What is the initial approach for managing hypertension with anti-hypertensive (blood pressure lowering) medications?

Initial Approach to Antihypertensive Medication Management

For most adults with hypertension, treatment should begin with a thiazide or thiazide-like diuretic, either alone for stage 1 hypertension or in combination with an ACE inhibitor, ARB, or calcium channel blocker for stage 2 hypertension or high-risk patients. 1, 2

Blood Pressure Thresholds for Initiating Pharmacotherapy

• Start medication when BP ≥140/90 mmHg in adults with confirmed hypertension 1
• Consider starting at BP 130-139 mmHg systolic in patients with existing cardiovascular disease (strong recommendation), high cardiovascular risk, diabetes, or chronic kidney disease (conditional recommendation) 1
• Target BP <140/90 mmHg for patients without comorbidities, and <130 mmHg systolic for those with known cardiovascular disease 1

First-Line Drug Classes

The following four drug classes have high-quality evidence for reducing cardiovascular events and should be used as initial therapy 1:

• Thiazide or thiazide-like diuretics (chlorthalidone preferred over hydrochlorothiazide when available) 3, 4
• ACE inhibitors 1, 5
• Angiotensin receptor blockers (ARBs) 1
• Long-acting dihydropyridine calcium channel blockers 1

Thiazide Diuretics: The Preferred Starting Point

Thiazide diuretics should be the initial choice for most patients because they have the strongest evidence for reducing mortality, stroke, and cardiovascular events 1, 4. Chlorthalidone is superior to hydrochlorothiazide, providing greater 24-hour blood pressure reduction (12.4 vs 7.4 mmHg systolic) and better nighttime control 3. When chlorthalidone is unavailable, hydrochlorothiazide 12.5-25 mg daily is an acceptable alternative 4, 6.

Monotherapy vs. Combination Therapy Strategy

Stage 1 Hypertension (BP 140-159/90-99 mmHg)

Start with a single agent at low dose in patients with stage 1 hypertension and low-to-moderate cardiovascular risk 1, 2. The recommended initial dose for lisinopril is 10 mg once daily, adjustable to 20-40 mg based on response 5.

Use a stepped-care approach: Start one drug, then add a second drug from a different class before reaching maximum dose of the first agent if BP goal is not achieved 2. This strategy is more effective than maximizing monotherapy doses 1, 2.

Stage 2 Hypertension (BP ≥160/100 mmHg or >20/10 mmHg above target)

Initiate treatment with two drugs from different classes simultaneously, either as separate agents or fixed-dose combinations 1. This approach achieves BP control faster and reduces cardiovascular events more rapidly 1.

Preferred Drug Combinations

The most effective and well-tolerated two-drug combinations are 1:

• Thiazide diuretic + ACE inhibitor (e.g., hydrochlorothiazide 12.5-25 mg + lisinopril) 1, 5
• Thiazide diuretic + ARB 1
• Calcium channel blocker + ACE inhibitor 1
• Calcium channel blocker + ARB 1
• Calcium channel blocker + thiazide diuretic 1

Fixed-dose combination pills should be considered to improve adherence and simplify the treatment regimen 1, 7.

Special Population Considerations

Black Patients

Initial therapy should include a thiazide diuretic or calcium channel blocker, either alone or combined with a RAS blocker 1. Diuretics and calcium channel blockers are more effective as monotherapy in black patients compared to ACE inhibitors or ARBs 1.

Patients with Comorbidities

• Heart failure with reduced ejection fraction: Use ACE inhibitor (or ARB if intolerant), beta-blocker, diuretic, and MRA as indicated 1
• Chronic kidney disease with proteinuria: Include RAS blocker (ACE inhibitor or ARB) as part of treatment strategy 1
• Diabetes: Target systolic BP <130 mmHg; thiazide diuretics remain effective despite causing mild hyperglycemia 1, 4

Contraindications to Avoid

Never combine ACE inhibitor + ARB + renin inhibitor - this is potentially harmful and increases risk of adverse events without additional benefit 1. Other absolute contraindications include 1:

• Thiazide diuretics: Gout (compelling), pregnancy (possible)
• Beta-blockers: Asthma, 2nd/3rd degree AV block (compelling)
• ACE inhibitors/ARBs: Pregnancy, angioedema, hyperkalemia, bilateral renal artery stenosis (compelling)

Monitoring and Titration

• Follow up monthly after initiating or changing medications until BP target is reached 1
• Add second agent before maximizing first drug dose if BP remains uncontrolled at initial doses 2
• Achieve BP control within 3 months as the goal 2
• Monitor every 3-5 months once BP is controlled 1

Common Pitfalls

Avoid waiting too long to add a second medication - approximately 75% of patients require multiple drugs for adequate control, and delaying combination therapy postpones achieving target BP 2, 5. Do not use two drugs from the same class (e.g., two different ACE inhibitors) or drugs targeting the same system (ACE inhibitor + ARB) 1. Do not avoid thiazide diuretics due to metabolic concerns - their proven mortality benefit outweighs concerns about glucose or lipid effects, which do not translate to worse cardiovascular outcomes 1, 4.