Arterial hypertension is by far the biggest risk factor for cardiovascular diseases. Thiocyanates, barbiturates, bromides and bismuth were tested in the treatment of arterial hypertension in the early 1940s. The use of these drugs was discontinued because they were proven ineffective and had several side effects. In the mid-1950s, ganglion blockers such as hexamethonium, pentolinium, mecamylamine and peripherally acting sympatholytic substances (guanethidine) were tested as treatment of arterial hypertension and were shown effective in reducing blood pressure, but little tolerated. New drugs were introduced to treat hypertension in the 1950s, including diuretics.

In 1956, in an observational study, Moser and Magaulay followed up 106 hypertensive patients who received rauwolfia, hydralazine, reserpine, mecamylamine and chlorothiazide as treatment for arterial hypertension, alone or in combination. The dose of chlorothiazide used in this study ranged from 0.5 to 1.5 grams and the combination of chlorothiazide resulted in better control of blood pressure. Since that observational study by Moser and Magaulay to the present day, several studies related to the pharmacological treatment of hypertension have been carried out. The first randomized, placebo-controlled study conducted on the treatment of arterial hypertension was the Veterans Administration (VA), published in 1967. It is worth noting that the study inclusion criterion for active versus placebo treatment was diastolic pressure between 115 and 129 mmHg. After the publication of the VA-I study in 1967 and the VA-II in 1970, several randomized controlled studies addressing the treatment of arterial hypertension were carried out. The initial focus of treatment for arterial hypertension was renal sodium excretion, as renal disorders were initially thought to be the main cause of hypertension. Subsequently, the pathophysiological mechanisms of hypertension were elucidated and the therapy was directed to the main pathophysiological mechanisms. The activation of the sympathetic nervous system as an important pathophysiological mechanism of hypertension had already been perceived in the 1950s, and various forms of sympathetic nervous system block and even sympathectomy were then attempted. Beginning in the 1980s, with the introduction of the microneurography and the norepinephrine spillover technique, the importance of activation of the sympathetic nervous system in the pathophysiology of hypertension was even more evident.^, Although poorly tolerated, central and peripheral adrenergic blockers have always been part of the treatment of arterial hypertension. The activation of the renin-angiotensin aldosterone system (RAS) and the altered natriuresis pressure curve are two other important mechanisms in the pathophysiology of arterial hypertension. Currently, the use of diuretics to correct the altered natriuresis pressure curve and inhibitors of the renin-angiotensin aldosterone system, which act at different sites, has been routine in the treatment of arterial hypertension.

[…]

Between July 2012 and March 2014, the Department of Arterial Hypertension of the Brazilian Society of Cardiology prepared and published four documents addressing some specific aspects on hypertension care^–. Similarly, between July 2013 and January 2014, major international institutions also produced documents updating their guidelines regarding hypertension^–. Some of the Brazilian documents were published before the international ones, while others were published concurrently.

The first Brazilian document, published in 2012, addressed resistant arterial hypertension, and extensive review of the subject was performed based on evidence available at the time. In addition to definition, care with diagnosis and possible causes, there was a concern regarding that most cases are, in fact, pseudo-resistant cases, mainly caused by lack of adherence, while highlighting the importance of possible secondary hypertension. The document finally proposed treatment that included the classic and known – but almost always overlooked – nonpharmacological treatment and an objective indication of pharmacological treatment, which takes into account the use of full doses of drugs that inhibit the renin-angiotensin-aldosterone system (ACEI or ARB), of a calcium channel antagonist and long-acting, of a thiazide diuretic and, as a fourth drug, proposed the use of spironolactone. The following was the indication of a beta-blocker with vasodilating action or a drug with central action.

[…]