Cheating Death: The Heart Attack Survivor

Written By Ian Riddock

Case Presentation:

Let’s say you have a heart attack and you’re lucky enough to make it to your local hospital’s catheterization laboratory (cath lab) in a timely fashion [well under the “door to balloon time” goal of 120 minutes from contact with Emergency Medical Services (EMS) to balloon inflation] to receive a “drug eluting stent (DES)” in your left anterior descending artery (LAD - some call this the “Widowmaker” (consider watching the documentary:  The Widowmaker on Amazon, Netflix or YouTube). Your symptoms resolve and you sleep well overnight. The attending cardiologist rounds on you the next morning, tells you your troponins were minimally elevated and your echo shows no gross heart muscle damage. She deems you fit for discharge. 

Whew! That was a close one! After some brief education and perhaps some lecturing about this teachable moment, you feel thankful to be alive and motivated to change habits. You thank all of the caretakers and your friend or loved one takes you home. Quick, easy and some might say it’s like “drive thru” medicine!

Flying Under the Radar

You might ask “if we already know who they are, why on Earth would they be flying under our radar?”

Turns out that despite being identified by a heart attack, the highest likelihood of having another heart attack is within the ensuing first year. We call this “residual risk.”

Why? Multiple reasons, but in a nutshell - undertreatment of the disease of atherosclerosis. Despite a plethora of published guidelines, scientific statements and expert consensus documents, too many (some studies find it’s the overwhelming majority) of secondary prevention patients fail to receive intense treatment. As an example, despite recommendations for high intensity statins published in guidelines > 20 years ago, implementation is embarrassingly low (High-Intensity Statin Use Among Patients With Atherosclerosis in the U.S. | Journal of the American College of Cardiology).

The evolution of ASCVD treatment has reached a point in medicine where we are capable of not only halting the progression of disease, but potentially reversing it in the majority of patients (GLAGOV Trial:Effect of Evolocumab on Progression of Coronary Disease in Statin-Treated Patients: The GLAGOV Randomized Clinical Trial). There will always be “residual risk” (which by the way keeps the study and practice of medicine interesting). But if you fail to employ the latest treatments, or as in the case above, not employing any statin in ½ of the patients, it’s like taking a time machine back to 1986 medicine (statins first arrived in 1987).




CardioAdvocate Checklist:

Please see What's Your ApoB? A Practical Approach to Lipid Biomarkers

Patients who have already had an atherosclerotic cardiovascular event, like a heart attack, stroke or even a stent, represent our very highest risk patients.  

In the case of the heart attack or stroke victim, it tried to kill them - or at least maim them severely. 

Why on Earth would anyone wait around for ANOTHER EVENT before taking the most aggressive action? They have ADVANCED atherosclerosis!

We don’t want to have any more “Repeat Offenders.”

Better put in this expert White Paper call to action (Eliminating atherosclerotic cardiovascular disease residual risk): ‘Residual risk’ is a euphemism for failure to prevent. 

We tell our patients: “No more! Not on our watch!”

We  therefore adhere to the most aggressive guidelines in such patients.

Lipid Goals:

Lipid Lowering Drug Therapy:

  • High intensity statin preferred 

    • Atorvastatin 40 to 80 mg daily (generic)

    • Rosuvastatin 20 to 40 mg daily (generic)

  • Combo approach with modest intensity statin and additional nonstatins may work better for some patients as long as high intensity lipid lowering and goals achieved: 

    • Ezetimibe 10 mg daily (generic)

      • 10-15% LDL-C lowering when used as monotherapy

      • 20-25% additional LDL-C lowering when combined with statin

      • Hyperabsorbers may respond better

      • Hypersynthesizers may respond less

      • Range may be anywhere from 5-60% LDL-C reduction with individual variability

    • PCSK9i mAb (branded): ~ 50-70% LDL-C reduction

      • Recommended by 2018 ACC/AHA Cholesterol Guidelines when LDL-C ≥ 70 mg/dL despite max tolerate statin + ezetimibe

      • Evolocumab (Repatha - branded) 140 mg subcutaneous every 2 weeks or 420 mg subcutaneous every 4 weeks

      • Alirocumab (Praluent - branded) 75 or 150 mg subcutaneous every 2 weeks or 300 mg subcutaneous every 4 weeks

    • Inclisiran (Leqvio - branded) 240 mg subcutaneous every 6 months

      • siRNA (small interfering ribonucleic acid)

      • 2 initial doses 3 months apart, then 2 doses per year

    • Bempedoic acid (NEXLETOL® (bempedoic acid) | Official Patient Site- branded) 180 mg daily

  • Acute Coronary Syndrome (presenting with) and LDL-C not at goal despite max statin and ezetimibe

    • PCSK9i initiated early, ideally while in hospital (Class IIa ESC/EAS)

    • Repeat lipids at 4-6 weeks after max statin + ezetimibe. If not at goal, add PCSK9i (Class I ESC/EAS

Icosapent Ethyl: Vascepa 1g twice daily

  • EPA only Omega 3 Polyunsaturated Fatty Acid (PUFA)

    • Pharmaceutical grade

    • This is a drug, not a supplement. Big difference

      • Drugs are FDA approved, undergo rigorous scientific investigation, scrutiny and peer reviewed clinical trials

      • Supplements are “foods”

        • This is not the same as “Over The Counter”

        • Not regulated by the FDA

        • Not required to list ingredients accurately

Antiplatelet Therapy:

  • Aspirin 81 mg daily, or if contraindicated or allergic to aspirin, clopidogrel 75 mg daily may be substituted

Diet/Nutrition:

  • Dash or Mediterranean Diet

Exercise:

  • 150 to 300 minutes per week of modest activity (brisk walking), or 

  • 75-150 minutes per week of vigorous activity 

Environmental Toxins:

  • Stop smoking! Continuing to smoke guarantees a repeat offense. 

    • Even if you do all of the above, but continue to smoke, we will have no chance in stopping the disease.

  • Avoid Plastics 

    • This may be easier said than done - it’s everywhere - perhaps impossible to avoid.

    • A recent study published 3/7/2024 on Microplastics and Nanoplastics in Atheromas and Cardiovascular Events | NEJM demonstrated a 4.5 times increased risk of heart attack, stroke and all cause mortality in those found to have plastics in their carotid artery at the time of carotid endarterectomy, compared with those who did not.

    • While association does not prove causation and more studies need to be done, evidence is mounting about the harms of plastics.

    • Until we know more, it may be wise to choose packaging that reduces the risk of ingesting plastics.


Deep Dive

Why Me?

After surviving a heart attack, patients understandably want answers. The question typically comes in the form of “why did I have a heart attack?” Or, “I’ve been seeing my doctor regularly, wouldn’t this have been detected?”

The answers are complicated but best summed up by a slide Dr. Matthew Budoff, preventive cardiologist, frequently puts up during his lectures:

“Superior doctors prevent the disease

Mediocre doctors treat the disease before evident

Inferior doctors treat the full-blown disease”

– Huang Dee Nai-Chang –

( 2600 BC 1st Chinese Medical Text)

Atherosclerosis develops over several decades. There are multiple opportunities along the way to recognize risk factors, identify its presence and get in front of the disease.

But once it fully manifests, it becomes much more challenging to stabilize or reverse. We now have the tools and it can be done. It’s been a process. 

History 

In 1964 the US Surgeon General issued a report concluding that smoking was a “probable” cause of coronary heart disease. Since then various other lifestyle recommendations have been made, such as reducing saturated fats, getting plenty of exercise and reducing stress. 

In 1987, arguably the greatest therapeutic advancement in modern medicine beyond vaccinations and antibiotics was released in the United States. Statins. Lovastatin, under the trade name Mevacor hit the stage  (and just in time for this author’s father, who at age 46, 1 year after quitting smoking, developed angina while carrying a 10 lb bag up a flight of stairs and required balloon angioplasty in 5 locations). In the 80’s and 90’s we were just hoping to slow down the disease. Give patients a few more years. 

In 2004 we first saw evidence of halting of the progression of plaque in the REVERSAL trial (JAMA. 2004;291(9):1071-1080. doi:10.1001/jama.291.9.1071) which used IVUS (Intravascular Ultrasound). Patients treated with the highest intensity statin at that time, Lipitor (atorvastatin) 80 mg daily to achieve a mean LDL-C ~ 70 mg/dL (mean 79) vs Pravachol (pravastatin) 40 mg daily to achieve LDL-C ~ 100 mg/dL (mean 110) showed plaque regression in a small percentage of patients. 

In 2006 the ASTEROID trial (JAMA. 2006;295(13):1556-1565. doi:10.1001/jama.295.13.jpc60002) showed evidence for the first time, of plaque regression when using Crestor (rosuvastatin) 40 mg daily to achieve a mean LDL-C of 60 mg/dL. 

Fast forward to 2016, when the GLAGOV trial (JAMA. 2016;316(22):2373-2384. doi:10.1001/jama.2016.16951), using evolocumab (Praluent - link to company website) demonstrated plaque regression in ~ ⅔  of patients achieved atheroma regression, after achieving a mean LDL-C of 36 mg/dL, whereas the placebo group (statin only) showed no evidence of regression at a mean LDL-C of 93 mg/dL.

Do you see the trend here? With every iteration of these clinical trials, therapies capable of greater LDL-C reduction yield not only greater reductions in ASCVD outcomes (less heart attacks and heart deaths), but mechanistically demonstrate the evolution from slowing the progression, to halting plaque developement, to regression of the disease.

So what causes atherosclerosis?

Blood cholesterol, trafficked in “atherogenic” lipoprotein particles - predominantly Low Density Lipoprotein (LDL) is causal to atherosclerosis, all by itself. This fact is recognized by every cardiovascular organization in the world.

Cumulative exposure to atherogenic lipoproteins is all that is needed to produce atherosclerosis. By checking someone’s blood concentration of LDL-C in mg/dL, which is a surrogate for the LDL-particles, we get a good approximation of what is and has been traveling through the bloodstream of that individual every second or every day of their life.  That lifetime exposure to ApoB containing particles (atherogenic particles) is largely what drives the risk for atherosclerosis.

In a population, the higher the LDL-C, the higher the risk of atherosclerosis. But even “normal LDL-C” levels are plenty. This comes as a surprise to many of our patients following that first heart attack when they declaire “But I’ve always been told my cholesterol was normal!”

Bell-shaped curves showing the cholesterol levels of those admitted with their first heart attack compared with bell-shaped curves of those of the general population are nearly superimposable. Meaning, the only levels of LDL-C that essentially guarantee a life free of atherosclerosis, is maintaining LDL-C in the pediatric range of 20-40 mg/dL. Heart disease is the #1 killer for a reason. It’s damn common.

Many other risk factors may accelerate this process however, such as smoking, hypertension, diabetes, adiposity, becoming sedentary etc.  But the presence of atherogenic lipoprotein particles, even in the absence of all other risk factors is enough.

So why are people STILL dying from this preventable and treatable disease?

Underrecognition of the disease

  • Access: For many, it’s an issue of access to health care. Men are less likely to seek it out. Women are less likely to be identified even when they do seek it out. 

  • Screening: Appropriate screening is available, but not implemented regularly. Traditional risk calculators often fall short. 3 out of 4 younger patients presenting with their first cardiac event, would have never qualified for a statin using standard risk calculators. So, even if they had reliable check ups, they may not have been recognized.

    • Coronary Artery Calcium Scores offer superior screening when used on top of traditional risk calculators

      • Highest Net Reclassification Index

      • Highest C-statistic (Receiver Operator Curve)

      • Even benefit low risk patients

  • Cost: Many patients lack insurance or cannot even afford the copays to see their doctor or obtain coverage for screening tests

    • Despite Calcium scores being recognized in multiple guidelines, insurance companies refuse to cover them

    • Most calcium score testing has been made affordable ($79 - $199) however some places charge much higher or don’t offer them at all

Undertreatment of the disease

  • Guideline Confusion and Popularity: There are many guidelines, some more conservative than others. Some are more popular than others. 

    • This impacts cholesterol treatment goals/thresholds - choosing a more conservative goal/threshold runs the risk of undertreatment

  • Misinterpretation of recommendations: Most guidelines recommend that high risk patients achieve a particular threshold or goal LDL-C and > 50% lowering from baseline LDL-C!

    • Many forget that last part - meaning a patient may have an LDL-C of 72 mg/dL and are placed on a low or modest regimen aimed at getting below 70 mg/dL. 

  • Adherence:

    • Patients: It’s been well documented that > 50% of patients prescribed statins following an ASCVD event will stop taking their statin by 1 year

    • Providers: By CMS not declaring LDL-C a “Quality Measure” healthcare providers and healthcare systems are not held accountable for achieving LDL-C goals. 

    • Statin intolerance: 

      • Way over-diagnosed

        • 90% of patient complaints of statin myalgias are attributable to the “nocebo” effect (insert reference). 

        • But, 10% are real and many patients are simply diagnosed as “statin intolerant” and no treatment alternatives implemented

          • Both patients and provider become fatigued and simply don’t want to go through the painful process of prior authorization for expensive alternatives

  • Insurance denials: Despite a 60% cut in the cost of PCSK9i from ~$15,000/year to $5500/year in 2018, insurance companies continue to deny coverage of life-saving non-statin therapies.

  • Provider Education and Awareness:

    •  It takes, on average, 13 years for published guidelines to infiltrate mainstream clinical practice. Medicine moves slowly. As advocates, we can help it move faster. 

  • Discordance - Over reliance on LDL-C. Yes, you heard that right. 

    • LDL-C needs to be a “Quality Measure” because it’s by far the more commonly used lipid biomarker and does a pretty good job

    • However LDL-C has limitations

      • When TG are high and HDL-C is low, LDL-C is discordant to and may drastically underestimate LDL particles and therefore risk. 

    • NonHDL-C is a better biomarker than LDL-C

      • It’s been in the guidelines for decades - when triglycerides are elevated (now we say > 150 mg/dL), one must look at non-HDL-C (again, discordance).

      • Few clinicians even know what non-HDL-C is

      • Of those that do, few take the time to either calculated it or look at it

      • Non-HDL-C is not always “listed” in lab reports, relying on the clinicians to calculate it themselves

      • Most clinicians (most people) don’t like doing math during a busy visit

    • ApoB (apolipoprotein B) is better when it comes to recognizing residual risk in the presence of discordance

  • Ignoring triglycerides

    • Aside from being a visual cue to look for discordance when TG elevated, residually elevated TGs are a prerequisite for a therapy that can reduce ASCVD events by an additional 25%

      • Icosapent ethyl (Vascepa - insert link to company website)

“Even lower is even better, for even longer”

Don't be a Repeat Offender

Our mission at Cardiawareness.com is to eradicate atherosclerotic cardiovascular disease in everyone. We wish to make published resources and expert recommendations more available, thereby facilitating a more informed personalized discussion. 

In our highest risk patients, such as  the heart attack survivor, we tend to align ourselves with the more aggressive lipid lowering recommendations, to include expert consensus opinion, rather than the more conservative recommendations of others, despite their popularity.

We agree with the following statement when it comes to our highest risk patients:

“LDL-C levels should be lowered as much as possible to prevent cardiovascular disease, especially in high and very high risk patients” - 2019 Joint ESC/EAS Dyslipidemia Guidelines

Put another way by Dr. John Kastelein at the ESC meeting in 2019: “LDL-C is a toxic agent that in principle needs eradication, but in practice needs early, long-term and aggressive lowering”

By way of comparison, the more conservative 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol calls for a more conservative LDL-C threshold of 70 mg/dL for the addition of non-statins to maximally tolerated statins. It also calls for multiple major ASCVD events to occur (becoming a Repeat Offender) or to have had a major ACVD event combined with multiple risk factors before the most aggressive action is taken.  In our view, simply having any major ASCVD event is plenty and requires the most aggressive and urgent action ASAP!

Ian Riddock
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