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Study Summary

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The POISE trial investigated the potential benefit of perioperative β-blockade in reducing myocardial ischemia in 8,351 patients with, or at risk of, atherosclerotic disease who were undergoing non-cardiac surgery. The 30-day data, published in 2008, demonstrated a reduced risk of myocardial infarction, but an increased risk of stroke and mortality with extended-release metoprolol succinate compared to placebo. This current 1-year follow-up study further confirmed these outcomes: risk of myocardial infarction (HR 0.78, 95% CI 0.65-0.94, p = 0.008) as well as cardiac revascularization (HR 0.47, 95% CI 0.28-0.78, p = 0.004) were significantly decreased in the metoprolol succinate cohort; however, risk of stroke (HR 1.52, 95% CI 1.09-2.12, p = 0.014) and all-cause mortality (HR 1.16, 95% CI 1.01-1.34, p = 0.036) were increased. These data suggest that, at 1 year, for every 1,000 patients undergoing non-cardiac surgery, extended-release β-blockade would potentially prevent 12 patients from experiencing a myocardial infarction and 6 from undergoing cardiac revascularization, but might result in an additional 13 deaths and 6 strokes (see accompanying Hurst’s Central Illustration).

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Perioperative β-Blockade in Patients Undergoing Non-Cardiac Surgery

Commentary

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Study Strengths: The strength of the original POISE trial arose from its broad inclusion of over eight thousand patients at 191 sites in 23 countries. Its shorter-term conclusions released in 2008 tempered the enthusiasm for perioperative beta-blockade at the time. These longer-term data confirm the lower rate of non-fatal myocardial infarction in the metoprolol succinate group, revealing a potential cardiac benefit of the perioperative beta-blockade, though at the expense of stroke and mortality. Moreover, the higher rate of deaths in the control arm in the 30-day follow-up was hypothesized to be associated with nosocomial infections. These 1-year follow-up data are revealing in confirming that these findings were not merely a short-term phenomenon.

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Study Limitations: There were several study limitations. First, for the Canadian patients, who represent nearly half of the cohort, the follow-up data were obtained from administrative databases rather than active follow-up. Second, while the study intervention was carried out for 1 month, there is little biologic plausibility for perioperative beta-blockade to have long-term significance. The increase in mortality in the control group was largely attributed to sepsis or infection; these patients either were unable to mount a necessary hemodynamic response, or their compensatory tachycardia was masked and therefore unnoticed by clinicians. Therefore, long-term follow-up would be unlikely to be different after the first postoperative month. Third, the difference in the relative risk of each outcome is quite small. Some of the data in the original study were excluded due to inclusion inconsistency. Lastly, the dose of metoprolol succinate administered in this study may have been excessive (100 mg two to four hours before surgery and six hours after surgery) and not reflective of clinical practice.

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Next Steps/Clinical Perspective: This study further demonstrates the potential benefit of perioperative beta-blockade in preventing adverse coronary events in non-cardiac surgical patients. However, starting routine preoperative beta-blockade on surgical admission for risk reduction might be detrimental in certain clinical scenarios. It has been surmised that recent initiation of beta blockers may alter compensatory physiologic responses. The next step would likely be to investigate the role of initiating low-dose beta-blockade in higher-risk cardiac patients in anticipation of future surgeries, allowing the patients to reach a routine steady-state in advance. For now, the most prudent practices may be to continue beta-blockade perioperatively in those patients receiving it chronically but to not begin (or withdraw) this therapy in the days leading up to a surgery or procedure unless a specific indication.

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