The role of angiotensin II type 1 receptor antagonists in elderly patients with hypertension

Abstract

Hypertension is a major risk factor for stroke and coronary events in elderly people and clinical trials have shown that treatment of hypertension with various drugs can result in a substantial reduction in cerebrovascular and cardiovascular events. The angiotensin II type 1 (AT1) receptor antagonists are the newest class of antihypertensive agents to be used widely in clinical practice. AT1 receptor antagonists can generally be given once-daily. They are also extremely well tolerated with minimal first-dose hypotension and an incidence of adverse effects similar to that seen with placebo. Adverse event rates are significantly lower than with other classes of antihypertensive drugs including ACE inhibitors. These factors result in improved compliance and increased rates of continuance on therapy. AT1 receptor antagonists show similar efficacy in lowering blood pressure to other classes of antihypertensive agents and their antihypertensive effect is potentiated when they are given concomitantly with low-dose thiazide diuretics. AT1 receptor antagonists are eliminated predominantly by the hepatic route but most are not subject to extensive metabolism and interactions with other drugs are uncommon. This is an advantage in the elderly, who are often receiving multiple medications which increases the risk for adverse drug interactions. Dose adjustments are not usually required in the elderly unless there is plasma volume depletion. Although plasma AT1 receptor antagonist concentrations are generally higher in the elderly than in younger subjects, this pharmacokinetic difference may be balanced by decreased activation of the circulating renin-angiotensin-aldosterone system in the elderly. Recent clinical studies in high-risk hypertensive patients with left ventricular hypertrophy or in patients with diabetic nephropathy or heart failure have demonstrated that AT1 receptor antagonists can improve clinical outcomes to a similar or sometimes greater extent than other antihypertensive agents. Many of these studies have included large numbers of older patients and have confirmed the excellent tolerability profile of these drugs. Thus, AT1 receptor antagonists should be considered as a possible first-line treatment or as a component of combination therapy in patients with type 2 diabetes mellitus and microalbuminuria or nephropathy and as an alternative or additional treatment to ACE inhibitors in patients with heart failure or left ventricular dysfunction. AT1 receptor antagonists also appear to reduce the onset of new diabetes compared with some other antihypertensive drugs. The benefits in terms of organ protection have mainly been seen in studies using higher doses of particular AT1 receptor antagonists and it is not certain at present whether these results can be extrapolated to other members of the class. As the elderly are more likely to have developed organ damage related to hypertension or to have heart failure or diabetes as concomitant conditions, AT1 receptor antagonists represent an appropriate option for many elderly patients. The main disadvantage of these drugs is the cost of the medication but this may be offset by their improved tolerability with fewer adverse reactions and thus increased compliance, resulting in better blood pressure control and fewer clinical events. Overall, AT1 receptor antagonists are well tolerated and efficacious for blood pressure-lowering when given as a single daily dose in elderly patients and have many potential benefits in high-risk hypertensive subjects.