Hypotensive agents

Arterial hypertension is associated with high morbidity and mortality indices and constitutes a major health problem worldwide, specially due to its high prevalence and low rate of control with the standard treatment. This problem can be explained, at least in part, because we still use empiric measures when choosing treatment options, instead of a rational approach for each case. The determinants of the hypertension remain unknown in the majority of patients and is designated as essential or primary hypertension. Hypertension is a model of complex disease in which several genes may be affected and influenced by a variety of environmental interactions, such as diet, salt and obesity, among others. The use of molecular biology strategies is offering new opportunities for the understanding of complex biological phenomena, like hypertension. However, only in a minority of cases, arterial hypertension occurs by individual specific mutations, called mendelian forms of hypertension, involving distal nefron transporter gene products. These syndromes are of particular interest since they highlight the importance of cell pathways that can be affected in the more common forms of hypertension.

The antihypertensive drug classes that have reduced cardiovascular events safely either in large placebo-controlled trials or in comparison with other effective antihypertensive drugs in large morbidity trials are diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers (CCBs). Although control of blood pressure (BP) is a primary goal of therapy, evidence from several clinical trials suggests that certain antihypertensive agents provide clinical benefits independent of their effect on BP. In the recently reported Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), an ACE inhibitor, a CCB, and an alpha-blocker reduced coronary events and mortality to a similar extent as a thiazide-type diuretic, but the diuretic reduced one or more major cardiovascular events, especially heart failure, more than the other agents. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial, the ARB losartan reduced cardiovascular morbidity (primarily stroke) more than the beta-blocker atenolol. Although an ARB has not yet been compared with a diuretic in a morbidity trial, as most patients require more than one drug to control BP, and a diuretic plus an ARB is a very effective and well-tolerated combination, this uncertainty applies to a minority of patients. A primary goal in treating hypertension should be to reach a patient's goal BP, but initial selection of drugs based on hypertension morbidity study results and other compelling indications should be given priority.

Curr Opin Cardiol. 1999 Sep;14(5):375-80.
New drugs for the treatment of hypertension.
Mancia G, Stella ML, Grassi G.
Cattedra di Medicina Interna, Universita di Milano, Ospedale San Gerardo, Monza, Italy.

Despite the many outstanding favorable results achieved in the treatment of hypertension, several unmet goals of antihypertensive therapy remain, such as better blood pressure control, greater protection against the organ damage associated with hypertension, better tolerability, and ultimately a more effective prevention of cardiovascular disease. These unmet goals are the reasons why new antihypertensive drugs are synthesized and tested in the clinical practice. This paper briefly mentions the goals of new antihypertensive agents and examines the main pharmacological and clinical features of new classes of antihypertensive drugs, such as angiotensin II receptor blockers, central agents, vasopeptidase inhibitors, and endothelin antagonists. The results of experimental and clinical studies with these new drugs are reviewed, emphasizing some advantages and potential disadvantages of these drugs compared with traditional antihypertensive drugs.