Benefits and side effects of blood pressure lowering treatment: what was wrong with doxazosin in the ALLHAT?

The lowering of high blood pressure is supposed to protect target organs from hypertensive damage. The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial was designed to compare the cardioprotective properties of three antihypertensives from different classes (lisinopril, amlodipine and doxazosin) with chlorthalidone. Despite effective blood pressure lowering and a favorable metabolic profile, the doxazosin arm of the trial had a significantly higher relative risk of cardiovascular disease and heart failure compared with the chlorthalidone arm. This article speculates on possible causes for this unexpected result and suggests that the culprit may be accentuation of the vascular effects of vasopressin, which are maximized under α-adrenergic blockade. These findings may have implications for the large number of older men who receive monotherapy with α-blockers for treatment of prostatic symptoms

Fixed Combinations in Antihypertensive Therapy

Several studies have now confirmed that optimal targets of blood pressure (BP) could rarely be reached by monotherapy and various drug combinations are required to do this more effectively. However, the best way to increase patient compliance may be fixed combinations of two or more drugs in a single pill.  With further research into mechanisms of action and development of new drugs, it became evident that the most effective combinations were those whose mechanisms are complementary or synergistic. Thus, for the treatment of hypertension, the use of fixed combination therapy is gaining ground as a more practical and convenient approach for today’s clinical practice

Role of Angiotensin and its Inhibition in Hypertension, Ischemic Heart Disease and Heart Failure

Suppression of the renin-angiotensin system (RAS) has proven efficacy not only in the treatment of hypertension, but it also greatly benefits and protects patients with ischemic cardiomyopathy and heart failure. This inhibition not only leads to symptomatic and functional improvement but it also prolongs life. The role of angiotensin inhibition in cardiovascular disease is herein briefly discussed

Therapeutic Advances: Hypertension in the Elderly

The incidence of hypertension and attendant biological disorders (loss of arterial wall elasticity, endothelial dysfunction, insulin resistance) increases with age and so does the frequency of cardiovascular complications. Women have a lower incidence of hypertension and a later—by an average of 10 years—onset of cardiovascular complications. During the premenopausal years, women seem to be relatively protected from cardiovascular events, in part through the effects of estrogen on endothelial function and lipid profile. After menopause however, the incidence of cardiovascular events tends to become similar in both genders, and the severity of such events, in terms of morbidity and mortality, is actually higher in women. The role of hormone replacement for cardiovascular protection has been shown to offer no long-term benefits:  indeed, despite improvement in surrogate endpoints (endothelial function, lipid profile), in long-term prospective randomized trials there was no advantage in outcomes, possibly because benefits are offset by the thrombogenic and carcinogenic properties of estrogen....(excerpt

First Choice of Antihypertensive Therapy

The first choice of antihypertensive therapy should include an agent with the best metabolic profile, usually an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB), but additional agents should be used as needed to attain optimal blood pressure control, usually a diuretic or calcium-channel blocker (CCB) or both, whereas β-blockers should be used only if specially indicated for co-morbidities, such as in cases of coexisting coronary disease or chronic heart failure

Fixed Combinations in Antihypertensive Therapy

Several studies have now confirmed that optimal targets of blood pressure (BP) could rarely be reached by monotherapy and various drug combinations are required to do this more effectively. However, the best way to increase patient compliance may be fixed combinations of two or more drugs in a single pill.  With further research into mechanisms of action and development of new drugs, it became evident that the most effective combinations were those whose mechanisms are complementary or synergistic. Thus, for the treatment of hypertension, the use of fixed combination therapy is gaining ground as a more practical and convenient approach for today’s clinical practice

The Role of Double Renin-Angiotensin System Blockade

Blockade of the renin-angiotensin system (RAS) is now recognized as an effective means of lowering blood pressure and protecting hypertensive patients from end-organ damage.  There are three pharmacologic approaches to blockade of the RAS, with angiotensin-converting enzyme (ACE) inhibitors, with angiotensin II receptor blockers (ARBs), and with direct renin inhibitors. Clinical studies with the first two classes have shown that neither one achieves complete blockade of the RAS. However, an almost complete blockade of the RAS can be achieved by combination of an ACE inhibitor plus an ARB, albeit not with consistent benefits. A complete blockade of the RAS can also be obtained by combination of an ARB with a renin inhibitor. Further outcome trials are needed to show which combination offers long-term advantages in terms of end-organ protection

Role of Angiotensin and its Inhibition in Hypertension, Ischemic Heart Disease and Heart Failure

The renin-angiotensin system (RAS) was extensively investigated and characterized throughout the first half of the 20th century. However, its contribution to the maintenance of high blood pressure (BP) in essential hypertension and to the development of hypertensive cardiac complications remained under debate until the advent of the first pharmacologic probes capable of blocking its actions, namely the angiotensin receptor blocker (ARB) saralasin and the angiotensin-converting enzyme inhibitor (ACEI) teprotide in the early 1970???s. Using these probes, we could demonstrate that even in normal-renin and low-rein hypertension, blockade of the RAS produced a fall in BP. And this fall was maximized if the patient had been previously submitted to sodium depletion by diuretics or low salt diet, which might produce only a small BP fall by itself, but rendered the hypertension RAS-dependent and far more responsible to RAS blockade

Antagonistas da angiotensina II: experiência clínica com o tratamento da hipertensão, prevenção de desfechos cardiovasculares e proteção renal na nefropatia diabética e proteinúria

Angiotensin II antagonists (AIIAs) were introduced to treat hypertension about 10 years ago. During this period they were evaluated not only in terms of efficacy and safety but also in several large studies with clinical outcomes. They are efficacious in all clinical forms of hypertension and are effective also in all ethnic groups. Cardiovascular and renal protection in proteinuric diabetic nephropathy beyond blood pressure reduction was proved in major clinical studies: Losartan Intervention For Endpoint reduction in hypertension study (LIFE), Reduction of Endpoint in Non-Insulin dependent Diabetes Mellitus with the AII Antagonist Losartan (RENAAL) and Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT). Their blood pressure independent protective effect is also mentioned by the blockade of AT1 receptor. As a class AIIs have a tolerability profile similar to placebo.Os antagonistas da angiotensina II (AAIIs) foram introduzidos para o tratamento da hipertensão arterial há cerca de 10 anos. Durante esse período eles foram avaliados não apenas em termos de eficácia e segurança, mas também em vários estudos grandes com desfechos clínicos. Os AAIIs são eficazes em todas as formas clínicas de hipertensão e, também, em todos os grupos étnicos. Os principais estudos clínicos em pacientes diabéticos com nefropatia e proteinúia comprovaram, além da redução da pressão arterial, proteção cardiovascular e renal: Losartan Intervention For Endpoint reduction in hypertension study (LIFE), Reduction of Endpoint in Non-Insulin dependent Diabetes Mellitus with the AII Antagonist Losartan (RENAAL) e Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT). O seu efeito protetor independente da pressão sanguínea também é mencionado pelo bloqueio do receptor AT1. Os AAIIs, como classe medicamentosa, apresentam um perfil de tolerabilidade semelhante ao placebo.UNIFESP Fundação Oswaldo Ramos Hospital do Rim e HipertensãoUniversity School of Medicine Hypertension and Atherosclerosis SectionUNIFESP, Fundação Oswaldo Ramos Hospital do Rim e HipertensãoSciEL