REVIEW OF LIPID GUIDELINES

2011 to 2017

- Dr. Mohammed Sadiq Azam MD

DNB Resident Cardiology

KIMS

ESC GUIDELINES 2011

Patients are considered to be very high risk for documented CVD,

T2DM, T1DM with target organ damage, moderate to severe CKD, or

estimated 10-year absolute risk of fatal CVD ≥10%.

High-risk individuals are those with a 10-year risk of fatal CVD of 5%

to 9.9% or marked elevations in risk factors such as familial

dyslipidemia or severe hypertension.

Moderate risk is defined as a 10-year risk of fatal CVD of 1% to 4.9%,

and low risk is defined as an estimated 10-year risk of fatal CVD event

<1%.

ESC GUIDELINES 2011

Extrapolating from clinical trials, the task force recommended LDL-C

goals of:

<70 mg/dL (1.8 mmol/L) for very high risk,

<100 mg/dL (2.5 mmol/L) for high risk,

<115 mg/dL (3.0 mmol/L) for moderate risk, and,

<190 mg/dL (4.9 mmol/L) for low risk.

ACC/AHA GUIDELINES 2013

ACC/AHA GUIDELINES 2013

Instead of setting specific LDL-C targets, the 2013 ACC/AHA

guideline essentially suggested a fixed dose (or intensity) of

statin for each risk category, with intended LDL-C reductions of

30% to 49% and ≥50% for moderate- and high intensity statins,

respectively.

The authors also suggested that nonstatin medications could be

considered for those at high risk (secondary prevention,

diabetes mellitus, LDL-C ≥190 mg/dL) if they are intolerant of

the recommended dose of statin or have an inadequate

response to statins.

ACC/AHA GUIDELINES 2013

ACC/AHA GUIDELINES 2013

RISK FACTORS

RISK CALCULATORS

The most commonly used risk algorithms developed with United States population

cohorts include the following:

Framingham Risk Score (FRS; multiple adaptations)

Reynolds Risk Score (RRS)

ACC/AHA-ASCVD

Commonly used risk algorithms developed with European population cohorts include:

Systematic Coronary Risk Evaluation (SCORE)

QRisk2

ASCVD RISK CALCULATOR

The American College of Cardiology (ACC)/American

Heart Association(AHA) Arteriosclerotic Cardiovascular

Disease (ASCVD) Risk Estimator, released in 2013, was

designed to assess the risk of an initial cardiovascular

event and includes participants from racially and

geographically diverse cohorts such as the Framingham

Heart Study (FHS), the Atherosclerosis Risk in

Communities (ARIC) study, the Coronary Artery Risk

Development in Young Adults (CARDIA), and the

Cardiovascular Health Study (CHS).

ASCVD RISK CALCULATOR

SCORE

The Systematic COronary Risk Evaluation (SCORE) utilized pooled

data of over 250,000 individuals from 12 European studies in its

development.

First published in 2003, the algorithm calculated the 10-year CVD death

risk with separate scores for CHD and stroke fatality.

In subsequent revisions, the total CVD risk was also calculated.

In the 2012 revision, published in the CVD guidelines released by the

Fifth Joint Task Force of the European Society of Cardiology, a

cardiovascular risk age calculation was added

SCORE

SHORTFALLS OF RISK SCORES

A 2015 study utilizing data from the Multi-Ethnic Study of Atherosclerosis

(MESA), measured calibration for five risk scores and found the following

overestimates for the risk of cardiovascular events:

FRS-CHD: 53% in men, 48% in women

FRS-CVD: 37% in men, 8% in women

FRS-ATP-III: 154% in men, 46% in women

ACC/AHA-ASCVD: 86% in men, 67% in women

In this study, the RRS was the best calibrated model, with investigators

reporting the lowest discordance between actual and predicted events (-3%).

RISK SCORES IN INDIANS

Bansal M et al. IHJ

2014

ESC GUIDELINES 2016

ESC GUIDELINES 2016

ESC GUIDELINES 2016

LEIBOWITZ et al JAMA 2016

A population-based study of more than 31,000 statin-taking adults in

Israel who had stable ischemic heart disease showed no significant

differences in MACE (incl all cause mortality) between those with LDL-C

levels that were between 70 and 100 mg/dL after 1 year of treatment and

those with LDL-C <70 mg/dL.

However, there was a significantly lower risk for MACE in those with LDL-C

of 70 to 100 mg/dL vs those with LDL-C levels of 100 to 130 mg/dL

(P<0.001).

LEIBOWITZ et al - LIMITATIONS

Observational, population based meta-analysis

Did not define baseline levels of LDLc/did not comment on statin intensity

We know where they ended-up but not where they began!

Those who got to an LDL-C < 70 mg/dL, were much more likely to have

diabetes than the groups that got to higher LDL-C levels. At baseline

they're already at higher risk for CVD.

At the other end of the spectrum, the people who got to an LDL-C between

100 and 130 mg/dL had far more comorbidities. They‘re more likely to die

of something else than to have a CV event and get benefit from a statin.

BANGALORE et al – Am J MeD 2016

13,937 patients included in this study

Percent LDL-C reduction added incremental prognostic value over both statin

dose and attained LDL-C levels (p <0.0001).

However, attained LDL-C level did not provide incremental prognostic value

over statin dose and percent LDL-C reduction.

Among patients with attained LDL-C ≤70 mg/dL, those with percent LDL-C

reduction of <50% had a significantly higher risk of primary outcome

(hazard ratio [HR], 1.51; 95% CI, 1.16-1.97; p = 0.002) and stroke (HR, 2.07;

95% CI, 1.46-2.93; P <.0001) and a numerically higher risk of death (HR,

1.37; 95% CI, 0.98-1.90; P = 0.06) when compared with the group with

percent LDL-C reduction of ≥50%.

BANGALORE et al vs LEIBOWITZ et al

Randomised, strong study design

We not only know where they ended-up but also know where they began

Also considered the intensity of statin therapy used

The strong suggestion from thE data is that the percent lowering of LDL-C

and the dose of statin are the two most important pieces of the equation,

whether or not you get to an LDL-C of < 70 mg/dL.

Their other observation is that the actual achieved LDL-C levels don't really

tell you much about residual risk.

AACE 2017: EXTREME RISK

Extreme-risk goals: LDL < 55 mg/dL, non-HDL < 80 mg/dL, apolipoprotein B

(apoB) < 70 mg/dL

Progressive ASCVD, including unstable angina, in patients after achieving

an LDL-C <70 mg/dL.

Established clinical cardiovascular disease in patients with DM, CKD

stages 3/4, or heterozygous familial hypercholesterolemia (HeFH).

History of premature ASCVD (< 55 years of age in men, < 65 in women).

AACE 2017: VERY HIGH RISK

Very high-risk goals: LDL < 70 mg/dL, non-HDL < 80 mg/dL, apoB

< 80 mg/dL

Established or recent hospitalization for acute coronary

syndrome, coronary, carotid, or peripheral vascular disease, 10-

year risk > 20%.

Diabetes or CKD stages 3/4 with one or more risk factors.

HeFH.

AACE 2017: HIGH & MOD RISK

High-risk goals: LDL < 100 mg/dL, non-HDL < 130 mg/dL, apoB

< 90 mg/dL

Two or more risk factors and 10-year risk 10% to 20%.

Diabetes or CKD stages 3/4 with no other risk factors.

Moderate risk: Same goals as high risk

Two or more risk factors and 10-year risk < 10%.

AACE 2017: LOW RISK

Low-risk goals: LDL < 130 mg/dL, non-HDL < 160 mg/dL,

apoB not relevant)

0 risk factors.

BEYOND STATINS ...

IMPROVE-IT: In patients after an ACS, addition of

Ezetimibe to statin reduced MACE including CV mortality

FOURIER & ODESSEY: Adding a PCSK9 inhibitor

(Evolocumab/Alirocumab) to max tol statin lead to > 50%

reduction in LDLc with no demonstrated reduction in CV

death (final results due in 2017/2018)

OUR RECOMMENDATION (as of now)