1. Cardioprotective Agents in the Total Joint Arthroplasty Patient: Are We Doing Enough? Eric Schwenk MD*, Kishor Gandhi MD MPH*, Javad Parvizi MD^, Eugene Viscusi MD* *Department of Anesthesiology, Thomas Jefferson University Hospital ^Rothman Institute for Orthopedics, Thomas Jefferson University Hospital

2. Introduction For patients undergoing noncardiac surgery, cardiovascular complications represent one of the biggest risks in the perioperative period. For patients undergoing noncardiac surgery, cardiovascular complications represent one of the biggest risks in the perioperative period. The Revised Cardiac Risk Index (RCRI) is a simple way to assess cardiac risk for patients undergoing noncardiac surgery. 1 The Revised Cardiac Risk Index (RCRI) is a simple way to assess cardiac risk for patients undergoing noncardiac surgery. 1 RCRI Predictors of Cardiovascular Complications RCRI Predictors of Cardiovascular Complications High Risk Surgery1 point High Risk Surgery1 point Coronary Artery Disease1 point Coronary Artery Disease1 point Congestive Heart Failure1 point Congestive Heart Failure1 point Cerebrovascular Disease1 point Cerebrovascular Disease1 point DM on Insulin1 point DM on Insulin1 point Serum Cr > 2.0 mg/dl1 point Serum Cr > 2.0 mg/dl1 point The risk of major cardiac events during the perioperative period as predicted by RCRI: The risk of major cardiac events during the perioperative period as predicted by RCRI: No point = Low risk (0.4% complications) No point = Low risk (0.4% complications) 1 point = Low risk (0.9% complications) 1 point = Low risk (0.9% complications) 2 point = Intermediate risk (6.6% complications) 2 point = Intermediate risk (6.6% complications) More than 2 points = High risk (11.0% complications) More than 2 points = High risk (11.0% complications) 1. Lee TH et al. Circulation 1999;100:1043.

3. Introduction The use of cardioprotective agents for the prevention of CV complications in noncardiac surgery is controversial, particularly with beta blockers. The use of cardioprotective agents for the prevention of CV complications in noncardiac surgery is controversial, particularly with beta blockers. The 2006 ACC/AHA guidelines update on perioperative beta blocker use described major limitations in prior studies, including inadequate power, lack of titration to a target heart rate, omission of low- and intermediate-risk patients, and lack of evidence on which beta blocker to choose. 2 The 2006 ACC/AHA guidelines update on perioperative beta blocker use described major limitations in prior studies, including inadequate power, lack of titration to a target heart rate, omission of low- and intermediate-risk patients, and lack of evidence on which beta blocker to choose. 2 The POISE trial, a large, prospective, randomized controlled trial, addressed some of these concerns and found that beta blockers reduced the risk of postop MI but increased the risk of stroke and overall mortality. However, BBs were not titrated to a target heart rate and, in addition, a high dose of the BB was given. This could account for some of the strokes that were observed. 3 The POISE trial, a large, prospective, randomized controlled trial, addressed some of these concerns and found that beta blockers reduced the risk of postop MI but increased the risk of stroke and overall mortality. However, BBs were not titrated to a target heart rate and, in addition, a high dose of the BB was given. This could account for some of the strokes that were observed. 3

4. Introduction The risk of perioperative myocardial ischemia during noncardiac vascular surgery is reduced in patients whose heart rates are tightly controlled (HR < 65 bpm). 4 The risk of perioperative myocardial ischemia during noncardiac vascular surgery is reduced in patients whose heart rates are tightly controlled (HR < 65 bpm). 4 A 2008 meta-analysis suggested that beta blockers are cardioprotective if the patients’ maximal heart rate is <100 bpm. It also found that calcium channel blockers combined with beta blockers result in more effective control of heart rate. 5 A 2008 meta-analysis suggested that beta blockers are cardioprotective if the patients’ maximal heart rate is <100 bpm. It also found that calcium channel blockers combined with beta blockers result in more effective control of heart rate. 5 Short-term statin use has been shown to reduce cardiac events in patients undergoing vascular surgery. 6 They may also be cardioprotective in other noncardiac surgeries. 7 Short-term statin use has been shown to reduce cardiac events in patients undergoing vascular surgery. 6 They may also be cardioprotective in other noncardiac surgeries. 7 4 Poldermans D et al. J Am Coll Cardiol 2006;48(5):964-9. 5 Beattie WS et al. Anes Analg 2008;106(4):1039-48. 6 Durazzo AE et al. J Vasc Surg 2004;39(5):967-75. 7 Lindenauer PK et al. JAMA 2004; 291(17):2092-9.

5. Objectives To assess the percentage of total joint arthroplasty patients experiencing postop CV complications who took preoperative beta blockers, calcium channel blockers, and statins. To assess the percentage of total joint arthroplasty patients experiencing postop CV complications who took preoperative beta blockers, calcium channel blockers, and statins. To determine if beta blockers and calcium channel blockers are being titrated to a target heart rate. To determine if beta blockers and calcium channel blockers are being titrated to a target heart rate.

6. Methods  Retrospective cohort study of 3529 patients who underwent total joint arthroplasty (hip or knee replacement) at a large, urban teaching hospital.  Postoperative complications were recorded into a database by a team of researchers and linked to a database containing patients’ past medical history, medication history, preoperative medications, and preoperative vital signs.  Postoperative cardiovascular complications were defined as: angina, myocardial infarction, atrial fibrillation, tachycardia, supraventricular tachycardia, miscellaneous arrythmias, pulmonary edema, acute congestive heart failure, hypotension, and bradycardia.  Bivariate analysis was conducted on RCRI risk stratification. Analysis was based on Pearson’s Chi Square analysis with alpha = 0.05 and was conducted with use of SPSS software (version 11.0, Chicago, Illinois).

7. Results Cardiovascular Complications (n=188) Low Risk (n=129, 68.6%) Intermediate Risk (n=56, 29.8%) High Risk (n=3, 1.6%) Age>60 (n=131) 84 (64.1%)* 44 (33.6%)* 3 (2.3%) Angina/MI (n=49) 23 (46.9%)* 25 (51.0%)* 1 (2.0%) Tachycardia/Arrhythmias(n=65) 47 (72.3%) 17 (26.2%) 1 (1.5%) Pulmonary Edema/CHF (n=14) 8 (57.10%) 5 (35.7%) 1 (7.10%) Hypotension (n=47) 40 (85.1%)* 7 (14.9%)* 0 (0%) Bradycardia (n=13) 11 (84.6%) 2 (15.40%) 0 (0%) Table 1: Postoperative Cardiovascular Complications by Risk Stratification N (%) * p<0.05

8. Results Figure 1: Preoperative Cardioprotective Agents

9. Results Table 2: Tight Rate Control (<65 bpm) Rate Control Agent Percentage of Patients with Tight Rate Control None 32.0% (n=58) Long-term BB 33.3% (n=19) BB on day of surgery 32.1% (n=18) Long-term CCB 45.7% (n=16) CCB on day of surgery 37.5% (n=12) Long-term BB and CCB 40.0% (n=2) BB and CCB on day of surgery 33.3% (n=3)

10. Results Figure 2: Tight Rate Control by Complication

11. Discussion  The majority of patients who experienced cardiovascular complications were not taking beta blockers, calcium channel blockers, or statins before surgery. Most of these patients were low- or intermediate-risk, emphasizing the importance of including these patients in future studies.  Our results suggest that adequate rate control is not being achieved in the majority of patients taking beta blockers or calcium channel blockers before total joint arthroplasty. Combining the two agents might lead to better rate control, but a prospective trial is needed to confirm this.

12. Discussion  For patients in whom a beta blocker or calcium channel blocker is deemed appropriate, adequate rate control may need to be achieved by more aggressive titration in the perioperative period, combining the agents as appropriate to avoid bradycardia and hypotension.  The use of short-term statins in noncardiac surgery may be cardioprotective 8,9 and some of the patients who experienced cardiovascular complications may benefit from a statin. 8. Durazzo AE et al. J Vasc Surg 2004;39(5):967-75 9. Lindenauer PK et al. JAMA 2004; 291(17):2092-9.

13. Thank You Dr. Kishor Gandhi – Regional Anesthesia Fellow; St. Luke’s Hospital, New York, NY Dr. Kishor Gandhi – Regional Anesthesia Fellow; St. Luke’s Hospital, New York, NY Dr. Eugene Viscusi – Director, Acute Pain Management Service; Thomas Jefferson University Hospital, Philadelphia, PA Dr. Eugene Viscusi – Director, Acute Pain Management Service; Thomas Jefferson University Hospital, Philadelphia, PA Dr. Zvi Grunwald – Chair, Department of Anesthesiology; Thomas Jefferson University Hospital, Philadelphia, PA Dr. Zvi Grunwald – Chair, Department of Anesthesiology; Thomas Jefferson University Hospital, Philadelphia, PA