Combination indicated to reduce risk of stroke in hypertensive patients with LVH
Hyzaar Losartan-hydrochlorothiazide tablets
MERCKCombination indicated to reduce risk of stroke in hypertensive patients with LVH
This combination angiotensin II receptor antagonist and diuretic produces its antihypertensive effect by preventing vasoconstriction and reducing plasma volume. Losartan-hydrochlorothiazide was approved on April 14, 2005, to reduce the risk of stroke in patients with hypertension and left ventricular hypertrophy (LVH). There is evidence that this benefit does not apply to Black patients.
Efficacy. The efficacy of losartan-hydrochlorothiazide for the prevention of stroke was established in a study of 9,193 patients with hypertension and LVH. Patients were randomized to receive once-daily losartan 50 mg or atenolol 50 mg. If blood pressure goal (<140/90 mmHg) was not reached, hydrochlorothiazide 12.5 mg was added first, followed by an increase in losartan or atenolol dose to 100 mg daily if needed. Further antihypertensive therapy (hydrochlorothiazide dose increase to 25 mg daily or addition of other agents) was added if blood pressure goal was still not reached. Seventy-seven percent of patients in the study received hydrochlorothiazide with their losartan or atenolol dose. The primary end point in the study was first occurrence of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. Treatment with losartan resulted in a 13% reduction (P=.021) in the risk of the primary end point compared with the atenolol group. This difference was primarily due to the effect of the drug on fatal and nonfatal stroke, with the losartan group experiencing a 25% reduction in risk of stroke relative to atenolol (P=.001). Conversely, Black patients treated with atenolol were at lower risk for experiencing the composite end point than Black patients treated with losartan. Therefore, the results of the study provided no evidence that the benefits of losartan on reducing the risk of cardiovascular events in hypertensive patients with LVH apply to Black patients.
Safety. Lightheadedness may occur with losartan-hydrochlorothiazide treatment, especially during the first days of therapy. If syncope occurs, losartan-hydrochlorothiazide therapy should be discontinued immediately until a physician is consulted. Inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive decline in blood pressure, and ultimately lightheadedness and syncope. All patients receiving thiazide therapy should be monitored for clinical signs of fluid or electrolyte imbalance, including hyponatremia, hypochlor-emic alkalosis, and hypokalemia. Drugs such as losartan that inhibit the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. If pregnancy is detected, losartan-hydrochlorothiazide therapy should be discontinued immediately. The most common adverse events associated with losartan-hydrochlorothiazide include abdominal pain, edema/swelling, palpitation, back pain, dizziness, cough, sinusitis, upper respiratory infection, and rash. Adverse events associated with losartan-hydrochlorothiazide are somewhat more frequent in the elderly (aged ≥65 y) patient population compared to the non-elderly population.