Starting and Adjusting Antihypertensives for Uncomplicated Hypertension
For uncomplicated hypertension, start with a thiazide-type diuretic as monotherapy for mild elevation (BP 140-159/90-99 mmHg), but initiate dual therapy immediately with two drugs (usually thiazide diuretic plus ACE inhibitor, ARB, or calcium channel blocker) if BP is ≥160/100 mmHg or if BP is >20/10 mmHg above goal. 1, 2
Initial Treatment Strategy
Blood Pressure Thresholds for Drug Initiation
BP 140-159/90-99 mmHg (Stage 1): Start with monotherapy using a thiazide-type diuretic (hydrochlorothiazide 12.5-25 mg or chlorthalidone 12.5-25 mg daily) as first-line therapy 1, 3
BP ≥160/100 mmHg (Stage 2): Initiate immediate dual therapy with two drugs from different classes, preferably as a single-pill combination 1, 2
BP >20/10 mmHg above goal: Start with two-drug combination therapy regardless of absolute BP level 1
First-Line Medication Classes
The four major drug classes proven to reduce cardiovascular morbidity and mortality are 1, 3:
- Thiazide or thiazide-like diuretics (hydrochlorothiazide, chlorthalidone)
- ACE inhibitors (lisinopril, enalapril)
- Angiotensin receptor blockers/ARBs (losartan, candesartan)
- Long-acting dihydropyridine calcium channel blockers (amlodipine)
Preferred Two-Drug Combinations
When dual therapy is indicated, use one of these evidence-based combinations 1, 2:
- Thiazide diuretic + ACE inhibitor
- Thiazide diuretic + ARB
- Calcium channel blocker + ACE inhibitor
- Calcium channel blocker + ARB
- Calcium channel blocker + thiazide diuretic
The combination of thiazide diuretic with beta-blocker, while historically used, should be avoided in patients with metabolic syndrome due to dysmetabolic effects. 1
Specific Dosing Recommendations
Starting Doses for Monotherapy
- Lisinopril: 10 mg once daily (can start at 5 mg if on diuretics) 4
- Losartan: 50 mg once daily (25 mg if volume depleted) 5
- Hydrochlorothiazide: 12.5-25 mg once daily 1
- Amlodipine: 5 mg once daily 3
Dual Therapy Dosing
When initiating two drugs simultaneously, use low doses of each agent to minimize side effects while maximizing efficacy 1. For example:
- Lisinopril 10 mg + hydrochlorothiazide 12.5 mg daily
- Amlodipine 5 mg + lisinopril 10 mg daily
Adjusting Antihypertensives
When to Escalate Therapy
Add a second drug from a different class when a single drug at adequate doses fails to achieve BP goal after 3-6 months of treatment. 1
Stepwise Escalation Algorithm
If on monotherapy and BP not at goal: Add a second agent from a complementary class 1
If on dual therapy and BP not at goal: Optimize doses of both agents before adding a third drug 1, 6
If on optimized dual therapy and BP still not at goal: Add a third agent to create triple therapy (typically ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic) 1, 6, 7
If on triple therapy and BP not at goal (resistant hypertension): Add spironolactone 25-50 mg daily as the preferred fourth-line agent 6, 7
Target Blood Pressure Goals
- Most adults <65 years: <130/80 mmHg 6, 3
- Adults ≥65 years: SBP <130 mmHg 3
- Minimum acceptable target: <140/90 mmHg 1
- Patients with diabetes or chronic kidney disease: <130/80 mmHg 1
Focus primarily on achieving systolic BP goal, as most patients—especially those ≥50 years—will reach diastolic goal once systolic target is achieved. 1
Monitoring and Follow-Up Schedule
- Initial follow-up: 2-4 weeks after starting or adjusting medication 6, 2
- Goal achievement timeframe: Target BP should be reached within 3 months of initiating or modifying therapy 6, 2
- Once at goal: Continue monitoring every 3-6 months 2
What to Monitor
- Office BP measurements (confirm with home BP monitoring: goal <135/85 mmHg) 6
- Serum potassium and creatinine 2-4 weeks after starting ACE inhibitor, ARB, or diuretic 6, 7
- Medication adherence at every visit 1
Critical Pitfalls to Avoid
Do not use sequential monotherapy (trying multiple single agents) in patients with stage 2 hypertension or high cardiovascular risk—this delays BP control and increases cardiovascular risk. 1, 2
Do not combine an ACE inhibitor with an ARB—this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 6, 7
Do not add a third drug class before maximizing doses of the current two-drug regimen—this violates guideline-recommended stepwise approaches and may expose patients to unnecessary polypharmacy. 6, 7
Do not use immediate-release nifedipine for hypertension management due to risk of precipitous BP drops. 8
Avoid beta-blockers as first-line therapy in uncomplicated hypertension unless there are compelling indications (heart failure, post-MI, angina, or need for heart rate control). 6, 7
Lifestyle Modifications (Essential Adjunct)
All patients should receive intensive lifestyle counseling 1, 2:
- Sodium restriction: <2 g/day (ideally <1.5 g/day)
- Weight loss: Target BMI 20-25 kg/m² if overweight
- Physical activity: Regular aerobic exercise
- Alcohol limitation: <100 g/week
- DASH-like dietary pattern: High in potassium, fruits, vegetables
Lifestyle modifications can provide additive BP reductions of 10-20 mmHg and enhance the efficacy of pharmacologic therapy. 1, 3
Special Considerations
Elderly Patients (>80 years)
Consider starting with monotherapy and titrating gradually to avoid orthostatic hypotension, but do not withhold appropriate treatment intensification solely based on age 1, 2
Patients at Risk for Orthostatic Hypotension
Start with single-agent therapy at low doses and monitor standing BP 1, 2