Beta-blockers are first-line drugs for the treatment of hypertension, coronary artery disease, and chronic heart failure, yet they are significantly underutilized in clinical practice. Many physicians are concerned that the use of beta-blockers is prone to adverse effects, and to some extent this concern is related to the “demonization” of beta-blockers. In fact, the safety of β-blockers is not inferior to other classes of antihypertensive drugs, and most of the adverse reactions can be prevented and appropriately treated. Contraindications to the use of drugs and the occurrence of adverse reactions In clinical practice, few patients can not apply beta-blockers due to absolute contraindications (such as bronchial asthma, second-degree or higher atrioventricular conduction block). In addition, 3% to 5% of patients are truly intolerant of beta-blockers, mainly in the form of symptomatic hypotension or bradycardia that occurs immediately after taking a small dose of the drug. Most of the adverse effects of beta-blockers are related to their pharmacologic effects, such as dizziness, fatigue, heart rate slowing, conduction block, Raynaud’s phenomenon, sexual dysfunction, and exacerbation of airway obstruction in patients with asthma. In addition, certain preparations can cause adverse effects such as headache, hypersensitivity, weight gain, or depression that do not appear to be related to beta-blockade per se. Getting Past the Misconceptions of Contraindications and Adverse Effects Beta Blockers and COPD Chronic obstructive pulmonary disease (COPD) is not a contraindication to beta blockers; on the contrary, many patients with COPD should be on beta blockers because of comorbid coronary artery disease or heart failure. An observational cohort study in the Netherlands followed 2,230 patients with COPD for an average of 7.2 years, during which 686 deaths and 1,055 cases with at least 1 COPD exacerbation occurred.Cox risk regression analyses showed that the rates of overall mortality [hazard ratio (HR)=0.70, 95% confidence interval (CI) 0.59-0.84] and COPD exacerbation in those who used beta-blockers (HR=0.73, 95% CI 0.63 to 0.83) were significantly lower, and patients with or without cardiovascular disease benefited equally. A retrospective cohort study in Scotland followed 5977 patients with COPD for a mean of 4.35 years, of whom 819 were treated with beta-blockers. As a result, β-blockers reduced overall mortality by 22% (P < 0.001, Figure 1), had no adverse effect on lung function, and significantly reduced hospitalization due to COPD exacerbation and COPD-related mortality. Based on the results of a number of recent studies, the idea that β-blockers have a dual cardioprotective effect on the heart and lungs has been put forward by experts. Beta Blockers and PAD Doctors have been reluctant to prescribe beta blockers to patients with peripheral arterial disease (PAD) because of an alleged increase in α1-receptor-mediated vasoconstriction following blockade of vascular β2-receptors, which can exacerbate limb ischemia. However, the claim has never been substantiated. A pooled analysis of 11 studies by Radack found that beta blockers do not impair walking ability in patients with mild to moderate PAD. Another prospective clinical study included 128 hypertensive patients with symptoms of intermittent claudication. After 48 weeks of randomization to nebivolol or metoprolol extended-release tablets, both groups showed significant improvement in ankle-brachial index and a significant increase in absolute walking distance (Fig. 2), and there was no significant difference in the therapeutic benefit between the two groups. These results suggest that patients with PAD can tolerate β-blockers in the long term. β-blockers and sexual dysfunction Many physicians and patients believe that sexual dysfunction is a common side effect of β-blockers, but this view lacks evidence. The reality is that (1) sexual dysfunction is a common symptom in patients with cardiovascular disease regardless of medication; (2) sexual dysfunction is often associated with psychological factors; and (3) β1-blockers are no more likely to cause sexual dysfunction than any other class of antihypertensive medication. Several randomized controlled studies have shown that the incidence of sexual dysfunction in patients who did not know that the drug they were taking was a β-blocker ranged from 3% to 8%; after they were told that the drug was a β-blocker, the incidence of sexual dysfunction ranged from 13% to 16%; and after they were told that the drug they were taking was a β-blocker and that the drug had such a side effect, the incidence of sexual dysfunction ranged from 31% to 32% (P < 0.01). For these patients with sexual dysfunction, placebo and sildenafil were equally effective, strongly suggesting that the symptoms were primarily psychological in origin. ADVERSE REACTIONS PREVENTABLE AND TREATABLE Most of the adverse effects of beta-blockers are related to their pharmacologic effects and are therefore preventable and treatable, with particular attention to the following points. First, the cardioprotective effects of β-blockers are mainly due to the blockade of β1 receptors, while the adverse effects on bronchial, peripheral vascular, glucose and lipid metabolism and sexual function are mainly due to the blockade of β2 receptors. Therefore, in most clinical situations, especially those with COPD, PAD or diabetes mellitus and young and middle-aged male patients, cardioselective β1-blockers such as metoprolol extended-release tablets or bisoprolol should be used. The newer β-blockers nebivolol or carvedilol, which have both vasodilator effects, may have less adverse effects on, for example, glucose-lipid metabolism, but large clinical trials confirming their clinical effects are lacking in many areas. Second, the cardiac selectivity of β1-blockers is dose-dependent, with selectivity diminishing or even disappearing at high doses. Therefore, the appropriate dose of the drug should be used according to the clinical situation. For example, when metoprolol extended-release tablets are used in patients with uncomplicated hypertension, whether as a first-line or second-line drug, the dose is usually no more than 95 mg/d, and a combination of drugs should be considered for those whose blood pressure is still not up to the standard; when used in patients with heart failure, one should strive for a gradual upward adjustment of the dose to 190 mg/d, in order to obtain the maximum cardiovascular protective effect. Thirdly, due to individual differences in patients' tolerance of the drug, beta-blockers are usually started at a small dose, and the dose is gradually adjusted upward according to the patient's tolerance. In particular, patients with heart failure should start with a very small dose to avoid sudden deterioration of their condition. Clinical trials have shown that when metoprolol extended-release tablets, bisoprolol, or carvedilol are used according to a standardized regimen, patients with heart failure not only experience clinical benefit, but also tolerate them well. Fourth, adverse reactions to the use of beta-blockers should be managed appropriately and promptly. For example, when patients with heart failure start to apply β-blockers or upwardly adjust the dose, if the condition worsens, the dosage of diuretics and angiotensin-converting enzyme inhibitors (ACEIs) should first be increased to stabilize the clinical situation; if the worsening of heart failure is more severe, the dosage of β-blockers can be temporarily reduced or discontinued as appropriate, and then the dosage can be increased or continued to be applied when the clinical situation is stabilized. β-Blockers of different preparations exist heterogeneity. There is heterogeneity in the different preparations of beta-blockers, and patients respond differently to different preparations. Therefore, if you cannot tolerate one agent, try another. The dose of β-blockers is not fixed for patients who have received long-term treatment, and the dosage can be temporarily reduced for observation when a slow heart rate or low blood pressure is found, but the drug should not be stopped suddenly to avoid the withdrawal syndrome. In conclusion, beta-blockers are a relatively safe class of drugs, even if adverse reactions occur, as long as they are detected in time and handled appropriately, they rarely leave long-term or irreversible serious damage.