Reducing Perioperative Cardiac Risk: Do Beta blockers Help?
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Review of the effect of beta blockers on perioperative cardiac events including updated recommendations by the ACC/AHA (August 2014. Watch my YouTube video (http://youtu.be/WPLXDm9Nzoc) describing these slides.
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Reducing Perioperative Cardiac Risk: Do Beta blockers Help?
- 1. Reducing Perioperative Cardiac Risk: Beta Blockers Terry Shaneyfelt, MD, MPH Assoc. Professor, UAB Department of Medicine
- 2. Devereaux PJ et al., CMAJ 2005; 173:627
- 3. Academic Impropriety Bouri et al. Heart published online first July 31, 2013
- 4. • Bouri et al • Wijeysundera et al for the updated ACC/AHA perioperative cardiac eval and mgmt guidelines (Circulation published online Aug 1, 2014) 2 recent systematic reviews on beta-blockers have similar findings
- 6. ACC/AHA review also found increased mortality
- 8. ACC/AHA review also found reduced non-fatal MI
- 10. ACC/AHA review also found increased strokes
- 11. Perioperative Strokes are Devastating!
- 12. Do Higher Risk Patients Benefit From β-Blockers?
- 13. What About Vascular Surgery Patients? London et al. JAMA 2013;309:1704
- 14. POISE Investigators. Lancet (published online May 13, 2008)
- 15. • Class I • BB should be continued in patients on them chronically • Class IIb • In pts with intermediate or high risk ischemia noted on preop testing reasonable to begin BB • In pts with RCRI ≥ 3 reasonable to begin BB • Begin more than 1 day prior to surgery • Class III (Harm) • BB should not be started on day of surgery ACC/AHA guidelines 2014
- 16. • If they are initiated: • Heart rate 60-70 bpm • SBP > 115-120 mm Hg • Start more than 1 day prior to surgery • ? Titration • ? Which one to choose Should Patients Be Prescribed β-Blockers Perioperatively?
Hinweis der Redaktion
- These PowerPoints are one of a series of PowerPoints on interventions that might reduce perioperative cardiac risk. These will focus on the research data on beta blockers (BB).
- This figure shows the pathophysiological cascade thought to explain perioperative myocardial infarction. On the middle right surgery is shown to induce a stress state with increased blood pressure and heart rate. BBs reduce BP and HR. BBs have been shown in CAD models to reduce recurrent MIs. Thus it makes sense that if BBs can reduce factors leading to myocardial ischemia they should be able to reduce perioperative MIs. Lets see if the data bears that out.
- The DECREASE studies have been discredited due to academic impropriety by the lead researcher. You can see what he did on the right hand side of the figure. Thus we have lost a large body of evidence on BB effects perioperatively.
- 2 systematic reviews have been published recently reviewing RCTs of perioperative beta-blockers. They both show essentially the same results. I review them both here for completeness sake.
- Bouri and colleagues did a metaanalysis on “secure” trials of BBs in the perioperative period. Secure means not DECREASE and only those studies felt to be scientifically valid. What you can see in the top figure is that BBs significantly increased the risk of mortality in patients undergoing noncardiac surgery (dark black diamond). The bottom figure shows a metaanalysis of the DECREASE studies which shows that fabricated data can show what you want- in this case a reduction in mortality.
- The Wijeysundera systematic review found a similar result that perioperative beta blockers increased in-hospital or 30 day mortality. Similar to the previous slide, the DECREASE studies suggested a reduction in mortality.
- Nonfatal MI was significantly reduced by perioperative BBs (see black diamond at top of figure).
- The Wijeysundera systematic review found a similar result that perioperative beta blockers reduced non-fatal MI
- Stroke was significantly increased by perioperative BBs.
- The Wijeysundera systematic review found a similar result that perioperative beta blockers increased nonfatal strokes.
- This table (from the POISE trial) shows the outcomes of perioperative MIs and strokes. Unfortunately strokes are more common in metoprolol users and they were devastating- 26% of patients were totally incapacitated vs 0% on the placebo arm. While stroke rates are increased in patients receiving metoprolol they are relatively rare compared to MI (which is reduced by metoprolol).
- So if in general BBs don’t help the average person in these studies do they help those at highest risk? This is the Lindenauer data. He looked at the effect of in hospital use of BBs on in hospital death in patients based on their RCRI score (higher score means higher predicted cardiac risk). This was a large cohort study using a managed care database containing over 300,000 patients from 329 hospitals undergoing major noncardiac surgery. Patients at low risk (RCRI of 1 or less) there was greater risk of in hospital death with BBs. High risk patients (RCRI 3 or greater) had less risk of death with BBs. Thus BBs seem to help high risk patients. This study (like any observational study) is at risk of residual confounding because of the limitations in what could be controlled for. Specifically the investigators did not know the date of surgery so there was no real way of knowing the timing of BB usage related to surgery. They didn’t know the indications for BBs. They didn’t know if BBs were used preoperatively. They didn’t know if they were stopped preoperatively.
- London and colleagues also did a retrospective cohort study trying to evaluate the effect of BBs on mortality in vascular surgery patients. They used the VA surgical quality improvement program database to study 136,745 veterans undergoing vascular surgery from Oct 2005 thru Sept 2010. On the bottom of the figure you can see that, at all levels of the RCRI, BBs had no effect on mortality in patients undergoing vascular surgery. AT the top of the figure, like Lindenauer, they showed that patients at high risk (with high RCRI scores) gained benefit from BBs when looking at all surgeries (not just vascular surgery like the bottom of the figure). This too is an observational study and has limits in what confounders can be controlled for. So lets look at the results from an RCT (next slide).
- The POISE study is the largest (to date) study of BBs in the perioperative period. This figure shows subgroup analyses from this study. Focusing on the bottom half of the figure you can see that there was a suggestion that BBs reduced cardiac outcomes in vascular surgery but the test of interaction was not statistically significant. You can see the confidence interval lines all overlap for the different types of surgery. Thus vascular surgery patients didn’t gain any different benefit (or harm) than other surgical patients. At the top of the figure the POISE investigators found the reverse relationship between RCRI risk and outcomes of BBs. Specifically, BB seem to lead to worse cardiac complications of surgery in patients at high risk and less complications in patients at low risk. The test for interaction though was not significant.
- These are the recommendations from the updated ACC/AHA recommendations on perioperative cardiac risk evaluation and management. It is recommended that beta blockers be continued in patients on the chronically (Class I recommendation: benefit>>risk). It is reasonable to consider starting beta blockers in patients with intermediate or high risk ischemia found on preoperative testing (assuming the patient is not at high risk of stroke or in decompensated CHF). It is also reasonable to start beta blockers in patients with high RCRI scores as demonstrated by the Lindenauer and London data. If you begin beta blockers the ACC recommends starting them more than 1 day prior to surgery so the effectiveness and tolerability can be assessed.
- If you do start them start them as early as possible aiming for a pulse of 60-70 bpm. BBs should not be initiated unless the systolic blood pressure is at least 115-120 mm Hg. This should also be the floor blood pressure while patients are on BBs. There is limited data on how and when to titrate beta blockers. Many of the patients in studies were on the starting dose. Data doesn’t support one beta blocker over another. Data from POISE suggests initiating long-acting beta blockers on the day of surgery is harmful.