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Dr. Deepak Bhatt Discusses the REDUCE-IT trial, Live from AHA 2018

Dr. Deepak Bhatt Discusses the REDUCE-IT trial, Live from AHA 2018

Hello. I’m Dr. Deepak Bhatt, executive director of
interventional cardiovascular programs at Brigham and Women’s Hospital in
Boston, Massachusetts, where I’m also a professor of medicine at Harvard Medical
School, and I’m really excited to be talking here today with a lot of viewers
of the New England Journal of Medicine about the REDUCE-IT trial, which I
literally just presented five minutes ago
as a late-breaking clinical trial at the American Heart Association annual
sessions and, I’ve got to be honest, I’m extremely excited about this trial and
discussing it with all of you. I’ve been involved in a lot of different
clinical trials through the years and honestly, I love them all — the ones that
are positive, the ones that are negative, the ones that are somewhere in between,
as long as they advance patient care and contribute in some way to science.
With this particular trial, of all the trials that I’ve been involved to to date, I
think has the greatest potential to be practice changing and paradigm shifting.
And I’m careful in using such terminology that I typically avoid,
because here I believe we might be at the dawn of a new scientific era with
respect to cardiovascular prevention, akin to what happened decades ago with
statins as they were first entering clinical trials.
Why do I say that? Well, let me recap to you exactly what REDUCE-IT is, and for
those of you who want greater detail that I provide, I should mention just
today in the New England Journal of Medicine, REDUCE-IT was published
simultaneously my presentation that was given here at
the AHA, so the paper, and importantly, the supplement as well, don’t forget the
supplement, has lots of information — the protocol, and statistical analysis plan,
are posted there as well, so everything is out there in the open for everyone to
take a look. REDUCE-IT randomized 8,000 patients who
had triglycerides between 135 and 500 milligrams per deciliter and had
additional cardiovascular risk to receive either 4 grams a day of icosapent ethyl or placebo. Icosapent ethyl is a highly-purified EPA, or
eicosapentaenoic acid, so 4 grams a day of that drug versus a placebo in
patients with elevated triglycerides and additionally have cardiovascular risk,
defined as follows: about 70 percent of the patients had secondary prevention-type indications — stable coronary artery disease, stable cerebrovascular disease,
stable peripheral artery disease, and the remaining 30% or so had what we called primary prevention type indications, but specifically, it was
diabetic patients with at least one additional cardiovascular risk factor, so a hybrid population of secondary and higher risk primary prevention. In this
population, then we randomized patients as I mentioned to the study drug or
placebo, follow them for a median of about five years, and examined
cardiovascular events, and by cardiovascular events, I mean a 5-point MACE — cardiovascular death, MI, stroke,
hospitalization for unstable angina, and coronary revascularisation — and in that
endpoint there was a 25% relative risk reduction, a 4.8% absolute risk
reduction, a number needed to treat of only 21, and that was a
highly significant finding. I also see in the New England Journal of Medicine
paper less than 0.001, though, in fact, the actual p-value, the New England Journal of Medicine truncates the p-values, the actual p-value was 0.00000001. I might have forgotten a zero, there might have been an
additional zero. There so there’s a very statistically significant finding, but in
convention, in keeping with their convention, it’s .001 in New England Journal, so a very robust finding. Now some doctors might say, well,
you know, hospitalization for unstable angina
revascularization procedure, show me the really hard endpoints, quote unquote. That was
our pre-specified key secondary endpoint, cardiovascular death, MI, stroke, and
that was reduced by 26%, again over 3% absolute risk
reduction, number needed to treat 28, so clinically robust and a p-value there, again the paper<.001 but in actual fact so once more very statistically robust findings. therefore if we look at subgroups and there were multiple pre-specified that i presented are the paper those a consistency of benefit pretty much across board for both primary key secondary endpoint including such as prevention cohorts where was males females u.s. non diabetes no triglycerides greater than or less also it turned out about population enrolled had between findings subgroups. now did so-called hierarchical statistical analysis is what means you can one positive keep going down list until something not general shouldn further. then exploratory opposed to definitive. found here all endpoints examine hierarchy things like fatal non-fatal heart attack stroke reduced by hospitalization unstable angina emergent urgent procedures these different significantly relative risk reduction death from cardiovascular causes significant included reductions sudden cardiac arrest. final thing on cause mortality trend lower rate all-cause with p-value difference non- driven mortality. really nutshell data presented. far safety obviously examined drug well tolerated placebo was. adverse event rates note atrial fibrillation adjudicated higher absolute importantly most feared complication icosapent ethyl versus study while physicians should be aware possibility other hand doesn seem associated which least trial-wide level. serious events lumped together major bleeding ... say actually wasn when looking gi cns differences two arms. again doctors they using this patients terms relatively modest increases strictly speaking even significant. overall great tolerability good outstanding efficacy benefits think. quite substantial. lots ongoing analyses might imagine have planned cost-effectiveness leading academic number needed treat probably highly cost effective. got biomarker genetic detailed trying get mechanism here. saw hscrp biggest change epa levels increase group try tease apart sake science future studies exactly drove trial. mentioned bunch elective revascularisation tertiary point albeit seems lot just an anti-inflammatory triglyceride-lowering some antithrombotic capabilities wouldn expect necessarily large degree know think will practice-changing. questions been asked me minutes after presentation statins our goal indeed ldl coming into trial average well-treated patient statins. better many practice truly incremental advance over five milligrams per deciliter year oh mineral oil causing harm line inquiry flawed somebody concerned would years reduction. projected maybe optimistic extrapolation cholesterol clinical collaboration explain people forget older jelis japanese done showed ischemic dose nonetheless somewhat opening door concept cardiovascular-protective agent randomized open label meaning either nothing background low-dose statin don open-label still time criticized saying double-blind rigorous way use could used sugar pill getting unblinded worked. olive negative said guys stupid why settled because similar appearance reason it. folks aren satisfied answers isn published results section new england journal medicine alludes rather who case toxic substance raising hurting expected see didn increase. raised crp up harming patients. first transparent biomarkers analyzed able present prespecified log-transformed supplementary table correct log- transformed takes outliers arm decrease has reported previously comparing arms years. working robustly funny comparator reasons honestly important raise sort permeating twittersphere thought let opportunity address sorts head-on. interesting end late-breaking session audience surveyed do based reduce-it remember exact percent population. answered plan continue analyzing database genetics only perhaps total recurrent potential haven yet seen. work top-line go established given reducing my hope whole era harkening back early days being appreciated ldl-lowering drugs reduce causes. perspective useful unclear misstated news supplement long thank your attention.>

16 comments on “Dr. Deepak Bhatt Discusses the REDUCE-IT trial, Live from AHA 2018

  1. Very clear and informative Dr. Bhatt, and also answering those issues that appear to rearing their ugly heads on the Boards right now, espc re the Mineral oil/Placebo mini controversy. You laid it all out there for me, and I am very thankful for that peace of mind.

  2. Excellent trial and interview. However, I'd like to note that using the word "trend" (watch 6:24 and 7:41) to describe "almost" but not quite statistically significant differences (eg, P=0.09) is an error. The outcome of an inferential test is either rejection of the null hypothesis, or failure to reject the null hypothesis. There is no other outcome. Describing some "almost significant" P-values as a trend but not others introduces a large element of subjectivity. Does a P-value of 0.04 suggest a trend towards non-significance? What range of P values are considered "almost significant"? To be consistent, either all P values within this hypothetical range suggest or support a trend or none. For those who want to read more about this, Gibbs and Gibbs offer a fascinating insight into the misuse of "trend" (doi:10.1093/bja/aev149).

  3. Dr. Bhatt is obviously a sell-off doctor, because other independent cardiologists have rather doubtful opinions about Amarin. You can read some of them here, for example.

  4. Well, firstly it is not a drug, but an additive. This was confirmed by the FDA. Secondly Amarin, stop bribing doctors and AHA, otherwise they will go to prison, as I hope and your CEO's and all who participated in the study Vascepa. And you people, do not believe everything that they say to you, read the article, make your conclusions. Then you will understand that they are just scammers.

  5. It has previously been proven that fish oil has no effect in reducing CVD mortality. But no, they want your money and are willing to do anything for it.

  6. Hi. What are your thoughts on Matinas BioPharma (MTNB) and Acasti Pharma (ACST)? Any better than AMRN? Good investments? I would appreciate your opinion on the two I mentioned. Thank you very much.

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