From the Guidelines
For patients with hypertension refractory to HCTZ, the most effective approach is to optimize the current treatment regimen, including health behavior change and diuretic-based treatment, and consider 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 recommended by the 2020 international society of hypertension global hypertension practice guidelines 1. When managing hypertension that is refractory to HCTZ, it is essential to first exclude causes of pseudoresistance, such as poor BP measurement technique, white coat effect, nonadherence, and suboptimal choices in antihypertensive therapy, as well as substance-induced increases in BP 1. Key considerations in the management of refractory hypertension include:
- Optimizing the current treatment regimen, including health behavior change and diuretic-based treatment, with maximally tolerated doses of diuretics and optimal choice of diuretic 1
- 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, to achieve BP targets 1
- Considering alternative agents, such as amiloride, doxazosin, eplerenone, clonidine, and beta-blockers, if spironolactone is contraindicated or not tolerated 1
- Managing resistant hypertension in specialist centers with sufficient expertise and resources necessary to diagnose and treat this condition 1. It is crucial to prioritize the management of refractory hypertension, as uncontrolled blood pressure can lead to significant morbidity, mortality, and decreased quality of life.
From the FDA Drug Label
If goal blood pressure (<140/90 mmHg) was not reached, hydrochlorothiazide (12.5 mg) was added first and, if needed, the dose of losartan or atenolol was then increased to 100 mg once daily. If necessary, other antihypertensive treatments (e.g., increase in dose of hydrochlorothiazide therapy to 25 mg or addition of other diuretic therapy, calcium-channel blockers, alpha-blockers, or centrally acting agents, but not ACE inhibitors, angiotensin II antagonists, or beta-blockers) were added to the treatment regimen to reach the goal blood pressure.
The management of hypertension refractory to HCTZ may involve adding other antihypertensive treatments, such as:
- Increasing the dose of HCTZ to 25 mg
- Adding other diuretic therapy
- Adding calcium-channel blockers
- Adding alpha-blockers
- Adding centrally acting agents Losartan can be used as an alternative to other antihypertensive agents, such as atenolol, and may be effective in reducing blood pressure in patients with hypertension, including those with left ventricular hypertrophy 2.
From the Research
Management of Hypertension Refractory to HCTZ
- Hypertension refractory to HCTZ (hydrochlorothiazide) is a challenging condition to manage, and several studies have investigated the optimal treatment approach 3, 4, 5, 6, 7.
- According to the European hypertension guidelines, a rational combination for triple therapy includes an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic 3.
- The use of olmesartan medoxomil, amlodipine, and HCTZ as a triple fixed-dose combination has been shown to be effective in reducing blood pressure in patients with uncontrolled hypertension 3.
- In patients with resistant hypertension, the addition of spironolactone or amiloride to the standard 3-drug antihypertensive regimen can be effective in achieving blood pressure control 5.
- Refractory hypertension, defined as uncontrolled blood pressure despite the use of ≥5 antihypertensive agents, may require a different treatment approach, including the use of mineralocorticoid receptor antagonists and device-based therapies such as renal denervation 5, 6, 7.
- Lifestyle modification and adherence to antihypertensive medication are also crucial in managing hypertension refractory to HCTZ 4, 5, 7.
- Novel agents, such as aldosterone synthase inhibitors and dual endothelin receptor antagonists, are being developed and may provide potent blood pressure lowering in patients with resistant hypertension 7.