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Therapeutics

Losartan was as effective as enalapril for essential hypertension

ACP J Club. 1996 Jan-Feb;124:10. doi:10.7326/ACPJC-1996-124-1-010


Source Citation

Gradman AH, Arcuri KE, Goldberg AI, et al. A randomized, placebo-controlled, double-blind, parallel study of various doses of losartan potassium compared with enalapril maleate in patients with essential hypertension. Hypertension. 1995 Jun;25:1345-50. [PubMed ID: 7768585]


Abstract

Objective

To compare 5 doses of losartan potassium with enalapril maleate and placebo in adults with mild-to-moderate essential hypertension.

Design

Randomized, double-blind, placebo-controlled trial.

Setting

41 clinical centers in the United States.

Patients

After a 4-week placebo run-in period, 576 patients (mean age 53 y, 66% men, 76% white) with mild-to-moderate essential hypertension were enrolled. Inclusion criteria were age ≥ 21 years; body weight within 30% of the ideal; and diastolic blood pressure (DBP) > 90 mm Hg at baseline, ≥ 95 mm Hg after 2 weeks of placebo, and 100 to 115 mm Hg after 4 weeks. Exclusion criteria were other major illnesses; regular use of nonsteroidal anti-inflammatory agents, psychotropic agents, or antidepressant drugs; use of medications that could lower blood pressure; drug or alcohol abuse; sensitivity to angiotensin-converting enzyme (ACE) inhibitors; and previous exposure to losartan potassium.

Intervention

All drugs were taken orally, once daily for 8 weeks. 78 patients were allocated to placebo; 83 patients to enalapril, 20 mg; 80 patients to losartan, 10 mg; 82 patients to losartan, 25 mg; 79 patients to losartan, 50 mg; 90 patients to losartan, 100 mg; and 84 patients to losartan, 150 mg. Follow-up was 94%.

Main Outcome Measures

Changes from baseline in systolic blood pressure (SBP) and DBP and adverse effects.

Main Results

Maximum benefit from losartan was achieved at 3 to 6 weeks. For all doses of losartan ≥ 50 mg/d, decreases in DBP and SBP were greater than those for placebo (P ≤ 0.01), and decreases in DBP were similar to those achieved with enalapril. Mean changes in SBP/DBP (24 hours after last dose) for placebo, enalapril, and losartan, 10, 25, 50, 100, and 150 mg/d, were 3.8/5.6, 14.7/11.2, 7.6/7.9, 7.8/6.8, 13.0/10.1, 8.9/9.9, and 10.5/9.7 mm Hg, respectively. Headache (10% to 20%), upper respiratory infection (1% to 12%), and cough (2% to 8%) were reported in all groups and were not related to dose.

Conclusions

In adults with mild-to-moderate essential hypertension, losartan and enalapril taken once daily were similarly effective at reducing diastolic blood pressure. Adverse effects occurred in all groups and were not dose or drug dependent.

Source of funding: Not stated.

For article reprint: Dr. C.S. Sweet, Clinical Cardiovascular Research, Merck Research Laboratories, West Point, PA 19486, USA. FAX 908-735-1726.


Commentary

Losartan is a new antihypertensive agent that blocks the angiotensin II (AII) receptor. The study by Gradman and colleagues helps to define some clinical guidelines for the use of losartin by showing that 1) the optimal dose is 50 mg daily, 2) at ≥ 50 mg/d it is almost, but not quite, as effective as enalapril, 20 mg/d, in lowering blood pressure, 3) it is well tolerated over an 8-week period, and 4) the overall discontinuation rate was 8.4%.

Where does losartan fit in the antihypertensive armamentarium? It is distinct from ACE inhibitors, which inhibit AII formation but may also increase kinin and prostaglandin levels, actions that may contribute to many of the salutary and possibly some of the adverse effects of ACE inhibitors. Losartan is not less expensive than most ACE inhibitors (1), nor is it more effective. Its side effects are similar to those of enalapril except for lower rates of cough. Moreover, no studies to date have shown that losartan lowers morbidity or mortality rates in heart failure or after myocardial infarction, attenuates the development of diabetic nephropathy, or slows the progression of chronic renal failure—all apparent effects of ACE inhibition not shown to be caused exclusively by the inhibition of AII effects. Studies designed to examine the possible beneficial effects of losartan in these patients are currently under way.

In patients who cannot tolerate ACE inhibitors because of intractable cough or allergic reaction, substituting losartan may not result in equally beneficial effects, but these groups are the most logical ones to receive treatment with losartan. The long-term efficacy and side effects of losartan remain to be determined.

Gregory K. Buller, MD
St. Mary's HospitalWaterbury, Connecticut, USA


Reference

1. Losartan for hypertension. Med Lett Drugs Ther. 1995;37:57-8.