Evidence-based Treatment of Hypertension
Many large studies have confirmed the importance of controlling hypertension in reducing cardiovascular morbidity and mortality. Prescribers are now faced with a wide choice of antihypertensives and a growing body of evidence about their effects.

This article reviews recent evidence about angiotensin II receptor blockers (ARBs). It concludes that they are effective in reducing blood pressure and cardiovascular disease. ARBs also have a renoprotective effect in diabetes. They are generally better tolerated than ACE inhibitors or beta blockers. Newer members of the class may be more effective than older ones at controlling hypertension, and combinations of ARBs with ACE inhibitors may be more effective than either drug alone. Many patients will require combinations of different classes of antihypertensive agents, and ARBs have an important place in providing therapy tailored to the needs of the individual patient.

High blood pressure is one of the three most important risk factors for cardiovascular disease and is a major burden for global health. In the UK, about 40% of people aged 35-64 years are hypertensive (i.e. have a blood pressure above 140/90 mmHg). Each year around 212,000 people in the UK die from cardiovascular disease and, of these, nearly 60,000 deaths are due to stroke (figures for 2001). In recent years, the relative frequency of stroke has been increasing compared with coronary heart disease, and the primary goal of antihypertensive therapy is now the prevention of stroke.

Although hypertension responds well to treatment, only 10-30% of hypertensive patients in the UK have their blood pressure controlled and suboptimal blood pressure control may account for 62,000 unnecessary deaths per year. Theoretical models of the effects of poor blood pressure control have been confirmed by a study in general practice, which showed that the risk of stroke was related to the quality of blood pressure control, and that inadequate control may account for about 21% of strokes.

Prescribers are faced with many data from an expanding pool of large studies, yet, beyond the sheer time needed to update the evidence base, it can be difficult to translate and synthesise results into rational treatment decisions for individual patients.

One important factor affecting the application of clinical trial evidence into routine practice is the range of study designs. Most new treatments are licensed on the basis of relatively small studies conducted over fairly short timeframes in tightly controlled populations. These studies are designed to demonstrate the efficacy of the drug either against placebo or current best treatment. Efficacy is usually expressed in terms of the treatments' effects on mean blood pressure, expressed in mmHg. Such outcomes are easily quantified and such study designs limit the number of patients who are exposed to the new treatment. These patients will be carefully selected, and those with complicating factors such as other illnesses or those receiving other medication are usually excluded. These studies produce simple and unequivocal results, but they may not be applicable to the broader patient population.

Furthermore, a fall in blood pressure is only a surrogate end point. The real reason for treating hypertension is to reduce the risk of cardiovascular disease. Much larger and longer studies are needed to measure end points such as the incidence of stroke or the death rate from cardiovascular disease. Not only are such studies difficult (and costly) to perform, but their results are often harder to interpret. This is because, in long-term studies, a significant proportion of patients will stop taking the study treatment, many patients require more than one antihypertensive agent and other factors may change over time. For example, the proportion of patients in hypertension treatment trials also receiving statins has increased considerably over the past five years and this independently influences cardiovascular morbidity and mortality. Other risk factors, such as patients' concurrent diseases, may also vary unpredictably over the course of the study.

Because these large-scale effectiveness studies are so expensive to organise, and take such a long time to generate meaningful data, they have not been performed for every member of every class of antihypertensive agent, let alone for the enormous number of possible treatment combinations. Results of single studies may therefore fail to provide answers about individual treatment decisions. Doctors have to decide whether results of studies are applicable to other members of the same class of drug to different combinations or to different patient populations.

The newest class of antihypertensive agents is the angiotensin II receptor blockers (ARBs). This article reviews recent evidence on ARBs, with the aim of helping prescribers make rational decisions when selecting antihypertensive therapy for their patients.