Transcript بسم الله الرحمن الرحيم

‫بسم هللا الرحمن الرحيم‬
Should all patients receive statins
before major noncardiac and cardiac
surgeries?!!
By
Amr Abdelmonem,MD
Assistant professor of anesthesia ,
faculty of medicine ,Cairo university
Thus we should beware of clinging to vulgar opinions ,
and judge things by reason‘s way ,not by popular say.
MONTAIGNE(1533-1592)
The world of statins
The lipidemic effects of
statins
What is cholesterol ?
Pearly –colored ,waxy ,
solid alcohol
that is soapy to touch
Where does cholesterol come from?
80 % comes from the body itself , every cell in the
body is capable of making its own cholesterol ,
most don’t and rely instead on that made in the
liver and skin.
Cholesterol and triglycerides are insoluble in blood
Lipoproteins are envelops that enclose cholesterol
and triglycerides Making them soluble in blood,so
that they can be transported to tissues
The cholesterol factory
Stryer L:Biochemistry.New york,W.H.Freeman Co.,1988
The rate limiting step
3- hydroxy-3 methyl-glutaryl-coenzyme A reductase
HMG-CoA Reductase
The LDL cholesterol from the blood
Fall in LDL cholesterol
Ashen DM ,blumenthal SR.low HDL levels .N Engl Med.2005;353:1252
Ginsberg NH,Zhanng LYet al .metabolic syndrome:focus on dyslipidemia .Obes Res ;2006:14s
Are the beneficial effects of
statins limited to patients of
hypercholesterolemia ?
No
Albert MA, Danielson E, Rifai N, et al: Effect of statin therapy
on C-reactive protein levels: The pravastatin inflammation/CRP evaluation
(PRINCE): A randomized trial and cohort study. JAMA 286:
64-70, 2001
Cipollone F, Fazia M, Iezzi A, et al: Suppression of the functionally
coupled cyclooxygenase-2/prostaglandin E synthase as a basis
of simvastatin-dependent plaque stabilization in humans. Circulation
107:1479-1485, 2003
Harris MB, Blackstone MA, Sood SG, et al. Acute activation and
phosphorylation of endothelial nitric oxide synthase by
HMG-CoA reductase inhibitors. Am J Physiol Heart Circ Physiol
2004; 287: H560–6
Pleiotropic effects of statins
Modulate the immune properties of cells by regulation
of endothelial , platlet , and leukocyte function
Kinlay S, Schwartz GG, Olsson AG, et al: High-dose atorvastatin
enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study. Circulation 2003; 108:15601566,
Shishehbor MH, Brennan ML, Aviles RJ, et al: Statins promote
potent systemic antioxidant effects through specific inflammatory pathways.Circulatio 2003; 108:426-431,
Attenuate the release of acute phase proteins thus reducing the
inflammation
Hack CE, Zeerleder S: The endothelium in sepsis: Source of and
a target for inflammation. Crit Care Med 2001; 29:S21-S27,
Inhibit monocyte activation by certain endotoxins and
reducing cytokine release and adhesion molecule expression
Weber C, Erl W, Weber KS, et al: HMG-CoA reductase inhibitors decrease CD11b expression and CD11b-dependent adhesion of
monocytes to endothelium and reduce increased adhesiveness of monocytes
isolated from patients with hypercholesterolemia. J Am Coll Cardiol 1997; 30:1212-1217,
Pleiotropic effects of statins (cont.)
Thmbosis is suppressed and fibrinolysis is enhanced by
reducing platlet aggregation and adhesion
and thromboxane formation
enhancing tissue plasminogen activator synthesis and
reducing plasminogen activator inhibitor
Schwarts GC,Olsson AG. The case for intensive statin therapy after acute coronary
syndromes .Am J Cardiol.2005;96:45-53F
Modulate microvascular remodeling and attenuate
vasoconstriction by increased expression of endothelial nitric oxide
synthase (eNOS), in conjunction with down-regulation of
inducible nitric oxide synthase and inhibiting the release of
angiotensin II and endothelin
McGrown C and Brookes Z.Beneficial effects of statins on the microcirculation during sepsis .Br J
Aneaesth 2007 ;98:163-75
Unfortunately , statins don’t work their magic without
side effects or without expense
ACC/AHA/NHLBI clinical advisory on
monitoring the side effects and follow
up schedule for statins
Monitoring
parameter
Headache ,dyspepsia
Muscle soreness ,tenderness or
pain
ALT/AST
Follow up schedule
Evaluate symptoms initially ,68 weeks after starting
Evaluate muscle symptoms and
ck before starting , muscle
symptoms 6-12 weeks after
starting and obtain CK when
syptoms occure
Evaluate initially , 12 weeks
after starting and then
annually or more frequently
What is the Strength of evidence for
routine perioperative use of statins to
reduce cardiovascular risk
18 studies –two randomised trials ,15 cohort
studies and one case control studies – assessed
whether statins provide perioperative
cardiovascular protection .
Statins were not randomly allocated , results in
retrospective studies were larger than those in
prospective cohort studies , and dose ,duration
and safety of statin use was not reported
Conclusion
The evidence base for routine
adminstration of statins to reduce
perioperative cardiovascular risk for
patients without established
coronary artery disease is
inadequate
Kapoor S,Kanji H,McAlister F. Strength of evidence for perioperative use of
statins to reduce cardiovascular risk: systematic review of controlled
studies. BMJ 2006;333:1149
It is not recommended by evidence that patients
with RCRI less than 2 recieve routine statins to
reduce perioperative cardiac risk
Beattie W , Elliott R. Evidence – based perioperative risk reduction .
Canadian Journal of Anesthesia 2005 ;52:R5
What about the patients with coronary
artery disease independent for the proposed
operation
Major noncardiac surgery
In a case-control study of 2,816 patients undergoing major
noncardiac vascular surgery, patients who received statins
preoperatively had an approximately 4.5-fold reduction in the
risk of postoperative mortality compared with patients who did
not receive statins
Poldermans D, Bax JJ, Kertai MD, et al: Statins are associated with a reduced incidence of perioperative mortality
in patients undergoing major noncardiac vascular surgery. Circulation 2003;107:1848-1851,
Both Durazzo et al and Schouten et al observed a lower incidence
of postoperative nonfatal acute MI among statin users
(6% v 16% and 6.6% v 10.7%, respectively).
Schouten O, Kertai MD, Bax JJ, et al: Safety of perioperativestatin use in high-risk patients undergoing
major vascular surger Am J Cardiol 95:658-660, 2005
Recommendations
Kapoor S,Kanji H,McAlister F. Strength of evidence for perioperative use of statins to reduce cardiovascular risk:
systematic review of controlled studies. BMJ 2006;333:1149
Beattie W , Elliott R. Evidence – based perioperative risk reduction . Canadian Journal of Anesthesia 2005 ;52:R5
Wright RS, Murphy JG, Bybee KA, et al: Statin lipid-lowering therapy for acute myocardial infarction and unstable
angina: Efficacy and mechanism of benefit. Mayo Clin Proc 77:1085-1092
Waters D, Schwartz GG, Olsson AG . The Myocardial IschemiaReduct2002 ;ion with Acute Cholesterol Lowering
(MIRACL) trial: A newfrontier for statins? Curr Control Trials Cardiovasc Med2001; 2:111-114,
Statins shoud be started preoperatively in eligible patients who
would warrant statin therapy for medical reasons :
Patients with coronary artery disease
Patients with multiple cardiac risk factors
Patients with LDL >100 mg/dl
Questions about timing
The minimum length of preoperative statin adminstration
necessary to protect against acute perioperative outcomes has
yet to be determined
Hindler K, Collard C.influence of statins on perioperative outcomes.journal of cardiothoracic and vascular anesthesia
2006;20:251-258
Previous studies have shown that statin therapy improves
endothelial function and lowers serum inflammatory markers as
early as 6 to 16 weeks after beginning administration
Chan AW, Bhatt DL, Chew DP, et al: Early and sustained
survival benefit associated with statin therapy at the time of percutaneou
coronary intervention. Circulation 2002;105:691-696,
Kinlay S, Schwartz GG, Olsson AG, et al: High-dose atorvastati
enhances the decline in inflammatory markers in patients with acute
coronary syndromes in the MIRACL study. Circulation 2003;
108:1560-1566
If you started statins preoperatively
, you should continue it in the
perioperative period
Durazzo AE, Machado FS, Ikeoka DT, et al. Reduction in cardiovascular
events after vascular surgery with atorvastatin: a randomized
trial. J Vasc Surg 2004; 39:967–975
Poldermans D, Bax JJ, Kertai MD, et al. Statins are associated with
a reduced incidence of perioperative mortality in patients undergoing
major noncardiac vascular surgery. Circulation 2003;
107:1848–1851..
Statin therapy in patients undergoing CABG
Statins have been shown to prevent neointimal formation in
saphenous vein grafts by inhibiting cellular matrix
metalloproteinase activity and the proliferation and migration of
smooth muscle cells
Porter KE, Turner NA: Statins for the prevention of vein graft
stenosis: A role for inhibition of matrix metalloproteinase-9. Biochem
Soc Trans 2002; 30:120-126
Statins have been shown to protect arterial bypass grafts.
Treatment of radial and left internal thoracic artery specimens
With cerivastatin in vitro was recently found to preserve
endothelium- dependent vasodilatation
Nakamura K, Al-Ruzzeh S, Chester AH, et al: Effects of cerivastatin
on vascular function of human radial and left internal thoracic
arteries. Ann Thorac Surg 73:1860-1865, 2002
Statin pretreatment before CABG imparts a beneficial effect with
regard to reduced rates of acute morbidity and mortality
Clark L, Ikonomidis J , Crawford F,et al.preoperative statin treatment is associated with
reduced postoperative mortality and morbidity in patients undergoing cardiac surgery
:8 -year retrospective cohort study.J thorac cardiovasc SURG 2006;131:679-85
Dosages , types of statin and safety issues
80 mg of atorvastatin is the most common high intensity statin
used and has been associated with better outcomes in patients
compared with moderate doses with other statins and the
benefits of this high dose appear to outweigh any potential
risks
Lazar H.should all patients receive statins before cardiac surgery :are more data necessary ?. J thorac cardiovasc
surg 2006;131:520-2
Statins and valve surgery
Several recent studies have suggested that statins may also
reduce the progression of calcific aortic stenosis and bioprosthetic
valve degeneration
Rosenhek R, Rader F, Loho N, et al: Statins but not angiotensinconverting enzyme inhibitors delay progression of aortic stenosis.
Circulation 2004; 110:1291-1295,
Luo JD, Zhang WW, Zhang GP, et al: Effects of simvastatin onleft ventricular hypertrophy and function in rats with
aortic stenosis.Zhongguo Yao Li Xue Bao 20:345-348, 1999
Statin administration in humans has also been associated with a
reduction in the progression of aortic stenosis, including a
decrease in the aortic valve area in patients receiving statins
compared with nonstatin Users
Novaro GM, Tiong IY, Pearce GL, et al: Effect of hydroxymethylglutaryl coenzyme a reductase inhibitors on the
progression o calcific aortic stenosis. Circulation 2001; 104:2205-2209,
Shavelle DM, Takasu J, Budoff MJ, et al: HMG CoA reductase
inhibitor (statin) and aortic valve calcium. Lancet 2002; 359:1125-1126,
In an experimental animal model of aortic stenosis, statin
administration inhibited the development of left ventricular
hypertrophy and improved left ventricular function
Luo JD, Zhang WW, Zhang GP, et al: Effects of simvastatin onleft ventricular hypertrophy and function in rats with
aortic stenosis.Zhongguo Yao Li Xue Bao 1999 20:345-348,
Summary
Statins can be classified into lipophilic HMG-CoA reductase
inhibitors (atorvastatin, simvastatin, cervastatin, fluvastatin, and
lovastatin) and hydrophilic HMG-CoA reductase inhibitors
(pravastatin and rosuvastatin).
Statins or hydroxy methyl glutaryl-CoA (HMG-CoA) reductase
inhibitors are widely used clinically as cholesterol-lowering agents
because of their ability to block hepatic conversion of HMG-CoA
to L-mevalonate
under low and normal cholesterol conditions , statins exert
antiinflammatory actions independent of their lipid-lowering
effects
Although an accumulating body of evidence suggests that
preoperative statin therapy may reduce the risk of adverse
postoperative outcomes, many of the studies performed to date
have important limitations
First, administration of preoperative statin therapy was neither
prospective nor randomized in many studies
Second, the influence of the duration of preoperative statin
therapy on the risk of postoperative outcomes has not yet been
adequately addressed
Third, further study is needed to evaluate the effect of
discontinuing statins in the postoperative period because acute
discontinuation may increase postoperative risk in patients with
severe, unstable CAD . Heeschen C, Hamm CW, Laufs U, et al: Withdrawal of statins
increases event rates in patients with acute coronary syndromes. Circulation 2002; 105:1446-1452
ACC/AHA recommendations
Patients undergoing CABG should receive statins
to achieve LDL levels of less than 100 mg /dl
Or less than 70mg /dl for patients with hihgest
risk factors ( diabetes , hypertension, obesity ,
smoking ,metabolic syndrome and acute
coronary syndromes)
Statins should be continued thropughout the
perioperative period