1. Updated Peri-operative Guidelines AND POISE Trial

2. “The overriding theme of this document is
that intervention is rarely necessary to simply lower the risk of surgery unless such intervention is indicated irrespective of the preoperative context.”

3. Risk Assessment Stepwise Approach: - Urgency of Surgery
- Clinical Assessment
- Functional Capacity
- Surgical Risk
B. Disease Specific Issues

4. Clinical Assessment Major Predictors: now ‘Active Cardiac Conditions’.
Prior guidelines divided patients into major, intermediate and minor predictors of increased cardiovascular risk
Major Predictors: now ‘Active Cardiac Conditions’.
Defined as: 1 documented MI 7 days or less before examination or between 7-30 days w/ evidence of important ischemic risk by clinical symptoms or non-invasive study

5. Clinical Assessment, continued
Intermediate Predictors:
-Now termed ‘Clinical Risk Factors’ and based on the Revised Cardiac Risk Index (RCRI) Lee TH, Circ 1999; 100:1043-9
History of MI or abnormal Q waves on EKG
Cr >2.0 mg/dl or low GFR

6. Clinical Assessment, continued
Minor Predictors
-were recognized as markers for CV disease but not proven to increase peri-operative risk independently i.e. advanced age (>70), abnl EKG (LVH, LBBB, ST-T abnormalities), rhythm other than sinus and uncontrolled systemic hypertension
-no longer incorporated into guidelines

7. Functional Capacity

8. -548 patients, >60 y.o. or known CV disease scheduled for major intra-abdominal surgery.
-The patients were assigned to one of three management strategies (ICU, high-dependency unit, or ward) based on the anaerobic threshold (AT) and ECG evidence of myocardial ischemia as determined by CPX testing

10. Poor Exercise tolerance defined as: -Inability to walk 4 blocks
-inability to climb two flights of stairs
Arch Intern Med 1999, 159;

12. Surgical Risk

13. Disease Specific Risks
HTN
Stage 1 and Stage 2 HTN (SBP < 180 and DBP <100) not associated with increased perioperative events
-Goldman L, NEJM 1977; 297
-Ashton CM, Ann Intern Med 1993; 118
-Lette J, Ann Surg 1992; 216
-Eagle KA, Ann Intern Med 1989; 110
-Raby KE, JAMA 1992; 268
-Detsky AS, Arch Intern Med 1986; 146

14. HTN - continued For stage III HTN (SBP >180, DBP >110mmHg
-989 chronically treated HTN patients with DBP mmhg
-no known CAD, AS, LVH, renal failure, arrythmias or CVAs
-control group hospitalized and BP controlled x 3 consecutive days
-intervention group given nifedipine 10mg intransally and then surgery until DBP >110mmHg (no pts required more than one dose)
Results: no cardiovascular or neurological complications in either group

15. Disease Specific Risks
B. Heart failure
Multiple studies have shown that signs and symptoms of heart failure are associated with poorer outcomes in non-cardiac surgery.
-Goldman L, NEJM 1977; 297
-Detsky AS, J Gen Intern Med 1986; 211
-Cooperman M, Surgery 1978; 84
-Lee TH, Circ 1999; 100:1043-9

16. Disease Specific Risks
C. Valvular Heart Disease
-Aortic stenosis: severe stenosis associated with high risk in non-cardiac surgery
AVR should be considered prior to elective surgery

17. In patients who were not candidates for or refuse AVR
19 patients, 28 procedures
2 patients (11%) with post-operative CV complications, resulting in death

18. Disease Specific Risks
D. Pulmonary Hypertension
-No major studies to define risk in noncardiac surgery

19. Exercise Stress testing

20. Exercise Stress testing

21. Radionuclide Myocardial Perfusion Imaging

22. Radionuclide Myocardial Perfusion Imaging
Numerous trials looking at reversible defects and peri-operative MI or cardiac death.
In these trials, ischemic myocardium detected in 23 to 69% of patients, but positive predictive value for peri-operative event ranged from 2 to 20%.
However, negative predictive value of a normal MPI and peri-operative event approximately 99%.

23. Radionuclide Myocardial Perfusion Imaging
Increasing risk with increasing myocardium at risk:
Etchells et al, meta-analysis of 9 studies, 1179 patients
-in patients with < 20% of at risk myocardium by MPI, had small, non-significant increase risk of MI
-in patients with >20% at risk myocardium significantly higher risk of peri-operative cardiac death or MI; increasing risk with increasing extent of reversible defects.

24. Radionuclide Myocardial Perfusion Imaging
Conclusions:
-high sensitivity for detection of peri-operative cardiac events
-cardiac risk directly proportional to amont of at risk myocardium
-low PPV suggests that stress MPI best used in patients with high clinical risk of peri-operative cardiac event

25. Dobutamine Stress Echocardiography

26. Dobutamine Stress Echocardiography
Range of positive DSE in trials was 5-50%, but positive predictive value for peri-operative MI or cardiac death ranged from 0-33%
Negative predictive value of %

27. Dobutamine Stress Echocardiography
Predictive value of DSE linked to number of clinical risk factors:
Das et al, 530 patients undergoing non-vascular surgery
-positive DSE assoc with 4% event rate peri-operatively if no clinical RFs and 22% if 2 or more RFs present

29. Pre-Operative Evaluation of LV function
Resting LV function has not been shown to be an independent predictor of peri-operative ischemic events.
-Halm EA, Ann Intern Med, 1996
-Rohde LE, Am J Card, 2001
-Kertai MD, Heart 2003
Resting LV Function <35% does predict post-operative heart failure.

30. Peri-operative Therapy
Pre-operative CABG
-Some cohort studies suggest lower mortality after high-risk surgery in post-CABG patients
-Eagle et al, Circ 1997 ; CASS database
-Patients w/ prior CABG had lower rate of cardiac death (1.7% vs 3.3, p=.03) after GI, Vascular or H&N surgery
-Hertzer et al, Ann Surg 1984

31. Peri-operative Therapy
Pre-Operative revascularization
-Randomized trials
CARP:
-510 patients, excluded LM disease, severe AS, severe LV dysfunction (<20%)
258 revascularized (41% CABG, 59% PCI)
225 medically managed
-Deaths at 30 days: 3.1% in revasculazed group, 3.4% in medically managed group (p=NS)
-Peri-operative cardiac enzyme elevation: 12% vs 14% (p=NS)
-at 2.7 years, mortality was 22%(revascularized) vs 23% (medical) p=NS.

32. Peri-operative Therapy
Pre-Operative revascularization, continued
-Randomized trials
DECREASE-V, pre-vascular surgery study
-101 high risk clinical patients (3+ RFs) w/ extensive ischemia on stress testing
-52 medically treated
-49 revascularization (65% PCI, 35% CABG)
-94% of the PCIs were with DES
-Vascular surgery: median 29 days after CABG, 31 days after PCI
-30 day mortality and MI: 43% (revascularized) vs 33% (medical), p=0.30
-1 year mortality and MI: 49% vs 44%, p=0.48

33. Pre-operative revascularization Guidelines

34. Pre-operative revascularization Guidelines

35. Pre-operative revascularization Guidelines

36. Proposed algorithm for patients that require PCI prior to surgery

37. Perioperative Beta Blockers
B-Blocker use is controversial
● Most trials are inadequately powered.
● Few randomized trials of medical therapy to prevent perioperative MACE have been performed.
● Few randomized trials have examined the role of perioperative beta-blocker therapy, and there is particularly a lack of trials that focus on high-risk patients.
● Studies to determine the role of beta blockers in intermediate- and low-risk populations are lacking.
● Studies to determine the optimal type of beta blockers are
lacking.
● No studies have addressed care-delivery mechanisms in the
perioperative setting, identifying how, when, and by whom
perioperative beta-blocker therapy should be implemented
and monitored.

39. Perioperative Beta Blockers
Poldermans et al
-173 pts with positive stress tests prior to vascular surgery,
-112 included in study (61 excluded: markedly abnl stress or already on BB)
-Randomized to Bisoprolol x 7 days to HR <60 pre-operatively and HR <80 peri-operatively
-Rate of cardiac death: 3.4% vs 17% (p=0.02) and non-fatal MI 0% to 17% (p=0.001)
-unblinded design, only high risk patients

40. Perioperative Beta Blockers
Multiple meta-analyses and reviews:
-Auerbach and Goldman, 2002, review of 5 studies
-supported BB use
-Stevens, 2003, review of 11 studies
-benefit only in high risk patients
-included unblinded studies
-McGory, 2005, review of 6 randomized trials
-marked benefit with BB (OR 0.25 for Cardiac death)
-did not include two negative studies
-Lindeauer 2005, review of 700,000 patients at 300+ hospitals
-benefit seen only in patients with RCRI ≥ 3
-no benefit in RCRI 1-2, and increased risk of early death after surgery in RCRI 0
-non-randomized
Devereaux 2005, review of 22 studies
-no clear benefit with BB
-may be due to different pt populations, beta-blockers

41. Perioperative Beta Blockers

43. Large RCT to look at effects of metoprolol on 30 day MACE in patients with CAD or at-risk for CAD undergoing non-cardiac surgery
Blinded, randomized in 1:1 ratio
182 centers in 21 countries, planned enrolment of 10,000 patients
One of the trial investigators (Yusuf) receives research grants from AstraZeneca who makes controlled-release metoprolol
Final Results not yet published; Interim analysis presented at AHA 2007 Late-breaking session

44. Inclusion Criteria: ≥ 45 years old AND
h/o CAD (angina, prior MI, +stress test, prior coronary stenosis >50%, Q waves on EKG OR
h/o PAD (claudication, abnl ABIs, +angio or doppler study)
h/o CVA 2/2 to atherosclerotic disease
h/o CHF hospitalization w/i past 3 years
undergoing major vascular surgery (excluding AVF or CEA)
Multiple RFs (≥3 out of the following 7: CKD, CHF, TIA, DM, emergent/urgent surgery, high-risk surgery, >70 years old)

45. Exclusion Criteria
-bradycardia (<50bpm)
-active asthma or COPD
-already on BB
-low-risk surgery
-already on verapamil

46. Methods:
2-4 hours prior to surgery, patients receive metoprolol CR 100mg
Within first 6 hours of surgery, if pts HR>80 and SBP >100, then receive additional dose of 100mg; those who do not receive this dose will receive 100mg at 6 hours post-surgery
Starting at 12 hours post-surgery, patients receive 200mg Qday x 30 days.
Dose held or delayed if HR<50 or SBP <100
Those who could not take PO, given IV metoprolol

47. Statistical Analysis:
-Planned intention-to-treat analysis
-Assumed control event rate of 6% based on published data
-Estimating 25-30% RRR based on population size

48. At time of AHA presentation 8351 patients randomized
Baseline characteristics and types of surgery of first 6345 patients:

49. Primary outcome and major secondary outcomes
Metoprolol (n=4174), n (%)
Placebo (n=4177), n (%)
Hazard ratio p
Primary composite
243 (5.8)
290 (6.9)
0.83
0.04
Nonfatal MI
151 (3.6)
215 (5.1)
0.70
0.0007
Total mortality
129 (3.1)
97 (2.3)
1.33
0.03
Stroke
41 (1.0)
19 (0.5)
2.17
0.005

50. Secondary outcomes Outcome Metoprolol (n=4174), n (%)
Placebo (n=4177), n (%)
Hazard ratio p
Revascularization
11 (0.3)
27 (0.6)
0.41
0.01
Atrial fibrillation
91 (2.2)
120 (2.9)
0.76
0.04
Significant hypotension
626 (15.0)
404 (9.7)
1.55
<0.0001
Significant bradycardia
274 (6.6)
101 (2.4)
2.71

51. Conclusions
-For every 1000 patients, metoprolol CR would prevent 15 MIs, but there would also be 8 deaths and 5 severe disabling strokes
Criticisms
-results do not apply to patients already on BB
-dose of BB too high, and goal SBP >100 too low