Review of Guidelines for management of dyslipidemia from ESC 2011 to AACE 2017. A short review of CAD risk scoring systems included.

1. REVIEW OF LIPID GUIDELINES
2011 to 2017
- Dr. Mohammed Sadiq Azam MD
DNB Resident Cardiology
KIMS

2. 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%.

3. 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.

4. ACC/AHA GUIDELINES 2013

5. 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.

6. ACC/AHA GUIDELINES 2013

7. ACC/AHA GUIDELINES 2013

9. RISK FACTORS

10. 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

11. 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).

12. ASCVD RISK CALCULATOR

13. 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

14. SCORE

15. 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%).

16. RISK SCORES IN INDIANS
Bansal M et al. IHJ

17. ESC GUIDELINES 2016

18. ESC GUIDELINES 2016

19. ESC GUIDELINES 2016

20. 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).

21. 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.

22. 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%.

23. 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.

24. 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).

25. 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.

26. 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%.

27. AACE 2017: LOW RISK
 Low-risk goals: LDL < 130 mg/dL, non-HDL < 160 mg/dL,
apoB not relevant)
 0 risk factors.

28. 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)

29. OUR RECOMMENDATION (as of now)