Deepak L. Bhatt, M.D., M.P.H., Ph.D., author of the REDUCE-IT trial, explains the results of this multicenter, placebo-controlled trial involving statin-treated patients with hypertriglyceridemia. Visit the NEJM AHA page for full-text access this study and all NEJM papers released at #AHA18:
Hello. i’m dr. deepak bhatt, executive director of at brigham and women’s hospital in boston, massachusetts, where i’m also a talking here today with a lot of viewers of the new england journal of medicine american heart association annual sessions and, i’ve got to be honest, i’m i’ve been involved in a lot of different clinical trials through the years and the ones that
Are somewhere in between, as long as they advance patient care and trials that i’ve been involved to to date, i practice changing and paradigm shifting. and i’m careful in using such the dawn of a new scientific era with respect to cardiovascular prevention, you exactly what reduce-it is, and for those of you who want greater detail my presentation that was given here at
Supplement as well, don’t forget the supplement, has lots of information — the is out there in the open for everyone to take a look. milligrams per deciliter and had additional cardiovascular risk to receive either 4 grams a day of icosapent ethyl or placebo. icosapent of that drug versus a placebo in patients with elevated triglycerides and the patients had secondary
Prevention-type indications — stable coronary artery and the remaining 30% or so had what we called primary prevention type additional cardiovascular risk factor, so a hybrid population of secondary and as i mentioned to the study drug or placebo, follow them for a median of cardiovascular events, i mean a 5-point mace — cardiovascular death, mi, reduction, a 4.8%
Absolute risk reduction, a number needed 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 statistically significant finding, but in convention, in keeping with their convention, it’s .001 in new england journal, so a very robust the really hard endpoints,
Quote unquote. that was cardiovascular death, mi, stroke, and that was reduced by 26%, again clinically robust and a p-value there, again the paper <.001, there were multiple pre-specified subgroups that i presented and are the for both the primary and the key secondary endpoint, including key was a consistency of benefit males and triglycerides greater than or less than
200, and also triglycerides greater than triglycerides between 135 and 150. so therefore, very robust so-called pre-specified hierarchical statistical analysis, that going down the list until something’s not positive, and if something’s not more exploratory as opposed to definitive. what we found here was all of fatal or non-fatal heart attack, stroke or fatal or non-fatal
Stroke, that was reduced different things were significantly reduced, including a 20% relative risk significant and included in that are significant reductions in sudden cardiac cause mortality that was not significantly reduced but there was a there was no difference in non- cardiovascular mortality so that cardiovascular mortality. so that, really in a nutshell, in general
The drug was as well tolerated as placebo was. the adverse fibrillation was significantly higher by the most feared complication of atrial ethyl versus placebo, in fact, there’s a 28% reduction in that endpoint with fibrillation is a possibility, on the other hand, it doesn’t seem to be which is stroke, at least on the trial-wide level. the other adverse event of note was a
Significant … well, i shouldn’t say significant, it was actually a trend, it wasn’t significant bleeding, as serious cns bleeding, looking at fatal bleeding no significant they’re using this drug in patients but in absolute terms relatively overall a great tolerability, good safety, overall benefits, i think. of the drug in this population are quite substantial. planned a
Cost-effectiveness analysis for the leading academic but as you might imagine with a number needed to treat of 21, this is probably going to be highly cost trying to get at what is the mechanism of benefit here. we saw reductions in biggest change was in epa levels — a 360% increase in epa levels with studies, what exactly drove the benefit on multiple endpoints in this
Trial. i significantly reduced, a tertiary point albeit pre-specified, if it were just an anti-inflammatory, or just a triglyceride-lowering drug, or just a drug with some antithrombotic capabilities, endpoints, so, you know, i think the findings will be practice-changing. you presentation, what about statins? well our and indeed the ldl coming into the trial on average was
75 so this was many patients in actual practice so this is truly an incremental advance over deciliter difference between the study drug and placebo at one year causing some harm? i’ve got to say i think that line of inquiry is flawed but milligrams per deciliter in ldl over five years wouldn’t cause a 25% relative risk reduction. it would be projected to cause maybe a 2,
3% the most optimistic would be maybe 4% so again, it wouldn’t explain it, and people forget there was an older trial, jelis, a japanese trial, very well done lower dose of epa, not exactly this drug, but nonetheless somewhat opening the trial was randomized but it was open label, meaning that there was no actual of low-dose statin, so that’s there for people well that was
An open-label trial with no mineral oil placebo and still a at the time, many people (i was one of those people) criticized jelis saying, oh, it’s in a rigorous way and if you think about it, what would we use as a placebo? we obviously the patient would know they’re getting a sugar pill and they’d be unblinded, so that wouldn’t have worked. we could have negative, people
Would have said, oh, what are you guys, stupid? why did you use olive oil? consistency in appearance as icosapent ethyl, so that was the reason for it. think that there’s something there which there isn’t, we actually did an medicine paper, it’s just a line in there but placebo versus patients … study drug, rather, versus placebo in patients who either of benefit was
Really quite similar in those two arms. so it it really was the it’s hurting patients, well, then we wouldn’t have expected to see a benefit in those patients who didn’t have an ldl increase. so i think the trial results are robust placebo, well that’s the reason that there’s benefit with the study drug, that the biomarkers that we’ve analyzed and we’re able to present at
This time and looking at crp, and that was presented, and we also prespecified looking at log-transformed crp and that’s also presented in the supplementary table 4. and what we showed is, first of all, the correct way to look at crp is really log- transformed crp, because that takes out the outliers, and, done that way, there is no decrease in crp with icosapent ethyl,
As has been reported previously, such think the study drug is working, it’s working robustly, there’s not something mentioned and honestly i don’t really think this is such an important point i permeating the twittersphere, and therefore i thought, let me use this interesting, at the end of the late-breaking clinical trial session the reduce-it and i don’t remember the
Exact number, i think was something like 90+ percent, said population. so, obviously, there’s still questions to be answered and we plan to continue the genetics, and in terms of clinical endpoints we only presented time to events there are other potential benefits that we haven’t yet seen. so we’ve established the safety of icosapent ethyl given as a cardiovascular that
This trial really will open up a whole new era in cardiovascular statins were first being appreciated not to reduce cardiovascular events including death from cardiovascular something i said was unclear or i misstated something the good news is new england journal of medicine at www.nejm.org. thank you so much for your attention.
Transcribed from video
Dr. Deepak Bhatt Discusses the REDUCE-IT trial, Live from AHA 2018 By NEJM Group
