The Place of Angiotensin II Antagonists in Relation to the Canadian Hypertension Society Guidelines

Summary

Angiotensin (Ang) II antagonists are a novel class of drugs developed to block Ang II receptors. This approach is deemed more direct and more likely to be effective than the earlier pharmacological approach of inhibiting the enzyme (ACE inhibitor) responsible for converting Ang I to Ang II. Furthermore, it is expected that the approach will avoid problems associated with pathways that bypass ACE, e.g., tissue chymase.

Two major subtypes of receptor have been identified, AT₁ and AT₂. Blockade of the AT₁ receptor by a new class of agents typified by losartan lowers blood pressure in hypertensive subjects and has a theoretical role in blocking the action of Ang II in the pathophysiology of other disease states such as congestive heart failure (CHF) and left ventricular hypertrophy (LVH).

The Canadian Hypertension Society Consensus Reports on the drug treatment of hypertension were last updated in a series of publications in the Canadian Medical Association Journal in 1993. Specific reviews dealt with the pharmacotherapy of hypertension, the treatment of hypertension in the elderly, and the treatment of the diabetic hypertensive. The choice of antihypertensive therapy is driven by factors that include concurrent cardiovascular risk factors and the presence or absence of other disease states. The physician is challenged to find an appropriate medication for the individual patient that is not contraindicated, that is effective and affordable for the patient, and that does not cause adverse effects in managing this largely asymptomatic disorder.

Although no long-term studies of AT₁ blockers have been done in sufficiently large populations to determine the changes in clinical outcomes that are desirable in treating hypertension (e.g., reduction of myocardial infarction, stroke, and end-stage renal disease), the surrogate endpoint of blood pressure lowering indicates that AT₁ blockers will have an important place in the management of hypertension that is akin to that presently held by ACE inhibitors, alpha-1 blockers, and calcium channel blockers. Recent evaluation of losartan in the elderly (ELITE) indicates a potentially valuable role for losartan in the treatment of elderly hypertensive patients with impaired left ventricular function.