Losartan: a review of its use, with special focus on elderly patients.
Losartan is an orally active, nonpeptide, selective angiotensin subtype 1 (AT1) receptor antagonist. It provides a more specific and complete blockade of the actions of angiotensin II than renin or ACE inhibitors. Short term (up to 12 weeks' duration) clinical trials have shown losartan to be as effective at lowering blood pressure (BP) [causes a decrease in BP < or = 26/20 mm Hg] in elderly patients with hypertension as recommended dosages of captopril, atenolol, enalapril, felodipine and nifedipine. In patients with isolated systolic hypertension (ISH) the efficacy of losartan was similar to that of atenolol. The addition of hydrochlorothiazide to losartan therapy provides greater antihypertensive efficacy, equivalent to that seen with captopril plus hydrochlorothiazide. Preliminary evidence also indicates that losartan therapy contributes to the regression of left ventricular hypertrophy associated with chronic hypertension. Exercise capacity is increased by losartan in patients with either asymptomatic or symptomatic heart failure. Results from the Losartan Heart Failure Survival or ELITE II (Evaluation of Losartan in the Elderly II) study indicate that there was no statistically significant difference between losartan and captopril in reducing overall deaths or in reducing sudden cardiac death and/or resuscitated cardiac arrest in patients with heart failure. Other than ELITE II, little conclusive long term mortality and morbidity data exist for losartan. Additional long term trials to evaluate the survival benefits of losartan in elderly patients with hypertension, renal disease or after an acute myocardial infarction are currently in progress. In elderly patients with hypertension, the incidence of treatment-related adverse events associated with once daily losartan (alone or in combination with hydrochlorothiazide) [19 to 27%] was similar to felodipine (23%) and nifedipine (21%), however, losartan tended to be better tolerated than captopril (11 vs 16%). Losartan was also better tolerated than atenolol in patients with ISH (10.4 vs 23%). In patients with heart failure the renal tolerability of losartan was similar to that of captopril, but losartan was associated with a lower withdrawal rate because of adverse events. No dosage adjustment is required in elderly or in patients with mild to moderate renal dysfunction, and the risk of first-dose hypotension is low.


CONCLUSIONS
comparative data have shown losartan to be as effective as other antihypertensive agents in the treatment of elderly patients with hypertension. Treatment with losartan is therefore an option for first-line therapy in all patients with hypertension, particularly those who are not well managed with or who are intolerant of their current therapy. Morbidity and mortality data from the Losartan Heart Failure Survival (ELITE II) study show that losartan has potential in the treatment of heart failure.
Simpson
K L
KL
Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz
McClellan
K J
KJ
D000368:Aged / Q000502:physiology*; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D019808:Losartan / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D019808:Losartan