From the Guidelines
For a patient with persistent hypertension despite lisinopril 20mg monotherapy, I recommend adding a second antihypertensive medication, specifically a thiazide diuretic like hydrochlorothiazide 12.5-25mg daily or a calcium channel blocker such as amlodipine 5-10mg daily, as combination therapy is more effective than increasing the ACE inhibitor dose beyond 20mg, according to the 2024 ESC guidelines 1. This approach is supported by the latest evidence, which suggests that combining drugs from different classes can have additive or synergistic effects, leading to greater blood pressure reduction than increasing the dose of one drug 1. The major four drug classes, including ACE inhibitors, ARBs, dihydropyridine CCBs, and thiazide or thiazide-like diuretics, are recommended as first-line BP-lowering medications, either alone or in combination 1. Some key points to consider when adding a second medication include:
- Ensuring the patient is adhering to the current regimen and following lifestyle modifications, such as sodium restriction, regular exercise, and weight management
- Ruling out secondary causes of hypertension
- Monitoring for potential side effects after adding the second agent, including electrolyte disturbances with diuretics or peripheral edema with calcium channel blockers
- Reassessing blood pressure within 2-4 weeks after initiating combination therapy to evaluate efficacy and adjust dosing if needed It's also important to note that the 2020 International Society of Hypertension global hypertension practice guidelines recommend optimizing the current treatment regimen, including health behavior change and diuretic-based treatment, before adding a new medication 1. However, the most recent and highest-quality study, the 2024 ESC guidelines, takes precedence in guiding clinical decision-making 1.
From the Research
Next Steps for Persistent Hypertension
- For patients with persistent hypertension despite monotherapy with lisinopril 20mg, the next step could be to increase the dose of lisinopril to 40mg once daily 2, 3.
- Another option is to add a diuretic, such as hydrochlorothiazide, to the treatment regimen, as the combination of lisinopril and hydrochlorothiazide has been shown to be effective in reducing blood pressure 2.
- Alternatively, the dosing frequency of lisinopril could be increased to twice daily, as twice-daily administration has been associated with greater reductions in blood pressure compared to once-daily administration 4.
- The choice of next step will depend on individual patient factors, such as the severity of hypertension, presence of comorbidities, and potential side effects of the treatment options.
Considerations for Treatment
- Lisinopril has been shown to have a satisfactory antihypertensive effect in about 40% of patients when used as monotherapy 3.
- The addition of hydrochlorothiazide to lisinopril has been shown to be as effective as increasing the dose of lisinopril to 40mg once daily 2.
- Twice-daily administration of lisinopril has been associated with greater reductions in blood pressure compared to once-daily administration, but may not be necessary for all patients 4, 5.