In this most recent analysis of REDUCE-IT, results show a consistent benefit favoring icosapent ethyl versus placebo irrespective of the actual statin type, said Deepak L. Bhatt, MD, MPH, of Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School.
Absolutely so what we’ve done in this most recent analysis of reduce it that was just presented at the european society of cardiology is examine the outcomes of the patients in the trial as a function of their baseline type of statin so for example we looked at patients who were on really intense statins things like atorvastatin and resubstatin or more modest
Types of statins such as synthestatin or pravastatin even and just look to see how the patients did and we also bunched it by uh hydrophobic and hydrophilic statins there’s some old literature i’m not sure necessarily how valid it is really but uh showing that those different types of statins might have different interactions with different drugs and so forth
But the bottom line was any way you sliced it there was a benefit consistent benefit favoring icosapent ethyl versus placebo irrespective of the actual statin type or category of statin so it further bolsters the results of reduce it that this isn’t a story that is contingent upon statin use though as a general principle i would recommend high-intensity
Statins in high-risk patients if they can tolerate it of course again not every patient is going to tolerate very intense statins so for example if one thought that you know the only statins that are appropriate in high-risk patients or torvastatin or zubastatin well the results look terrific in those patients and those particular subgroups and you know
While it’s not really appropriate to look at statistical significance in subgroups really we’re looking for directionality and consistency and it was definitely a consistent story here but if one wanted to go to that somewhat statistically inappropriate way of looking for or demanding statistical significance within the subgroups well then it was in fact a
Statistically significant reduction uh even if we were looking at just a torbostatin and reservostatin which are the most potent statins out there well it’s a great question how many are actually taking them may be different from how many you should be taking them of course but essentially every patient in the secondary prevention universe that is where they
Have atherosclerosis in their coronary or cerebral or peripheral arteries should be on a statin irrespective of their baseline ldl cholesterol and then beyond that in a primary prevention setting patients with elevated ldl cholesterol uh should be on the stand to the exact level depends on their baseline level of risk whether they have diseases like familial
Hypercholesterolemia other risk factors at their different risk calculators they can be useful in the primary prevention setting to see exactly when a statin should be initiated so based both on their ldl level but also their overall cardiovascular level of risk so between those two camps of people that is secondary in primary prevention it’s of course tens
Of millions of people that should be on statins but how many are actually on it is probably far less than would be optimal and now in part that’s still due to persisting patterns of undertreatment which is a bit disappointing and surprising given that statins are now widely available multiple generics but i think the other bigger part is statin intolerance
Or at least perceived statin intolerance now and reduce it we as a matter of protocol insisted that all the patients be on a stabilized dose of statin and tolerating it and continuing in the trial so that took the statin question out of there but in real world practice of course there are many patients who don’t take their statin because they think they’re
Having a side effect a proportion of those actually are having a side effect that is if you did a placebo-controlled switch on them as has been done in other studies it would turn out that they really are having symptoms to the statin and not a placebo but a fair amount are actually having side effects that aren’t related to the drug that is if you switch in
The placebo the side effects would still have been there and in part it’s because many things happen at once the patient’s identified it being at high cardiovascular risk they’re start on a statin but they’re also told to exercise they’re exercising for the first time in a few decades their muscles ache and they blame the statin and not the new exercise regimen
And the other parts there’s just a lot of misinformation in in social media and on the internet about statins and unfortunately some people read that and then they believe it and there can be sort of a harmful effect that they believe is there sort of like a placebo or nocebo type effect so uh all together that leads to pretty vast rates of under treatment with
Statins especially if we follow patients over time with respect to the reduced story again we had insisted patients be on standards for the purposes of the trial and the fda wisely in terms of their labeling for icosapent ethyl says that patients should be on maximally tolerated doses of statins but that includes then a maximally tolerated dose of zero milligrams
So the statins should be used in patients that are high risk which is the type of patient’s ricosta pentethyl would be considered but having said that the label doesn’t insist on it so that if there is a patient that’s truly statin intolerant and in a sense it almost then doesn’t matter if they think they’re statin intolerant or they’re really statin intolerant
In either case it’s still acceptable for the label to use icosapent ethyl i think there was a separate analysis looking at the baseline ldl cholesterol tertiles and even the lowest tertile of ldl cholesterol there was still consistent benefit of icosapent ethyl versus placebo and again one shouldn’t really look for statistical significance in the subgroup it’s
Just looking for consistency but for those folks that will do that nonetheless it was in fact a statistically significant reduction in the primary and key secondary endpoint with icosapent detail versus placebo including in that lowest tertile of ldl cholesterol so that i think is really useful information to physicians because if they’re thinking well you
Know does icosapent detail work if i blast the ldl down to a really low level in fact the answer is yes it does so these are completely complementary pathways so yes lower the ldl cholesterol as much as you can to the extent a patient can tolerate that without side effects with statins with acetamide with pcsk9 inhibitors if that works in terms of the cost
Effectiveness in the healthcare system one is practicing in but then if their triglycerides are elevated and by that for the label that would be greater than or equal to 150 milligrams per deciliter in the u.s and that can be a fasting or non-fasting triglyceride there if they essentially are a reduce it like patient that is secondary prevention or diabetes
And high-risk primary prevention those sorts of patients should also be on icosapent ethyl so those are distinct pathways towards risk reduction ldl lowering and then use of icosapent ethyl now the mechanism that you alluded to does seem to be distinct from ldl cholesterol lowering although there are some data that icosapent ethyl or its active ingredient of
Epa icosapenoic acid does in fact prevent oxidation of ldl so there may be some interconnectedness there but the predominant mode of action of icosapent ethyl is through epa and downstream effects of epa that we’re just only now being able to disentangle on the basic science level there are all sorts of downstream mediators created by epa so certainly there’s
An effect on lowering triglycerides and effect on reducing oxidation of ldl cholesterol but beyond all that it does appear that there are things that are produced that are anti-inflammatory and perhaps not in the conventional way we think of anti-inflammatories such as with crp or il-6 i mean really more fundamental molecules things like resolvins and so forth
That do appear to have anti-inflammatory effects that could be providing some of the cardiovascular benefit we see in the reducer trial
Transcribed from video
Dr Deepak Bhatt Highlights Latest REDUCE-IT Data By AJMCtv