Lipid lowering after an Acute Coronary Syndrome -strategies for success

1. Lipid Lowering after an ACS -
Strategies for Success
DR AWADHESH SHARMA
LPS INSTITUTE OF
CARDIOLOGY

2. LDL-C levels are a major risk factor for ACS
• Despite advances in prevention, diagnosis and management, ACS remains one
of the major causes of morbidity and mortality worldwide.
• Low density lipoprotein cholesterol (LDL-C) levels are a major risk factor for the
development of ACS and for recurrent events after ACS.
•Lowering LDL-C after ACS leads to a significant reduction in recurrent events
and overall mortality.
•The data supporting early use of intensive statin therapy among patients with
acute coronary syndrome (ACS) represented an important change in clinical
practice.
Current Treatment Options in Cardiovascular Medicine (2013) 15:33–40

3. GOULD Registry : Improved understanding of LDL-C &
Dyslipidemia management
• Observational registry analysed LDL-C treatment patterns over time in 5006 patients with
ASCVD across 119 US centers.
• At 1 year follow-up
- 13.2% of patients had lipid-lowering therapies (LLT) intensification
- Overall only 31% had LDL-C < 70 mg/dL at 1 year
Am Heart J 2020;219:70- 77
More intensive efforts
are needed

4. 2019 ESC/EAS Dyslipidaemia Guidelines
Treatmentgoalsfor LDL-CacrossCVDrisk categories
Low
Moderate
High
Very-High
3.0mmol/L
116mg/dL)
Treatmentgoal
forLDL-C
2.6mmol/L
(100mg/dL)
1.8mmol/L
(70mg/dL)
1.4mmol/L
(55mg/dL)
& ≥50%
reduction
frombaseline
Low Moderate High very-High CVRisk
•SCORE<1%
•SCORE≥1% and<5%
•Youngpatients(T1DM<35years;T2DM<50years) withDM
duration<10yearswithoutotherriskfactors
•SCORE≥5% and<10%
•Markedlyelevatedsingleriskfactors,inparticular TC>8mmol/L(310
mg/dL)orLDL-C>4.9mmol/L(190mg/dL)orBP≥180/110mmHg
•Family Historywithoutothermajorriskfactors
•ModerateCKD(eGFR30–59mL/min)
•DMw/otargetorgandamage,withDM
duration≥10yearsorotheradditionalriskfactor
•ASCVD(clinical/imaging)
•SCORE≥10%
•Family HistorywithASCVDorwithanother major
riskfactor
•SevereCKD(eGFR<30mL/min)
•DM&targetorgandamage:≥3 majorriskfactors;
orearlyonsetof T1DMoflongduration(>20years)
EUROPEAN HEART JOURNAL (2019) 00, 178)

5. 2019 ESC/EAS Dyslipidaemia Guidelines
Recommendationsforlipid-loweringtherapyinvery-high-riskpatients withacutecoronary
syndromes
©ESC
Recommendations Classa Levelb
In all ACS patients without any contra-indication or definite history of
intolerance, it is recommended to initiate or continue high dose statinas
early as possible, regardless of initial LDL-Cvalues.
I A
Lipid levels should be re-evaluated 4–6 weeks after ACS to determine
whether a reduction of at least 50% from baseline and goal levels of LDL-
C <1.4 mmol/L (<55 mg/dL) have been achieved. Safety issues need to be
assessed at this time and statintreatment doses adapted accordingly.
IIa C
Ifthe LDL-C goal is not achieved after 4–6 weeks with the maximally
toleratedstatindose, combination with ezetimibe is recommended.
I B
EUROPEAN HEART JOURNAL (2019) 00, 178)

6. 2019 ESC/EAS Dyslipidaemia Guidelines
Recommendationsforlipid-loweringtherapyinvery-high-riskpatients undergoing
percutaneouscoronaryintervention
©ESC
Recommendations Classa Levelb
Routine pre-treatment or loading (on the background of chronic therapy)
with high-dose statin should be considered in patients undergoing PCI for
an ACS or elective PCI.
IIa B
EUROPEAN HEART JOURNAL (2019) 00, 178)

8. Expected clinical benefit oflow
-density lipoproteincholesterol
loweringtherapies
Intensity of lipid loweringtreatment
Treatment Average LDL-C reduction
≈30%
≈50%
≈65%
≈60%
≈75%
≈85%
Moderate intensity statin
High intensity statin
High intensity statin plus ezetimibe
PCSK9 inhibitor
PCSK9 inhibitor plus high intensity statin
PCSK9 inhibitor plus high intensity statin
plus ezetimibe
% reduction LDL-C Baseline LDL-C
Absolute reduction LDL-C
Relative risk reduction Baseline risk
Absolute risk reduction
LDL-C = low-density lipoprotein cholesterol;
PCSK9 = proprotein convertase subtilisin/kexin type9.
2019 ESC/EAS GUIDELINES FOR THE MANAGEMENT OF DYSLIPIDAEMIAS: LIPID MODIFICATION TO REDUCE
CARDIOVASCULAR RISK (EUROPEAN HEART JOURNAL 2019 -DOI: 10.1093/EURHEARTJ/EHZ455)

9. Recommendations for Statin Therapy Use in Patients With ASCVD
COR LOE Recommendations
I A
In patients who are 75 years of age or younger with clinical
ASCVD,* high-intensity statin therapy should be initiated or
continued with the aim of achieving a 50% or greater
reduction in LDL-C levels.
I A
In patients with clinical ASCVD in whom high-intensity statin
therapy is contraindicated or who experience statin-
associated side effects, moderate-intensity statin therapy
should be initiated or continued with the aim of achieving a
30% to 49% reduction in LDL-C levels.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA
Guideline on the Management of Blood Cholesterol
Secondary ASCVD Prevention

10. Secondary ASCVD Prevention
Recommendations for Statin Therapy Use in Patients With ASCVD
COR LOE Recommendations
IIa B-R
In patients older than 75 years of age with clinical ASCVD, it
is reasonable to initiate moderate- or high-intensity statin
therapy after evaluation of the potential for ASCVD risk
reduction, adverse effects, and drug–drug interactions, as
well as patient frailty and patient preferences.
IIa C-LD
In patients older than 75 years of age who are tolerating
high-intensity statin therapy, it is reasonable to continue
high-intensity statin therapy after evaluation of the potential
for ASCVD risk reduction, adverse effects, and drug-drug
interactions, as well as patient frailty and patient
preferences.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA
Guideline on the Management of Blood Cholesterol

11. Secondary ASCVD Prevention
Recommendations for Statin Therapy Use in Patients With ASCVD
COR LOE Recommendations
IIb B-R
In patients with clinical ASCVD who are receiving maximally
tolerated statin therapy and whose LDL-C level remains 70
mg/dL (≥1.8 mmol/L) or higher, it may be reasonable to add
ezetimibe.
IIb B-R
In patients with heart failure (HF) with reduced ejection
fraction attributable to ischemic heart disease who have a
reasonable life expectancy (3 to 5 years) and are not already
on a statin because of ASCVD, clinicians may consider
initiation of moderate-intensity statin therapy to reduce the
occurrence of ASCVD events.
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA
Guideline on the Management of Blood Cholesterol

13. 2018 AHA/ACC Blood cholesterol guidelines
Secondary ASCVD Prevention
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol

15. Expert Consensus on Intensive Statin Therapy for Patients with
Acute Coronary Syndrome
Cardiol Plus 2016;1:35-8.

16. • 14 trials with 3368 individuals were included in our meta-analysis.
• Objective: To identify and quantify the potential cardioprotective benefits of high-
dose rosuvastatin preloading in patients undergoing PCI.
Pan et al. Lipids in Health and Disease (2015) 14:97

17. High-dose Rosuvastatin preloading before PCI lead to a 58 % reduction in MACE
(odds ratio [OR] = 0.42, 95 % confidence intervals [CI]: 0.29-0.61, P < 0.00001)
Pan et al. Lipids in Health and Disease (2015) 14:97
ORs for MACE in patients with different coronary syndromes

18. High-dose Rosuvastatin preloading before PCI in ACS patients associated with 57%
reduction in PMI (peri-procedural myocardial injury)
Pan et al. Lipids in Health and Disease (2015) 14:97
ORs for PMI in patients with different coronary syndromes

19. Conclusion
High-dose Rosuvastatin preloading can significantly improve myocardial
perfusion and reduce both MACE and PMI(peri-procedural myocardial injury )in
patients undergoing PCI.
The cardioprotective benefits of Rosuvastatin preloading were significant in
not only stable angina and ACS patients but also statin naïve and previous
statin therapy patients.
Pan et al. Lipids in Health and Disease (2015) 14:97

20. ROsuvastatin LOading and Clinical Outcomes (ROLOCO) Trial
299 patients with stable ischemic heart disease (SIHD) and de novo lesions
appropriate for PCI were randomized to rosuvastatin-treatment (n=153) and to
no-treatment (n=146) groups.
A 40 mg loading dose of rosuvastatin was administrated 24 h before the PCI.
Four-year follow-up period was planned (long-term follow-up of previously
published study).
JACC Volume 62, Issue 18 Supplement 2, October 2013

21. Single high loading dose of rosuvastatin (40mg) was associated with a reduction in major
adverse cardiac and cerebrovascular events (MACCE) at 4 years, driven primarily by a
reduction in TVR(target vessel revascularization).
JACC Volume 62, Issue 18 Supplement 2, October 2013

22. Comparison of Lipid-Modifying Efficacy of Rosuvastatin Versus Atorvastatin in
Patients With Acute Coronary Syndrome (From the LUNAR Study)
The LUNAR study compared the efficacy of rosuvastatin with that of atorvastatin in
decreasing LDL cholesterol in patients with acute coronary syndrome.
Adult patients with coronary artery disease who were hospitalized for an acute
coronary syndrome within 48 hours of first symptoms were randomized (n = 825) to
an open-label, once-daily treatment with rosuvastatin 20 mg (RSV20), rosuvastatin
40 mg (RSV40), or atorvastatin 80 mg (ATV80) for 12 weeks.
Am J Cardiol 2012;109:1239 –1246

23. Mean percent change from baseline by weeks 2, 6, and 12 in LDL-c reduction
The efficacy of Rosuvastatin 40 in lowering LDL cholesterol was significantly greater
than that of Atorvastatin 80 (46.8% vs 42.7% decrease, p = 0.02).
Am J Cardiol 2012;109:1239 –1246

24. • Introduction High-sensitivity C-reactive protein (hs-CRP) has emerged to be a very useful
and reliable clinical marker of primary as well as secondary cardiovascular morbidity and
mortality.
• Open-label randomized trial, group A was given rosuvastatin 40 mg daily and group B was
given atorvastatin 20 mg daily along with standard post-ACS therapy.
• Lipid profile (mg/dL), hs-CRP (mg/L) and erythrocyte sedimentation rate (ESR) (mm/Hr)
were recorded.
Cureus 2019 Jun; 11(6): e4898.

25. % reduction in hs-CRP levels with Rosuvastatin vs Atorvastatin
-60%
-50%
-40%
-30%
-20%
-10%
0%
Rosuvastatin Atorvastatin
51%
35%
Rosuvastatin more effective than atorvastatin in reducing micro-inflammation in
ACS patients patients.
Cureus 2019 Jun; 11(6): e4898.
(p<0.0001)
• In Rosuvastatin group there was
a mean 51% decrease in hs-CRP
levels compared with 35%
reduction was seen with
atorvastatin group. (p<0.0001)
• Rosuvastatin showed lower ESR
levels than atorvastatin after four
weeks of therapy (19.59 ± 11.83
vs. 20.52 ± 12.13) (p<0.0001).

26. Patients with de novo coronary artery disease requiring intervention were randomized
to rosuvastatin 10mg or atorvastatin 20mg daily.
Optical coherence tomography and intravascular ultrasound were performed at
baseline, 6 months, and 12 months.
Am J Cardiol 2019;123:1565−1571

27. Interval increase in fibrous cap
thickness
(A) Baseline OCT imaging, minimum FCT is approximately 50 mm
(white arrow). (B) 12-month OCT imaging, minimum FCT has
increased to approximately 300mm (white arrow). This patient was
randomized to rosuvastatin.
• The majority of acute coronary
syndromes (ACS) are due to the
rupture of vulnerable atherosclerotic
plaques.
• Features of plaque vulnerability
include thin fibrous cap.
• Increase in Fibrous cap thickness (FCT)
indicates plaque stabilization
• FCT tripled by 12 months in the
Rosuvastatin group vs doubled by 12
months in the Atorvastatin group
Am J Cardiol 2019;123:1565−1571

28. Conclusion
The rosuvastatin group had significantly faster and greater increase in FCT
(Fibrous cap thickness) .
Rosuvastatin group showed more rapid and robust plaque stabilization, and
regression of plaque volume compared to the atorvastatin group.
Am J Cardiol 2019;123:1565−1571

29. Summary
 It is important that clinicians recognize ACS patients as being at very high risk, and
provide these patients with intensive lifestyle and pharmacologic therapy for all
modifiable risk factors.
Increasing evidence suggest that statin therapy reduces morbidity and mortality in
patients experiencing an acute coronary event, when initiated immediately after
patients' admission.
 Both 2019 SEC/EAS & 2018 AAC/AHA cholesterol guidelines recommend aggressive
LDL-C targets for patients at high risk & very high risk of future ASCVD events.
 Within this framework, either a strategy of “intensive statin treatment after ACS” or a
strategy of “aggressive LDL-C targets after ACS” would be appropriate based on
currently available data.

30. Thank You