Sympathetic hyperactivity is an important pathophysiological mechanism for the development of many cardiovascular diseases such as coronary heart disease, hypertension, heart failure, tachyarrhythmia, sudden cardiac death, etc., and an important factor in the occurrence of perioperative cardiovascular events in non-cardiac surgery. β-blockers act on the neuroendocrine axis and reduce sympathetic activity, which can effectively prevent and treat a variety of cardiovascular diseases, reduce the incidence of cardiovascular events, and significantly The β-blocker is the cardiovascular drug with the most indications! However, the clinical dosage of β-blockers is very insufficient, which is a common problem at home and abroad.The PACI-MI study showed that although 93.2% of AMI patients were prescribed β-blockers when they were discharged from the hospital, only 17% of them took a dose of more than 50% of the recommended dose. This shows how clinically stingy beta blocker dosing can be! What is the reasonable dose of β-blockers measured by?There are individual differences in the dose of β-blockers applied, and the change in heart rate is an important indicator to guide the dose of β-blockers applied.The target heart rate after β-blocker administration is: in the case of sinus rhythm, the heart rate decreases by 20% to 25% or the heart rate decreases to 50-60 bpm; in the case of tachy-type AF, the ventricular rate decreases by 20% to 25% or the ventricular rate decreases to <100 bpm.Different dosages are used in the following ways: the heart rate decreases by 20% to 25%, or the ventricular rate decreases to <100 bpm. to <100 bpm. Different doses and different formulations of beta blockers achieve different blood concentrations and have different effects on heart rate. For example, the Cmax of metoprolol extended-release tablets 100 mg, metoprolol extended-release tablets 200 mg, and metoprolol flat tablets 100 mg were 231±52 nmol/L, 426±75 nmol/L, and 1105±245 nmol/L, respectively, and the reduction in exercise heart rate was 18.1±2.1 bpm, 21.5±1.7 bpm, and 22.3±2.7 bpm. bpm. It is evident that the Cmax achieved by metoprolol extended-release tablets 200 mg is much lower than that of metoprolol flat tablets 100 mg, and obviously the safety profile is much greater. In general, blockade of β1 receptors shows beneficial drug efficacy and blockade of β2 receptors shows adverse effects. Metoprolol extended-release tablets of 50 to 200 mg administered orally have a blood concentration distribution within the therapeutic window of safety (45 to 400 nmol/L) and show no significant blockade of β2 receptors. Comparison of sensitivity to metoprolol between Eastern and Western populations showed that: after oral administration of metoprolol flat tablets 100 mg, the percentages of post-exercise heart rate decrease were 22±3% and 22±4% for Chinese and Caucasian respectively after 2 hours, and 4±2% and 3±6% at 24 hours; after oral administration of metoprolol extended-release tablets 200 mg, the percentages of post-exercise heart rate decrease were 21±2%, 22±5% and 22±5% for Chinese and Caucasian respectively at 2 hours, and 24 hours; and the percentages of post-exercise heart rate decrease were 21±2%, 22±5%, 22±5% and 22±5% for Chinese and Caucasian respectively at 24 hours. ±5% at 2 hours, and 13±2% and 16±7% at 24 hours. This indicates that the sensitivity of Chinese to metoprolol is similar to that of Caucasians. Heart rate control plays an important role in the treatment of coronary heart disease. 2007 China's "Diagnostic and Treatment Guidelines for Chronic Stable Angina" requires that the resting heart rate be reduced to 55-60 beats/min, and for patients with severe angina pectoris, if there are no symptoms of bradycardia, the heart rate can be reduced to 50 beats/min. 2006 ESC "Guidelines for the Diagnosis and Treatment of Stable Angina Pectoris" mentions that the heart rate needs to be controlled to be 50-60 beats/min in order to control angina attacks better, and the beta-agonist can be used to control angina pectoris. To control angina attacks, the antianginal efficacy of beta blockers needs to be adjusted to adequate doses, i.e., metoprolol controlled-release tablets 200 mg/d, bisoprolol 10 mg/d, to provide 24-hour ischemic protection. It is now generally accepted that the hallmark of an adequate dose of beta blockers in the treatment of coronary artery disease is a resting heart rate of 50 to 60 beats per minute and a total of 70,000 to 80,000 heart beats over 24 hours. Those whose heart rate does not reach the mark should continue to increase their beta blocker dose if there are no other adverse effects; those whose heart rate reaches the mark should continue long-term beta blocker therapy if their symptoms are satisfactorily controlled. The individualization of β-blocker application in sufficient quantity, patients benefit more. Herlitz et al. reported in 2000, myocardial infarction 5-year mortality without β-blocker 61%, the application of betalactam 50, 100, 200mg per day for 43%, 33%, 24% respectively. This indicates that the individualized and adequate application of Betalucil can improve the survival rate of patients. The higher technical requirements of β-blockers are chronic congestive heart failure, which requires small starting dose, slow incremental dose, and gradual target. β-blockers for heart failure in large-scale controlled studies applied daily starting dose of bisoprolol 1.25mg, extended-release metoprolol succinate 12.5/25mg, carvedilol 3.125mg, and target dose of 10mg, 200mg, and 50mg, respectively, 50 mg.The starting and target doses of beta blockers for the treatment of chronic heart failure recommended by China's Diagnostic and Therapeutic Guidelines for Chronic Heart Failure in 2007 were metoprolol tartrate 6.25 mg tid, 50 mg tid; metoprolol succinate 12.5-25 mg/d, 200 mg/d; bisoprolol 1.25 mg/d, 10 mg/d, respectively; carvedilol 3.125 mg bid, 25 mg bid. The preset target doses and actual mean doses achieved in multiple heart failure clinical studies of beta blockers were: bisoprolol 5 mg, 3.8 mg (CIBIS), 10 mg, 7.5 mg (CIBIS-II); metoprolol 100-150 mg, 108 mg (MDC), 200 mg, 159 mg (MERIT-HF); carvedilol 50 to 100 mg, 45 mg (Carvedilol US), 50 mg, 41 mg (ANZ).At the end of the MERIT-HF study, 87% of patients had achieved a daily dose of metoprolol of 100 mg or more, and 64% of patients had achieved 200 mg. Heart failure guidelines stipulate that an early morning resting heart rate of 55 to 60 bpm is considered the target dose or maximum tolerated dose of beta blocker. The early morning resting heart rate should not be lower than 55 bpm, nor is the dose determined according to the patient's response to therapy. AMI large-scale clinical trial CCS-2 done in China showed that the incidence of III degree AV block was 0.85% and 0.84% in the metoprolol group and placebo group, respectively, and the incidence of II degree type II AV block was 0.18% and 0.15%, respectively, with no significant difference. It indicates that standard dose of metoprolol does not cause severe AV block. From clinical practice and personal experience and realization, different diseases require different doses of beta blockers. For example, the dose of metoprolol should be higher for hypertension with aortic coarctation, mostly 300 mg/d, 200 mg/d for coronary angina, and 100-200 mg/d for general hypertension, heart failure, tachyarrhythmia, or for the prevention of sudden death, and this dose is very safe in the country. The 2004 ESC expert consensus document mentions that the appropriate dose of beta blockers should vary with the clinical characteristics of the patient and the drug chosen. In other words, attention should be paid to individualized dosing. It is important to note, however, that "individualization" does not always mean "small doses"! Commonality and individuality, universality and specificity are never opposites or contradictions, and it is clear that an inadequate dose of beta blockers will not result in better symptom control and improved prognosis. Heart rate is an important indicator to guide the dosage of β-blockers, the selection of β-blocker therapeutic dose should refer to large-scale clinical trials or relevant guidelines, mainly based on the target resting heart rate and the maximum tolerated dose, the dose should be reasonable and adequate, so that the "heart rate to meet the standard" to achieve the full therapeutic effect.