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Losartan potassium as initial therapy in patients with severe hypertension
M C Dunlay1, V Fitzpatrick, S Chrysant
1Clinical Cardiovascular Research, Merck Research Laboratories, West Point, PA 19486, USA.
Insights
Losartan potassium effectively lowers blood pressure in severe hypertension patients. Combination therapy with hydrochlorothiazide and other agents further improved control in this clinical experience study.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Hypertension Research
Background:
- Severe hypertension poses significant cardiovascular risks.
- Angiotensin II receptor antagonists offer a therapeutic option for blood pressure management.
- Experience with losartan potassium in severe hypertension requires further investigation.
Purpose of the Study:
- To evaluate the efficacy and tolerability of losartan potassium in patients with severe hypertension.
- To assess the role of losartan potassium as initial monotherapy and in combination regimens.
- To determine the safety profile of losartan potassium in this patient population.
Main Methods:
- A 12-week, open-label study involving 179 patients with severe hypertension.
- Initial treatment with losartan potassium 50 mg once daily, titrated to 100 mg as needed.
- Add-on therapy with hydrochlorothiazide, calcium channel blockers, and/or atenolol for uncontrolled blood pressure.
Main Results:
- Statistically significant reductions in sitting diastolic blood pressure (SiDBP) were observed throughout the study (P < 0.001).
- By the end of the trial, 68 patients achieved SiDBP < 90 mm Hg.
- 25% of patients experienced drug-related adverse events, with headache being the most common (26%).
Conclusions:
- Losartan potassium is effective as initial therapy for severe hypertension.
- Concurrent administration with hydrochlorothiazide, calcium channel blockers, and atenolol is feasible and improves blood pressure control.
- Losartan potassium demonstrates a favorable safety profile in this patient cohort.
Abstract:
This 12-week, open-label study was conducted to gain experience with losartan potassium, an angiotensin II receptor antagonist, in patients with severe hypertension. Patients were either untreated or withdrawn from current therapy for at least 48 h before initiation of losartan 50 mg once daily. Patients were titrated to 100 mg as needed to achieve a goal of sitting diastolic blood pressure (SiDBP) 90 or 95 mm Hg. Hydrochlorothiazide (12.5 mg once daily titrated to 25 mg) was added and followed by either a dihydropyridine calcium channel blocker (CCB) and/or atenolol, if BP was not controlled. A total of 179 patients with a pretreatment mean baseline BP of 172 +/- 17/112 +/- 18 mm Hg enrolled in the trial and BP was recorded 24 h after dosing at baseline and weeks 2, 4, 8 and the final week (10-12 weeks). The mean reductions in SiDBP from baseline were 7.3, 9.3, 15.9 and 18.9 mm Hg, respectively, and these changes from baseline were statistically significant, P < 0.001. At the end of the trial, 22% of patients remained on losartan monotherapy, 30% required the addition of hydrochlorothiazide (HCTZ) and 31% required both HCTZ and a CCB; 11% required HCTZ and atenolol while 4% required HCTZ, a CCB and atenolol; 2% of patients were on regimens not specified by the protocol. SiDBP < 90 mm Hg was achieved in 68 patients by the final visit; 24% of these patients were treated with losartan monotherapy (50 or 100 mg), 41% achieved control with the addition of HCTZ (12.5 or 25 mg) and 24% required triple therapy which included losartan, HCTZ and a CCB. As assessed by the investigator, 25% of the patients in the study had drug-related clinical adverse experiences. Headache was the most frequently reported clinical adverse event (26% of patients). No clinically significant changes in laboratory parameters were observed. It is concluded that losartan potassium can be used as initial therapy for patients with severe hypertension and can be administered concurrently with hydrochlorothiazide, calcium channel blockers and atenolol.