First-Line Treatment for Stage 2 Hypertension
Start combination therapy immediately with two antihypertensive agents from different classes—specifically an ACE inhibitor (or ARB) plus either a calcium channel blocker or a thiazide diuretic—together with lifestyle modifications, and schedule follow-up in one month. 1, 2
Immediate Pharmacologic Regimen
For this 58-year-old woman with blood pressure 160/110 mm Hg, initiate dual therapy at the first visit without delay. 1, 2 Stage 2 hypertension (≥140/90 mm Hg) requires two agents because monotherapy is insufficient and delays blood pressure control. 2
Preferred Two-Drug Combinations
Choose one of these evidence-based regimens:
- ACE inhibitor + thiazide diuretic: Lisinopril 10 mg daily plus chlorthalidone 12.5–25 mg daily 2, 3
- ACE inhibitor + calcium channel blocker: Lisinopril 10 mg daily plus amlodipine 5 mg daily 2, 3
- ARB + thiazide diuretic: Losartan 50 mg daily plus chlorthalidone 12.5–25 mg daily 1, 2
Chlorthalidone is preferred over hydrochlorothiazide because of its longer half-life and superior cardiovascular outcome data from the ALLHAT trial. 2, 3 If the patient is Black, prioritize a thiazide diuretic plus calcium channel blocker over an ACE inhibitor/ARB-based combination as initial therapy. 1, 3
Use single-pill combination formulations when available to improve adherence. 2
Concurrent Lifestyle Modifications
Start these interventions immediately alongside medications—do not delay drug therapy while attempting lifestyle changes alone: 2
- Weight loss targeting BMI 20–25 kg/m² and waist circumference <80 cm for women 2
- DASH or Mediterranean diet with reduced saturated fat, increased fruits, vegetables, and low-fat dairy 2
- Sodium restriction and limit alcohol to ≤100 g pure alcohol per week 2
- Physical activity: ≥150 minutes/week of moderate-intensity aerobic exercise plus resistance training 2–3 times/week 2
Blood Pressure Target
Aim for systolic blood pressure 120–129 mm Hg if well tolerated; at minimum achieve <140/90 mm Hg. 2 For patients with 10-year ASCVD risk ≥10% (likely in this 58-year-old with stage 2 hypertension), target <130/80 mm Hg. 1, 2
Monitoring Schedule
- Recheck blood pressure in 1 month after initiating therapy 1, 2
- Check serum electrolytes (sodium, potassium) and renal function (creatinine, eGFR) at 2–4 weeks after starting ACE inhibitor or thiazide diuretic 1, 2
- Continue monthly follow-up visits until blood pressure goal is achieved 2
- Once controlled, reassess every 3–6 months 2
Dose Escalation Strategy
If blood pressure remains ≥140/90 mm Hg after 1 month on dual therapy, add a third first-line agent to create triple therapy (ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic). 1, 2 Do not wait longer than 1 month between dose adjustments in uncontrolled stage 2 hypertension. 2
Blood pressure control must be achieved within 3 months of initial diagnosis. 1, 2
Critical Pitfalls to Avoid
- Never use monotherapy for stage 2 hypertension—it is inadequate and delays control 2
- Never combine two RAS blockers (ACE inhibitor + ARB) as this increases hyperkalemia and acute kidney injury without cardiovascular benefit 2, 3
- Never delay medication initiation while attempting lifestyle modifications alone—both must start simultaneously 2
- Do not use beta-blockers as first-line therapy unless compelling indications exist (recent MI, heart failure, angina) 3
Rationale for Dual Therapy
The 2017 ACC/AHA guideline explicitly recommends initiating two agents when systolic/diastolic pressure is ≥160/100 mm Hg or exceeds target by >20/10 mm Hg (Class I recommendation). 1, 2 This patient's blood pressure of 160/110 mm Hg meets both criteria. Early aggressive treatment markedly reduces stroke, myocardial infarction, heart failure, and cardiovascular mortality. 2
A 10 mm Hg systolic blood pressure reduction decreases cardiovascular events by approximately 20–30%. 4