From the Guidelines
After losartan, adding a thiazide diuretic like hydrochlorothiazide (12.5-25mg daily) or chlorthalidone (12.5-25mg daily) is typically the next step for blood pressure management. These diuretics work synergistically with losartan by removing excess fluid while losartan blocks angiotensin II receptors, providing complementary mechanisms for blood pressure reduction. The most recent and highest quality study 1 supports the use of thiazide diuretics as a first-line addition to losartan for blood pressure management. If this combination is insufficient, adding a calcium channel blocker such as amlodipine (5-10mg daily) would be appropriate as a third agent. For patients with specific comorbidities, different additions might be preferred - beta-blockers like metoprolol for those with coronary artery disease, or spironolactone for resistant hypertension. Before adding any medication, ensure losartan is at its optimal dose (typically 50-100mg daily) and verify patient adherence. Blood pressure should be monitored regularly after adding new medications, with laboratory tests to check electrolytes and kidney function, particularly in the first few weeks of therapy. It is also important to note that ACE inhibitors and ARBs should not be given together, as this can increase the incidence of adverse events without improving survival, as stated in 1. Additionally, the use of aldosterone antagonists, such as spironolactone, may be useful in the management of heart failure and can have an additive blood pressure-lowering effect, as mentioned in 1 and 1. However, the most recent study 1 provides the strongest evidence for the use of thiazide diuretics as the next step after losartan.
Some key points to consider when adding a new medication to losartan include:
- Monitoring blood pressure regularly to assess the effectiveness of the new medication
- Checking electrolyte and kidney function laboratory tests, particularly in the first few weeks of therapy
- Adjusting the dose of the new medication as needed to achieve optimal blood pressure control
- Considering the patient's comorbidities and medical history when selecting a new medication to add to losartan.
Overall, the addition of a thiazide diuretic to losartan is a well-supported and effective strategy for blood pressure management, and should be considered as the next step in treatment.
From the FDA Drug Label
2.2 Hypertensive Patients with Left Ventricular Hypertrophy The usual starting dose is 50 mg of losartan once daily. Hydrochlorothiazide 12. 5 mg daily should be added and/or the dose of losartan should be increased to 100 mg once daily followed by an increase in hydrochlorothiazide to 25 mg once daily based on blood pressure response [see CLINICAL STUDIES (14.2)].
Hydrochlorothiazide should be added after losartan, starting with a dose of 12.5 mg daily, with the option to increase the dose of losartan to 100 mg once daily and/or increase hydrochlorothiazide to 25 mg once daily based on blood pressure response 2.
From the Research
Addition to Losartan Therapy
To enhance the antihypertensive effect of losartan, an angiotensin II receptor antagonist, several options can be considered based on existing studies:
- Hydrochlorothiazide (HCTZ), a diuretic, has been shown to be effective when added to losartan in patients with hypertension 3, 4, 5, 6.
- The combination of losartan and HCTZ has been demonstrated to lower blood pressure more effectively than losartan alone 3, 4, 5, 6.
- The optimal dose of HCTZ to add to losartan may vary, but doses of 12.5 mg or 25 mg have been found to be effective in reducing diastolic blood pressure compared to losartan alone or losartan with a lower dose of HCTZ (6.25 mg) 6.
Rationale for Combination Therapy
The rationale behind adding a diuretic like HCTZ to an angiotensin II receptor antagonist like losartan includes:
- Enhancing the antihypertensive effect by targeting different mechanisms of blood pressure regulation 7.
- Providing a synergistic effect, as diuretics can enhance the efficacy of other antihypertensive agents, including angiotensin II receptor blockers 7.
- Addressing potential salt-sensitivity of blood pressure in some patients, which can be more effectively managed with the inclusion of a diuretic in the treatment regimen 7.