What are the first-line and second-line treatments for managing hypertension?

From the Guidelines

First-line treatments for hypertension should include ACE inhibitors, ARBs, dihydropyridine CCBs, and diuretics, as these have demonstrated the most effective reduction of BP and CVD events. The choice among these depends on patient characteristics, with ACE inhibitors or ARBs often preferred for patients with diabetes or chronic kidney disease, and calcium channel blockers for older patients or those of African descent 1.

Key Considerations

• ACE inhibitors, such as lisinopril 10-40 mg daily, are a good option for patients with diabetes or chronic kidney disease.
• ARBs, such as losartan 25-100 mg daily, are also a good option for patients with diabetes or chronic kidney disease.
• Calcium channel blockers, such as amlodipine 5-10 mg daily, are a good option for older patients or those of African descent.
• Diuretics, such as hydrochlorothiazide 12.5-25 mg daily, are a good option for patients with hypertension.

Second-Line Treatments

Second-line treatments are implemented when blood pressure remains uncontrolled on first-line medications and typically involve adding a different class of medication to the existing regimen. These include beta-blockers (such as metoprolol 25-100 mg twice daily), aldosterone antagonists (spironolactone 25-50 mg daily), or combining two first-line agents 1.

Lifestyle Modifications

Lifestyle modifications are essential alongside medication therapy, including reducing sodium intake to less than 2,300 mg daily, regular physical activity (150 minutes of moderate exercise weekly), weight management, limiting alcohol consumption, and following the DASH diet 1.

Mechanisms of Action

These medications work through different mechanisms: diuretics reduce blood volume, ACE inhibitors and ARBs relax blood vessels by affecting the renin-angiotensin-aldosterone system, calcium channel blockers prevent calcium from entering heart and blood vessel cells, and beta-blockers reduce heart rate and cardiac output 1.

Additional Considerations

It is recommended that beta-blockers are combined with any of the other major BP-lowering drug classes when there are other compelling indications for their use, e.g. angina, post-myocardial infarction, heart failure with reduced ejection fraction, or for heart rate control 1.

Combination Therapy

Combination BP-lowering treatment is recommended for most patients with confirmed hypertension (BP ≥140/90 mmHg) as initial therapy, with preferred combinations being a RAS blocker (either an ACE inhibitor or an ARB) with a dihydropyridine CCB or diuretic 1.

Fixed-Dose Single-Pill Combination

In patients receiving combination BP-lowering treatment, fixed-dose single-pill combination treatment is recommended 1.

Titration

If BP is not controlled with a two-drug combination, increasing to a three-drug combination is recommended, usually a RAS blocker with a dihydropyridine CCB and a thiazide/thiazide-like diuretic, and preferably in a single-pill combination 1.

Additional Agents

If BP is not controlled with a three-drug combination, adding spironolactone should be considered, and if not effective or tolerated, treatment with eplerenone instead of spironolactone, or the addition of a beta-blocker if not already indicated, and next, a centrally acting BP-lowering medication, an alpha-blocker, hydralazine, or a potassium-sparing diuretic should be considered 1.

From the FDA Drug Label

In controlled clinical studies, metoprolol has been shown to be an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics, at dosages of 100 mg to 450 mg daily In controlled, comparative, clinical studies, metoprolol has been shown to be as effective an antihypertensive agent as propranolol, methyldopa, and thiazide-type diuretics, to be equally effective in supine and standing positions

The first-line treatments for managing hypertension include:

• ACE inhibitors
• beta-blockers such as metoprolol
• thiazide-type diuretics
• methyldopa The second-line treatments are not explicitly stated in the provided text, and therefore, no conclusion can be drawn about second-line treatments. 2 3

From the Research

First-Line Treatments for Hypertension

• The 2018 ESH/ESC guidelines indicate that the first-choice therapy in the majority of hypertensive patients should be a fixed combination of a drug that blocks the renin-angiotensin-aldosterone system and a calcium antagonist or a diuretic 4.
• A fixed combination of ramipril and amlodipine represents a first choice therapy for hypertension, as demonstrated by numerous controlled clinical studies 4.
• Calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, and they have been shown to reduce the incidence of major adverse cardiovascular events compared to beta-blockers 5.
• Diuretics are also effective in reducing major cardiovascular events and congestive heart failure, and may be considered as a first-line treatment for hypertension 5, 6, 7.

Second-Line Treatments for Hypertension

• Beta-blockers may be considered as a second-line treatment for hypertension, although they have been shown to be less effective in reducing cardiovascular events compared to CCBs and diuretics 8, 5, 6, 7.
• Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) may also be considered as second-line treatments for hypertension, although their effectiveness compared to CCBs and diuretics is still debated 4, 5.
• Combination therapy with two or more antihypertensive agents may be necessary to achieve blood pressure control in some patients, and has been shown to be effective in reducing cardiovascular events 8, 7.