Introduction

Hypertension as a disease process was borne out of epidemiologic studies demonstrating that increased blood pressure (BP) was associated with an increase in cardiovascular events. As a result, the primary goal in the treatment of hypertension is to reduce the incidence of cardiovascular events in hypertensive patients to the levels seen in normotensive subjects. Meta-analyses of studies performed to assess the impact of treating hypertension have demonstrated very impressive reductions in the incidence of strokes among hypertensive patients, but very disappointing reductions in the incidence of coronary artery disease (CAD).1,2 Although there are several reasons that contribute to the lower-than-predicted reductions in CAD, perhaps the most important is related to the fact that in the vast majority of both treated and untreated hypertensive patients, BP is inadequately controlled. Data from the National Health and Nutrition Examination Survey has demonstrated that if a BP of 140/90 mm Hg is considered to be normal, only 27% of hypertensive patients are adequately controlled in the United States. In fact, only 50% of treated hypertensives are adequately controlled.3,4 To make matters worse, 140/90 mm Hg is now regarded as high-normal by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI report), and 130/85 mm Hg is now regarded as normal. Still lower BP goals are suggested for diabetic patients (125/75 mm Hg) and for patients with underlying CAD (120/80 mm Hg). This creates a major dilemma in clinical practices because physicians have had difficulty achieving the previous goal of 140/90 mm Hg. Further lowering of BP goals results in a monumental increase in the difficulty of treating hypertension. This has resulted in despondency among physicians who believe that their new BP goals are impossible to achieve in many patients. This is particularly true of patients with isolated systolic hypertension, which has proven to be extremely difficult to control, as well as of diabetic patients with renal dysfunction, in whom lower BP goals have been shown to be renoprotective. It is clear that, to be more successful in achieving the newly recommended BP goals, we have to make some changes to our approach to the treatment of hypertension. One area of particular interest in this regard has been more aggressive use of low-dose combination therapy as first-line treatment, or the use of combination therapy much earlier in the course of treating hypertensive patients. It has been well demonstrated that monotherapy with any class of drug (even at high doses) will, at best, result in the control of approximately 40% to 50% of patients if only diastolic criteria were applied.5–7 Compounding this is that several drug classes exhibit dose-dependent side effects (ie, calcium channel blockers and edema), that may be more likely if higher doses are necessary. When systolic and diastolic criteria are applied, these rates of control are even lower. The reason for this is that hypertension is a multifactorial disease involving several physiologic mechanisms. Simply interrupting one of these mechanisms is usually insufficient to achieve BP control. Using complementary antihypertensive drugs in combination increases control rates to the 75% to 85% range. Despite these findings, there has been a reluctance of physicians to use combination drugs because, mainly, it is contrary to what is taught in medical school. With the availability of good outcomes data that have demonstrated the very poor reductions in the incidence of CAD among hypertensive patients, it is probably time to reassess the place of combination therapy in the management of hypertension. Studies have demonstrated that low-dose combination therapy has several advantages: 1) greater efficacy than high-dose monotherapy8; 2) fewer side effects than monotherapy9; 3) can be dosed once daily; 4) more convenient than polypharmacy; 5) fewer cardiovascular events than monotherapy10; 6) better target organ protection than monotherapy11; 7) greater response rates than monotherapy12; and 8) may be cheaper than multiple drug therapy. One “ideal” combination that meets these criteria is the combination of an angiotensin converting enzyme inhibitor and a calcium channel blocker. These advantages address several of the problems associated with higher dose monotherapy. The use of combination therapy, either as first-line or as earlier treatment in the course of managing hypertension, may be the most important change that we make in our approach to improve control rates in the treatment of hypertension and to reduce CAD. The goal of this supplement is threefold: 1) to discuss the reasons for the newer BP goals and their importance in further protecting hypertensive patients from cardiovascular events; 2) to suggest drug treatment strategies that may be useful to physicians in achieving BP goals, particularly in elderly patients with systolic hypertension, in diabetes patients, and in patients with renal insufficiency; and 3) to discuss what future recommendations should be considered by groups such as the JNC to help clinicians achieve their new BP goals.