Any experience with Nexletol or Nexlezet?

@jahman57 Why Zetia + Nexletol may appear to be doing “nothing”.

What you are describing does happen, and there are several plausible explanations—often more than one at the same time.

1. These drugs lower LDL less than statins.
Zetia (ezetimibe) typically lowers LDL by ~15–25%.
Nexletol (bempedoic acid) lowers LDL by ~15–20%.
Together, the average LDL reduction is ~30–35%.

If someone:
Started with very high LDL, or
Previously had large LDL reductions on statins
…the change can feel disappointing or negligible, even though the drugs are working within their expected range.

2. Underlying genetic cholesterol disorders.
If LDL remains very high despite therapy, possibilities include:

Familial hypercholesterolemia (FH) (even milder or late-diagnosed forms).
Other inherited lipid metabolism issues.

In these cases:
Oral medications often cannot overcome the genetic signal
Injectable therapies may be needed (see below).

3. Absorption or metabolic variability:

Some people:
Absorb less ezetimibe from the gut
Metabolize bempedoic acid differently
Have liver pathways that respond weakly to these mechanisms.
This is not rare and usually not detectable without trial-and-error treatment.

4. Secondary causes raising cholesterol:

Even if medications are correct, LDL may stay high if something else is driving it, such as:

Hypothyroidism.
Insulin resistance or diabetes.
Chronic kidney disease.
High saturated-fat intake.
Certain medications (steroids, some psych meds, etc.).
If these aren’t addressed, lipid drugs can look ineffective.

5. Statin intolerance is real—but often complex.
True statin intolerance does occur, especially:

Muscle pain, stiffness, weakness
Symptoms returning consistently with re-challenge.

However, some patients tolerate:

Very low-dose statins (e.g., once or twice weekly).
Hydrophilic statins (pravastatin, rosuvastatin) better than others.
That said, if symptoms are reproducible, forcing statins is not appropriate.
What usually works when this happens:

If LDL remains high despite Zetia + Nexletol, guidelines typically move to PCSK9 therapy, such as:

Repatha (evolocumab).
Praluent (alirocumab).

These:
Lower LDL by 50–60%.
Are not statins.
Rarely cause muscle symptoms.
Work well in statin-intolerant patients.
Some people also benefit from:
Inclisiran (twice-yearly injection).
Combination therapy tailored to genetics and risk.
Why they may feel “no symptoms”:

That part is actually expected:
High cholesterol does not cause symptoms.
Muscle pain comes from medications, not cholesterol itself.
Cardiovascular risk accumulates silently over years.
So feeling fine does not mean cholesterol isn’t a problem.

Bottom line:

This situation is:
Not rare.
Not a failure.
Often a sign that stronger, non-statin therapy is needed.
A lipid specialist or preventive cardiologist would likely:

Rule out secondary causes.
Confirm true statin intolerance.
Consider PCSK9 inhibitors or inclisiran.

Here are links to trustworthy sources that support the key points from the above explanation about Zetia (ezetimibe), Nexletol (bempedoic acid), statin intolerance, and other non-statin LDL-lowering therapies:

1. Non-statin therapies:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635697/ (PMC article on non-statin options and guidelines) �
PMC

2. Ezetimibe (Zetia) reduces LDL by about 15–25% non-statin option:
https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/cholesterol-medications �
http://www.heart.org

3. Bempedoic acid (component of Nexletol / Nexlizet) statin-intolerant
https://consultqd.clevelandclinic.org/statin-intolerance-and-new-lipid-lowering-treatments �
Cleveland Clinic
NEXLIZET & NEXLETOL prescribing info page (with indication for statin-intolerant patients):
https://www.nexlizethcp.com/statin-intolerance-evidence/ (trial and safety details for bempedoic acid) �
ESPNEX

4. Study showing additive LDL lowering from ezetimibe + bempedoic acid:
https://www.tctmd.com/news/bempedoic-acidezetimibe-combo-lowers-ldl-cholesterol-high-risk-patients �
tctmd.com
Wikipedia summary of LDL reductions with the combination:
https://en.wikipedia.org/wiki/Bempedoic_acid/ezetimibe �
Wikipedia

5. PCSK9 inhibitors (e.g., evolocumab & alirocumab) statin-intolerant patients:
https://consultqd.clevelandclinic.org/statin-intolerance-and-new-lipid-lowering-treatments (ODYSSEY ALTERNATIVE trial results showing ~45% LDL reduction) �
Cleveland Clinic

6. Guidelines & consensus statements:
https://www.jacc.org/doi/10.1016/j.jacc.2022.07.006 �
JACC
NIH/NLM cholesterol management guideline overview including non-statin substitutions:
https://www.ncbi.nlm.nih.gov/books/NBK305897/ �

@tommy901 Hello there. I have a question for you.

I am certain that we should not blindly trust what doctors say. My question is should we trust medical test results like blood labs, blood pressure measurement, studies of the the arteries, etc. Is the medical lab system unreliable?

@tatiana987 Medical tests are generally reliable—but they are not infallible, and they are often misunderstood or misused.

1. Are medical lab tests and measurements “unreliable”?

In general, no.
Modern medical testing (blood labs, imaging, blood pressure measurements, vascular studies, etc.) is built on decades of validation, quality control, and standardization.
That said, "reliability is not the same as perfection".
Most common lab tests are highly reproducible *when done correctly.*
Imaging and physiologic tests are usually accurate within known limits.
Errors are uncommon, but *interpretation errors* are more frequent than technical errors.

2. Where problems actually arise (most common issues):

A. Biological variability (normal human fluctuation):

Many values change naturally:

Blood pressure varies minute to minute.

Cholesterol and glucose fluctuate day to day.

Creatinine and eGFR vary with hydration, illness, medications.

A single abnormal result does not always equal disease.

B. Pre-analytical factors (very important):

Results can be affected by:

✓Fasting vs non-fasting
✓Dehydration
✓Recent exercise
✓Acute illness or inflammation
✓Timing of the test
✓Improper cuff size for blood pressure

Lab handling issues *(rare, but possible)*----
These factors can skew results without the lab itself being “wrong.”

C. Reference ranges are statistical—not personal.

“Normal ranges”:

✓Are based on large populations
✓Do not account for individual baselines
✓May not reflect what is normal for you

Someone can be:

✓“In range” and still unwell
✓“Out of range” and clinically fine
**This is where clinical judgment matters.

D. Interpretation errors *(more common than lab errors)*
✓Tests do not diagnose people—clinicians interpret them.

Problems occur when:

✓Results are taken out of context
✓Trends over time are ignored
✓Symptoms are dismissed because “labs look okay”
✓Borderline abnormalities are over- or under-reacted to
✓This is often what patients experience as “the system failing.”

3. How accurate are specific types of tests?

✓Blood tests generally very accurate
✓Most errors come from interpretation, not measurement
✓Blood pressure Is accurate only if *measured correctly*
✓One reading in a clinic is often misleading
✓Home or ambulatory monitoring is often more reliable
✓Imaging (CT, MRI, ultrasound) is technically precise

Findings can be:

✓Overcalled
✓Undercalled
✓Clinically insignificant but alarming
Vascular and cardiac studies are usually reliable
✓False positives and false negatives do occur
✓Best interpreted alongside symptoms and risk factors

4. Should you “trust” medical tests?

A healthier mindset is this:

✓Trust medical tests as useful tools—not as absolute truth.

They are best used to:

✓Identify trends
✓Support or rule out hypotheses
✓Guide further evaluation
✓Monitor change over time

They are not crystal balls and should not replace clinical reasoning or patient experience.

Here are links to credible sources that support the above information:

1) Medical labs and variability in test results

Biological:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200014/ �
PMC

“Preanalytical Variables:
https://australianprescriber.tg.org.au/articles/preparation-for-blood-tests-what-can-go-wrong-before-the-sample-reaches-the-lab.html �
Australian Prescriber

2) Blood pressure measurement accuracy and variability:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10453092/ �
PMC

American Heart Association:

https://www.aafp.org/pubs/afp/issues/2021/0900/p237.html �

https://www.heart.org/en/health-topics/high-blood-pressure/understanding-blood-pressure-readings/monitoring-your-blood-pressure-at-home �
http://www.heart.org

Wikipedia overview:
https://en.wikipedia.org/wiki/Blood_pressure_measurement �
Wikipedia

3) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200014/ �
PMC

https://academic.oup.com/clinchem/article/61/7/914/5611492 �

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10453092/ �
PMC

https://www.aafp.org/pubs/afp/issues/2021/0900/p237.html �

@tommy901 Again, thanks for yr help. A question: the 24 hour blood pressure monitor I wore last August has caused more harm than help for me. The cuff was clearly too big so measurement too low imo. So I have perfect blood pressure in the doctor’s notes. One of the errors the monitor made is that during the time I was on Repatha and the long detox period, I had fainting spells and a lot of falls. When I wore the BP 24 hour monitor, the machine simply turned itself off and did not record the event. I was outraged, wanted to know what happened to my BP during an my fainting spell.

I asked the doctor who prescribed the monitor. No answer except that the 24 hour monitor provides the most reliable data. That mistaken conclusion follows me.

I am perhaps the only patient in the universe at my advanced age to have perfect BP. And when I faint, nothing is happening with my BP? In the real world, what is likely happening in the monitor during the shut down? Why does it shut itself down in yr educated guess?

@tatiana987 A 24-hour ambulatory blood pressure (ABPM) monitor is not designed to reliably capture fainting (syncope) events, and when it shuts itself off during such an episode, it is usually because the device cannot obtain a valid reading, not because “nothing happened” to your blood pressure.
So yes — important physiological changes may have occurred, but the monitor simply failed to record them.
That limitation is often under-acknowledged in clinical notes, which is what you’re experiencing now.
Why a fainting episode may NOT be recorded
1. ABPM devices are intermittent, not continuous*

Most ABPMs:
Measure BP every 15–30 minutes during the day
Every 30–60 minutes at night
If you faint between readings, there is no data point captured.
A faint that lasts seconds to minutes can easily occur completely outside the measurement window.

2. Why the monitor may shut itself off:

During syncope or near-syncope, several things can happen that break the measurement algorithm:
a) Very low blood pressure
If systolic BP drops too low (often < 70–80 mmHg):
The cuff cannot detect Korotkoff oscillations.
The device interprets this as a measurement failure.
Many monitors are programmed to:
Abort the reading.
Log an “error”.
Or stop cycling after repeated failures.

b) Irregular heart rhythm

If you had:
Bradycardia.
Tachycardia.
Atrial fibrillation.
Or pauses.
The oscillometric algorithm may fail completely, especially during sudden hemodynamic instability.

3. Movement and collapse
During a fall or loss of consciousness:

Arm position changes.
Muscle tone drops.
The cuff may slip or kink.

Any of these cause the monitor to:

Cancel the reading.
Power down after repeated invalid attempts.

4. Cuff size really does matter:

You are correct here.
Too large a cuff → falsely LOW readings.
Too small a cuff → falsely HIGH readings.
If the cuff was oversized and your BP dropped suddenly:

The monitor may not detect pressure changes at all.
Leading to shutdown or “no data”
This is not user error — it is a known limitation.
What was likely happening physiologically during the faint
In the real world, fainting at your age and in that context often involves one or more of the following:

Sudden BP drop (orthostatic or neurally mediated hypotension).
Transient cerebral hypoperfusion
Heart rate changes (too slow, too fast, or irregular).
Medication-related autonomic effects (Repatha timing is notable).
None of these require chronic hypertension or hypotension to occur.
You can have “normal” BP on paper and still experience dangerous episodic drops.
Why the conclusion “perfect BP” is flawed

The statement:
“The 24-hour monitor provides the most reliable data”
is only true for average BP trends, not for:
Syncope.
Falls.
Medication reactions.
Autonomic dysfunction
ABPM cannot rule out episodic hypotension.

A more accurate statement would be:
“The monitor did not capture an event — therefore no conclusion can be drawn about BP during that episode.”

Unfortunately, that nuance is often lost.

Important clinical point (this matters):

Unexplained fainting + falls at advanced age is NEVER benign, even if:

Office BP looks “perfect”.
ABPM averages look normal.
This scenario usually warrants other. testing, such as:

Orthostatic BP testing.
Continuous ECG (Holter or event monitor).
Autonomic testing.
Medication review
ABPM alone is not sufficient.

Bottom line:

The monitor shutting down does NOT mean nothing happened.
It usually means the device could not measure during instability.
The “perfect BP” conclusion is over-interpreted.
Your concern is medically justified.

Source's:

https://pmc.ncbi.nlm.nih.gov/articles/PMC7356999/ — explains what ABPM is and how it’s used for hypertension care. �
PMC

https://www.aafp.org/pubs/fpm/issues/2020/0500/p19.html — describes how ABPM takes repeated measurements, not continuous data.

https://www.researchgate.net/publication/362529150_Feasibility_of_Blood_Pressure_Measurement_With_a_Wearable_Watch-Type_Monitor_During_Impending_Syncopal_Episodes — highlights that diagnosing syncope with ambulatory monitors is possible but imperfect and that criteria are still evolving. �
ResearchGate

https://pmc.ncbi.nlm.nih.gov/articles/PMC10227244/ — . �
PMC

About Cuff Size:

https://www.acc.org/Latest-in-Cardiology/Articles/2023/06/05/19/18/Why-Is-Cuff-Size-So-Important-and-Other-Factors-That-Affect-Accurate-BP-Measurement — explains how incorrect cuff size changes systolic/diastolic readings. �
American College of Cardiology

https://www.ama-assn.org/public-health/prevention-wellness/4-big-ways-bp-measurement-goes-wrong-and-how-tackle-them — covers general inaccuracies in BP measurement.

@tommy901 Again, thank-you for helping me. I stole some of your ideas to ask the vasular doc who is so enamoured of AMBP results. We’ll see what he says. It could be that he does understand that data that stops at the critical time of collection has a big hole in it. It could be he understands but he thinks I am too stupid to get it. Possible.

The harm is passed along in his notes imo. Harm is done as other doctors read about my wonderful blood pressure number and base treatment, I suppose, on that great blood pressure for such an old lady.

What you say makes so much sense that it is a real pleasure to read. Thanks. Common sense is not common any more.

@jahman57 Why Zetia + Nexletol may appear to be doing “nothing”.

What you are describing does happen, and there are several plausible explanations—often more than one at the same time.

1. These drugs lower LDL less than statins.
Zetia (ezetimibe) typically lowers LDL by ~15–25%.
Nexletol (bempedoic acid) lowers LDL by ~15–20%.
Together, the average LDL reduction is ~30–35%.

If someone:
Started with very high LDL, or
Previously had large LDL reductions on statins
…the change can feel disappointing or negligible, even though the drugs are working within their expected range.

2. Underlying genetic cholesterol disorders.
If LDL remains very high despite therapy, possibilities include:

Familial hypercholesterolemia (FH) (even milder or late-diagnosed forms).
Other inherited lipid metabolism issues.

In these cases:
Oral medications often cannot overcome the genetic signal
Injectable therapies may be needed (see below).

3. Absorption or metabolic variability:

Some people:
Absorb less ezetimibe from the gut
Metabolize bempedoic acid differently
Have liver pathways that respond weakly to these mechanisms.
This is not rare and usually not detectable without trial-and-error treatment.

4. Secondary causes raising cholesterol:

Even if medications are correct, LDL may stay high if something else is driving it, such as:

Hypothyroidism.
Insulin resistance or diabetes.
Chronic kidney disease.
High saturated-fat intake.
Certain medications (steroids, some psych meds, etc.).
If these aren’t addressed, lipid drugs can look ineffective.

5. Statin intolerance is real—but often complex.
True statin intolerance does occur, especially:

Muscle pain, stiffness, weakness
Symptoms returning consistently with re-challenge.

However, some patients tolerate:

Very low-dose statins (e.g., once or twice weekly).
Hydrophilic statins (pravastatin, rosuvastatin) better than others.
That said, if symptoms are reproducible, forcing statins is not appropriate.
What usually works when this happens:

If LDL remains high despite Zetia + Nexletol, guidelines typically move to PCSK9 therapy, such as:

Repatha (evolocumab).
Praluent (alirocumab).

These:
Lower LDL by 50–60%.
Are not statins.
Rarely cause muscle symptoms.
Work well in statin-intolerant patients.
Some people also benefit from:
Inclisiran (twice-yearly injection).
Combination therapy tailored to genetics and risk.
Why they may feel “no symptoms”:

That part is actually expected:
High cholesterol does not cause symptoms.
Muscle pain comes from medications, not cholesterol itself.
Cardiovascular risk accumulates silently over years.
So feeling fine does not mean cholesterol isn’t a problem.

Bottom line:

This situation is:
Not rare.
Not a failure.
Often a sign that stronger, non-statin therapy is needed.
A lipid specialist or preventive cardiologist would likely:

Rule out secondary causes.
Confirm true statin intolerance.
Consider PCSK9 inhibitors or inclisiran.

Here are links to trustworthy sources that support the key points from the above explanation about Zetia (ezetimibe), Nexletol (bempedoic acid), statin intolerance, and other non-statin LDL-lowering therapies:

1. Non-statin therapies:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635697/ (PMC article on non-statin options and guidelines) �
PMC

2. Ezetimibe (Zetia) reduces LDL by about 15–25% non-statin option:
https://www.heart.org/en/health-topics/cholesterol/prevention-and-treatment-of-high-cholesterol-hyperlipidemia/cholesterol-medications �
http://www.heart.org

3. Bempedoic acid (component of Nexletol / Nexlizet) statin-intolerant
https://consultqd.clevelandclinic.org/statin-intolerance-and-new-lipid-lowering-treatments �
Cleveland Clinic
NEXLIZET & NEXLETOL prescribing info page (with indication for statin-intolerant patients):
https://www.nexlizethcp.com/statin-intolerance-evidence/ (trial and safety details for bempedoic acid) �
ESPNEX

4. Study showing additive LDL lowering from ezetimibe + bempedoic acid:
https://www.tctmd.com/news/bempedoic-acidezetimibe-combo-lowers-ldl-cholesterol-high-risk-patients �
tctmd.com
Wikipedia summary of LDL reductions with the combination:
https://en.wikipedia.org/wiki/Bempedoic_acid/ezetimibe �
Wikipedia

5. PCSK9 inhibitors (e.g., evolocumab & alirocumab) statin-intolerant patients:
https://consultqd.clevelandclinic.org/statin-intolerance-and-new-lipid-lowering-treatments (ODYSSEY ALTERNATIVE trial results showing ~45% LDL reduction) �
Cleveland Clinic

6. Guidelines & consensus statements:
https://www.jacc.org/doi/10.1016/j.jacc.2022.07.006 �
JACC
NIH/NLM cholesterol management guideline overview including non-statin substitutions:
https://www.ncbi.nlm.nih.gov/books/NBK305897/ �

@tommy901 Thank you for the info. Very informative. I'm seeing my doc this week and we'll talk about my situation.