The first instance of angina pectoris treatment using a drug was described by Professor T Lauder Brunton in 1857 in Edinburgh. Professor Brunton documented patients’ experiences with “intense anxiety of having their chest compressed” and alleviated promptly by amyl nitrite. Almost a century later, Mason et al.elegantly demonstrated the effects of this volatile vasodilator in men in 1965. In addition to its intense vasodilator effects on the arteriolar and venous systems, an intense adrenergic response was elicited by hypotension that followed. The use of organic nitrates started in 1946, followed by beta-blockers (BBs) in the 1960s, establishing them as a basis for preventing or reducing angina episodes and relieving pain using sub-lingual or oral spray formulas of nitrates. A combination of BBs with oral long-acting nitrates was used to avoid angina for many years. Due to its protective effect against ischemia and ventricular arrhythmia, BBs were reinforced as the first-choice antianginal drugs after being tested in patients with acute myocardial infarction (AMI) during the 1980s and 1990s.

The results of the trials^,showed a relative reduction of 15–20% in the AMI incidence and cardiovascular mortality during the follow-up period up to 2.5 years. More recently, the COMMIT trial with metoprolol tartrate only reduced mortality by 1%(relative risk). Besides, there are concerns regarding how long the effects shall last, especially in patients with normal left ventricular ejection fraction (LVEF). In patients with chronic coronary syndrome (CCS) and preserved LVEF, no trial tested BBs in the reduction of cardiovascular events. Recently big data registries allowed statistical approaches using propensity scores to test with results that do not support the use of BBs as a preventive measure against mortality or AMI in patients even in those 1 year after AMI.^, A recently published trialtested metoprolol or bisoprolol after AMI, in patients with normal LVEF; with a median follow-up period of 3.5 years; no advantages were observed regarding mortality or myocardial infarction incidence. Therefore, we need to re-think the widespread use of BBs in CCS. The more recent antianginal drugs include nicorandil, trimetazidine, ivabradine, and ranolazine, which were tested in patients with angina who were already receiving BB therapy.

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