Ep. 50: The Drug Worked. Did You? — with Dr. Regina Druz, MD, MBA, FACC, FMCP-M

Your cholesterol number can improve in twelve weeks while your actual risk of a heart attack barely moves. That gap is the subject of this episode. Dr. Regina Druz walks through three major cholesterol trials reported over the past year — STAREE, AMUNDSEN and VESALIUS-CV — covering both statins and Repatha (evolocumab), and uses a simple cut-finger analogy to explain why a better lab result is not the same as a better outcome. Along the way she covers what “MACE” really means, how to read number needed to treat, the 3% crossover point where statin benefit meets diabetes risk, and the questions her patients ask most: muscle pain, diabetes, how low is too low, and whether this is forever.

Watch on YouTube: A video version of this episode is available on the Own Your Heart Health YouTube channel. Subscribe to be notified of new episodes.

Episode Chapters

[00:02] Welcome — and Why Some Cardiologists Called This Summer Disappointing
[04:41] What “MACE” Actually Means in a Cardiology Trial
[07:02] The Cut-Finger Analogy: What Number Needed to Treat Really Is
[09:26] When to Recheck Your Cholesterol — and What a Better Number Proves
[11:51] Why a Lower LDL Doesn’t Immediately Mean Fewer Events
[14:06] The Three Trials — and Four Questions to Ask of Any Study
[18:54] Number Needed to Treat, Relative vs Absolute Risk, and Patient-Years
[23:38] STAREE: Atorvastatin in Healthy Adults Over 70
[28:18] The 3% Crossover — Statin Benefit Against Diabetes Risk
[30:27] AMUNDSEN: Repatha on the Way to the Cath Lab
[35:03] VESALIUS-CV: High-Risk Patients Who Hadn’t Had a Heart Attack
[39:34] The Three Trials Compared — What We Actually Learned
[41:51] Patient Questions: Statin vs Repatha, and the Muscle-Pain Data
[44:00] Can These Drugs Cause Diabetes? The 3% Rule and ALARA
[46:17] Why Isn’t Everyone on Repatha? How Low Is Too Low? Is It Forever?
[48:38] Bringing This to Your Own Doctor — and Who Truly Benefits

Transcript

[00:02] Welcome — and Why Some Cardiologists Called This Summer Disappointing

Dr. Regina Druz (00:02): Welcome to Own Your Heart Health. I’m Dr. Regina Druz, your holistic cardiologist. This week, we will dive into common heart health concerns, uncovering root causes and unpacking scientific discoveries and controversies. The information provided does not constitute medical advice. Please contact your healthcare practitioner before making any changes that may impact your health.

Well, hello everybody. It’s another Friday fun day. And as you could tell, I took just a tiny little break over the summer. I had to enjoy the summer a little bit because you know the summer in my region is pretty short. It pretty much just runs from Memorial Day to Labor Day. And we are just over the hump. The Labor Day is gone. Everybody’s back to work, back to school. And I had a great summer, and I hope so did you.

And in many regards, I feel like from the cardiology perspective, from what we learned over the summer, some of my colleagues think that the summer was a bit disappointing for cardiology. and I’ll tell you why. The reason being is that some of the drug trials that we had a lot of hopes for didn’t really show the benefit that we thought they would.

Now, as an integrative cardiologist, of course, I look at these trials with a different lens because I always ask myself, well, if they didn’t show the benefit that we were expecting, what did they teach us? Because lack of benefit is not always a negative effect of the trial, or it’s not always implying that we haven’t learned something. We do learn a lot from both the studies that deliver.

On the hypothesis that is being tested and prove it, this hypothesis is appears to be correct, and also from the studies that don’t actually deliver on this hypothesis or deliver partially. And so, since you’re probably hearing a lot of this on the internet, a lot of this in the media, I wanted to give you a summary of what I think are the important cardiovascular trials, the ones that

were mentioned already that happened this summer and the ones that may have wrapped up you know in the past year or so. and specifically what we’re going to try to focus on is the impact of medications on lipids, most importantly your cholesterol and other areas in lipids such as lipoprotein(a). And the most important point of this episode, what

I’m going to try to make sure that you understand is that there is a big dissociation happening. And this dissociation is happening between just seeing your cholesterol numbers drop or improve and the impact that that drop or that improvement may actually have on the coronary arteries and the vascular events overall.

Right. So in cardiology, of course, we are not just after lowering a biomarker or lowering a parameter. We want to provide interventions that are likely to improve our patients’ lives, either help our patients live better or help our patients live longer. And when we prevent cardiovascular events, and the typical events that we look to prevent, of course, are myocardial infarction, stroke.

Cardiac death, overall mortality very often gets investigated in the trials, although not so many of them have actually shown the benefit for that. And certainly other things that commonly come with cardiovascular disease, for example, the need for revascularization, the need to open a blood vessel to restore the blood supply. So if we are going to actually make our patients live better and longer lives.

We do need to deliver more than just cholesterol lowering, or more than just liprotein little aid lowering. We need to deliver an improvement in disease process itself. And this improvement in cardiology usually means that we need to lower the rates of myocardial infarction, stroke, cardiovascular death, revascularization, hospital admission.

[04:41] What “MACE” Actually Means in a Cardiology Trial

Dr. Regina Druz (04:41): And these are very common endpoints that trials are exploring. And we call these major adverse cardiac events or MACE. And depending on which trial you look at, the investigators often either contract or expand MACE. Sometimes they include just a few of the event markers, sometimes they include a little bit more.

So that makes it more challenging, of course, to compare these trials because it’s not always apples to apples, but it’s still quite informative. So the main, main, main, main, main point from today is that I want you to think through two very important parameters or questions that we as clinicians ask ourselves. And what we ask ourselves when we read a scientific study is not only what it’s required.

In terms of the outcomes, we already covered that major adverse cardiac events. You know, the studies will show us if there was an impact or not. But how can we achieve those major adverse cardiac event outcomes? And usually that comes down to two very important parameters. One is called number needed to treat, and another one is called time to therapeutic benefit.

And so let’s go through the number needed to treat first, because I think this is something a little bit easier to understand. and then we go through time to therapeutic benefit. So number needed to treat literally refers to how many patients with a specific condition one needs to treat in a unit of time, and the unit of time is our time to therapeutic benefit in order to prevent or improve one event.

Right. So let’s say you are cooking dinner in the kitchen today, right? And you were not particularly careful with your knife, and you happen to nick your finger, and now your finger is bleeding. So of course, you know, you’re going to reach out for a band-aid, maybe put some antibiotic on, you’re going to bandage your finger, and maybe in about, you know, two to five minutes.

[07:02] The Cut-Finger Analogy: What Number Needed to Treat Really Is

Dr. Regina Druz (07:02): The finger is fine, you know, the wound had been bandaged and you handled it, right? So, what is the number needed to treat? Well, the number needed to treat is one, right? You were the one who potentially may have not been careful while making dinner. You nicked yourself, you nicked your finger. you got a very effective treatment for this minor injury, which is a band-aid, you applied it, and it took you maybe five minutes it to really

fix or improve the situation and prevent, you know, more bleeding or prevent wound infection, right? So number needed to treat is one person, you treat it yourself, and the time to therapeutic benefit for you was about five minutes. Now for more complex diseases of course, such as cardiovascular disease, the story is much more complicated. We need to treat not one but quite a few patients and a lot of it depends on their

Baseline level of risk. And usually this isn’t something that we treat them, we give them medication, let’s say for a few weeks or even a few months, and voila, you know, we manage to prevent events. And this is where a lot of patients, I think, are stuck, you know, in this particular point, right? So if I’ll give you a lifestyle intervention, or if I’ll give you a medication or even a supplement regimen, and obviously.

The holistic card centers, this is what we do routinely for most of our patients. You may expect a reasonable period of time, about eight to twelve weeks, there will be an improvement in your parameters. Let’s say if we are using a protocol for the dyslipidemia and we’re trying to address cardiometabolic issues that you have and lower your total cholesterol, your ApoB, your LDL cholesterol, reduce deoxidative stress.

We could reasonably well accomplish this depending on the type of interventions that we’re using in about eight to twelve weeks. So, this is why it’s not uncommon when you actually get medication prescribed or if you get, you know, supplements and lifestyle, whatever it is that you are getting from your physician, they may ask you to go and get to recheck your laboratory panel in approximately 12 weeks. You know, sometimes it takes a little longer.

[09:26] When to Recheck Your Cholesterol — and What a Better Number Proves

Dr. Regina Druz (09:26): But you know, most doctors would say, well, anywhere from 10 to 12 weeks is where the recheck should actually happen. And so once you recheck that laboratory panel, and let’s say your numbers are coming back and they have improved, some adjustment may need to take place depending on what the goals of these laboratory parameters are. But please understand that just because your numbers have improved in about 12 weeks, your risk.

Of cardiovascular disease has not materially changed, right? And so this is where it’s sort of the major disconnect, you know, the dissociation lives. Just improving your lipid parameters in 12 weeks is not really synonymous with improving the situation in your coronary arteries. Now, how do we know this? We know this from the studies that.

The changes in the arteries themselves, the changes in the vasculature, take time. Whether it’s the changes that are reflected in plaque composition, something that we could see, for example, from carotid imaging or from cardiac CT and geography or invasive imaging done during cardiac catharization, or changes in major adverse cardiac events or MACE, right? Those changes don’t happen in 12 weeks.

Those changes happen in years. And so what I want to drive home today is that when we are looking at biomarkers, and the most common biomarkers that we look at that are related to cardiovascular health, of course, include lipid biomarkers, inflammation biomarkers, oxidative stress biomarkers. But lipids are probably the most common ones. They’re easily available.

And you can even get them, you know, direct to consumer. At the holistic heart centers, we actually launched a Heartwell Toolkit, which is where you can get your blood biomarkers and your genetic biomarkers in one panel so that we can create that personalized understanding where you are with regard to your biomarker profile and gauge your cardiovascular risk. But the point is just changing those biomarkers successfully at 12 weeks mark.

[11:51] Why a Lower LDL Doesn’t Immediately Mean Fewer Events

Dr. Regina Druz (11:51): Does not necessarily translate into meaningful change in cardiovascular events. Why is that? Well, you know, in our band-aid example, the time to therapeutic benefit was minutes. You slap the band-aid on your finger and you were fine in a few minutes, right? but when it comes to complex diseases and when it comes to change in vascular biology, we need years for changes to take place.

Place. Remember that cardiovascular disease and vascular disease in general is a slow progressive process. It starts at birth and it continues throughout our lives. So let’s look how what we learned over the summer, what we learned as conventional cardiologists, and how it bridges these learnings from these new trials.

How they bridge into integrative cardiology so that you too could understand, you know, getting your news from the media or from the internet, what these trials mean and what they could potentially mean for you, and what they really didn’t tell us, and where the gaps are. And the gaps are substantial. Now I’m going to use a slide deck here. if you are listening to me.

Thank you for listening. I appreciate it very much. Please share this episode with your friends, your family, your social circle. I would encourage you to jump on YouTube though, because you will actually see my slides. And if you’d like a copy of these slides, feel free to join Holistic Card University. This is our patient learning community.

Where we educate our patients and just educate individuals who are interested in cardiovascular health optimization and longevity. And you will then upon joining Holistic Heart University, you get access to our e-books and all of our past recordings of specific events, our group classes, and you will get a copy of the slide deck as well. So this is a member benefit at the Holistic Heart University.

[14:06] The Three Trials — and Four Questions to Ask of Any Study

Dr. Regina Druz (14:06): So let’s go through this now that I promised that this is something that you know I wanted us to do, you know, to go to go through these trials. I want to make sure that you actually know what what they are and exactly what what they have shown us. And I’m going to share my screen a little bit. Now you’re going to see some of the slides here. Now the reason why.

I’m keeping them open is because I would like to jump in between them a little bit. but you know, once again, once you sign up for Holistic Art University, you just get, you know, a regular slide deck and you can flip through it on your own. So the three cholesterol lowering trials that we’re going to look at today are STAREE, AMUNDSEN, and a trial which is a little bit older. It’s called VESALIUS-CV. Right. And I’ll tell you why I’m bringing kind of

Three of these as opposed to just two of these, you know, one of these. So, first of all, these three studies focused on two cholesterol medications that are used very, very commonly, right? And so in STAREE trial, the medication was atorvastatin, that’s a very well-known statin medication. And the STAREE trial focused on healthy adults who were older. They were 70 years of age or older. They

Had no prior heart attacks, they had no prior strokes, they were healthy, older adults living in the community. And this trial attempted to answer a super important question. Does starting a statement help in this older population? Believe it or not, we don’t have good answers to that. Even after this trial, we still don’t have all the answers that we’re looking.

The second study that came at about the same time, right before Labor Day, is actually AMUNDSEN. And AMUNDSEN looked at the very well-known medication called Evalukumap, and you know this medication as Repatha. it’s of course is an injectable medication that some of our patients are using for dysleepidemia. And the idea was there to investigate.

If people who were in the middle of having a heart attack and they were en route, you know, or en route to the cardiac laboratory to get the diagnostic angiography and potentially get a stent, and the question that investigators were asking: does giving this medication immediately, right before they were having this artery opening procedure, does it help? Right? You know, should in other words,

We’re treating these patients aggressively. They’re the highest risk patients we have. They’re here in front of us having a heart attack. Shouldn’t we give them all the medications that are available to us, including Repatha? Maybe it’s going to make their lives better. And finally, we’re going to kind of go back on the older study. That study is actually from late 2025. It is also a study on Repatha. It’s called Basaleus CV.

and there, these patients were not having a heart attack, but they were high risk individuals. they were high risk patients, but they had no prior events. they were so called primary prevention patients, so high risk based on a number of risk factors, but they haven’t really had any of those adverse events that I mentioned earlier. No heart attacks, no strokes, and obviously they were alive. So certainly no cardiac dial.

And the question then was does adding Repatha to a statin medication actually prevents first events in these patients, right? It’s very important because remember how I said we don’t just do these things for the sake of doing them. We want to make a meaningful change. So every question, you know, when we look at the clinical trials, when I look at the clinical trials, I ask myself these four questions.

Every single time. It doesn’t matter what the clinical trial was, these are my core four questions. And when you read the media reports, when you get things on the internet about clinical trials, about medical news, you may also consider asking those four questions or at least figuring out if the article or the news source provides you with the answers. So, number one, I ask, what is the number needed to treat? In other words,

[18:54] Number Needed to Treat, Relative vs Absolute Risk, and Patient-Years

Dr. Regina Druz (18:54): How many people must take this drug or do this procedure for one person to avoid a bad event, heart attack, stroke, similar event, cardiac death, right? The smaller the numbers, is the better. In in my, you know, you cut your finger example, the number was the smallest it could possibly be. It was one. You know, in clinical trials of complex diseases, the numbers are usually not that small, but.

Any trial that produces a single digit number is remarkable, and usually they produce double digit numbers in terms of number needed to treat, but the lower that number is, is better because it means we have to treat fewer people for one of them to benefit. Of course, the problem is, and you know that already is that we usually in the in the trial setting, we’re not able to tell which of these persons that we’re treating will.

Actually benefit. This is where the whole precision cardiology comes in, because what we do with our patients is that we manage their risk very proactively in a very precise and personalized fashion because we want them to be that N of one, right? The N of one who benefits. But in the clinical trials, we are able to, based on the trial results, to compute how many people we need to treat in order for one of those people to.

actually benefit from this drug or the intervention. The second question that I ask myself is that, well, how long should this treatment be? And this is time to benefit. Again, in the finger cutting example, it was pretty simple. You put on a band-aid, it took you a few minutes, so you know, time to benefit, okay, five minutes. But you know, in the chronic lifelong diseases such as cardiovascular disease, as I said before, your 12 week

Improvement and laboratory parameters is not going to get your coronary magically healed because that takes years. Number three, what is the biggest lesson, right? What is the single takeaway that matters the most? And I usually like to summarize it in one sentence, right? And that’s what you should sort of aim to do when you interact with medical data, and now we have, you know, Chad GPT.

And Gemini and Claude and Perplexity and Grok and you know all the AI, you know, in every single corner. And you can actually type all of these things in when you’re reading an article and say, well, what is the biggest lesson? Summarize it for me in one sentence. And number four, of course, because it’s really important. Remember how I said that, you know, for most of our queries with regard to cardiovascular disease, time to benefit is.

Years, we want to know if there’s any side effects. You know, the drugs need to be safe, and they also need to be something that doesn’t make people’s lives miserable. And you know, if there’s a lot of side effects, people are not likely to take them. You know, the treatment may be worse than disease. So we want to know what should happen people taking this medication and was it actually because of the medication? Because you know, some of these side effects will show up.

The placebo arm in people who are not taking the medication or not getting an intervention. But we want to know if there’s a meaningful uptick in the amount of side effects as a consequence of this treatment. So let’s go back to older adults. And I have a lot of older patients in my practice, I have some amazing patients who are in their late 70s, early 80s, who are doing extraordinary things, they’re traveling all over, they’re

amazingly active, yeah, even though they have heart disease and they have different types of heart disease. They’re not heart disease free, but some of them are having structural heart disease and no coronary disease, others have coronary disease. But the question that has been sort of nagging at cardiologists for a long time is that should we give a statin to a healthy, otherwise active patient?

Who is 70 years of age or older? You know, is it worth it? Since we know that it takes time for these medications to actually help the patients to avoid events, does it make sense? So in this study, and this study was done in Australia, they recruited from a primary care setting. So these were all community dwelling older adults. you know, they were seeing their regular dogs and

[23:38] STAREE: Atorvastatin in Healthy Adults Over 70

Dr. Regina Druz (23:38): They were recruited based on age alone. and you know, there was no other sort of recruitment protocol. Like it was it wasn’t that you know some sort of a specific investigation was done to sort these patients into high risk and lower risk. You know, essentially it was kind of you’re 70 years of age or older, you’re otherwise healthy, you don’t have heart disease or stroke, but your cholesterol is elevated, let’s give you a turbostatin.

and you know tora statin 40 milligrams is a pretty significant regimen. It’s a fairly intense statin regimen. and these patients were followed up for six years, you know, with s with regard to what was happening to them, including checking their laboratory parameters. So what was found is that there were fewer heart events, but there was no meaningful gain in survival. In other words

These patients were not living longer, they were not freer from disability associated with their older age, they were not freer from dementia. So, what actually matters a lot for this older age group living longer, being able to do things, so less rates of disability, avoiding dementia, that did not change. What did change is that for

What was called 1000 patient years, there were approximately 30% fewer events. So what that translated to is that four to five events were prevented per 1000 patient years. Now you may ask, what are 1000 patient years? Like these patients were treated for six years, not for 1,000 years. So what is 1,000 patient years?

And so we commonly in clinical trials, we multiply the amount of patients by the duration of follow-up so that we can calculate the rate that essentially allows us to compare across different trials, because different trials recruited recruit different numbers of patients over different durations. So, you know, how would we be able to compare them? So, for example, if you recruited 100 patients and you studied them for 10 years.

You would get 1,000 patient years, right? So you so we basically are trying to standardize our unit of measurement. So you know, 30% fewer major cardiovascular events is so called relative risk reduction. In terms of the absolute risk reduction, it translated into five fewer events per 1,000 patient years in this trial. And so obviously it took years for this benefit to happen.

Not weeks, not even months. And as it is the case with all statins, actually all lipid lowering medications for the most part, this is a long game. So this modest absolute benefit occurred over a fairly long timeline. You know, in this study was about six years or so. Now the side effects, remember how I said we also need to be mindful of the side effects because.

You know, if it takes us that long to produce a modest benefit, and if the cost of side effects is too high, then we’re sort of not really hitting the mark, right? So the serious side effects were actually quite few. They were identical between the treatment group and the placebo group. But you could see there was a slightly higher rate of muscle endurance complaints, certainly higher rate of liver-related issues, you know, bumps in liver enzymes with statin medications.

And of course, modestly higher rate of new or worsening diabetes. Right. And this is a known issue with statin medications. You give higher doses for long enough time. You potentially may increase a person’s chance of becoming a diabetic. This is usually something that affects patients who already may have been with impaired glucose tolerance or pre-diabetes. And the magic number there is 3%, right? So the most recent ACC/AHA

dyslipidemia guidelines that were just published this year establish 10 year risk at 3% as a crossover point. So, in other words, if your cardiovascular risk is 3% chance of having MACE at 10 years, your and you being treated with a statin, you also have a 3% chance over the same 10 years.

[28:18] The 3% Crossover — Statin Benefit Against Diabetes Risk

Dr. Regina Druz (28:18): Of developing new-onset diabetes. So you’re kind of at the equilibrium, right? Now, if the risk is higher, let’s say your cardiovascular risk is 5% or 6%, then obviously that exceeds 3% chance. So you may opt for being on a medication. If your risk is lower, you probably will opt not to, because at that point it doesn’t really make sense, right? So what have we learned, right? What is the lesson that I want to summarize in one sentence?

the lesson is that age alone isn’t the reason to reach for a statin drug. In healthy older adults who have normal cholesterol or mildly elevated cholesterol, while statin reduced their heart attacks and their strokes, it really didn’t help them to live longer, to stay independent longer, to really avoid dementia, and they had a modest uptick in other stuff like muscle, liver, and blood sugar issues, right?

So, the real conversation here, the real lesson is that you must discuss your personal risk with your physician. And obviously, I’m not telling you to start a drug or to stop a drug. I can’t possibly do that because this is only a podcast and this is for educational purposes only. But what you should ask your doc is: Doc, what is my personal risk? And this is a hard

variable to pin down, right? Sort of like to triangulate what your personal risk is. We have made some gains in figuring it out with our HeartWell.ai application, but the deeper we go, the more we learn. And this is an opportunity for you to discuss it with your physician. Now

The second study that I want to bring looked at a much more powerful drug. And a lot of you are using this medication called Repatha or Evolucumab. And the study was called AMUNDSEN Study. And again, it was very recently published, I think like June or July of 2026. And it was a very interesting concept, right? So patient arrived, patients arrived at the hospital that were found to have a heart attack.

[30:27] AMUNDSEN: Repatha on the Way to the Cath Lab

Dr. Regina Druz (30:27): and the decision was to randomize those patients to conventional care, which included a lot of medications, of course. But another group, the treatment group, was getting an injection, their first injection of Repatha, in addition to that standard care. And then, of course, you know, they went down the line to had their artery open. So the injection took place before the stenting, before the arteries were open, and they were followed for a year to see.

did those patients who get injected, did they actually do better? And so this trial absolutely crushed cholesterol gall because Repatha is such a powerful drug, it literally managed to put 82% of patients who received it into their cholesterol target. And cholesterol target here was very aggressive, LDL less than 55.

and 50% reduction from baseline, right? So, you know, so that was really powerful. And you could see that the standard care group that got statins, high intensity statins, they did not, you know, they were not even close. You know, there were basically only 40% of them reached the goal, you know, versus 82% in this initial injection group, right? But remember that the goal of the trial was not to lower cholesterol and say, hey, we did it, did it, congratulate us.

The goal of the trial to see if it influences the clinical outcomes. And the clinical outcomes were basically MACE, right? You know, death on plate, heart hospitalization, another heart attack. And so you could see here that the clinical outcomes they really did not budge. Now, some of the trial

Critics and you know, experts looking at the trial said, Well, look, there’s sort of like a two-sided lesson here, right? We know that it is safe to actually lower LDL fairly quickly, but perhaps the year is just too short, right? Because I just told you that it takes several years. And remember that 3% number that I said sort of sits at the cross section, at the decision making point, the fork in the road.

Should you go down the cholesterol lowering pass with a statin, or should you not because of the risk of diabetes? Well, typically the time to benefit, the time to therapeutic benefit based on a lot of trials is about two and a half years. And that’s actually the number in the ACC 2026 guideline. So if you remember number three from from from my talk right now, that will serve you well because you know that 3%.

10-year risk is a decision point between statin and no statin because of the incidence of new-onset diabetes. And it does take approximately three years for this number needed to treat to materialize, right? And so a lot of the experts looking at the study said, well, they just haven’t really studied them long enough. They only studied them for a year. And yes, they were high-risk individuals that were having a heart attack, they were getting a stent, but you know.

We really didn’t give them enough time to show the benefit. And potentially, as the study goes on, we may end up, you know, two or three years down the road, seeing that the benefit was there. So, what is the major lesson? The major lesson is it’s safe to go low early, but there’s not going to be much payoff, right? So getting the cholesterol super low immediately during a heart attack, we can achieve it. It is safe. These patients didn’t have.

more side effects than people who got a standard treatment, but the benefit didn’t really happen in that short term horizon, right? You know, is r and that’s why the experts typically say, well, you know, it’s a marathon, it’s not a sprint, right? And so what

We did find in that trial is that remember that you know this trial followed on sort of on the heels of a major trial that happened in 2025 that also included Tripatha, right? So this the trial was called Visalis CV, and it was specifically giving medication Repatha for primary prevention. So these individuals that were enrolled in the VESALIUS-CV-CV.

[35:03] VESALIUS-CV: High-Risk Patients Who Hadn’t Had a Heart Attack

Dr. Regina Druz (35:03): They did not have a heart attack, they did not have a stroke, but they were high risk, right? So they’re in about 12,000 people. So this was a massive trial. They were followed for nearly five years. and they had arterial disease or they had high risk because of diabetes. They had high cholesterol despite the usual therapy, right? So they were already treated with what they were supposed to be treated.

They weren’t quite hitting the targets, and because of their high risk, they were enrolled in this trial and randomized to receive her patha or to continue with their usual care. So, what that trial found is that the LDL was cut by more than half, and there were fewer major cardiovascular events. There were 25% lower rate of heart attack, strokes, or coronary deaths.

almost 20%, well 19%, exactly fewer major events, including procedures that require to open the arteries, and 20% lower deaths from any cause. Now I want you to kind of repeat this for yourself. 20% lower death rate from any cause, and that’s all cause mortality. Now, this is very important, and this is probably why.

AMUNDSEN investigators thought that if they’ll give Repatha during an acute MI, they may actually see something comparable to the VESALIUS-CV-CV results, but they really didn’t. But anytime a drug delivers in the mortality department, it gets an hour radar screen, right? So this trial is different from the first two that I discussed because it actually delivered.

on the major cardiovascular events. Now remember that number needed to treat, right? It still was fairly high here. So one needed to treat approximately 56 people for five years. If we wanted to have one person avoid heart attack, stroke or coronary death.

and that was translated in about 55 major events prevented over 1,000 patient years, right? Again, that patient years comes up so that we can compare these different trials. So bigger benefit, real benefit, fewer people needed to treat, but these obviously were highest risk patients. And you know, there are a couple of other statistical and points that these investigators looked at.

And if one really looked to prevent almost all events that mattered, kind of in a broader major adverse cardiac event prevention, it was 36 people for five years. So that’s actually not bad at all because it’s a primary prevention trial and definitely beats stat in the primary prevention trial, right? So patients pays off because you know, it took these investigators.

a year to actually begin to see any results. And after that, you know, after that first year, the risk reduction started to take place. And so the what was called survival curves, they started to separate, right? And the idea there was is that the more established the disease, the sooner is the payoff. If disease is mild, it’s going to take longer. Now you could see though that it’s not always true because in the AMUNDSEN trial,

we didn’t see a proof of this. Important component here was is that Ray Patha, because it works a mechanism different from statins, didn’t really result in substantial uptick of muscle complaints, new-onset diabetes, or memory thinking problems, even though the LDL cholesterol was around 45 milligrams per deciliter. So that was pretty low. But you know, and they were followed for quite a few years and

not detected any of the complaints. So what can we learn from this? Well this is practice changing and this is what I often do with my patients. Treating higher risk people early is a must, right? You know, this is the first study to show that this particular medication injectable, which is actually a PCA skin inhibitor, it helps people who have not yet had a heart attack or a stroke.

[39:34] The Three Trials Compared — What We Actually Learned

Dr. Regina Druz (39:34): But they weren’t a high risk group. They had no known blockages that declared themselves, and the safety profile is was excellent. But of course, the largest benefit was really concentrated in that high risk cohort. So if we were to kind of compare these three trials at a glance, what have we learned? Right? We learned that statins in older people who otherwise were healthy.

Had a very modest benefit over a substantial period of time, but also carried muscle, liver, and diabetes upticks. Giving Repatha to patients who were in the midst of an acute MI produced tremendous LDL lowering, but didn’t really impact their outcomes. But giving Repatha patients who are at high risk but haven’t had their MI yet.

And were treated for a substantial period of time actually produced impactful reduction in major adverse cardiovascular events, right? So it’s not that clear cut, right? You know, when patients ask themselves, should I use a statin, should I use Rapatha? Well, the answer is it depends, because it depends what are the circumstances, what is the context. And you know, in addition to this number needed to treat and time to therapeutic benefit.

The major lessons from these studies, you know, you must discuss it with your doctor to understand what your unique context is, right? And so, but if we take these studies as an aggregate, what we’ll learn from them is that duration matters. lipid lowering and translation of lipid lowering into arterial hulls, this is a long game, right? It’s a marathon, it is not a sprint. And obviously, biologically,

The higher people are in their risk category, the biggest benefit they sustain. And there are trade-offs. You know, if you pick a statin medication, you know what you’re trading for. And I do use statin drugs in my practice, but I use them very carefully. So it does matter to a patient and to a physician what is it that they’re thinking.

[41:51] Patient Questions: Statin vs Repatha, and the Muscle-Pain Data

Dr. Regina Druz (41:51): So here I want to kind of go with a few questions that patients commonly ask me. and you already may know the answer is maybe you are on this medication, maybe you aren’t, but I kind of want to just give you a few questions that you know my listeners and my patients often ask me so that you can have the answers. What is the difference between statin and Repatha? Well, statin is a daily pill typically, it affects cholesterol synthesis in the liver.

It’s been studied in multiple studies over decades, and it will work well for most individuals. Again, you know, the context into individualization is very important. Repatha or evolocumab is a PCSK9 inhibitor. It is injected under the skin typically every two weeks. What it does is that it doesn’t affect cholesterol synthesis in the liver, it simply preserves.

The amount of LDL receptors on the liver so that your cholesterol is cleared out a little bit more effectively. And it is very powerful in lowering LDL cholesterol because of that. And usually in the trials, it’s added on top of the statins. Although for some of our patients, for example, the ones with elevated lipoprotein(a), we use it instead of a statin drop.

Muscle pain and blood sugar, what the data actually shows. A lot of the times patients say, aren’t statins dangerous? Am I going to develop muscle aches or pains? It is a reasonable question to ask because up to 30% of patients do. But depending on what population had been studied, you may find that in the placebo group, we also had patients developing that. The serious things like muscle breakdown, rapamyelysis is actually very

rare and a lot of the times patients who get these medications there are older patients that already have some aches or pains so it’s really difficult to know whether it’s coming from statin or not if you do think that you’re developing these muscle related complaints usually they’re in large muscle groups or like your thighs or your arms you must tell your doctor immediately.

[44:00] Can These Drugs Cause Diabetes? The 3% Rule and ALARA

Dr. Regina Druz (44:00): Can these drugs give me diabetes? This is a very serious concern, and I’m very careful with statins because of that, because I had seen quite a few cases of new-onset diabetes, not from the ones that I prescribe, but when patients come to us after prolonged utilization of statins for good reasons, but they are trending towards diabetes or they have already developed new-onset diabetes. It is a real concern. Remember the 3% number that I said.

3% is sort of a fork on the road, a decision-making point. And that 3%, if your cardiac risk is at 3%, giving you a statin will also increase your risk of diabetes at 3% over 10 years, right? So that’s sort of the equipoise. If your cardiac risk is higher, then potentially you may benefit from a statin.

Drug. You know, what we do with our patients is that we use something called ALARA, which stands for as low as reasonably achievable. And we are attempting to lower their statin exposure as much as possible to lifestyle and supplementation. And of course, to repair their metabolic balance, to offset the cardiometabolic drivers of the dyslipidemia.

To improve their insulin sensitivity so that we actually can de-risk the entire situation, not just because we want to use a drug, but because we want to protect patients’ vasculature and other important organs from the side effects of insulin resistance. Now, how soon does it work? And should everybody be in Repatha now that I gave you these results? Well, obviously, as I said, you will.

probably see the impact fairly quickly with regard to lipid numbers alone, right? You know, 12 weeks or so we’ll recheck and whatnot. But the real impact with regard to reduction of cardiovascular events that takes at least three years, right? Now, why isn’t everybody on Repatha? Well, it is an injection. It is expensive, although insurance coverage is expending.

[46:17] Why Isn’t Everyone on Repatha? How Low Is Too Low? Is It Forever?

Dr. Regina Druz (46:17): The trials primarily focused on patients who are high risk or they were not reaching their LDL goal in statin drugs. And I think we are now moving more toward realization that Repatha is a very viable non-statin alternative. And especially for patients who have a potential to do bad with statins, either because they’re pre-diabetic or because let’s say they have lipoprotein(a) elevation.

Repatha is a really great first choice. How low is too low, right? A patient asked me recently, you know, doc, my total cholesterol is now 115. I am concerned. You know, can it be that I lowered it a little bit too much? Now, the trial data tells us that we can hang out with LDL cholesterol below 50. And at least on the trial, you know, experience shows us that.

There has not been increased risk of side effects. However, I can tell you that I had some patients whose hormonal balance, testosterone, for example, especially in men, or who had cognitive issues with such low LDL levels. And I actually sometimes pull back from LDL lowering and try to achieve it in a different way or milder LDL lowering while monitoring what’s happening with a patient’s vasculature to offset some of those side effects.

And yes, for the most part, unless there is a specific reversible reason that we can treat to offset dyslipidemia, this is a long-term therapy. So the answer is yes, it is forever. Now, as I mentioned before, I’ll put the copy of the slide deck into Holistic Heart University. You will have the references there. You could copy those references, paste them in into Google, and AI will spit out.

Every single study that I just discussed. Remember that this information is only for your education. I certainly hope that it compels you to have a conversation with your physician about which medications you’re using, why you’re using them, what are you to expect from those medications, right? This is basically a conversation that.

[48:38] Bringing This to Your Own Doctor — and Who Truly Benefits

Dr. Regina Druz (48:38): The whole purpose of me saying this is to enable you to have knowledge that you can bring forward and discuss it with your licensed healthcare practitioner so that you can make the best decision for you. and certainly do not start or stop any drugs after listening to this. and if you believe you’re having an acute cardiac emergency, you must go to the nearest emergency room or call 911.

If you want to work with me and my team, we are here for you. You can find us in a number of places, certainly on the website and HeartWell.ai. you can call us, you can text us, you can listen to more of this on YouTube or participate in the holistic heart university, and that way get a little bit more information. So I hope this has been informative.

unlike my traditional colleagues, I don’t think that it was the summer of doom, you know, for the lipid hypothesis for cardiology. I think we continue to expand our understanding of what cardiovascular risk is, and we continue to learn that just focusing narrowly on a specific marker or specific pathway.

Is not likely to be enough, right? Because it sort of becomes a game of diminishing returns, right? You know, yes, we can reduce events when patients have lower LDL and ApoB levels for longer, especially if those patients are high risk patients, but that’s not enough because the reduction in events is not.

Something that reduces events 100%. As you had seen from number needed to treat, one needs to treat a substantial amount of patients, substantial group, to prevent just one event. and that is not happening over weeks, that is happening over years at a minimum of three years, right? And where we don’t have good

sort of playbook at is to figuring out who are those patients that definitely benefit from the treatment. Although we have gotten closer, as you had seen from the VESALIUS-CV-CV trial, you know, the high risk patients of course benefited. And so this was part of the reason for me, you know, why I became an integrative cardiologist is that I wanted to find answers to these questions. I wanted to understand who are the patients, you know, who is that person sitting in front of me?

What actually can I figure out about their cardiovascular risk, about their vascular aging trajectory, so that I can give them the interventions that would be meaningful to them. Because at the end of the day, I want them to be that one, that N of one whose risk is meaningfully reduced and who is able to live their life to the fullest without being trapped.

By chronic disease, of which the cardiovascular disease, of course, is the number one concern. So if it resonates with you, send me a comment, you know, tell me your story. I usually go and read through all the comments and all the stories, and who knows, maybe one of them will become an episode here. And I will see everybody at the Holistic Heart University.

Thank you for tuning in to Own Your Heart Health with Dr. Regina Druz. This podcast is powered by Holistic Heart Centers. If you enjoyed the show, please rate and review us on your favorite podcast platform. To learn more about our services, visit holisticheartcenters.com and subscribe to our YouTube channel. The link is in the show notes. See you next week.

Frequently Asked Questions

What is the difference between a statin and Repatha?

Dr. Druz explains that a statin is typically a daily pill that acts on cholesterol synthesis in the liver, and has been studied across multiple trials over decades. Repatha (evolocumab) is a PCSK9 inhibitor given as an injection under the skin, usually every two weeks. Rather than reducing cholesterol production, it preserves LDL receptors on the liver so that cholesterol is cleared more effectively — which is why it lowers LDL so powerfully. In most trials it is added on top of a statin, though for some patients — for example those with elevated lipoprotein(a) — it may be used instead.

Do statins really cause muscle pain?

Dr. Druz calls this a reasonable question to ask, noting that up to 30% of patients report muscle aches. She also points out that the rate depends heavily on which population was studied, and that placebo groups in trials report muscle symptoms too — which is why the question is more nuanced than a simple yes or no.

Can these medications cause diabetes?

Dr. Druz describes this as a serious and real concern, and says she is careful with statins because of it — she has seen patients arrive at her practice trending toward, or having developed, new-onset diabetes after prolonged statin use. She frames the decision around a 3% threshold: if your 10-year cardiac risk is about 3%, a statin raises your diabetes risk by roughly the same amount over 10 years, which is the point of equipoise. Above that, the cardiovascular benefit may outweigh it. In her own practice she uses an approach she calls ALARA — as low as reasonably achievable — minimising statin exposure using lifestyle, supplementation and repair of metabolic balance.

How soon do these drugs actually work?

Dr. Druz draws a distinction between the laboratory number and the clinical outcome. Cholesterol levels are usually rechecked at around 10 to 12 weeks, and they may well have improved by then. But meaningful reduction in cardiovascular events takes far longer — she cites roughly two and a half years as the time to therapeutic benefit across trials, a figure reflected in the ACC 2026 guideline, and says the real impact on events takes at least three years.

Why isn’t everyone on Repatha?

Dr. Druz gives several reasons: it is an injection rather than a pill, it is expensive — though she notes insurance coverage is expanding — and the trials focused primarily on patients who were high risk or not reaching their LDL goal on statins. She adds that she now sees it as a viable non-statin alternative, and a strong first choice for patients likely to do poorly on statins, such as those who are pre-diabetic or who have elevated lipoprotein(a).

How low is too low for LDL cholesterol?

Dr. Druz says trial data indicates LDL cholesterol below 50 has not been associated with increased side effects in the trial setting. In her own practice, however, she has seen individual patients — particularly men — with hormonal changes such as lower testosterone, or with cognitive symptoms, at very low LDL levels. In those cases she will sometimes pull back, aiming for milder LDL lowering while monitoring the patient’s vasculature.

Is this treatment forever?

For the most part, yes. Dr. Druz says that unless there is a specific reversible cause that can be treated to correct the dyslipidemia, lipid-lowering therapy is long-term.

Show Notes & Resources

About This Episode

This is a solo episode with Dr. Regina Druz, MD, MBA, FACC, FMCP-M — a board-certified integrative cardiologist and the founder of Holistic Heart Centers in Roslyn, New York. She reviews three cholesterol-lowering trials reported over the past year and explains how to read trial results for yourself: what the endpoints mean, how to tell relative from absolute benefit, and how long a treatment actually takes to change risk. Dr. Druz notes in the episode that she is posting the slide deck from this episode to Holistic Heart University.

Topics & Resources Mentioned in This Episode

STAREE — atorvastatin in healthy adults aged 70 and over, recruited on age alone; a roughly 30% relative reduction in major cardiovascular events, translating to about five fewer events per 1,000 patient-years, with muscle, liver and diabetes signals
AMUNDSEN — Repatha (evolocumab) given immediately, before angioplasty, to patients in the middle of a heart attack; substantial LDL lowering but no early impact on outcomes
VESALIUS-CV — roughly 12,000 high-risk patients without a prior heart attack or stroke, followed for nearly five years; a meaningful reduction in major adverse cardiac events, about 55 events prevented per 1,000 patient-years
MACE — how trials define their endpoints, and why definitions differ between studies
Number needed to treat, relative versus absolute risk reduction, and patient-years
The 3% crossover point — where statin cardiovascular benefit and new-onset diabetes risk meet, per the ACC/AHA dyslipidemia guidelines
Time to therapeutic benefit — roughly two and a half years, per the ACC 2026 guideline
ALARA — as low as reasonably achievable statin exposure
Lipoprotein(a) and ApoB as risk markers beyond LDL
Using AI tools to interrogate a study you are reading
Holistic Heart University — where Dr. Druz is posting the slide deck from this episode
HeartWell.ai — Holistic Heart Centers’ personalized cardiovascular-risk tool

Holistic Heart Centers

holisticheartcenters.com
HeartWell.ai — AI-powered cardiovascular risk assessment
Address: 55 Bryant Avenue, Suite #6, Roslyn, NY 11576
Phone: 877-511-5166
YouTube: @reginadruzmd
Instagram: @dr.reginadruz
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