Starting Beta Blockers Before Noncardiac Surgery May Be Harmful

Beta blockers are widely used and effective in treating high blood pressure, heart disease and heart failure and also are clearly beneficial in preventing complications from cardiac (heart) surgery. However, there is growing evidence that their risks may outweigh any benefits when started before noncardiac surgery.

Beta blocker use in noncardiac surgery The days and weeks after a major surgical procedure expose patients to a substantial risk of certain complications, such as heart rhythm disorders, heart attacks and other cardiac events. The American College of Cardiology (ACC) and the American Heart Association (AHA) noted that approximately 2 percent of patients experience "major cardiac complications" after surgery, with around 8 percent having evidence of injury to the heart muscles.[1]

Beta blockers have been given to patients before, during or after surgery based on the theory that their effects on the heart may reduce such complications. They have been found to be beneficial in patients undergoing coronary artery bypass graft surgery;[2] the ACC and AHA recommend beta blockers’ use for this purpose.

Their use in noncardiac surgery became more widespread after two small clinical trials in the 1990s showed positive results with the drugs in this setting.[3] In response, in 2002, the ACC and AHA recommended that patients at high risk for heart complications be given beta blockers prior to noncardiac surgery.[4] Since then, however, it has been revealed that some of the earlier noncardiac surgery trials, known as the Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) studies, may have contained falsified data and were therefore no longer considered reliable sources of evidence.[5]

Recent evidence sheds new light

More recent studies cast serious doubt on the usefulness of beta blockers in noncardiac surgery. The most important was the large 2008 PeriOperative Ischemic Evaluation (POISE) study of more than 8,000 subjects with, or at risk for, heart disease who were not previously treated with beta blockers.[6] The study found that although subjects started on the beta blocker metoprolol extended-release (TOPROL XL) two to four hours prior to surgery had less risk of a post-operative heart attack, they had increased risk of low blood pressure, stroke and — most importantly — death.

Critics pointed out that the POISE study started subjects who had not previously taken beta blockers on a high dose of a long-acting drug just a few hours before surgery,[7],[8] implying that a short-acting beta blocker started at a lower dose may not carry the same risks.

A comprehensive 2014 review analyzed 89 clinical trials involving more than 19,000 subjects combined, to whom beta blockers were given before, during or after cardiac or noncardiac surgery.[9] In cardiac surgery, beta blockers reduced the occurrence of potentially dangerous heart rhythm disorders. For noncardiac surgery, while beta blockers reduced the risk of heart attacks and heart rhythm disorders, they increased the risk of low blood pressure and heart rate and likely increased the risk of stroke and death.

The authors concluded that, while beta blockers should be used in cardiac surgery, their risks may outweigh any benefits for patients undergoing noncardiac surgery, but that more evidence was needed to reach a definitive conclusion.[10] The authors recommended that, until such evidence was found, a patient’s individual cardiovascular risk should determine the choice to start beta blockers prior to noncardiac surgery.

In 2014, the ACC and AHA published their own review of the evidence of beta blockers in noncardiac surgery.[11] They found that beta blockers started one day or less before noncardiac surgery helped prevent nonfatal heart attacks but increased the risk of low blood pressure, stroke, slow heart rate and death.

Finally, a study published last December in the Journal of the American Medical Association (JAMA) Internal Medicine raised yet more questions about the safety of beta blockers before noncardiac surgery.[12] After analyzing more than 55,000 patients with high blood pressure but no cardiovascular disease who were undergoing noncardiac surgery, investigators found that patients treated with beta blockers had an increased risk of death, as well as risk of nonfatal stroke, nonfatal heart attack or cardiovascular death, relative to patients treated with other antihypertensive drugs. The risks were especially high for patients 70 and older, men, and those undergoing emergency surgery.

Current recommendations

In their 2014 guidelines on noncardiac surgery, the ACC and AHA made different recommendations for beta blockers based on whether patients were already on the drugs for a chronic condition.[13] The guidelines recommended that patients already taking beta blockers continue on the medications. For patients not already on beta blockers, the ACC and AHA generally recommended against starting the drugs within a day before the surgery, but stated that it “may be reasonable” to begin beta blockers two or more days before surgery, or during or after surgery, if the patient is at risk for post-surgery heart complications.

When taken before heart surgery, beta blockers seem to be effective in preventing heart rhythm disorders and reducing the length of hospitalization after the procedure.[14] It is important to note that none of these drugs is approved specifically to prevent complications from cardiac surgery.

For noncardiac surgery, the evidence indicates that, while beta blockers started before surgery may decrease the risk of post-surgical heart attacks, they increase the risk of post- surgical stroke and death. These risks seem especially high when beta blockers are started within a day of the procedure and may also be present even if started two or more days before surgery.

There is a warning on all beta blockers on the potential adverse effects of both withdrawing chronically used beta blockers immediately before surgery and continuing beta blockers around the time of any major surgery.[15] There also is a warning on the label of extended-release metoprolol to avoid initiation of a high dose of the drug prior to noncardiac surgery, due to the risk of adverse effects.[16]

What You Can Do

If you are on beta blockers for a chronic condition, you should probably continue the medications, although you should speak with your doctor about the possible risks of doing so. These risks include low blood pressure and heart rate after surgery. Never stop taking a beta blocker on your own, as this can be dangerous.

If you are not on beta blockers, you should never start the medications on the day leading up to surgery. For cardiac surgery, you should start a beta blocker two or more days before the surgery.

For noncardiac surgery, you should discuss with your doctor whether you are at high risk for post-operative cardiac complications and, if so, whether the benefits of beta blockers outweigh their risks. If your doctor decides to start beta blockers to prevent these complications, the medications should be started as long as possible before the surgery.

Oral Beta Blockers in the U.S.

*Limited Use

References

[1] Wijeysundera DN, Duncan D, Nkonde-Price C, et al. Perioperative beta blockade in noncardiac surgery: A systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130(24):2246-2264.

[2] Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;58 (24):e123-210.

[3] Patorno E, Wang SV, Schneeweiss S, et al. Patterns of β-blocker initiation in patients undergoing intermediate to high-risk noncardiac surgery. Am Heart J. 2015;170(4):812-820.e6.

[4] Ibid.

[5] Jørgensen ME, Hlatky MA, Køber L, et al. β-blocker-associated risks in patients with uncomplicated hypertension undergoing noncardiac surgery. JAMA Intern Med. 2015;175(12):1923-1931.

[6] POISE Study Group, Devereaux PJ, Yang H, et al. Effects of extended-release metoprolol succinate in patients undergoing noncardiac surgery (POISE trial): A randomised controlled trial. Lancet. 2008;371(9627):1839-1847.

[7] Keane M. Beta-blocker therapy in non-cardiac surgery. Lancet. 2008;372(9644):1145; author reply 1146.

[8] Trevelyan J. Beta-blocker therapy in non-cardiac surgery. Lancet. 2008;372(9644):1145-1146; author reply 1146.

[9] Blessberger H, Kammler J, Domanovits H, et al. Perioperative beta-blockers for preventing surgery-related mortality and morbidity. Cochrane Database Syst Rev. 2014;9:CD004476.

[10] Ibid.

[11] Wijeysundera DN, Duncan D, Nkonde-Price C, et al. Perioperative beta blockade in noncardiac surgery: A systematic review for the 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;130(24):2246-2264..

[12] Jørgensen ME, Hlatky MA, Køber L, et al. β-blocker-associated risks in patients with uncomplicated hypertension undergoing noncardiac surgery. JAMA Intern Med. 2015;175(12):1923-1931.

[13] Fleisher LA, Fleischmann KE, Auerbach AD, et al. 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. J Am Coll Cardiol. 2014;64(22):e77-137.

[14] Blessberger H, Kammler J, Domanovits H, et al. Perioperative beta-blockers for preventing surgery-related mortality and morbidity. Cochrane Database Syst Rev. 2014;9:CD004476.

[15] DailyMed. Drug labels. https://dailymed.nlm.nih.gov/dailymed/. Accessed June 15, 2016.

[16] DailyMed. Label: metoprolol, extended-release (TOPROL XL). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm? setid=4a5762c6-d7a2-4e4c-10b7-8832b36fa5f4. Accessed June 15, 2016.