle Member Forum and its vast wealth of knowledge, are available only to our Members.
Becoming an Inner Circle Member will allow you to post topics, ask Dr. Davis questions, and view all replies.


HOPE-3: Remarks on a recent statin trial


Member Forum >> Coronary Disease & Cholesterol Protocol >> HOPE-3: Remarks on a recent statin trial

Bob Niland
No Avatar
STAFF
Join Date: 7/7/2014
Posts Contributed: 23635
Total Likes: 4050
Recommends Recd: 11
Ignores Issued: 0
Likes Recd: 1

Posted: 4/5/2016 9:44:11 AM
Edited: 2/18/2018 12:19:57 PM (7)

HOPE-3: Statin mildly beneficial (but in what context)

Remarks on the HOPE-3 Trial

Edition: 2018-02-17

The fulltext is available for open access on the NEJM:
Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease (PDF)
The Appendix PDF is here. The Protocol PDF is here.


Subsequent to my authoring the article following, a formal paper was published analyzing HOPE-3:
JCMBR: Recent Flaws in Evidence-Based Medicine: Statin Effects in Primary Prevention and Consequences of Suspending the Treatment
Even the deminimus touted news from HOPE-3 may be no such thing.


This was a 7-year randomized trial of 12705 “intermediate risk” subjects assigned to one of four arms, shown in the table below.

The results are being touted as: “The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. … The combination of rosuvastatin …, candesartan …, and hydrochlorothiazide … was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease.”.

Yes, they drove LDL (presumably the mythical LDL-C) down by a striking ~30%.

You may see headlines about a “24%” reduction in heart attack and stroke, and “5%” reduction in all-cause mortality, but those are the notorious “relative risk” numbers favored by Marketing. The absolute MI/stroke reduction was a less impressive 1.1%, and deaths from other causes went up. What really matters is all-cause mortality.

Arm All-cause
Mortality
Relative Risk
Improvement
Absolute Risk
Improvement
.vs
placebo + placebo
 
5.62%
(178/3168)
- - -
statin + placebo
 
5.38%
(171/3181)
4.46%
 
0.24%
 
placebo only
 
placebo + BP meds
 
5.64%
(179/3176)
0.36%
adverse
0.02%
adverse
placebo only
 
statin + BP meds
 
5.13%
(163/3180)
9.94%
10.49%
0.41%
0.45%
placebo only
statin+placebo

For driving LDL down by a whopping 30%, total all-cause mortality only went down by 0.24% or 0.41% (yep, ¼ or ½ of 1%).

You’d think that between this and the CETP results, they might figure out that there’s not very much leverage in shoving LDL-C around. Don’t count on it (video from the early 2016 conference): ’I Have a Patient Who Won’t Take a Statin...’ leads off with Captain Statin.

And due to confounders not recorded or reported in HOPE-3, we don’t even know if the ¼% or ½% are real. Apart from the normal suspicion of bias due to being funded by the product producer, suppose, for example, that the placebos were calcium pills (or capsules containing sugar or soybean oil). In real life, people declining statin treatment don’t take placebos that might actually be antagonist agents. Had they included an untreated arm, they might have been able to shed some light on that.

The statin was rosuvastatin (Crestor, 10 mg per day). The BP meds were candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day). The placebo was not specified (and so may have been no such thing).

You can check Table 1 (PDF page 5) for a list of other meds that the arms were on. It may or may not be comprehensive, excluding perhaps things like CoQ10 and K vitamins.

Persons with [diagnosed] cardiovascular disease and those with an indication for or contraindication to statins, angiotensin-receptor blockers, angiotensin-converting–enzyme inhibitors, or thiazide diuretics were excluded.

But these were not healthy people, despite lacking a CVD diagnosis:

Measure Average Baseline Reading
TG 128 mg/dL
BP 138:82
BMI 27
B100/A1 Ratio 0.75
HDL 45 mg/dL

HbA1c and actual lipoproteins were not reported. There’s no indication that any attention whatever was paid to diet, so the volunteers may well have continued to eat in the same manner that made them unhealthy (or followed their doctors’ advice on how to eat, which might amount to the same thing).

This trial is already being spun as a justification for broader prophylactic use of statins. As a commenter on a statin skeptic site put it: that’s not a study - it’s an advertisement.

___________
Bob Niland [disclosures] [topics]


Tags: Statins

HeartHawk
No Avatar
STAFF
Join Date: 12/20/2007
Posts Contributed: 5516
Total Likes: 951
Recommends Recd: 17
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags: Statins

Bob Niland
No Avatar
STAFF
Join Date: 7/7/2014
Posts Contributed: 23635
Total Likes: 4050
Recommends Recd: 11
Ignores Issued: 0
Likes Recd: 0

Posted: 4/5/2016 11:09:34 AM
Edited: 4/5/2016 8:15:01 PM (4)

{remarks merged into basenote}
Tags:

Boo
No Avatar
Join Date: 12/17/2009
Posts Contributed: 4798
Total Likes: 1078
Recommends Recd: 10
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Bob Niland
No Avatar
STAFF
Join Date: 7/7/2014
Posts Contributed: 23635
Total Likes: 4050
Recommends Recd: 11
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags: Statins

Join Date: 3/2/2009
Posts Contributed: 4092
Total Likes: 629
Recommends Recd: 8
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Boo
No Avatar
Join Date: 12/17/2009
Posts Contributed: 4798
Total Likes: 1078
Recommends Recd: 10
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Join Date: 2/22/2014
Posts Contributed: 2805
Total Likes: 920
Recommends Recd: 2
Ignores Issued: 0
Likes Recd: 0


Boo:

Can you recommend any citrulline and pycnogenol products and doses to take?

Thanks.
Tags:

Boo
No Avatar
Join Date: 12/17/2009
Posts Contributed: 4798
Total Likes: 1078
Recommends Recd: 10
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Join Date: 12/24/2007
Posts Contributed: 6648
Total Likes: 447
Recommends Recd: 15
Ignores Issued: 0
Likes Recd: 0


Boo is spot on for the Cit.
Tags:

Join Date: 12/7/2009
Posts Contributed: 2413
Total Likes: 462
Recommends Recd: 6
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Join Date: 3/2/2009
Posts Contributed: 4092
Total Likes: 629
Recommends Recd: 8
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Join Date: 2/22/2014
Posts Contributed: 2805
Total Likes: 920
Recommends Recd: 2
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Join Date: 12/7/2009
Posts Contributed: 2413
Total Likes: 462
Recommends Recd: 6
Ignores Issued: 0
Likes Recd: 0


Dr. Peter Langsjoen et al found that statin-induced impairment in heart muscle appears to be permanent.

https://www.youtube.com/watch?v=7HUUAvnALQo

Tags:

Bob Niland
No Avatar
STAFF
Join Date: 7/7/2014
Posts Contributed: 23635
Total Likes: 4050
Recommends Recd: 11
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Join Date: 2/8/2018
Posts Contributed: 476
Total Likes: 70
Recommends Recd: 0
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Bob Niland
No Avatar
STAFF
Join Date: 7/7/2014
Posts Contributed: 23635
Total Likes: 4050
Recommends Recd: 11
Ignores Issued: 0
Likes Recd: 0



Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:

Bob Niland
No Avatar
STAFF
Join Date: 7/7/2014
Posts Contributed: 23635
Total Likes: 4050
Recommends Recd: 11
Ignores Issued: 0
Likes Recd: 0

Posted: 3/12/2018 8:36:52 AM
Edited: 3/12/2018 8:41:56 AM (1)


Reply Content Hidden!

Post replies longer than 250 characters are restricted to Full Access Members (make certain you are logged-in!).

Sign Up Today!


Tags:


DISCLAIMER

The information contained within this Forum and website is of a general nature and intended purely as background reading for the participants taking part in Forum discussions and projects. It should not be construed as professional medical advice. Please read the website Medical Disclaimer for more information and limitations.

Changes may occur in circumstances at any time that may affect the accuracy or completeness of the information presented within any section of the Forum and website. This Forum and Track Your Plaque, LLC have taken reasonable care in producing and presenting the content contained herein, however, we do not accept responsibility for any loss, expense, or liability that you may incur from using or relying on the information sourced from this website, its forums and/or blogs.

Third-party content and links

This Forum and Track Your Plaque, LLC accept no responsibility for the accuracy of third-party content or links, or your reliance on any information contained within any such content available through our site. The comments published on this Forum represent a wide range of views and interests of the participating individuals and organizations. Statements made during online discussions are the personal opinions of the commentators and do not necessarily reflect those of others participating on this Forum. Track Your Plaque, LLC at all times and at its absolute discretion, reserves the right to remove reasonably offensive comments in line with our Moderation Guidelines.