What is the drug of choice for managing hypertension (high blood pressure)?

From the Guidelines

The drug of choice for hypertension is typically an ACE inhibitor or an ARB, such as lisinopril (10-40 mg daily) or losartan (50-100 mg daily), or a thiazide diuretic, such as hydrochlorothiazide (12.5-25 mg daily) or chlorthalidone (12.5-25 mg daily), depending on the patient's specific characteristics. According to the most recent guidelines, the choice of antihypertensive medication should be based on the patient's individual characteristics, such as age, comorbidities, and ethnicity 1. For patients under 55 without comorbidities, an ACE inhibitor or an ARB may be preferred, while for Black patients or those over 55, calcium channel blockers like amlodipine (5-10 mg daily) may be more effective 1. Beta-blockers, such as metoprolol, are no longer considered first-line except in specific situations like post-myocardial infarction or heart failure 1. Treatment should start with a low dose of a single agent and titrate up before adding a second medication from a different class if blood pressure remains uncontrolled, with the goal of achieving a blood pressure below 130/80 mmHg for most patients 1. Lifestyle modifications, including sodium restriction, weight loss, regular exercise, and limiting alcohol consumption, should accompany any pharmacological treatment 1. The major four drug classes (ACE inhibitors, ARBs, dihydropyridine CCBs, and thiazide or thiazide-like diuretics) are recommended as first-line BP-lowering medications, either alone or in combination, with a single-pill combination initially containing two of these major drug classes and initially at low dose, being recommended for most hypertensive patients 1. When BP is still uncontrolled under maximally tolerated triple-combination therapy, the patient should be considered resistant and referred to an expert centre for appropriate work-up, and the addition of spironolactone or other MRA, or beta-blockers, should be considered 1. It's worth noting that the evidence for reduced CVD outcomes with BP-lowering drugs in combination therapy is based on observational studies, and there are no outcomes data from prospective trials that prove superiority of upfront combination therapy over upfront monotherapy in the isolated treatment of hypertension 1. However, given the totality of evidence for outcomes benefit in observational studies, randomized trial data for better BP control and adherence, and importantly, also given CVD outcomes benefit for polypills in randomized trials, upfront combination therapy is recommended in adults with confirmed hypertension 1.

Some key points to consider when choosing an antihypertensive medication include:

• The patient's age and comorbidities
• The patient's ethnicity
• The presence of heart failure or post-myocardial infarction
• The patient's ability to tolerate certain medications
• The need for lifestyle modifications to accompany pharmacological treatment

Overall, the choice of antihypertensive medication should be individualized and based on the patient's specific characteristics, with the goal of achieving optimal blood pressure control and reducing the risk of cardiovascular disease.

From the FDA Drug Label

1 INDICATIONS & USAGE 1. 1 Hypertension Amlodipine besylate tablets is indicated for the treatment of hypertension, to lower blood pressure.

The drug of choice for hypertension is not explicitly stated in the label, as it mentions that many patients will require more than one drug to achieve blood pressure goals and that numerous antihypertensive drugs have been shown to reduce cardiovascular morbidity and mortality.

• The label does mention that Amlodipine besylate tablets may be used alone or in combination with other antihypertensive agents.
• It also states that some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and that these considerations may guide selection of therapy 2. However, the label does not provide a clear answer to the question of a single drug of choice for hypertension.

From the Research

Drug of Choice in Hypertension

The choice of drug for hypertension depends on various factors, including the patient's medical history, lifestyle, and other health conditions.

• According to a study published in 1988 3, Angiotensin-converting enzyme (ACE) inhibitors are effective in lowering blood pressure in over 50 percent of patients as monotherapy, and when combined with a diuretic, 80 to 95 percent of patients respond.
• However, a more recent study published in 2018 4 suggests that ACE inhibitors may not be the best choice due to their association with cough and a low risk of angioedema and fatalities, and that angiotensin receptor blockers (ARBs) may be a better alternative.
• Another study published in 2012 5 recommends the use of a combination of an ARB, a calcium channel blocker, and a thiazide diuretic as a rational combination for the treatment of hypertension, especially in patients who require triple therapy.
• A review published in 2021 6 compared the efficacy and safety of once- versus twice-daily administration of ACE inhibitors for the management of hypertension, and found that twice-daily dosing may promote added blood pressure-lowering effects.
• A recent review published in 2023 7 highlights the historical perspective and current insights of ACE inhibitors in hypertension, and suggests that ACE inhibitors and ARBs have an equal class of recommendation for first-line treatment, but ARBs may have improved tolerability and potential neuroprotective effects.

Comparison of ACE Inhibitors and ARBs

• Both ACE inhibitors and ARBs are effective in lowering blood pressure, but ARBs may have a lower risk of adverse events such as cough and angioedema 4, 7.
• The choice between ACE inhibitors and ARBs should be based on individual patient factors, such as medical history and lifestyle 7.
• Combination therapy with an ARB, a calcium channel blocker, and a thiazide diuretic may be a rational choice for patients who require triple therapy 5.

Dosage and Administration

• The dosage and administration of ACE inhibitors can affect their efficacy and safety, with twice-daily dosing potentially promoting added blood pressure-lowering effects 6.
• However, the choice of dosage and administration should be based on individual patient factors, such as medical history and lifestyle, and should be made via shared decision-making with the patient and clinician judgment 6.