What are the first 2 drugs to start with for resistant hypertension?

From the Guidelines

For resistant hypertension, the first two drugs to start with are an ACE inhibitor or angiotensin receptor blocker and a calcium channel blocker, as these are typically the foundation of treatment for hypertension, and then optimization of the regimen can occur based on patient response and tolerance. When managing resistant hypertension, it is essential to consider the patient's existing medication regimen and optimize it before adding new medications. According to the 2024 ESC guidelines for the management of elevated blood pressure and hypertension 1, the recommended treatment of resistant hypertension includes reinforcement of lifestyle measures, especially sodium restriction, and the addition of low-dose spironolactone to existing treatment. Some key points to consider when selecting the first two drugs for resistant hypertension include:

• The importance of using a diuretic, such as a thiazide diuretic, as part of the treatment regimen, as recommended by the 2020 International Society of Hypertension global hypertension practice guidelines 1
• The need to optimize the current treatment regimen, including health behavior change and diuretic-based treatment, before adding new medications
• The potential benefits of adding a low-dose of spironolactone as the 4th line agent in patients whose serum potassium is <4.5 mmol/L and whose eGFR is >45 ml/min/1.73m2 to achieve BP targets, as recommended by the 2020 International Society of Hypertension global hypertension practice guidelines 1
• The importance of monitoring for side effects, such as electrolyte abnormalities with diuretics or peripheral edema with calcium channel blockers, when adding new medications to the treatment regimen. It is crucial to prioritize the patient's safety and well-being when managing resistant hypertension, and to make decisions based on the most recent and highest-quality evidence available, such as the 2024 ESC guidelines 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Therapy should be initiated with the lowest possible dose. A single dose given in the morning with food is recommended; divided daily doses are unnecessary Hypertension Initiation Therapy, in most patients, should be initiated with a single daily dose of 25 mg. If the response is insufficient after a suitable trial, the dosage may be increased to a single daily dose of 50 mg. If additional control is required, the dosage of chlorthalidone may be increased to 100 mg once daily or a second antihypertensive drug (step 2 therapy) may be added

The first 2 drugs to start with for resistant hypertension are not explicitly stated in the provided drug labels.

• Losartan can be started at a dose of 50 mg once daily, and the dosage can be increased to a maximum dose of 100 mg once daily as needed to control blood pressure 2.
• Chlorthalidone can be started at a dose of 25 mg once daily, and the dosage can be increased to 50 mg or 100 mg once daily if additional control is required 3. However, the FDA drug label does not provide information on the specific combination of these drugs for resistant hypertension.

From the Research

First-Line Treatment for Resistant Hypertension

The first-line treatment for resistant hypertension typically involves a combination of antihypertensive agents. According to the studies, the following are commonly recommended as initial treatments:

• A blocker of the renin-angiotensin system (ACE inhibitor or angiotensin receptor blocker) 4, 5, 6, 7
• A diuretic, such as a thiazide diuretic or a loop diuretic in patients with reduced glomerular filtration rate 4, 5, 6, 7

Specific Drug Combinations

Some studies suggest the following specific drug combinations as initial treatments:

• An angiotensin receptor blocker (ARB) combined with a diuretic, such as hydrochlorothiazide (HCTZ) 8
• A calcium channel blocker (CCB) combined with a blocker of the renin-angiotensin system (ACE inhibitor or ARB) 4, 7

Key Considerations

When selecting the first two drugs to start with for resistant hypertension, it is essential to consider the patient's individual characteristics, such as age, ethnicity, comorbidities, and risk of drug-drug interactions 4, 6, 7. Additionally, lifestyle modifications, such as reduced sodium and alcohol intake, regular physical activity, weight loss, and discontinuation of substances that can interfere with blood pressure control, should be implemented concurrently with pharmacologic treatment 4, 5, 6, 7.