Beta Blockers Essay

Beta blockers (β-blockers or BBs) were invented and designed by Sir James Black, who was a Nobel Prize winning scientist. Black designed beta blockers to counteract stimulated adrenergic effects. He demonstrated that, by blocking the cardiac beta-receptors, these agents could cause inhibitory effects on the sinus node (chronotropic effect), atrioventricular node (dromotropic effect), and on myocardial contractility (inotropic effect).1
It is important to note that not all beta receptors (β-receptors) are the same. There are two clinically targeted types of beta receptors in the human body: beta 1 (β1) receptors which are mostly located on the cardiac muscle itself and when stimulated increase contractility by opening electro-physiological
calcium channels, beta 2 (β2) receptors which are mostly located on the lungs and when stimulated cause bronchodilation. It is important to note that there are, however, sizable populations of β2-Adrenoceptors in the myocardium, of about 20%–25%, which leads to the cardiac effects of any β2-Adrenoceptors stimulation. There is a relative up-regulation of these receptors to about 50% in heart failure.1
Chronic obstructive pulmonary disorder (COPD) is a systematic inflammatory response particularly located in the lungs due to tobacco smoking. The inflammatory response of COPD causes poor air flow through the airways of the lungs reducing lung function. The systemic inflammation of COPD can also contribute to the development of atherosclerosis which can lead to the development of cardiovascular disease (CVD) or add to an existing co-morbidity of CVD, making the use of beta agonists vital for treatment.
In clinical practice there is a generally accepted notion that beta blockers should never be prescribed to patients with COPD despite any potential benefits the medication may have on the patient’s cardiovascular disease (CVD).
In fact many practice guidelines advise against this, or counter-indicate BBs with COPD, for fear of the antagonistic actions of BBs will counteract the beta agonist actions of the patient’s COPD medication resulting in bronchospasms and other adverse effects. There has been a lot of controversial evidence about this topic, however, recent emerging studies have shown the BBs CVD benefits outweigh the risks associated with COPD. A compilation of retrospective studies show the benefits of beta blockade in this group appear to outweigh any potential risk of side effects according to the available evidence1. CVD and COPD are very common co-morbidities seen in clinical practice patient populations, in particular myocardial infarctions (MI) and COPD. Furthermore, the most common comorbid conditions associated with withholding BBs in elderly patients after myocardial infarction (MI) are COPD and asthma…many patients are diagnosed and treated for COPD with no objective evidence, such as pulmonary function tests or specialist assessment, to confirm the diagnosis, as recommended by most thoracic societies. This may indicate that a significant number of patient are deprived the prognostic benefits of using
BBs.1
More and more there is compelling evidence that the cardio-protective effects of BBs outweigh any risk of exasperating a patient’s COPD symptoms.
A group of recent studies show BBs are well tolerated in patients with cardiac disease and concomitant COPD with no evidence of worsening of respiratory symptoms or forced expiratory volume (FEV1) and the safety of BBs in patients with COPD has been demonstrated, but their use in this group of patients remains low. The cumulative evidence from trials and meta-analysis indicates that cardioselective BBs should not be withheld in patients with reactive airway disease or COPD.1 This evidence leads us to believe that placing a COPD patient with a larger risk of CVD complications would benefit from a cardioselective beta blocker. In fact, large meta-analyses were published where randomized, blinded, placebo-controlled trials that studied the effects of cardioselective BBs on FEV1, symptoms, and the use of inhaled β2-agonists in patients with reactive airway disease were selected, of which, there were 19 single dose treatment studies and 10 continued treatment studies. The outcomes measures were the change in FEV1 from baseline, the number of patients with respiratory symptoms, and the use of inhaled β2-agonists with active treatment compared with placebo. The results were that no significant treatment effect in terms of FEV1 was found in patients with concomitant COPD, whether single doses (change in FEV1, −5.28% [CI, −10.03% to
−0.54%]) or continued treatment (change in FEV1, 1.07% [CI, −3.3% to 5.44%]) was used.1 The study concluded that the use of cardioselective BBs do not in fact cause significant adverse reactions in COPD patients.
While clinicians should not throw away all caution, a conservative start low and go slow approach is warranted. Several studies show, any cardiac condition requiring BBs and who have concomitant COPD should be tried on BBs. A safe approach is to initiate cardio-selective BBs at a low dose and titrate them up as tolerated during the hospital admission. Metoprolol is cardioselective BBs with short half-life and has been shown to be safe and effective in patients with COPD and may be the BBs of choice to initiating therapy. This will allow close observation and assessment of tolerance of these medications and will ensure that these patients are not denied the prognostic benefits of a well-tolerated and effective treatment. It may be necessary to discontinue the drug in few patients due to bronchconstriction, but the potential benefit appears large enough to warrant this small risk.1
In the case of a patient post MI, the benefits of BBs have been evaluated in that by reducing myocardial oxygen demand, BBs limit cardiac ischemia and improve survival; therefore, following a myocardial infarction, they should be started early in the absence of contraindications.3 A recent study in the U.K. took a more direct approach in BB use in post MI patients. The results of which show BBs either started during the hospital admission for myocardial infarction or continued from before admission, were associated with substantial survival benefits.3

Based on the above evidence, it appears the common accepted practice of withholding BBs from patients with concurrent COPD diagnosis is not evidence based. On the contrary, not only have studies shown the lack of adverse reactions in patients with COPD on a cardioselective BB, but there are substantial cardioprotective benefits that COPD patients with CVD are desperately in need of are being withheld due to misplaced guidelines. COPD patients on BBs are at higher risk of ischemic heart disease1, and CHF where studies have shown BB may lower mortality in COPD patients2, but also decrease FEV1 scores and increase response to beta agonists2. The study results can not be ignored, and given a post MI patient the cardiovascular protective benefits of cardioselective beta blockers out weigh any risks of COPD exasperation, and should be heavily considered in such a scenario.