Estimated Effect on Blood Pressure When Changing from Lisinopril 20mg/Amlodipine 10mg to Lisinopril 40mg/Amlodipine 5mg
Changing from lisinopril 20mg with amlodipine 10mg to lisinopril 40mg with amlodipine 5mg will likely result in a net increase in blood pressure of approximately 5-8 mmHg systolic and 2-4 mmHg diastolic due to the greater antihypertensive effect of amlodipine 10mg compared to the additional effect of increasing lisinopril from 20mg to 40mg.
Mechanism of Action and Dose-Response Relationships
Amlodipine Dose-Response
- Amlodipine is a calcium channel blocker that provides potent blood pressure reduction
- Dose-response relationship:
- Reducing amlodipine from 10mg to 5mg will result in approximately 5-8 mmHg higher systolic BP and 2-4 mmHg higher diastolic BP
- The relationship between amlodipine dose and BP reduction is relatively linear in the therapeutic range 1
Lisinopril Dose-Response
- Lisinopril is an ACE inhibitor with a relatively flat dose-response curve at higher doses
- Doubling lisinopril from 20mg to 40mg typically provides only modest additional BP lowering effects (approximately 2-3 mmHg systolic and 1-2 mmHg diastolic) 1
- The ALLHAT study showed that lisinopril at doses up to 40mg provided less BP reduction than amlodipine, particularly in certain populations such as Black patients 1
Evidence-Based Analysis
The JNC 7 guidelines and subsequent hypertension management recommendations suggest that the dose-response relationship for most antihypertensive medications follows a logarithmic curve, with the greatest BP reductions occurring at lower doses 1. This is particularly true for calcium channel blockers like amlodipine.
In the ALLHAT study, amlodipine demonstrated superior blood pressure lowering compared to lisinopril at equivalent recommended doses 1. This suggests that reducing the amlodipine dose from 10mg to 5mg would have a more substantial negative impact on BP control than would be offset by doubling the lisinopril dose.
Studies examining combination therapy with amlodipine and lisinopril have shown that:
- The combination of lower doses of both drugs (amlodipine 2.5mg + lisinopril 5mg) provides better BP reduction than higher doses of either drug alone 2
- When patients are not adequately controlled on the combination of amlodipine and lisinopril, increasing the dose of amlodipine is often more effective than increasing the dose of lisinopril 3
Clinical Implications
Expected BP Changes
- Net effect: Approximately 3-6 mmHg increase in systolic BP and 1-3 mmHg increase in diastolic BP
- This estimate accounts for:
- Loss of BP control from reducing amlodipine (5-8/2-4 mmHg)
- Partial compensation from increasing lisinopril (2-3/1-2 mmHg)
Populations with Special Considerations
- Black patients: The effect may be more pronounced (greater BP increase) as this population typically responds better to calcium channel blockers than to ACE inhibitors 1
- Elderly patients: May be more sensitive to the change in amlodipine dose 1
- Patients with kidney disease: May benefit more from the higher lisinopril dose, potentially mitigating some of the BP increase 1
Common Pitfalls and Caveats
- Individual variability: Response to medication changes varies significantly between patients
- Medication adherence: Higher pill burden with separate medications (if not using a combination pill) may affect adherence
- Time to steady state: Full effect of dose changes may take 2-4 weeks to manifest
- Monitoring recommendation: Check BP within 2-4 weeks after making this medication change
- Chronotherapy considerations: The timing of medication administration may influence the overall effect on BP control
In conclusion, while increasing lisinopril from 20mg to 40mg will provide some additional BP lowering effect, it is unlikely to fully compensate for the reduction in BP control from decreasing amlodipine from 10mg to 5mg based on the available evidence from major hypertension trials and guidelines.