Role of statins in secondary prevention in

CABG

Complications after CABGLong-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.

Recommendations of current guidelinesAHA 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 indefinitelyHillis 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.

Evidence on Preoperative Statin Use

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

ConclusionsResults 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

MethodologyMeta analysis of 54 trials90000 cardiac surgery patientsEffects of preop statin therapy analyzedOutcomes were:

early all-cause mortality myocardial infarctionatrial fibrillation (AF)stroke and renal failure

Results

Conclusion

Pre operative statin use resulted in:31% odds reduction for early all-cause mortality

32% for new onset AF17% odds reduction for stroke

No statistical differences were found between groups with regard to myocardial infarction or renal failure.

Evidence on Post-operative Statin Use

MethodologySystematic 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 yearsOutcomes: incidence of

Repeat MICoronary revascularization

Forest Plot for repeat MI

Forest Plot for coronary revascularization

ConclusionsCompared with moderate statin therapy, long-term aggressive statin therapy:Lowered the LDL-C level significantlyFurther 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

Benefits of pre- & post-op CABG statin therapy

Pre-op statin therapy reduces risk of:Perioperative mortalityStroke AFLevels of systemic inflammatory markers

Post op aggressive statin therapy:Limits progression of SVG atherosclerosisReduces incidence of repeat MI & revascularization

Statin benefit attributed to pleiotropic effects

Improvement of endothelial functionIncreased level of eNOS leading to vasodilation

Antioxidant activityAnti inflammatory actionAnti platelet and anti thrombotic ctivity

Trials on High-dose statin and atheroma regression

Benefit in reducing plaque burden

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

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

*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 trialN = 349

Nissen SE et al. JAMA. 2006;295:1556-65.

ASTEROID: Treatment effect on primary efficacy parameters

IVUS Images

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

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)

Methods

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

Effect on Lipid Core Burden Index (LCBI)

Baseline

Follow-up

LC

BI

400

200

0

Standard Aggressive

P = 0.47 P = 0.0008

33%

Absolute LCBIReduction

Kini AS, et al. J Am Coll Cardiol 2013 Jul;62:21–9)

Conclusion

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.

SummaryAvailable 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.

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

ResultsA 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

Key PointsHigh 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

Thank you