Renin‐Angiotensin System Blockade: Therapeutic Implications Beyond Blood Pressure Control (2007)

The treatment of hypertension is one of the major marvels of modern science. Over the past 50 years, antihypertensive treatments have significantly reduced morbidity and mortality, to an extent second only to antibiotics. Their use has provided significant protection against all of the consequences of hypertension (eg, heart attack, renal damage, and stroke), with stroke perhaps benefitting the most. The availability of antihypertensive agents over the past 50 years has been slowly progressive. Progress has been sometimes serendipitous, as with the recognition of the effects of Indian snakeroot (ie, reserpine) but is mostly from the targeted application of biochemistry to develop molecules that either stimulate or inhibit the physiologic mechanisms that control blood pressure levels (Table I).1 Among the latter, the development of inhibitors of the renin-angiotensin system (RAS) has been especially productive. Blockage of aldosterone receptors with spironolactone came first. Its use has been revitalized with the recognition of profibrotic damages induced by presumably normal amounts of the hormones.2 Soon thereafter, a molecule that inhibits the angiotensin-converting enzyme (ACE) was synthesized, providing a framework for a host of ACE inhibitors that soon became the most widely used class of antihypertensive drugs. More recently, specific blockers of the angiotensin type 1 receptor, such as losartan (one of the first to be marketed), were developed and were soon thereafter followed by a number of other angiotensin receptor blockers (ARBs). These members of the ARB family differ primarily in their duration of action, with telmisartan having the longest duration (Table II).3 The papers in this supplement examine the multiple consequences of uncontrolled hypertension that are primarily induced by the RAS and the efficacy of both ACE inhibitors and ARBs in protection against these consequences. As the editor of the supplement, I chose colleagues at the University of Texas Southwestern Medical Center who have had extensive clinical experience with these agents. Their papers bring the reader an up-to-date and unbiased review of these remarkable antihypertensive drugs. The individual articles include Dr Ronald G. Victor's “Pathophysiology of Target-Organ Disease: Does Angiotensin II Remain the Key?” which examines clinical trials addressing issues involved in complex RAS blockade. Dr Wanpen Vongpatanasin's article is titled “Cardiovascular Morbidity and Mortality in High-Risk Populations: Epidemiology and Opportunities for Risk Reduction.” Dr Robert D. Toto has written “Reducing Cardiovascular Events in High-Risk Patients: The Challenge of Managing Hypertension in Patients With Diabetic Renal Disease,” and finally, Dr Shawna D. Nesbitt has contributed “Antihypertensive Combination Therapy: Optimizing Blood Pressure Control and Cardiovascular Risk Reduction.” The ARB family shares similar efficacy with ACE inhibitors, both in lowering blood pressure and in preventing hypertension-induced target-organ damage. The main advantage of ARBs over ACE inhibitors is the virtual absence of the adverse effects seen with ACE inhibitors, with the most common being cough and the most serious but rare being angioedema, which has been shown in multiple comparisons. ARBs induce no more adverse effects than those seen with placebo. This clean adverse-effect profile may lead to the adoption of ARBs as the agents for, hopefully, preventing hypertension or at least delaying its onset in the large population of prehypertensive people. The Trial of Preventing Hypertension (TROPHY) proved the principle that delay in hypertension onset is feasible.4 Larger and longer trials will be needed to prove the clinical usefulness of such preventive medication. Dr Kaplan is a member of the Boehringer Ingelheim Pharmaceuticals, Inc., Speakers' Bureau.