What medication should be started in an adult with stage‑2 hypertension (blood pressure 160/100 mm Hg)?

Initial Medication for Blood Pressure 160/100 mm Hg

Start two antihypertensive agents immediately from different drug classes—specifically a thiazide diuretic (chlorthalidone 12.5–25 mg daily preferred, or hydrochlorothiazide 25 mg daily) combined with either a calcium-channel blocker (amlodipine 5–10 mg daily) or an ACE inhibitor (lisinopril 10 mg daily). 1, 2, 3

Why Two Drugs at Once

• Stage 2 hypertension (BP ≥160/100 mm Hg) requires dual-agent therapy from the outset because monotherapy is inadequate and delays blood pressure control. 1, 2, 3
• The 2017 ACC/AHA guideline explicitly recommends initiating two first-line agents simultaneously when systolic/diastolic pressure is ≥160/100 mm Hg or >20/10 mm Hg above target. 1, 2
• Single-pill combination formulations should be used when available to improve adherence. 3

Preferred Drug Combinations

First Choice: Thiazide + Calcium-Channel Blocker or Thiazide + ACE Inhibitor

• Chlorthalidone 12.5–25 mg once daily is the optimal thiazide choice based on the ALLHAT trial demonstrating superiority over ACE inhibitors for stroke prevention and over calcium-channel blockers for heart failure prevention in over 50,000 patients. 2, 4
• If chlorthalidone is unavailable, use hydrochlorothiazide 25 mg daily, which has demonstrated cardiovascular benefit in multiple placebo-controlled trials. 2, 4
• Combine the thiazide with either:
  • Amlodipine 5–10 mg once daily (equally effective as thiazides for all cardiovascular events except heart failure, where thiazides are superior) 2, 5, OR
  • Lisinopril 10 mg once daily (effective first-line option, particularly for patients with albuminuria or established coronary artery disease) 2, 6

Alternative Combination: ACE Inhibitor/ARB + Calcium-Channel Blocker

• The combination of ARB/ACE inhibitor + CCB is a preferred two-drug combination across all major international guidelines. 5
• Research demonstrates that ARB/CCB combination therapy (losartan/amlodipine) reduced blood pressure more effectively than maximal doses of ARB with hydrochlorothiazide in stage 2 hypertensive patients. 5, 7

Race-Specific Considerations

• For Black patients, initiate treatment with a thiazide diuretic combined with a calcium-channel blocker rather than an ACE inhibitor or ARB as monotherapy, as beta-blockers and renin-angiotensin system inhibitors are less effective at lowering blood pressure in Black patients. 2, 5

Blood Pressure Target

• Aim for BP <130/80 mm Hg according to 2017 ACC/AHA guidelines. 5, 3, 8
• For patients ≥65 years, target systolic BP <130 mm Hg. 8

Monitoring Schedule

• Recheck blood pressure within 1 month after initiating therapy. 1, 3
• Check serum electrolytes and renal function 2–4 weeks after starting therapy, especially when using ACE inhibitors, ARBs, or diuretics. 1, 3, 6
• Continue monthly follow-up visits until the blood pressure goal is achieved. 3

Escalation if Uncontrolled

• If BP remains ≥140/90 mm Hg on two-drug combination after 1 month, add a third agent—typically the missing component of triple therapy: ACE inhibitor/ARB + calcium-channel blocker + thiazide diuretic. 5, 3
• Blood pressure control should be achieved within 3 months of initial diagnosis. 3

Critical Pitfalls to Avoid

• Never start with monotherapy for stage 2 hypertension—it is inadequate and delays blood pressure control. 3
• Never combine an ACE inhibitor with an ARB—this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 2, 5
• Do not use beta-blockers as first-line therapy unless specific comorbidities exist (angina, post-MI, heart failure with reduced ejection fraction), as they are less effective than diuretics for stroke prevention and cardiovascular events. 2, 9
• Avoid clonidine as first-line therapy—it is classified as a "secondary" (last-line) agent because of significant central nervous system adverse effects, especially in older adults, and risk of rebound hypertension on abrupt cessation. 2
• Do not delay medication initiation while attempting lifestyle modifications alone—both must start immediately. 3

Concurrent Lifestyle Modifications

• Initiate weight loss (target BMI 20–25 kg/m²), DASH or Mediterranean diet with reduced saturated fat, sodium reduction (<2 g/day), increased potassium intake, alcohol limitation (maximum 100 g/week), and physical activity (150 minutes/week of moderate-intensity aerobic exercise plus resistance training 2–3 times/week) simultaneously with medications. 3, 8