March 28, 2023

So good afternoon to all of you thanks to dr nita and dr sanjay for inviting me to be here so i’ll be speaking about statins particularly the outcomes with the various statins in people with diabetes and we all know that cardiovascular disease is the major problem in people with diabetes and and jocelyn almost a century back said this that with excess of lipids

Diabetes starts and with that itself patients develop various complications and die because of atherosclerosis so it is quite evident that we need to look at this aspect and try to understand them and the the various risk factors which are contributing to atherosclerosis and contributing to the vascular disease as you can see in this uh in this cartoon you

Can see the progression from the risk factors to the to the development of uh atherosclerotic plaque then leading to a mass i mean vascular event so we look at the prevalence of dyslipidemia i mean we look at the major causes of death in people with diabetes we see that ischemic heart disease remains as the most important cause contributing to almost more than i

Mean different studies have shown varying from 50 to 75 percent and as you can see here that remains the major cause for for morbidity and mortality in patients with diabetes and if you look at the prevalence of dyslipidemia we see that the prevalence is to the tune of this is not diabetic surround this is in the general population if you see the prevalence of

Distributement is probably 40 percent in in overall but males tend to have a higher prevalence as compared to females but if you look at diabetics you see that diabetics tend to have a much higher prevalence of of dyslipidemia and if you look at the ldl cutoff of 100 you find that there is a significant number of people with dyslipidemia amongst the diabetics and

We have very good data from the icmr in-depth study which is also shown that almost 85 percent of individuals have either one form of dyslipidemia that is either a elevated ldl cholesterol or is it the part of the elevation of triglycerides or low hdl cholesterol the low hdl being the probably the commonest abnormality that is identified so statins have been the

Buzzword in in the sense in the management of dyslipidemia for several years now uh maybe about three decades more than three decades now that statins have been being used and uh if you look at the mechanism action of various lipid lowering medications we see that statins act at the hmg coe reductase where they inhibit the hmg reductase we have newer molecules like

Benpedoic acid which is acting which is uh inhibiting more proximal atp citrate layers and then we have the pcsk9 inhibitors and we have we have all these other agents that are that are being developed so over the years if you look at the outcomes data of data with the use of statins as you can see whether it is primary prevention or secondary prevention you can

See clearly see that primary prevention you had studies like the voskov study we have uh f cap study the uh the statin used also is mentioned in this in this figure and uh the ascot uh escort trial all these trials have clearly shown that even in primary prevention they work well in terms of reducing the cardiovascular outcomes and if you look at the secondary

Prevention the impact is even greater because we know that people with cardiovascular disease have a much higher risk of recurrency recurrent events amongst the patients with diabetes so if you look back at what the ncp goals were about in almost 20 years back this is 2004. there they had suggested that less than 100 should be the goal for high-risk individuals

And their itself they had suggested the optimal goal of 70 and a moderately high risk is patients with with diabetes with one more risk factor they considered 130 as a cut off or targeting the ldl to less than 130 and those with lower risk that is non-diabetics or with one cardiovascular risk factor they suggested 160 as a as a cut off but over the years if you see

The there has been a change in the understanding about the goals of statin therapy as you can see this is from the 2018 aha acc algorithm where they have suggested that for primary prevention you need to look at a ldl target of i mean ldl level of more than 190 to start statin in all classes of a class 2 indication uh class one indication to start starting in all

In all those with a ldl of more than 190 those with diabetes they have suggested those diabetes more than 40 years all of them should be on statin although the those and then for diabetics between the age of 40 to 75 the risk assessment should be done to consider those with higher i mean those who need a higher intensity statin that is those who have got a previous

Cardiovascular disease or they have multiple cardiovascular risk factors they need a higher dose of statins so this is how the primary prevention algorithm was suggested and the second if you look at the secondary prevention algorithm they have again looked at identifying the the five year or ten year risk of uh atherosclerosvd events and suggested the targets

Of hdr have been ldl based on that and they’ve also spoken about additional therapies like htmi which was also considered in that situation so this was when the pcsk9 inhibitors were not available now if you look at the recent update from the esc that is the european society of cardiology in 2009 they have brought down the target ldl levels in those with high

Risk to less than 70 and those with very high risk that is those who have a previous cardiovascular event and diabetes to less than 55 and this has also been ah if you look at the ada position statement however we see that uh they also speak about uh similar to what the acce has been speaking they have they have been following the similar sort of targets but if

You look at the lipid association of india they have categorized people based on the risk factors and diabetes puts i mean presence of diabetes with even no other cardiovascular risk factor or one or even a one even a single other cardiovascular spectrum puts them at high risk and these are the individuals who are at high risk and those who have who have more

Than two other cardiovascular risk factors they because they come into the very high risk category and and those with previous events come in the extremely high risk category and the targets that they have suggested uh is that with diabetes without a cvd when there is no target organ damage and less than one other cardiovascular risk factor there is no other

Cardiovascular risk factor this they still suggest a target of ldl of less than 70 with two more cardiovascular factors additional to cardiovascular risk factors other than diabetes they put them in a very high risk category and suggested a target of less than 50. and those with atherosclerotic cardiovascular pre-existing atherosclerotic cardiovascular disease

They they are in the high risk and the extremely high risk and extremely high risk type a and type b where the targets are less than 15 in type a and type b is less than 30. so that’s how the liai has stratified the risk cardiovascular risk among patients in in with diabetes now let us look at some of the studies which have looked at the role of statins the

Outcomes with various statins so if you look at the hps trial which is basically which enrolled about five thousand uh or six thousand not patients with diabetes they had another fourteen thousand patients without diabetes and uh they were randomized to either simvastatin versus placebo a forty milligrams cell mass starting versus placebo and as you can see on

The right side of the figure you can see that the outcomes in terms of strokes and and other cardiovascular events were significantly reduced by close to 25 reduction in incidence of first non-fatal or fatal stroke amongst the diabetes diabetic participants there was no there was a significant uh 24 reduction in such strokes so overall 20 25 even in diabetics

It was 24 and as you can see uh when you start when they stratified the patients based on other cardiovascular risk factors previous mi other chd and other presence of cardiovascular disease in the form of peripheral vascular disease or cerebrovascular disease across the board all patients benefited from the use of statins and benefited similar to what was seen

With non-diabetics so clearly there was a 25 improvement of reduction cardiovascular events with the use of statin in patients with diabetes the escort ele trial looked at the use of randomized 19 000 patients who were on antihypertensive treatment and out of uh 19 000 patients uh they enrolled 10 000 into the lipid lowering arm and they were either receiving

A total statin 10 mg per day or placebo so 5000 on a total waste add in another 5 000 on on placebo and again you see that there was a 24 reduction in uh the the risk of fatal non-fatal strokes where it is by 33 amongst those with diabetes and by 24 in those without diabetes after total strain treatment so patients with diabetes tended to get a better result in

This in this in this trial with the use of wet wasting 10 mg per day and eternal strain was clearly shown to have this benefit now another important trial of that time i mean about a decade more than a decade old trial is the cards trial which actually changed our thinking about uh the use of statins because till that time the target ldl was kept at 130 and in this

Trial they have enrolled patients with ldl cholesterol levels between 100 to 130 and and found who were otherwise not indicated to have a statin and in that group also they found that there was a significant benefit with the use of stat with the use of 10 mg of heterostatic so 1400 patients randomized to heterostatic versus placebo the standard of care that time

Was not to treat them between 100 to 130 but with the treatment there was a 37 reduction in incidence of major cardiovascular events 48 reduction in the risk of stroke and 32 reduction in acute cardiovascular endpoints so this is probably one of the trials which changed our thinking about the use of statins in in people with diabetes so clearly there’s a benefit

In terms of the primary endpoints the stroke the secondary endpoints like death from any cause and any acute cardiovascular disease event then we have the jupiter trial which is again a primary prevention trial with rosuvastatin using 20 mg of rosewood statin as against placebo there was a 44 reduction in the risk of of the primary composite primary endpoint

Which is cardiovascular disease so uh here what we clearly see this was a trial which did not include patients with diabetes so this was in patients without diabetes and you found that there was a 44 reduction in the instance of cardiovascular events but the new onset diabetes as the chairperson was mentioning just now there was increase by 28 and that actually

Brought in the brought into focus the occurrence of new onset diabetes with the use of statins and there was a lot of debate on that and and we have after looking at all the data the conclusion that has been made is that the benefit that is provided by the use of statins probably far outweighs the risk that is there of nuance and diabetes in the hope 3 trial

You see that there was their patients were random it was a two by two factorial design with candy saturn or rosewaster in 10 mg candy saturn with hydrochlorothiazide and here again there was a 24 percent reduction with 10 milligrams of rose waste and there was a 24 reduction in the first co-primary outcome and the second group primary outcome of cv death mi

Stroke cardiac arrest revascularization in heart failure also came down by 25 percent clearly showing the benefits of roosevelt studying in this group treatment with those who are studying 10 mg per day resulted in significantly lower risk of cardiovascular events than placebo and intermediate risk at ethnically diverse population without cardiovascular disease

So now looking at another statin which is uh coming to the market recently that is the pittawad statin so this is although not been extensively studied but a few studies which are there have shown that there is probably less of glycemic disturbance with the use of this statin as compared to atomostatin or even pravastatin so amongst the older statins pravastatin

Had the lowest risk of nuanced diabetes and when you look at epitome the that risk was uh found to be uh almost not increased with with the use of metabolostatin so it did not increase fasting blood glucose or hbmc in people with diabetes unlike uterostatin and the live study which was a two year follow-up of beta was studying therapy in type 2 diabetes with

About 300 patients showed that there was a a stable hb1c of you know remaining at the same level or even coming down to a small extent so there was in long-term therapy also up to two years there was no increase in the hvac and so therefore it may be a good option in patients with type 2 diabetes there’s another study called the j predict study which which had

1200 patients who were on who had igt and who were treated with beta australian as compared to so this was the only large scale prospective study to evaluate the effect of starting therapy nuances diabetes in patients with impaired glucose tolerance and amongst this the primary endpoint was the percentage of patients developing new onset diabetes and what we

Saw in the study was that there was after almost 60 months of use of uh betavistatin there was a lower incidence of new onset diabetes in the group that was treated with betavista as compared to the control group so it significantly reduces and diabetes by 18 in igt patients so if you look at a meta-analysis now having looked at these individual studies if you

Look at a meta analysis of all studies what we see is that a 40 40 milligram reduction in ldl uh is brings down the major cardiovascular events by 22 percent coronary vascular revascularization by 25 20 21 reduction in strokes and major vascular events by 21 and this is data from a pool data from 18 000 odd patients with diabetes versus 71 000 patients without

Diabetes and 14 randomized trials of statins so studying therapy can clearly reduce cardiovascular events in patients with diabetes without even those without cbd now if you look at the comparative effect of statins of the various statins on lipid parameters you can see here that rosuvastatin is probably the one which has the maximum effect on in terms of ldl

Lowering has a very good effect on epo a1 upper b but also i mean and if you look at the triglyceride lowering probably it was best with lower statin and then followed by a rosewood starting at aurora starting at lower than that and if you look at so these are this is a comparative statement of the efficacy of various statins uh through a network meta-analysis

Of various studies so just a word about the new onset diabetes with statins we clearly know that that this is a i mean this is something which happens for for sure the predators of nuanced diabetes may be maybe the i mean what we have seen is that the type of statin used has has a effect on the on the development of neon side diabetes as we said the resource

Statin probably has the highest effect followed by tobacco in pravastatin and then peter was studying having the lowest effect and high dose of thoracic was studying therapy led to neurons and diabetes in some patients in this in this trial which was trying to identify predictors of neurons diabetes higher dose of statin the higher is the risk of nuanced diabetes

This is clearly seen from a meta-analysis of all the statin studies and 12 percent higher diabetes with intensive dose versus moderate dose so in spite of this statins continue to be to be the first line agents for diabetics live india because of the fact that uh they are providing a significant benefit in terms of reducing the cardiovascular events by almost

30 percent so i think with that i will conclude i thank you all for the patient hearing

Transcribed from video
Rakesh Sahay: Statins In Diabetes : The Outcomes By Rx Events