The future role of losartan.
The past few decades have seen a remarkable development in the field of pharmacological therapy, one of the most notable examples being the treatment of arterial hypertension. Some of the early anti-hypertensive agents were relatively crude by today's standards, but gradually efficacy, tolerability, or both, of blood pressure-lowering (BP) drugs have been improved. It is presently possible to choose from a number of effective and well-tolerated compounds for the treatment of hypertension. The latest additions to the anti-hypertensive armamentarium are the angiotensin II receptor antagonists, the most advanced of these being losartan. It is perhaps most relevant to compare losartan to the angiotensin converting enzyme (ACE) inhibitors, another class of anti-hypertensive agents which acts mainly by interfering with the renin-angiotensin-aldosterone system (RAAS). Studies have shown that losartan lowers BP at least as effectively as ACE inhibitors. However, the side-effect profile of losartan is more favourable. In particular cough, a relatively common side-effect of ACE inhibitors, has been shown to be significantly less common during losartan treatment. This is probably because losartan does not interfere with bradykinin metabolism, unlike the ACE inhibitors. Regarding the reversal of left ventricular hypertrophy (LVH), a powerful risk indicator for cardiovascular disease, we have shown that losartan is more effective in this regard than treatment with the beta-blocker atenolol. It appears, based on these and other findings, that interference with the RAAS is particularly useful in causing reversal of the cardiovascular hypertrophic changes. The prognostic implications remain to be demonstrated, but it would be logical to expect a benefit from this effect. It was recently shown that polymorphism of the ACE gene is associated with increased risk of coronary heart disease even in the absence of conventional risk factors. If these findings are confirmed the interest in interfering with the RAAS as a therapeutic modality in hypertension would obviously be strengthened. It is not easy to predict the future role of any new therapeutic modality. The positive relation between efficacy and tolerability of losartan, as well as the fact that several observations suggest that interference with the RAAS could be favourable from a prognostic point of view, suggest that losartan may come to play an important role in the future treatment of hypertension.