Statins for secondary prevention after CABG

1. Role of statins in
secondary prevention in
CABG

2. Complications after CABG
Long-term results after CABG are compromised by the
progression of atherosclerosis
Only 60% of vein grafts remain patent 10 years after
surgery, and 50% of those that are patent have clinically
important stenosis
This puts patients at high risk for subsequent ischemic
events after CABG, including death, myocardial
infarction, and stroke
Also, CP byapss & cardioplegic arrest during surgery are
associated with myocardial injury.

3. Recommendations of current guidelines
AHA ACCF 2011 guidelines recommend:
All patients undergoing CABG should receive statin
therapy, unless contraindicated and goal should be to
achieve LDL of less than 100 mg/dl
In patients undergoing CABG who are not on statin
therapy, initiate intensive statin therapy preoperatively
atleast 1 week before surgery
Postoperatively, statin use should be resumed when the
patient is able to take oral medications and should be
continued indefinitely
Hillis LD et al. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: a report of the American College
of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011 Dec 6;
124(23):e652-735.

4. Evidence on Preoperative Statin Use

5. Meta analysis of 19 studies
32000 cardiac surgery patients evaluated
for outcomes who were either on statins or
without statins
Study outcomes were early all-cause
mortality (30-day mortality), myocardial
infarction (MI), atrial fibrillation (AF),
stroke and renal failure

7. Conclusions
Results suggest that statin pretreatment
significantly reduces postoperative early
all-cause mortality, and incidence of AF
and stroke
Specifically, preoperative statin use was
followed by a 1.5% absolute and 40%
relative risk reduction in early all-cause
mortality

9. Methodology
Meta analysis of 54 trials
90000 cardiac surgery patients
Effects of preop statin therapy analyzed
Outcomes were:
early all-cause mortality
 myocardial infarction
atrial fibrillation (AF)
stroke and
renal failure

10. Results

11. Conclusion
Pre operative statin use resulted in:
31% odds reduction for early all-cause
mortality
32% for new onset AF
17% odds reduction for stroke
No statistical differences were found
between groups with regard to myocardial
infarction or renal failure.

12. Evidence on Post-operative Statin Use

13. Methodology
Systematic review of 10 RCTs in >6500 patients
Patients were given moderate-intensity or high-
intensity statin therapy post CABG
Follow up of 2 to 5 years
Outcomes: incidence of
Repeat MI
Coronary revascularization

14. Forest Plot
for repeat MI
Forest Plot for coronary
revascularization

15. Conclusions
Compared with moderate statin therapy, long-
term aggressive statin therapy:
Lowered the LDL-C level significantly
Further decreased atherosclerotic progression
of SVG
Reduced the risks of repeated myocardial
infarction and coronary revascularization after
CABG
Revealed similar patient compliance and
statin-related adverse effects

16. Benefits of pre- & post-op CABG statin
therapy
Pre-op statin therapy reduces risk of:
Perioperative mortality
Stroke
AF
Levels of systemic inflammatory markers
Post op aggressive statin therapy:
Limits progression of SVG atherosclerosis
Reduces incidence of repeat MI &
revascularization

17. Statin benefit attributed to
pleiotropic effects
Improvement of endothelial function
Increased level of eNOS leading to
vasodilation
Antioxidant activity
Anti inflammatory action
Anti platelet and anti thrombotic ctivity

18. Trials on
High-dose statin and atheroma regression
Benefit in reducing plaque burden

19. Plaque burden directly related to MACE
Plaque Burden (PB) is a significant predictor of
future MACE and mortality
Statins are known to not only induce plaque
stabilization but also plaque regression
These effects of statins help in reducing the long-
term cardiovascular morbidity and mortality.
• McPherson JA et al. JACC Cardiovasc Imaging. 2012 Mar;5(3 Suppl):S76-85
• http://www.merckmanuals.com/professional/cardiovascular_disorders/arteriosclerosis/atherosclerosis.html

20. ASTEROID:
A Study To evaluate the Effect of Rosuvastatin On
Intravascular ultrasound- Derived coronary
atheroma burden
ASTEROID:
A Study To evaluate the Effect of Rosuvastatin On
Intravascular ultrasound- Derived coronary
atheroma burden

21. *Patients with >50% luminal narrowing
were excluded
ASTEROID: Study design
Nissen SE et al. JAMA. 2006;295:1556-65.
Angiographic CAD (>20% luminal narrowing*)
Statin-naive
N = 507
Rosuvastatin 40 mg qd for 24 months
Primary efficacy parameters:
• Change in % atheroma volume of target vessel
• Change in total atheroma volume in most diseased 10-mm segment
Multicenter, open-label,
blinded end point
IVUS assessment at
baseline and study end
Completed trial
N = 349

22. Nissen SE et al. JAMA. 2006;295:1556-65.
ASTEROID: Treatment effect on
primary efficacy parameters

23. IVUS Images

24. ASTEROID- Conclusion
• Aggressive lipid-modulating strategies
in patients with CAD can reverse the
atherosclerotic disease process
Rosuvastatin is the only statin approved
for slowing the progression of
atherosclerosis

25. JACC March 27, 2012;Volume 59, Issue 13
YELLOW Trial
Objective:
• To evaluate short term impact of aggressive statin
therapy on changes in coronary plaque composition by
using Near Infra Red Spectroscopy (NIRS) technique
Primary Outcome:
• Change in Lipid content expressed as Lipid Core Burden
Index (LCBI)

26.  Prospective, single-center, single blinded randomized trial in
patients with multivessel, hemodynamically significant coronary
lesions who were eligible for PCI (N = 80)
 Randomization - Standard of Care (Standard) versus Intensive statin
therapy with Rosuvastatin 40mg daily (Aggressive).
 Plaque composition was assessed after 6 – 8 weeks during follow up
angiography

27. Effect on Lipid Core Burden Index (LCBI)
Baseline
Follow-up
LCBI
400
200
0
Standard Aggressive
P = 0.47 P = 0.0008
33%
Absolute LCBI
Reduction
Kini AS, et al. J Am Coll Cardiol 2013 Jul;62:21–9)

28. Aggressive lipid therapy results in significant reductions
in the lipid content of coronary atherosclerotic plaque in
a short time frame (6-8 weeks)
Modulates lipid composition of significant coronary
atherosclerotic plaque, properties that may contribute
to plaque stabilization and/or regression.

29. Summary
Available evidence supports that High dose
statin therapy should be prescribed not only pre
operatively but also post operatively
This approach helps to reduce mortality, atrial
fibrillation and stroke
The beneficial effects are attributed to LDL
lowering and also to the multiple pleiotropic
effects of statins.

30. Rosenson RS. J Am Coll Cardiol. 2015 Jan 27;65(3):270-7

31. Results
A retrospective cohort study using random sample of
Medicare beneficiaries (n=8762)
Only 27% of patients received high-intensity statin
prescription post discharge
More beneficiaries received highintensity statin
therapy when they presented with an acute MI
compared with hospitalization for CABG or PCI
High-intensity statin therapy was less frequently
filled in Medicare beneficiaries >75 versus <75 years
of age

32. Key Points
High intensity statin therapy, both pre- and post-
CABG/PCI has been shown to have benefits
Still, even in a country like the United States,
statins are underutilized
Clinicians should prescribe high-intensity statin
therapy for patients to get maximum benefit
Hence the acute need for prescribing appropriate
statin therapy both prior to and after CABG/PCI

33. Thank you