Which medication, Losartan (angiotensin II receptor antagonist) or Amlodipine (calcium channel blocker), has the greatest impact on diastolic blood pressure?

Amlodipine Has Greater Impact on Diastolic Blood Pressure Than Losartan

Amlodipine provides superior diastolic blood pressure reduction compared to losartan in hypertensive patients. This conclusion is supported by multiple clinical studies comparing these two antihypertensive medications.

Comparative Efficacy on Diastolic Blood Pressure

Direct Comparison Evidence

• In a multicenter, double-blind, parallel-group clinical trial, amlodipine demonstrated significantly greater reductions in diastolic blood pressure compared to losartan (-12.6 vs. -10.3 mmHg; p=0.002) 1
• A 24-hour ambulatory blood pressure monitoring study showed that amlodipine produced greater diastolic blood pressure reductions than losartan, with better maintenance of control throughout the 24-hour period 2
• Even when comparing combination therapies, amlodipine/losartan 5/50 mg users had significantly greater diastolic BP reductions compared to amlodipine 5 mg alone (p=0.02) 3

Mechanism of Action Differences

The superior diastolic blood pressure reduction with amlodipine can be attributed to its mechanism as a calcium channel blocker:

• Amlodipine directly relaxes vascular smooth muscle by blocking calcium influx
• Losartan blocks angiotensin II receptors, which primarily affects systemic vascular resistance
• Calcium channel blockers like amlodipine have particularly potent effects on arterial dilation, which directly impacts diastolic pressure

Clinical Implications

Duration of Action

• Amlodipine maintains better blood pressure control even after missed doses compared to losartan
• The trough-to-peak ratio of antihypertensive effect on blood pressure was significantly greater with amlodipine than with losartan (62 ± 5% vs. 55 ± 4%, p < 0.05) 2
• This extended duration of action is particularly important for diastolic blood pressure control throughout the 24-hour period

Special Populations

• Amlodipine showed significantly greater response rates compared to losartan in African American patients (62.5% vs. 41.4%; p=0.033) 1
• Similarly, Hispanic patients showed better response to amlodipine than losartan (67.7% vs. 53.5%; p=0.039) 1

Potential Pitfalls and Considerations

Side Effect Profiles

• Amlodipine may cause peripheral edema in some patients
• Losartan generally has fewer side effects but may be less effective for diastolic blood pressure control
• When diastolic hypertension is the primary concern, the superior efficacy of amlodipine may outweigh potential side effects

Combination Therapy Considerations

• For patients with inadequate response to monotherapy, adding hydrochlorothiazide to losartan is common
• However, even with this addition, amlodipine monotherapy at increased doses (10 mg) showed better diastolic blood pressure control than losartan/HCTZ combination 1

Algorithm for Decision Making

1. For patients with predominantly diastolic hypertension, start with amlodipine 5 mg daily
2. If inadequate response after 6 weeks, increase to amlodipine 10 mg daily
3. Consider losartan as an alternative only if:
   • Patient experiences significant edema with amlodipine
   • Patient has specific indications for RAAS blockade (e.g., proteinuria)
   • Patient has contraindications to calcium channel blockers

In conclusion, when specifically targeting diastolic blood pressure reduction, amlodipine demonstrates superior efficacy compared to losartan across multiple clinical studies and should be preferred as first-line therapy for diastolic hypertension.