Lipid-Modifying Therapy: A New Paradigm

Guideline Watch |
November 12, 2013

Lipid-Modifying Therapy: A New Paradigm

  1. Allan S. Brett, MD

An ACC/AHA guideline abandons treatment to specific LDL cholesterol targets.

  1. Allan S. Brett, MD

Sponsoring organization: American College of Cardiology/American Heart Association (ACC/AHA)

Target Population: Primary care providers, cardiologists

Background and Objective

To guide clinicians in treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults.

Key points

— Treating to LDL cholesterol targets is no longer recommended; rather, clinicians should determine whether a patient falls into one of four mutually exclusive high-risk groups and should initiate statin therapy as follows:

  • Patients with clinical atherosclerotic cardiovascular disease (ASCVD) should receive high-intensity (age, <75) or moderate-intensity (age, ≥75) statin therapy.

  • Patients with LDL cholesterol levels ≥190 mg/dL should receive high-intensity statin therapy.

  • Diabetic patients aged 40–75 with LDL cholesterol levels of 70–189 mg/dL and without clinical ASCVD should receive at least moderate-intensity statin therapy (and possibly high-intensity statin therapy when estimated 10-year ASCVD risk is ≥7.5%).

  • Patients without clinical ASCVD or diabetes but with LDL cholesterol levels of 70–189 mg/dL and estimated 10-year ASCVD risk ≥7.5% should receive moderate- or high-intensity statin therapy.

— High-intensity statin therapies are atorvastatin (40–80 mg) or rosuvastatin (Crestor; 20–40 mg). Moderate-intensity statin therapies include atorvastatin (10–20 mg), rosuvastatin (5–10 mg), simvastatin (20–40 mg), pravastatin (40–80 mg), and several others.

— With few exceptions, use of lipid-modifying drugs other than statins is discouraged.

— Ten-year ASCVD risk — which includes both coronary events and stroke — is determined using an online calculator that can be accessed through the AHA and ACC websites. For further discussion of the new risk-assessment tool, see NEJM JW Gen Med Nov 12 2013.

— Lifestyle modification is recommended for all patients, regardless of cholesterol-lowering drug therapy.

What's Changed

This guideline is designed explicitly to replace the widely used ATP3 guideline from the National Heart, Lung, and Blood Institutes, last updated in 2004. The obvious major change is that clinicians now are directed to initiate either moderate-intensity or high-intensity statin therapy for patients who fall into the four aforementioned categories, without titration to a specific LDL cholesterol target. Measuring lipids during follow-up of drug-treated patients is done to assess adherence to treatment and not to see whether a specific LDL cholesterol target has been achieved.


This guideline represents a paradigm shift for most clinicians and patients. The rationale for abandoning LDL cholesterol targets is that randomized trials showing benefits of statins generally have examined fixed-dose statin therapy, rather than titrated therapy, to achieve prespecified LDL cholesterol goals. Additionally, some drugs that “improve” the lipid profile (a surrogate endpoint) do not improve clinical outcomes, and statins are thought to exert benefit through pleiotropic effects apart from LDL cholesterol–lowering. The 7.5% risk threshold for primary prevention was selected based on analyses suggesting that benefit from treatment emerges at this threshold. The guideline writers do acknowledge that some patients do not tolerate statins (and might require treatment with lower doses) and that patient preferences for drug therapy should be discussed, particularly in primary prevention. However, the authors do not discuss drug costs: For some patients, the out-of-pocket cost of a high-intensity statin (including generic atorvastatin), compared with the cost for generic simvastatin or pravastatin, is a problem. An essay published last year, entitled “Three reasons to abandon low-density lipoprotein targets,” is a concise and readable analysis of the perspective embodied by this new guideline. (Circ Cardiovasc Qual Outcomes 2012; 5:2).

Editor Disclosures at Time of Publication

  • Disclosures for Allan S. Brett, MD at time of publication Nothing to disclose


Reader Comments (24)

John Foster, M.D. Physician, Family Medicine/General Practice

Astonishing how many guesses, assumptions, and arbitrary cut-offs went into these guidelines, which will immediately be miss-interpreted as laws.

For example, the guideline to not treat to an LDL target is not based ON research, but on LACK of research. Age range 40-75 was pretty much picked out of a hat. What about a 76 year old who is quite vigorous - stop statins? What about a 39 year old with multiple family members with ASCVD in 30's - not initiate statins?

Abel Debebe

I want to see this guidelines

Dr.Zahur Ahmed Physician, Cardiology, Ministry of health hospital Saudi Arabia

need to see guidelines

Luque Alejandro MD Physician, Cardiology, Celaya Gto Mexico

This new guidelines are a real disaster, the A.D.A. said thank you but no thanks simply this is nonsense


The one good thing about the new guidelines is that only the statins are recommended; it's about time the non-statin drugs such as ezetimibe have been discouraged; this should stop the drug companies from peddling these unproven therapies; they may lower cholesterol (and may increase small dense LDL particles which are most atherogenic) but they have not been shown in any decent RCTs to lower cardiovascular outcomes including mortality. One thing that the guidelines do not address is the significant number of patients who are intolerant or develop adverse drug reactions to statins (more than 10% in my practice and include myalgia, proximal myopathy, tendinitis often with tendon ruptures etc etc); none of the recommended therapies including Coenzyme-Q10, intermittent dosing or changing statins seem to be effective. We do need another class of drugs desperately (awaiting the PCSK9 inhibitors with interest).

Miguel Gambetta Physician, Cardiology

Reading the guidelines leaves me slightly confused: when I recommend a "high intensity " treatment, do I think of milligrams of statin or the relative "potency" of the drug, or the "intensity" of the therapeutic effect?
The targets gave me a more clear "target".

Miguel Gambetta MD

Carol Vassar, MD Physician, Internal Medicine, private practice

Huff and Michael above make good points. Why did Dr. Ridker sidestep, in a rather cheap way, when Dr. Brett asked about providing the patient the estimated benefit of treatment with a statin at the same time we present the calculated risk of ASCVD?
In addition, where is the evidence that these drugs are safe after decades of use? My 20 year experience in practice seems to show more than the minimal side effect profile admitted for statins. Between muscle ache and weakness and cognitive impairment I have had perhaps 10% stop their statins for ADR's, perhaps more. One patient was diagnosed and under treatment for Alzheimers for perhaps a year when I had to stop her statin when she developed severe itching unresponsive to other treatment. To my relief her itching resolved and to my disbelief, her dementia cleared. The only other substances discontinued at that time were oral B12, Calcuim, Magnesium and Vitamin D 1000 mg. Any cognitive impairment warrants a trial off statins.


I was surprised that no mention of Homocysteine levels were included in the recommendations. Especially when certain easily tested gene mutations influence cardiovascular risk factors.

SHANKARAGOUDA HOSAGOUDRU Physician, Internal Medicine

Am afriad if these guidelines are to target 3rd world countries like India.. How can previous evidence based guidelines be ignored.. No more CRP !! How to treat raised TGs which is an imp component of metabolic syndrome.. To some extent it can respond to statin and TLC but other drugs cant be avoided.. South asians are prone for metabolic syndrome at lower BMI and they form bulk of pts in near future

BASHEER FARAH Physician, Internal Medicine

You have made ​​us confused.

Mohammad Rajab, MD Physician, Cardiology

What about patients with ASCVD but their LDL less than 50 mg/dl? Would you still use statin for them? Those are supposedly falling in category one!

GARY ROBINSON Physician, Internal Medicine, Brevard Health Alliance

A welcomed study and analysis supporting a practice many had previously begun i.e. high dose statins for high risk pts. and moderate dose statins for lower risk pts. regardless of lipid status and dietary changes.

levon gabriel Physician, Cardiology, retired Shiraz Iran

Patients in primary and secondary prevention wants to know about
the number,and it was easy to explain to them.
In primary prevention LDL <100,in case high TG NONHDL <125
in sec.prevention LDL <70 , NONHDL <100 . It is very simple to get adherence of the patient to the statin.

john c islip MD Physician, Family Medicine/General Practice, Salisbury,Wiltshire,UK

This is a landmark paper and will change my practice a lot.

Gerard Abate, MD Physician, Cardiology

The reality is that this paradigm shift will result in an increase in CVD events. Patients are aware and want to know their numbers and have a goal. The reality is that there is significant evidence, albeit not from outcomes trials, that lipid subfractions, particle #/size and other biomarkers can be managed via medical therapy. Having been a proponent of advanced lipid testing for many years and having had a large lipid clinic with first hand evidence of improving my patients' morbidy by agressively modifying lipid subfractions, I find it hard to believe that we will even throw out true goals in patient management. We also all know that if you use lifestyle modification and wait that events happen. People don't modify their risk without seeing evidence. Many a patient agreed to be on a statin or increase their dose when they saw the results of their advanced lipid profile.
Those of us in the lipid field know that the process for developing these guidelines are severely flawed. Time will show that much like Obamacare, that these guidelines will have a negative effect on our healthcare system.

Brian Stoker, MD Resident, Family Medicine/General Practice, Oregon

You were going along well until the "like Obamacare" part. The millions of patients who are now covered (including numerous ones in our community) think Obamacare is pretty Obamacool. Oh, and hey, they aren't the lazy freeloaders that they've been accused of being.

June Marie Spooner Other, Other

I agree with Dr. Brett's comment. Many people who do not have High cholesterol or high LDL get heart attacks. Oddly no one ever comes up with the theory that underlying chronic inflamation can lead to cardio events. In time the chronic inflamatory process and chemicals running thru artery walls damages the walls and also can cause plaque, scar tissue etc.
Certain types of diabetes is involved in inflamtion. Dr. Brett is correct. This whole thery actually I believe is to improve the pharmaceutical cos. profits. Many people have gotten severe problems and kidney damage from a certain cholesterol med esp. ZOCAR.

TOM SLOAN Physician, Internal Medicine, houston

the logic has been fairly terrible. trials comparing higher dose, stronger statins with weaker, lower doses produced foregone conclusions and secondary prevention trials DID examine "under 70 is better than under a hundred". to take from this THIS "guidance" is foolish---giving a guy with a 90 ldl high dose, strong therapy is NUTS when the rational is that a trial comparing such to a nothing dose of a weak statin in a thousand guys showed stronger is better.

SCOTT SELINGER Physician, Internal Medicine

From an outpatient standpoint, I think this is a great shift. We've been running so many lipid checks and rechecks that have been unnecessary and with the quality goals and initiatives, being forced to harass people with LDL's of 104 to intensify their lifestyle changes so that we can meet these "quality" goals.

STEVEN HUFF Physician, Family Medicine/General Practice

A long-awaited and welcome update; well researched and reasoned. I worry only that the threshold risk of 7.5% for prescribing a statin is very low. Assuming full adherence to the regimen at goal dosages, a statin decreases cardiac risk by perhaps 30%. The greater the cardiovascular risk the greater the benefit. Therefore, for patients without known vascular disease or equivalent disease, I will continue to quote their risk of MI both with and without a statin, and let them decide.

Carol Vassar, MD Physician, Internal Medicine, private practice

Good points. You might want to listen to the interview with Dr. Ridker. Dr. Brett asks about providing to the patient the potential benefit from treatment with statins along with the calculated risk. Dr. Ridker replies that that is what the doctor does, but gives no suggestion of how we might calculate the potential benefit for a particular patient. His response felt to me like a "cheap shot" to avoid answering.
Later when Dr. Brett gave Dr. Ridker the chance to talk about hsCRP and the JUPITER Trial, Dr. RIdker referred to the 50% reduction in heart attacks with statins in primary prevention without mentioning the absolute reduction which would provide us the information we need to help our patient make a decision. This approach of deliberately misleading the reader, as with relative vs. absolute reduction thereby exaggerating results, is starting to backfire as the public sees through it even if physicians had tolerated it.
We are in a rather appalling position when the editorial board of the NYTimes sees fit to warn the public against recommendations from the ACC and the AHA.

Moses Michael MBBS Physician, Family Medicine/General Practice, Trinidad & Tobago

Re: LDL levels
What about the experimental findings of reversal of plaque size in the carotid intima when LDL levels are reduced to < 70mg/ dl. vs the increase of plaque size when LDL levels are > 100mg/dl.
Are these findings which suggest actual plaque reversal when LDL is brought to low levels to be ignored?

Carol Vassar, MD Physician, Internal Medicine, private practce

good question.

Humberto Salas Physician, Family Medicine/General Practice

Who are those Patients with clinical atherosclerotic cardiovascular disease? Angina, AMI...ischemic stroke


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