What is the recommended first‑line drug for a patient with newly diagnosed hypertension and no comorbidities or contraindications?

First-Line Antihypertensive Drug Therapy for Newly Diagnosed Hypertension

For patients with newly diagnosed hypertension and no comorbidities or contraindications, initiate treatment with a thiazide or thiazide-like diuretic, calcium channel blocker (CCB), or ACE inhibitor/ARB—with thiazide diuretics (especially chlorthalidone) and CCBs preferred as the most effective first-line options. 1

Recommended First-Line Drug Classes

Thiazide Diuretics (Preferred)

• Thiazide diuretics, CCBs, and ACE inhibitors or ARBs are designated as Class I first-line agents by the 2017 ACC/AHA guidelines. 1
• Chlorthalidone is superior to other first-line agents based on the ALLHAT trial, which demonstrated that chlorthalidone outperformed amlodipine in preventing heart failure and outperformed lisinopril in preventing both heart failure and stroke. 1
• Chlorthalidone 12.5–25 mg daily is preferred over hydrochlorothiazide due to its longer half-life (40–60 hours), superior 24-hour blood pressure control, and stronger cardiovascular outcome data. 2, 3
• Expected blood pressure reduction with thiazide diuretics is 5–10 mmHg systolic and 2–5 mmHg diastolic when used as monotherapy. 4
• Thiazide diuretics are particularly effective in elderly patients, Black patients, and those with low-renin hypertension. 2, 3

Calcium Channel Blockers (Co-Preferred)

• CCBs are equally effective as thiazide diuretics for reducing all cardiovascular events except heart failure, making them an excellent alternative when diuretics are not tolerated. 1
• Expected blood pressure reduction with CCBs is 8–10 mmHg systolic and 4–5 mmHg diastolic. 4
• For Black patients, CCBs and thiazide diuretics are the preferred first-line agents because ACE inhibitors are notably less effective in this population for preventing heart failure and stroke. 1
• Amlodipine 5–10 mg daily is the most commonly used and evidence-based CCB for hypertension treatment. 1

ACE Inhibitors or ARBs (Alternative First-Line)

• ACE inhibitors and ARBs are appropriate first-line agents, though they were less effective than thiazide diuretics and CCBs in head-to-head comparisons for certain outcomes. 1
• ACE inhibitors were inferior to thiazide diuretics and CCBs in lowering blood pressure and preventing stroke in the ALLHAT trial. 1
• Expected blood pressure reduction is 6–9 mmHg systolic and 4–5 mmHg diastolic for ACE inhibitors, and 8–10 mmHg systolic and 4–6 mmHg diastolic for ARBs. 4
• For Black patients, ACE inhibitors are less effective than CCBs or thiazide diuretics and should not be used as monotherapy unless there are compelling indications. 1
• ARBs may be better tolerated than ACE inhibitors in Black patients (less cough and angioedema), but offer no proven advantage over ACE inhibitors in preventing stroke or cardiovascular disease. 1

Blood Pressure Targets

• Target blood pressure is <130/80 mmHg for most adults after initiating antihypertensive therapy, regardless of cardiovascular disease risk. 1
• The minimum acceptable target is <140/90 mmHg, though this is suboptimal for most patients. 1, 5
• For patients aged ≥65 years, the target is SBP <130 mmHg. 1, 5

When to Initiate Dual Therapy

• For patients with stage 2 hypertension (BP ≥160/100 mmHg or ≥20/10 mmHg above target), initiate two antihypertensive agents from different classes immediately. 1, 5
• The overwhelming majority of persons with BP sufficiently elevated to warrant pharmacological therapy may be best treated initially with two agents. 1

Monitoring and Follow-Up

• Patients initiating drug therapy should be followed approximately monthly for drug titration until blood pressure is controlled. 1
• Re-measure blood pressure 2–4 weeks after initiating therapy, with the goal of achieving target blood pressure within 3 months. 1, 5

Drugs to Avoid as First-Line Therapy

• Beta-blockers are not recommended as first-line therapy unless there are compelling indications (angina, post-MI, heart failure with reduced ejection fraction, atrial fibrillation), as they are less effective than CCBs (36% lower stroke risk) and thiazide diuretics (30% lower stroke risk). 1
• Alpha-blockers should not be used as first-line therapy because they are less effective for preventing cardiovascular disease than thiazide diuretics. 1

Lifestyle Modifications (Essential Adjunct)

• All patients should receive lifestyle interventions concurrently with pharmacotherapy, including: 1, 5
  • Sodium restriction to <1500 mg/day (or at least 1000 mg/day reduction)
  • Increased dietary potassium intake (3500–5000 mg/day)
  • Weight loss if overweight/obese (target ≥1 kg reduction)
  • Aerobic exercise 90–150 minutes/week
  • Alcohol moderation (≤2 drinks/day for men, ≤1 drink/day for women)
  • DASH-like diet rich in fruits, vegetables, whole grains, and low-fat dairy

Common Pitfalls to Avoid

• Do not delay treatment intensification if blood pressure remains above target after 3–6 months of monotherapy; add a second agent from a different class. 1
• Do not combine an ACE inhibitor with an ARB (dual RAS blockade), as this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1
• Do not use loop diuretics as first-line therapy for uncomplicated hypertension, as there are no outcome data supporting their use; reserve them for heart failure or advanced renal failure. 2