Treatment Options for Hypertension in Primary Care
First-Line Medication Choices
For most patients with hypertension, initiate treatment with either an ACE inhibitor/ARB, a calcium channel blocker (CCB), or a thiazide-like diuretic as monotherapy, with the choice guided by patient race and comorbidities. 1
Initial Monotherapy Selection
For Non-Black Patients:
- Start with an ACE inhibitor (e.g., lisinopril 10-20 mg daily) or ARB (e.g., losartan 50 mg daily) as first-line therapy 1, 2
- Alternative: Calcium channel blocker (amlodipine 5 mg daily) is acceptable when there's uncertainty about medical history 1
For Black Patients:
- Prefer a dihydropyridine calcium channel blocker (amlodipine 5-10 mg daily) over ACE inhibitors/ARBs as initial therapy 1
- Alternative: Thiazide-like diuretic (chlorthalidone 12.5-25 mg daily or hydrochlorothiazide 25 mg daily) 1
Dosing Specifics from FDA Labels
Losartan (ARB):
- Starting dose: 50 mg once daily 3
- Maximum dose: 100 mg once daily 3
- Use 25 mg starting dose if patient is volume-depleted or on diuretics 3
Lisinopril (ACE Inhibitor):
- Indicated for hypertension treatment in adults and children ≥6 years 2
- May be administered alone or with other antihypertensives 2
Dual Therapy: When One Drug Isn't Enough
If blood pressure remains ≥140/90 mmHg on monotherapy after 2-4 weeks, add a second agent from a complementary class rather than simply increasing the first drug's dose. 1
Recommended Two-Drug Combinations
ACE Inhibitor/ARB + Calcium Channel Blocker:
- This combination provides superior blood pressure control through complementary mechanisms (vasodilation + RAS blockade) 1
- Particularly beneficial for patients with diabetes, chronic kidney disease, or coronary artery disease 1
- Example: Losartan 50-100 mg + amlodipine 5-10 mg daily 1
Calcium Channel Blocker + Thiazide Diuretic:
- Especially effective for Black patients, elderly patients, or those with volume-dependent hypertension 1
- May be more effective than CCB + ACE inhibitor/ARB in Black patients 1
- Example: Amlodipine 5-10 mg + chlorthalidone 12.5-25 mg daily 1
ACE Inhibitor/ARB + Thiazide Diuretic:
- Standard combination for many patients 1
- Example: Losartan 50-100 mg + hydrochlorothiazide 12.5-25 mg daily 1
Important Monitoring After Adding Second Agent
- Check serum potassium and creatinine 2-4 weeks after adding ACE inhibitor/ARB to detect hyperkalemia or acute kidney injury 1
- Monitor for hypokalemia, hyperuricemia, and glucose intolerance with thiazide diuretics 1
- Reassess blood pressure within 2-4 weeks 1, 4
Triple Therapy: For Uncontrolled Hypertension on Two Drugs
The guideline-recommended triple therapy is ACE inhibitor/ARB + calcium channel blocker + thiazide-like diuretic, which targets three complementary mechanisms: RAS blockade, vasodilation, and volume reduction. 1
When to Escalate to Triple Therapy
- Blood pressure remains ≥140/90 mmHg despite two optimally-dosed medications 1
- Stage 2 hypertension (≥160/100 mmHg) warrants adding a third agent rather than just uptitrating current medications 1
Preferred Third Agent Selection
If on ACE inhibitor/ARB + CCB:
- Add thiazide-like diuretic (chlorthalidone 12.5-25 mg daily preferred over hydrochlorothiazide due to longer duration of action) 1
If on ACE inhibitor/ARB + Thiazide:
- Add calcium channel blocker (amlodipine 5-10 mg daily) 1
If on CCB + Thiazide:
- Add ACE inhibitor or ARB 1
Critical Monitoring for Triple Therapy
- Check potassium and creatinine 2-4 weeks after adding diuretic 1
- Target BP <140/90 mmHg minimum, ideally <130/80 mmHg for high-risk patients 1
- Achieve target within 3 months of treatment modification 1, 4
Resistant Hypertension: Fourth-Line Agent
If blood pressure remains uncontrolled (≥140/90 mmHg) despite optimized triple therapy, add spironolactone 25-50 mg daily as the preferred fourth-line agent. 1
Evidence for Spironolactone
- Provides additional blood pressure reductions of 20-25/10-12 mmHg when added to triple therapy 1
- Addresses occult volume expansion that commonly underlies treatment resistance 1
Alternative Fourth-Line Agents (if spironolactone contraindicated)
Essential Steps Before Adding Fourth Agent
- Verify medication adherence first—non-adherence is the most common cause of apparent treatment resistance 1, 4
- Review for interfering medications: NSAIDs, decongestants, oral contraceptives, systemic corticosteroids 1
- Screen for secondary hypertension: primary aldosteronism, renal artery stenosis, obstructive sleep apnea, pheochromocytoma 1
When to Refer to Specialist
- Blood pressure remains ≥160/100 mmHg despite four optimally-dosed medications 1
- Multiple drug intolerances 1
- Concerning features suggesting secondary hypertension 1, 4
Blood Pressure Targets
Target blood pressure should be <140/90 mmHg minimum for most patients, with more aggressive targets of <130/80 mmHg for higher-risk patients including those with diabetes, chronic kidney disease, or established cardiovascular disease. 1
- Optimal target: 120-129 mmHg systolic if well tolerated 1
- Reassess within 2-4 weeks after any medication adjustment 1, 4
- Goal: Achieve target BP within 3 months of initiating or modifying therapy 1, 4
Critical Pitfalls to Avoid
Never combine an ACE inhibitor with an ARB—this dual RAS blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit 1
Do not add a beta-blocker as second or third agent unless compelling indications exist (angina, post-MI, heart failure with reduced ejection fraction, heart rate control needed), as beta-blockers are less effective than other classes for stroke prevention 1
Do not add a third drug class before maximizing doses of current two-drug regimen—this violates guideline-recommended stepwise approaches and exposes patients to unnecessary polypharmacy 1
Avoid non-dihydropyridine CCBs (diltiazem, verapamil) in patients with heart failure due to negative inotropic effects 1
Do not delay treatment intensification—prompt action is required for stage 2 hypertension to reduce cardiovascular risk 1
Lifestyle Modifications: Essential Adjunct to Pharmacotherapy
Lifestyle modifications provide additive blood pressure reductions of 10-20 mmHg and should be reinforced at every visit, even when medications are prescribed. 1
Evidence-Based Lifestyle Interventions
Sodium Restriction:
Weight Management:
- Target BMI 20-25 kg/m² 1, 6
- 10 kg weight loss associated with 6.0/4.6 mmHg reduction 1
- Weight loss is particularly effective in resistant hypertension 7
Physical Activity:
- Regular aerobic exercise (minimum 30 minutes most days) 1, 6
- Produces 4/3 mmHg reduction 1
- Has extensive benefits comparable or superior to other lifestyle changes 8
Alcohol Limitation:
- ≤2 drinks/day for men, ≤1 drink/day for women 1
- Maximum 14 drinks/week for men, 9/week for women 6
- Or <100 g/week total 1
DASH Diet:
- Emphasizes fruits, vegetables, low-fat dairy products 5
- Reduces systolic/diastolic BP by 11.4/5.5 mmHg more than control diet 1
Lifestyle Modifications in Resistant Hypertension
- Multi-component interventions (exercise + dietary modification + weight management) can reduce clinic and ambulatory blood pressure even in resistant hypertension 7
- These modifications improve cardiovascular risk biomarkers beyond blood pressure reduction alone 7
Special Populations
Elderly Patients:
- Do not withhold appropriate treatment intensification solely based on age 1
- Target BP <140/90 mmHg, individualized based on frailty 1, 4
Patients with Diabetes:
Patients with Chronic Kidney Disease:
Patients with Hepatic Impairment: