Updated Peri-operative Guidelines AND POISE Trial

Updated Peri-operative Guidelines

AND

POISE Trial

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

Risk Assessment

A. Stepwise Approach: - Urgency of Surgery - Clinical Assessment - Functional Capacity - Surgical RiskB. Disease Specific Issues

Clinical Assessment 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

Intermediate Predictors: -Now termed ‘Clinical Risk

Factors’ and based on the Revised Cardiac Risk Index (RCRI) Lee TH, Circ 1999; 100:1043-9

Clinical Assessment, continued

History of MI or abnormal Q waves on EKG

Cr >2.0 mg/dl or low GFR

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

Functional Capacity

-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

Arch Intern Med 1999, 159; 2185-92

Poor Exercise tolerance defined as:

-Inability to walk 4 blocks

-inability to climb two flights of stairs

Surgical Risk

Disease Specific Risks

A. 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

HTN - continuedFor stage III HTN (SBP >180, DBP

>110mmHg-989 chronically treated HTN patients with DBP 110-130mmhg

-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


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


C. Valvular Heart Disease -Aortic stenosis: severe stenosis

associated with high risk in non-cardiac surgery

- AVR should be considered prior to elective surgery

In patients who were not candidates for or refuse AVR

19 patients, 28 procedures2 patients (11%) with post-

operative CV complications, resulting in death


D. Pulmonary Hypertension -No major studies to define risk in

noncardiac surgery

Exercise Stress testing

Exercise Stress testing

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%.


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.


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

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 93-100%


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

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. -Kertai MD, Heart 2003

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

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.


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


Pre-operative revascularization Guidelines



Proposed algorithm for patients that require PCI prior to surgery

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.

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


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-randomizedDevereaux 2005, review of 22 studies -no clear benefit with BB -may be due to different pt populations, beta-blockers



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

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)

OR

h/o CVA 2/2 to atherosclerotic disease

OR

h/o CHF hospitalization w/i past 3 years

OR

undergoing major vascular surgery (excluding AVF or CEA)

OR

Multiple RFs (≥3 out of the following 7: CKD, CHF, TIA, DM, emergent/urgent surgery, high-risk surgery, >70 years old)

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

Methods: 2-4 hours prior to surgery, patients

receive metoprolol CR 100mgWithin 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

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

At time of AHA presentation 8351 patients randomized

Baseline characteristics and types of surgery of first 6345 patients:

Primary outcome and major secondary

outcomes

Outcome

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

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 <0.0001

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

Documents

Updated Peri-operative Guidelines AND POISE Trial