Beta Blockers Save Lives in COPD Patients After Heart Attacks

A recent study appearing in the British Medical Journal (BMJ) significantly adds to a growing body of evidence indicating that chronic obstructive pulmonary disease (COPD) patients who suffer a heart attack are nearly twice as likely to survive if they are treated with beta blockers.[1]

It has been well established for many years that use of beta blockers following a heart attack in the general patient population saves lives in the long term.[2] However, because of concerns that beta blockers may cause sudden worsening of COPD due to acute bronchospasm (sudden narrowing of the airways in the lungs, leading to wheezing and shortness of breath), use of these drugs in COPD patients often was avoided in the past, even after a heart attack. Indeed, clinical trials testing the use of these drugs in heart attack patients have generally excluded patients with COPD.[3]

For similar reasons, Public Citizen’s Health Research Group has long advised that COPD patients not use beta blockers. However, given the new data from the BMJ study in combination with prior data, we now recommend that COPD patients be treated with beta blockers following heart attacks unless there is another clear reason for avoiding them.

Beta blocker overview

Beta blockers are a widely used class of drugs for treating high blood pressure (hypertension), chest pain due to coronary artery disease (angina), heart attacks, irregular heartbeats (arrhythmias) and tremors of unknown cause. These drugs can be divided into two groups: those that work primarily by binding to beta receptors in the heart (cardioselective beta blockers) and those that act by binding to beta receptors throughout the body, including those in the lungs (noncardioselective).[4] (See table for a list of available oral beta blockers.)

Beta blockers likely benefit heart attack patients by inducing one or more of the following actions:[5]

• decreasing the heart muscle’s demand for oxygen by reducing heart rate and blood pressure, as well as by directly affecting the metabolism of heart muscle tissue;
• hanging the electrical activity of the heart muscle, which lowers the risk of life-threatening abnormal heart rhythms;
• increasing blood flow to the coronary arteries that supply oxygen to the heart muscle;
• slowing the rate of cholesterol plaque buildup in coronary arteries; and
• inhibiting platelets, decreasing the risk of clot formation in the coronary arteries.

Oral Beta Blockers Available in the U.S.

*Limited Use (These drugs also contain a diuretic.)
**Cardioselective at low doses of 10 milligrams (mg) daily or less. At commonly used doses higher than 10 mg, nebivolol loses its cardioselectivity and blocks the beta receptors throughout the body.

Prior concern about possible harms of beta blockers in COPD patients was based on the fact that blocking beta receptors in the airways of the lungs can cause bronchospasm in patients with asthma and, to a lesser extent, those with COPD. (In contrast, inhaled beta agonist drugs, which stimulate beta receptors in the lung, have the opposite effect. They widen the airways of the lung and therefore are used to treat asthma and COPD.)

COPD: Worse prognosis after a heart attack

COPD is a chronic, progressive lung disease diagnosed in 15 million people in the U.S. It is characterized by difficulty moving air into and out of the lungs. The condition may be treated with bronchodilator medications, but it is not fully reversible. Smoking is by far the leading cause of COPD. The disease classically can present as either emphysema (replacement of normal lung tissue with large air pockets) or chronic bronchitis (inflammation of the airways in the lungs), although many patients have clinical features of both.

Common symptoms of COPD include coughing (with mucus or phlegm production), shortness of breath, wheezing and chest tightness. In mild COPD, shortness of breath may occur only with exertion. As COPD progresses, the shortness of breath may occur with minimal activity, such as slow walking, or even at rest.

Studies have shown that heart attack patients who have COPD have a significantly worse short- and long-term prognosis than those without COPD. For example, one observational study showed that, after adjusting for differences in severity of illness, COPD patients hospitalized for a heart attack had more than an 80 percent higher risk of either developing shock due to cardiac injury or dying during such hospitalizations than non-COPD patients.[6]

Likewise, another study revealed that heart attack patients with COPD had a twofold greater mortality rate during the subsequent year than those who did not have COPD.[7] Similar trends have been found in other studies.

Prior evidence of beta blocker benefit in COPD patients

Earlier evidence showing a survival benefit with beta blocker treatment following heart attacks in COPD patients came from two large observational studies. In the first study, published in the New England Journal of Medicine in 1998, researchers at the University of Maryland School of Medicine examined the medical records of approximately 200,000 Medicare patients diagnosed with a heart attack.[8] Among this group were about 40,000 patients who had COPD, only a fifth of whom received a beta blocker upon being discharged from the hospital after their heart attacks.[9] The researchers found that the risk of dying within two years following a heart attack was 40 percent lower in COPD patients who received beta blockers compared with those who did not receive such drugs.[10]

In the second study, published in the Journal of the American College of Cardiology, researchers at Yale University School of Medicine and the Health Care Financing Administration (HCFA, now the Centers for Medicare and Medicaid Services) looked at the medical records of nearly 55,000 Medicare patients who had survived hospitalization following a heart attack.[11] Among this group, one-fifth had COPD or asthma.[12] Patients with COPD or asthma in this study were significantly less likely to be prescribed beta blockers after their heart attacks compared to those without these conditions.[13]

The Yale and HCFA research team found that beta blocker treatment was associated with a 15 percent reduction in one-year mortality following heart attack in asthma and COPD patients who were not on inhaled bronchodilator treatment for their lung disease.[14] This reduction in mortality rate was similar to that seen in patients without COPD or asthma. A statistically significant survival advantage was not seen with beta blocker treatment in heart attack patients with COPD or asthma who were taking inhaled bronchodilator drugs for their lung disease or who had severe COPD or asthma.[15]

The researchers concluded that beta blocker therapy may be beneficial for patients with mild COPD or asthma.[16] Also, there was no evidence that patients with moderate to severe COPD or asthma were harmed by use of beta blockers following a heart attack, and the data suggested a trend toward benefit in these sicker patients.

The recent BMJ study builds on these prior research results showing that beta blockers improve survival in COPD patients following a heart attack.

The BMJ study

This large, well-designed observational study was performed by researchers in the U.K. and published Nov. 22, 2013. The researchers used a large national registry containing data from all admissions for heart attacks to all hospitals in England and Wales. They combined this registry data with information from a national computerized database of primary care medical records covering about 5 million active patients at 625 primary care practices throughout the U.K.[17] The primary study goal was to assess whether the use and timing of beta blockers after a COPD patient’s first heart attack were associated with better survival.[18]

From two health care databases, the researchers identified 1,063 COPD patients who experienced a first heart attack between January 2003 and December 2008.[19] They excluded from the study those patients for whom information on beta blocker use could not be determined, as well as those for whom beta blocker use was noted as being inadvisable without an explanation why.[20]

The primary outcome being studied was death from any cause.[21] Death certificate records were used to identify deaths of study patients and to determine whether the cause of death was cardiac or noncardiac.

Of the 1,063 patients included in the study, 55 percent never took a beta blocker, 23 percent were taking a beta blocker before their heart attacks and 22 percent were prescribed a beta blocker after their heart attacks.[22] Of note, COPD patients prescribed a beta blocker during their hospital stays for first heart attacks were younger and less likely to have a history of hypertension, stroke, peripheral vascular disease, heart failure, high cholesterol levels or angina before their heart attacks.[23]

After adjusting for all differences in baseline health status and risk factors for cardiac disease, the researchers found that COPD patients prescribed beta blockers during their hospital admission for a first heart attack had an approximately 50 percent lower risk of death at one year compared with those COPD patients never prescribed a beta blocker. Likewise, COPD patients already treated with a beta blocker at the time of their first heart attack had a one-third lower risk of death compared with patients never prescribed a beta blocker.[24] Of interest, the improved survival in COPD patients treated with beta blockers was due to a reduction in both cardiac and non-cardiac deaths.

Conclusions

The BMJ study researchers concluded that the use of beta blockers before and at the time of a heart attack was associated with improved survival in COPD patients and that such treatment should be used more widely.[25] They expressed concern that, at least in the U.K., the limited use of beta blockers in COPD patients as seen in their study may contribute to increased mortality in such patients after heart attacks. They also stated the following:[26]

Though a randomised controlled trial of [beta] blockers in patients with COPD could examine some of the perceived safety concerns that remain around their prescription, there is sufficient evidence to suggest it would be unethical to withhold [beta] blockers after [heart attacks] in patients with COPD and perform a trial of this nature.

We strongly agree with this assessment. There are now sufficient data to recommend that COPD patients who have a heart attack be treated with beta blockers unless there is a clear reason for not doing so in an individual patient (for example, a clear serious adverse reaction linked to beta blockers or failure to tolerate such drugs). Interestingly, a recent study conducted in Massachusetts suggests that in the U.S., unlike in the U.K., the use of beta blockers in COPD patients following a heart attack has increased substantially, reaching levels greater than 90 percent, a rate almost as high as that seen in non-COPD patients following heart attacks.[27]

The beta blocker used in treating a COPD patient after a heart attack should be a cardioselective one, and the initial dose should be on the low end of the recommended dose range.

What You Can Do

If you have COPD, have previously suffered a heart attack and have never been prescribed a beta blocker, you should consult with your primary health care provider about whether you should start taking one. If you have COPD and suffer a heart attack, you should be taking a cardioselective beta blocker unless you are unable to tolerate such treatment.

References

[1] Quint JK, Herrett E, Bhaskaran K, et al. Effects of β blockers on mortality after myocardial infarction in adults with COPD: population based cohort study of UK electronic healthcare records. BMJ. 2013;347:f6650.

[2] Freemantle N, Cleland J, Young P, et al. β blockade after myocardial infarction: systematic review and meta regression analysis. BMJ. 1999;318 (June 26):1730-1737.

[3] Chen J, Radford MJ, Wang Y, et al. Effectiveness of beta-blocker therapy after acute myocardial infarction in elderly patients with chronic obstructive pulmonary disease or asthma. J Am Coll Cardiol. 2001;37(7):1950-1956.

[4] Rosenson RS, Reed GS, Kennedy HL. Acute myocardial infarction: role of beta blocker therapy. UpToDate. http://www.uptodate.com/contents/acute-myocardial-infarction-role-of-beta-blocker-therapy?source=search_result&search=beta+blockers&selectedTitle=4%7E150. Last updated January 23, 2014. Accessed March 14, 2014.

[5] Ibid.

[6] Wakabayashi K, Gonzalez MA, Delhaye C, et al. Impact of chronic obstructive pulmonary disease on acute-phase outcome of myocardial infarction. Am J Cardiol. 2010;106(3):305-309.

[7] Salisbury AC, Reid KJ, Spertus JA. Impact of chronic obstructive pulmonary disease on post-myocardial infarction outcomes. Am J Cardiol. 2007;99(5):636-641.

[8] Gottlieb SS, McCarter RJ, Vogel RA. Effect of beta-blockade on mortality among high-risk and low-risk patients after myocardial infarction. N Engl J Med. 1998;339(8):489-497.

[9] Ibid.

[10] Ibid.

[11] Chen J, Radford MJ, Wang Y, et al. Effectiveness of beta-blocker therapy after acute myocardial infarction in elderly patients with chronic obstructive pulmonary disease or asthma. J Am Coll Cardiol. 2001;37(7):1950-1956.

[12] Ibid.

[13] Ibid.

[14] Ibid.

[15] Ibid.

[16] Ibid.

[17] Quint JK, Herrett E, Bhaskaran K, et al. Effects of β blockers on mortality after myocardial infarction in adults with COPD: population based cohort study of UK electronic healthcare records. BMJ. 2013;347:f6650.

[18] Ibid.

[19] Ibid.

[20] Ibid.

[21] Ibid.

[22] Ibid.

[23] Ibid.

[24] Ibid.

[25] Ibid.

[26] Ibid.

[27] Stefan MS, Bannuru RR, Lessard D, et al. The impact of COPD on management and outcomes of patients hospitalized with acute myocardial infarction: A 10-year retrospective observational study. Chest. 2012;141(6):1441-1448.