Follow The Leader: The cost of listening to only 1 guideline
Case Presentation:
Setting:
American College of Cardiology(ACC) 62nd Annual Scientific Session, San Francisco, CA March 9-11, 2013
A packed crowd, spilling out into the foyer of the lecture hall, awaited the much anticipated release of the new 2013 ACC/AHA Blood Cholesterol Guidelines. They weren’t quite ready and they were not released at that time, so a Q&A session with the Guideline writing committee members was held instead, offering a hint of what we might expect from these guidelines.
Based on what they had already heard, an audience participant asked one of the Guideline writers what they would do in the following situation:
A patient who had had an ASCVD event who was placed on a maximum high intensity statin, like Atorvastatin 80 mg daily, but achieved an on-treatment LDL-C of just over 100 mg/dL (previous guidelines called for LDL < 70 mg/dL). What next?
Guideline writer’s reply: “I think you’re done.”
This was a stark departure from prior and existing guidelines and in this particular scenario, offered a treatment strategy that was inferior to the current standard of care, leaving countless high risk patients at risk for undertreatment and exposing them unnecessarily to excess residual risk.
It seemed to promote the outdated “fire and forget” strategy (enjoyed by the lazy practitioner and described here: Strategies for prescribing statins - PMC), where all you needed to do was place your high risk patients on a “high intensity statin” and call it a day. “Poof”, done. Never check a lipid panel again. Obviously, that’s not exactly what was said, nor intended by the Guideline Committee, but that’s how it was received by many.
Flying Under the Radar:
“But my doctor is following the guidelines - is it possible that I am being undertreated?” Yes, it is. Providers are human and they often “follow the leader.” When it comes to cardiovascular guidelines, the leader is often the American College of Cardiology and the American Heart Association (ACC/AHA).
However guidelines are just that - guidelines. They don’t always apply to everyone (for instance, certain ethnic groups - see below). They don’t always apply to every situation. There are many of them out there and they’re not always created equal. And yes, as well respected as these organizations are, sometimes they get it wrong. That was the case with the 2013 ACC/AHA Blood Cholesterol Guidelines. They were well intentioned and they had their reasons, but it was a swing and a miss and set the lipid community back several years.
Fortunately, medicine is a team sport. Other stakeholders picked up the baton, ran with it and tried to make up for lost ground.
CardioAdvocate Checklist:
(For patients and providers)
Know your baseline risk
Highest Risk - we adhere to the most aggressive guidelines (ESC, NLA, AACE/ACE
Secondary prevention:> 20% ten year risk of ASCVD event. The Heart Attack Survivor
CAC > 300: Carries similar risk as “heart attack survivors”
Familial Hypercholesterolemia: Hiding in Plain Site - Familial Hypercholesterolemia
Elevated Lp(a) > 325 nmol/L Little Napoleon Complex - Lipoprotein (a)
High Lifetime risk
> 75th percentile rank on Coronary Artery Calcium Score: A Picture is Worth a Thousand Words - Coronary Artery Calcium Scores
Mayo Clinic Statin Choice Decision Aid: Statin Choice Decision AID - Site
Contains multiple Risk calculators to include:
ACC/AHA PCE
Reynolds (includes family history and hs CRP)
Framingham
European: HeartScore
Consider multiple guidelines
Choose the guideline(s) most applicable to the individual being treated
Consider Expert Opinion within the framework of a patient-centered discussion with your care team members.
If in doubt, seek expert advice from a cardiometabolic specialist or lipidologist
Recommended Resources
Expert Thought Leaders:
John Kastelein (@JohnKastelein) / X
Thomas Dayspring (@Drlipid) / X
Deep Dive
The 2013 ACC/AHA Blood Cholesterol Guidelines were created under the strictest interpretation of “Evidence Based Medicine,” allowing only for data obtained from Randomized Controlled Trials (RCT) and/or meta-analysis of Randomized Controlled Trials in crafting recommendations. This painted them into a corner and effectively created a situation where they undermined existing guidelines and were forced to abandon any sort of lipid goal or target. Instead, they vehemently declared that clinical trials to date had only shown that a particular dose of statin had achieved the positive outcomes, rather than a particular LDL-C goal attained, for instance.
What led to the ACC/AHA producing the 2013 Blood Cholesterol Guidelines is an interesting story. Since 1985 the National Cholesterol Education Program has been managed by the NHLBI, a division of the NIH and produced guidelines on cholesterol. The last guideline published was the Adult Treatment Panel III (NCEP ATPIII) in 2001 and updated in 2004 (ATP III Report on High Blood Cholesterol) to include an optional goal of LDL-C < 70 mg/dL for very high risk patients. Its 284 pages is a tour de force in how to write a guideline. It was chaired by Scott Grundy M.D., Ph.D., a legend in the field of atherosclerosis. The guideline reviewed and appropriately weighted the totality of available scientific evidence, providing useful and balanced recommendations. Within its text is an abundance of educational material to include the criteria for metabolic syndrome. It remains a great resource for anyone interested in understanding atherosclerosis.
The next iteration of guidelines were nearly complete, when in 2013 the NHLBI decided to no longer participate in the publication of various cardiometabolic guidelines to include cholesterol, high blood pressure, obesity and nutrition (Guidelines for the Management of High Blood Cholesterol - Endotext - NCBI Bookshelf), turning these duties over to various stakeholders such as the ACC/AHA for the cholesterol guidelines. The guidelines writers remained intact. In trying to adhere to the Institute of Medicine’s “guidelines for writing evidence-based guidelines,” which prioritized RCTs above all other sources of evidence, it decided to completely restrict the 2013 Blood Cholesterol Guidelines from anything but RCT data, rather than simply prioritizing it.
Ironically, the ACC/AHA’s risk calculator, the so-called Pooled Cohort Equation (ASCVD Risk Estimator +), which was derived from and promoted by the guidelines, had never been evaluated in any sort of RCT.
What About Other Ethnic Groups?
Many ethnic groups have published lipid guidelines or consensus statements more applicable to their risk, such as the Lipid Association of India (Proposed low-density lipoprotein cholesterol goals for secondary prevention and familial hypercholesterolemia in India with focus on PCSK9 inhibitor monoclonal antibodies: Expert consensus statement from Lipid Association of India - ScienceDirect) and the Asian Pacific Society (Asian Pacific Society of Cardiology Consensus Recommendations on Dyslipidaemia - PMC.
Other Populations:
The Veterans Affairs/DOD promotes their CPG (Clinical Practice Guideline), which may be found here: The Management of Dyslipidemia for Cardiovascular Risk Reduction (Lipids) (2020) - VA/DoD Clinical Practice Guidelines
Lipid Goals by Risk Categories of Various Guidelines and Statements:
Unfortunately, as is often the case in medicine when multiple stakeholders are involved, there is no standardization of nomenclature when it comes to defining and categorizing risk.
Thus we have attempted to break down some of the more popular guidelines and statements with their respective risk categories, definitions and related lipid goals and recommendations.
We start with the more intense recommendations but also conclude with expert opinion or “white paper” statements for your awareness.
There are many others guidelines and consensus documents and we will continually update them here:
AACE/ACE Risk Categories
Extreme Risk:
Risk Factors:
Progressive ASCVD including unstable angina
Established clinical ASCVD + diabetes or CKD ≥3 or HeFH
History of premature ASCVD (<55y Male, < 65y Female)
Treatment Goals:
LDL-C <55 mg/dL “and” ≥ 50% reduction from baseline
This is important: for example, if your LDL-C is 72 mg/dL at baseline, the goal would be < 36 mg/dL!
It is not 54 mg/dL! Far too many clinicians mistakenly practice this way - It is more of a threshold to treat with high intensity (> 50% reduction of LDL-C). That's a huge difference!
Non-HDL-C < 70 mg/dL
ApoB <70 mg/dL
TG < 150 mg/dL
Very High Risk:
Risk Factors:
Established clinical ASCVD or recent hospitalization for ACS, carotid or peripheral vascular disease, or 10 y risk > 20%
Diabetes w/ ≥1 risk factor
CKD ≥3 w/ albuminuria
HeFH
Treatment Goals:
LDL-C <70 mg/dL “and” ≥ 50% reduction from baseline
Non-HDL-C < 100 mg/dL
ApoB <80 mg/dL
TG < 150 mg/dL
High Risk:
Risk Factors:
≥2 risk factors & 10 y risk >10-20%
Diabetes or CKD ≥3 & no other risk factors
≥3 & no other risk factors
Treatment Goals:
LDL-C <70 mg/dL“and” ≥ 50% reduction from baseline
Non-HDL-C < 100 mg/dL
ApoB <80 mg/dL
TG < 150 mg/dL
Moderate Risk
Risk Factors:
<2 risk factors & 10 y risk <10%
Treatment Goals:
LDL-C <100 mg/dL
Non-HDL-C < 130 mg/dL
ApoB <90 mg/dL
TG < 150 mg/dL
Low risk
Risk Factors:
No risk factors
Treatment Goals:
LDL-C <1300 mg/dL
Non-HDL-C < 160 mg/dL
ApoB - not recommended
TG < 150 mg/dL
ESC/EAS Risk Categories
Very High Risk
Recurrent ASCVD events (more than 1)
Extensive atherosclerotic cardiovascular disease
Higher global cardiovascular risk scores.
Lipid Goals: (Primary Prevention or Secondary Prevention):
LDL-C < 55 mg/dL “and” ≥ 50% reduction from “baseline”
This is important: for example, if your LDL-C is 72 mg/dL at baseline, the goal would be < 36 mg/dL!
It is not 54 mg/dL! Far too many clinicians mistakenly practice this way - It is more of a threshold to treat with high intensity (> 50% reduction of LDL-C). That's a huge difference!
If not previously on a statin, this will likely require “high intensity LDL-lowering therapy”
Notice they say “LDL-lowering therapy,” not necessarily “statin” therapy
The benefits derived from “high intensity statin” are dependent on the achieved LDL-C levels in individual trial participants: Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events: A Meta-Analysis of Statin Trials | Journal of the American College of Cardiology
Notice they also say “LDL-lowering,” not necessarily “LDL-C”
This is a subtle distinction. LDL-C is a surrogate biomarker for LDL.
Apo B and LDL-P are other acceptable biomarkers.
If currently on LDL-lowering treatment: “an increased treatment intensity is required”
LDL-C < 40 mg/dL
Patients with ASCVD with another vascular event within 2 years (not necessarily the same type of event)
Non-HDL-C < 85 mg/dL
Apolipoprotein B (ApoB)
< 65 mg/dL
High Risk:
Markedly elevated single risk factor
LDL-C ≥ 190 mg/dL - severe hypercholesterolemia, including FH
BP ≥ 180/110 mmHg
Familial Hypercholesterolemia (FH) without any additional risk factors
Moderate CKD (Stage 3: eGFR 30-59 mL/min/1.73 m2)
DM without target damage
DM ≥ 10 years or with another risk factor
European HeartScore ≥ 5% and < 10% 10 year risk of fatal CVD
Lipid Goals:
LDL-C < 70 mg/dL “and” ≥ 50% reduction from “baseline”
This is important: for example, if your LDL-C is 72 mg/dL at baseline, the goal would be < 36 mg/dL!
It is not 69 mg/dL! Far too many clinicians mistakenly practice this way - It is more of a threshold to treat with high intensity (> 50% reduction of LDL-C). That's a huge difference!
Non-HDL-C < 100 mg/dL
Apo B < 80 mg/dL
Moderate Risk:
Young patients; (T1DM < 35 years, T2DM < 50 years) with DM < 10 years, without other risk factors
European HeartScore ≥ 1% and < 5% 10 year risk of fatal CVD
Lipid Goals:
LDL-C < 100 mg/dL
Low Risk:
European HeartScore < 1% 10 year risk of fatal CVD
Lipid Goals:
LDL-C < 116 mg/dL
All Patients:
Lipoprotein a, or “Lp(a)” (pronounced Lp “little a”)
Considered at least once in every adult person’s lifetime to identify those with very high inherited Lp(a) levels > 180 mg/dL (430 nmol/L) who have a lifetime risk of ASCVD equivalent to HeFH. Class IIa, Level C
Considered in those with family history of premature CVD. Class IIa, Level C
Considered for reclassification of risk in those borderline between moderate and high risk. Class IIa Level C
Triglycerides (no goal per se)
TG < 150 mg/dL indicates lower risk
TG > 150 mg/dL, look for other risk factors
Diabetes: A1C < 7%
2014 National Lipid Association Management of Dyslipidemia Guidelines
Very High Risk:
ASCVD
DM - Type 1 or 2 with ≥ 2 other major ASCVD risk factors or end organ damage (microalbuminuria ≥ 30 mg/g, CKD, retinopathy)
Lipid Goals:
LDL-C < 70 mg/dL and > 50% reduction from baseline
nonHDL < 100 mg/dL
ApoB < 80 mg/dL
High Risk:
LDL-C ≥ 190 mg/dL - severe hypercholesterolemia, including FH
CKD ≥ Stage 3B
DM with 0-1 other major ASCVD risk factors
Lipid Goals for High, Moderate and Low Risk: Primary Prevention
LDL-C < 100 mg/dL
nonHDL < 130 mg/dL
ApoB < 90 mg/dL
2018 AHA/ACC
The AHA/ACC Cholesterol guidelines are best summed up with the following slides regarding secondary prevention (ASCVD) and primary prevention:
Expert Opinion
Advanced atherosclerosis:
LDL-C range between 20-40 mg/dL
Expert Opinion White Papers based upon PCSK9i trials: FOURIER, ODYSSEY, GLAGOV:
A patient centered discussion may be had to discuss safety, efficacy and cost ratios
Other Guidelines:
Canadian Cardiovascular Society: 2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in Adults
So Which Guidelines Do I Follow?
In our opinion, that is up to the joint decision making of the patient and their care team.
There are numerous Cholesterol guidelines published by various organizations and medical societies around the globe. Some are more conservative than others. Some are more popular than others and get more attention. That doesn’t always mean they are the most applicable to each unique patient with their own unique characteristics and circumstances.
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 Cheating Death (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 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!
