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SESSION 2:2 3:3 pm Strategies to Reduce Cardiac Risk for Noncardiac Surgery SPEAKER Lee A. Fleisher, MD Presenter Disclosure Information The following relationships exist related to this presentation: Lee A. Fleisher, MD: No financial relationships to disclose. Off-Label/Investigational Discussion In accordance with pmicme policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations. Scenarios Scenarios PATHOLOGY: FATAL PERIOPERATIVE MI PLAQ RUPTURE NON-PMI N = 2 PMI N = 42 PLAQ HEMORRHAGE OTHER ACUTE THROMBUS DAWOOD MM: INT J CARDIOL 1996 7: 37-44

Preoperative, Intraoperative, and Postoperative Factors Associated with Perioperative Cardiac Complications in Patients Undergoing Major Noncardiac Surgery. Guidelines Devereaux PJ, Sessler DI. N Engl J Med 21;373:228-2269 Prominent Dutch Cardiovascular Researcher Fired for Scientific Misconduct Should we test? Recommended action Threshold Probability of key outcome Clinical judgement Clinical findings Reading of the literature Prior experience

Potential Interventions Coronary revascularization Medical optimization A Conceptual Framework for Appropriateness in Surgical Care: What a patient wants Anesthesiology. 21;123(6):14-144. 99 What should we worry about first? Myocardial infarction Death % Risk of reinfarction Days from MI 4 4 3 3 2 2 1 1 1-year Postop Mortality -3 31-6 61-9 91-18 Days from MI Livhits et al. Ann Surg 23:87;211 Revised Cardiac Risk Index Event rate (%) 12 1 8 6 4 2 Class I () Class II (1) Class Class III (2) IV (>2) Derivation Validation Lee et al. Circulation 1999;1:143

Self-reported exercise capacity 2 2 1 % 1 Perioperative complications Poor Good P<.1 Reilly et al. Arch Int Med 1999 % of Patients 1 12 9 6 3 Postoperative Cardiac Complications Within 3-Days Following Surgery Deaths Revascularization No Revascularization Myocardial Infarction Days (Median) 7 6 4 3 2 1 Total Days ICU Days McFalls et al. NEJM 24;31:279 Probability of Survival 1. Long-Term Survival.8 77%.6 Survival Assigned to Revascularization.4.2 Assigned to No Revascularization 1 2 3 4 6 Time From Randomization (Years) RR=.98 9% CI (.7. 1.37) P=.92 Outcomes from CARP McFalls et al. Am J Cardiol 28 Perioperative and long-term cardiac events 1 3 risk factors 1 Stepwise Approach to Perioperative Cardiac Assessment for CAD 1 1 +Goal directed medical therapy 1 or 2 risk factors Testing Fleisher, et al. JACC 214;64:e77 No risk factors No testing 1 2 3 1 2 3 Years since screening Years since screening Patients 1476 144 736 388 77 6 39 22 Poldermans, D. et al. J Am Coll Cardiol 26;48:964-969 Colors correspond to the Classes of Recommendations in Table 1. Continued on the next slide.

Stepwise Approach to Perioperative Cardiac Assessment for CAD (cont d) Stepwise Approach to Perioperative Cardiac Assessment for CAD (cont d) CPG = Clinical Practice Guidelines Colors correspond to the Classes of Recommendations in Table 1. Continued on the next slide. Colors correspond to the Classes of Recommendations in Table 1. Continued on the next slide. Leveraging the preoperative consult for patient decision making Ann Surg Oncol 214;2:1929 Prehabilitation versus Rehabilitation in Patients Undergoing Colorectal Resection for Cancer The Perioperative Journey NEOADJUVANT PREHAB REHAB REHAB FULL RECOVERY BASELINE SURGERY RECOVERY ADJUVANT HARM SURVIVAL THRESHOLD Gillis et al. Anesthesiology 214;121:937 M Grocott

Association of preoperative stress testing with one year survival in the subgroup analyses Wijeysundera, D. N et al. BMJ 21;34:b26 Ann Surg 213;27:73 Assessment of LV Function It is reasonable for patients with dyspnea of unknown origin to undergo preoperative evaluation of LV function. IIa C It is reasonable for patients with HF with worsening dyspnea or other change in clinical status to undergo preoperative evaluation of LV IIa C function. Reassessment of LV function in clinically stable patients with previously documented LV dysfunction may be considered if there has been no assessment within a year. IIb C Routine preoperative evaluation of LV function is not recommended. III: No Benefit B JAMA Int. Med 21;17:161 Proportion of patients with major adverse cardiac events (death, readmission for acute coronary syndrome, coronary revascularization) Wijeysundera D N et al. Circulation 212;126:13-1362

Discontinuation of clopidogrel The Incremental Risk of Noncardiac Surgery on Adverse Cardiac Events Following Coronary Stenting Metzler et al. EJA 21 Holcomb Et al. Journal of the American College of Cardiology, Volume 64, Issue 2, 214, 273-2739 Association of Coronary Stent Indication With Postoperative Outcomes Following Noncardiac Surgery Second-Generation Drug- Eluting Stent Implantation Followed by 6- Versus 12- Month Dual Antiplatelet Therapy : The SECURITY Randomized Clinical Trial JAMA Surg. December 3, 21 Colombo et al. Journal of the American College of Cardiology, 214 64:286-297 Twelve or 3 Months of Dual Antiplatelet Therapy after Drug-Eluting Stents Three vs Twelve Months of Dual Antiplatelet Therapy After Zotarolimus-Eluting Stents: The OPTIMIZE Randomized Trial Feres et al. JAMA. 213;31(23):21-222.

Perioperative Management: Timing of Elective Noncardiac Surgery in Patients Treated With PCI and DAPT COR LOE Recommendations I B NR Elective noncardiac surgery should be delayed 3 days after BMS implantation and optimally 6 months after DES implantation I C EO In patients treated with DAPT after coronary stent implantation who must undergo surgical procedures that mandate the discontinuation of P2Y 12 inhibitor therapy, it is recommended that aspirin be continued if possible and the P2Y 12 platelet receptor inhibitor be restarted as soon as possible after surgery IIa C EO When noncardiac surgery is required in patients currently taking a P2Y 12 inhibitor, a consensus decision among treating clinicians as to the relative risks of surgery and discontinuation or continuation of antiplatelet therapy can be useful IIb C EO Elective noncardiac surgery after DES implantation in patients for whom P2Y 12 inhibitor therapy will need to be discontinued may be considered after 3 months if the risk of further delay of surgery is greater than the expected risks of stent thrombosis. Elective noncardiac surgery should not be performed within 3 days after III: B NR BMS implantation or within 3 months after DES implantation in patients Harm in whom DAPT will need to be discontinued perioperatively Levine GN, et al. 216 ACC/AHA Guideline Focused Update on Duration of DAPT in Patients with CAD. JACC 216 Treatment Algorithm for the Timing of Elective Noncardiac Surgery in Patients With Coronary Stents Levine GN, et al. 216 ACC/AHA Guideline Focused Update on Duration of DAPT in Patients with CAD. JACC 216 POISE-11 Kaplan Meier Estimates of the Primary Composite Outcome of Death or Nonfatal Myocardial Infarction at 3 Days. Bisoprolol in high risk vascular patients 4% P <.1 3% 2% 1% Placebo Bisoprolol % 7 14 21 28 Days after surgery Poldermans et al. NEJM 1999;341:1789 Adjusted Odds Ratio for In-Hospital Death Associated with Perioperative Beta-Blocker Therapy POISE 6 p<. % 4 3 2 1 p<. p<. Metoprolol Placebo Nonfatal MI CV death Mortality Stroke Lindenauer, P. et al. N Engl J Med 2;33:349-361 Devereaux, et al. Lancet 28

Association of Perioperative β-blockade With Mortality Following Major Noncardiac Surgery Administrative databases of 48,13 patients aged 66 years who underwent major noncardiac surgery London, et al. JAMA. 213;39(16):174-1713. Wijeysundera et al. Can J Cardiol 214 Perioperative Beta-Blocker Therapy Beta blockers should be continued in patients undergoing surgery who have been on beta blockers chronically. I B SR It is reasonable for the management of beta blockers after surgery to be guided by clinical circumstances, independent of when the agent was started. IIa B SR In patients with intermediate or high risk myocardial ischemia noted in preoperative risk stratification tests, it may be reasonable to begin perioperative beta blockers. In patients with 3 or more RCRI risk factors (e.g., diabetes mellitus, HF, CAD, renal insufficiency, cerebrovascular accident), it may be reasonable to begin beta blockers before surgery. See the ERC systematic review report, Perioperative beta blockade in noncardiac surgery: a systematic review for the 214 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery for the complete evidence review on perioperative beta-blocker therapy (8), and see Online Data Supplement 19 for more information about beta blockers (http://jaccjacc.cardiosource.com/acc_documents/214_periop_gl_data_supplement_tables.pdf). The tables in Data Supplement 19 were reproduced directly from the ERC s systematic review for your convenience. These recommendations have been designated with a SR to emphasize the rigor of support from the ERC s systematic review. IIb IIb C SR B SR Perioperative Beta-Blocker Therapy (cont d) In patients with a compelling long term indication for beta blocker therapy but no other RCRI risk factors, initiating beta blockers in the perioperative setting as B IIb an approach to reduce perioperative risk is of uncertain benefit. In patients in whom beta blocker therapy is initiated, it may be reasonable to begin perioperative beta blockers long enough in advance to assess safety and tolerability, preferably more than 1 day before surgery. Beta blocker therapy should not be started on the day of surgery. See the ERC systematic review report, Perioperative beta blockade in noncardiac surgery: a systematic review for the 214 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery for the complete evidence review on perioperative beta-blocker therapy (8), and see Online Data Supplement 19 for more information about beta blockers (http://jaccjacc.cardiosource.com/acc_documents/214_periop_gl_data_supplement_tables.pdf). The tables in Data Supplement 19 were reproduced directly from the ERC s systematic review for your convenience. These recommendations have been designated with a SR to emphasize the rigor of support from the ERC s systematic review. IIb III: Harm B SR B SR

Relationship Of Hemoglobin to Major Adverse Cardiac Event Liberal versus restrictive blood transfusion strategy: 3-year survival and cause of death results from FOCUS Beta-blocker group g/l From: Acute Surgical Anemia Influences the Cardioprotective Effects of β-blockade: A Single-center, Propensity-matched Cohort Study Anesthesiology. 21;112(1):2-33. doi:1.197/aln.b13e3181cdd81 Jeffrey L Carson, et al. Lancet 21 POISE-II Clonidine Arm Kaplan Meier Estimates of the Primary Outcome Association between Withholding Angiotensin Receptor Blockers in the Early Postoperative Period and 3-day Mortality: A Cohort Study of the Veterans Affairs Healthcare System Lee et al. Anesthesiology. 21;123(2):288-36 Durazzo et al. J Vasc Surg 24;39:967 Le Manach, Y. et al. Anesth Analg 27;14:1326-1333

Perioperative Statin Therapy Statins should be continued in patients currently taking statins and scheduled for noncardiac surgery. I B Perioperative initiation of statin use is reasonable in patients undergoing vascular surgery. IIa B Perioperative initiation of statins may be considered in patients with clinical indications according to Goal Directed Medical Therapy who are undergoing elevated risk procedures. IIb C Association Between Postoperative Troponin Levels and 3-Day Mortality Among Patients Undergoing Noncardiac Surgery JAMA. 212;37(21):229-234. Surveillance and Management for Perioperative MI Surveillance and Management for Perioperative MI (cont d) Measurement of troponin levels is recommended in the setting of signs or symptoms suggestive of myocardial ischemia or MI. I A Obtaining an ECG is recommended in the setting of signs or symptoms suggestive of myocardial ischemia, MI, or arrhythmia. I B The usefulness of postoperative screening with troponin levels in patients at high risk for perioperative MI, but without signs or symptoms suggestive of myocardial ischemia or MI, is uncertain in the absence of established risks and benefits of a defined management strategy. IIb B The usefulness of postoperative screening with ECGs in patients at high risk for perioperative MI, but without signs or symptoms suggestive of myocardial ischemia, MI, or arrhythmia, is uncertain in the absence of established risks and benefits of a defined management strategy. IIb B Routine postoperative screening with troponin levels in unselected patients without signs or symptoms suggestive of myocardial ischemia or MI is not useful for guiding perioperative management. III: No Benefit B