From the Guidelines
The patient's blood pressure remains elevated despite being on multiple antihypertensive medications, suggesting resistant hypertension, and I recommend optimizing the current regimen by adding a low dose of spironolactone as the 4th line agent, if serum potassium is <4.5 mmol/L and eGFR is >45 ml/min/1.73m2, as per the 2020 international society of hypertension global hypertension practice guidelines 1. The patient is currently on metoprolol 50 mg twice daily, lisinopril-hydrochlorothiazide 20-25 mg, and clonidine. To optimize the treatment regimen, the following steps should be taken:
- Exclude causes of pseudoresistance, such as poor BP measurement technique, white coat effect, nonadherence, and suboptimal choices in antihypertensive therapy 1
- Consider screening patients for secondary causes as appropriate, such as sleep apnea, primary aldosteronism, and renal artery stenosis 1
- Optimize the current treatment regimen, including health behavior change and diuretic-based treatment, with maximally tolerated doses of diuretics and optimal choice of diuretic 1
- Add a low dose of spironolactone as the 4th line agent, if serum potassium is <4.5 mmol/L and eGFR is >45 ml/min/1.73m2, to achieve BP targets 1 Lifestyle modifications are essential and include:
- Reducing sodium intake to less than 2 grams daily
- Maintaining regular physical activity of at least 150 minutes per week
- Limiting alcohol consumption
- Following the DASH diet Medication adherence should be emphasized, and home blood pressure monitoring is recommended twice daily. The rationale for these changes is that resistant hypertension often requires 4 or more medications from different classes to achieve control, with one being a diuretic, as stated in the 2017 acc/aha/aapa/abc/acpm/ags/apha/ash/aspc/nma/pcna guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1.
From the FDA Drug Label
In controlled clinical studies of patients with mild to moderate hypertension, patients were treated with lisinopril 20 mg to 80 mg daily, hydrochlorothiazide 12. 5 mg to 50 mg daily or atenolol 50 mg to 200 mg daily; and in other studies of patients with moderate to severe hypertension, patients were treated with lisinopril 20 mg to 80 mg daily or metoprolol 100 mg to 200 mg daily. Lisinopril demonstrated superior reductions of systolic and diastolic compared to hydrochlorothiazide in a population that was 75% Caucasian Lisinopril was approximately equivalent to atenolol and metoprolol in reducing diastolic blood pressure, and had somewhat greater effects on systolic blood pressure.
The patient is on metoprolol 50 mg bid, lisinopril-hydrochlorothiazide 20-25, and clonidine.
- The current dose of lisinopril is within the range of 20 mg to 80 mg daily, which has been shown to be effective in reducing blood pressure.
- The current dose of metoprolol is 50 mg bid, which is within the range of 50 mg to 200 mg daily used in clinical studies.
- Since the patient's BP is elevated, it may be necessary to adjust the dose of these medications or add another medication to achieve better blood pressure control 2.
- However, the FDA label does not provide specific guidance on how to adjust the dose in this scenario, and the decision should be made based on clinical judgment and careful monitoring of the patient's response to treatment.
- Additionally, the patient is also taking clonidine, and the label warns that beta-adrenergic blockers may potentiate the postural hypotensive effect of the first dose of prazosin, probably by preventing reflex tachycardia, and that rebound hypertension that can follow withdrawal of clonidine may be increased in patients receiving concurrent beta-blocker treatment 3.
From the Research
Current Medication Regimen
The patient is currently taking metoprolol 50 mg bid, lisinopril-hydrochlorothiazide 20-25, and clonidine for elevated blood pressure.
Combination Therapy for Hypertension
- More than 70% of adults treated for primary hypertension will eventually require at least two antihypertensive agents, either initially as combination therapy or as add-on therapy if monotherapy and lifestyle modifications do not achieve adequate blood pressure control 4.
- Four main classes of medications are used in combination therapy for the treatment of hypertension: thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) 4.
- ACEIs and ARBs should not be used simultaneously 4.
Efficacy of Combination Therapy
- The combination of amlodipine plus valsartan compared with lisinopril plus hydrochlorothiazide in adult patients with stage 2 hypertension showed that both regimens were generally well tolerated and efficacious, and both treatments were associated with achievement of BP goals in the majority of patients 5.
- The combination of losartan, amlodipine, and hydrochlorothiazide was found to be effective in reducing blood pressure in stage 2 hypertensive patients 6.
Metoprolol Dosage
- A study compared the efficacy of metoprolol as an antihypertensive agent in 20 previously untreated patients with mild to moderate hypertension, and found that all patients had satisfactory control of their blood pressures on a twice-daily regimen, with an average dosage of 200 mg daily 7.
- The study also found that once-daily therapy was as effective as twice-daily therapy in controlling blood pressure 7.
Angiotensin II Receptor Blocker Combinations
- European guidelines recommend a combination of at least two antihypertensive drugs to achieve blood pressure goals in the majority of patients, and encourage simplification of treatment regimens using single-pill, fixed-dose combinations (FDCs) to aid compliance 8.
- Angiotensin II receptor blocker combinations, such as with amlodipine or hydrochlorothiazide, have been found to be effective in reducing blood pressure and improving control rates compared with component monotherapies 8.