What is the initial approach to starting anti-hypertensive treatment in patients with hypertension?

How to Start Antihypertensive Treatment

Begin with two-drug combination therapy as a single-pill combination for most patients with confirmed hypertension, using an ACE inhibitor or ARB plus a dihydropyridine calcium channel blocker as first-line treatment. 1

Confirm the Diagnosis First

Before initiating any antihypertensive therapy, confirm hypertension using validated automated upper arm cuff devices with appropriate cuff size, measuring BP in both arms and using the higher reading. 1 Office BP ≥140/90 mmHg defines hypertension, but must be confirmed with home BP monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg). 2, 1

Start with Lifestyle Modifications for ALL Patients

Implement lifestyle interventions immediately for all patients, regardless of whether drug therapy is initiated: 2, 1

• Sodium restriction to <1500 mg/day or reduce by at least 1000 mg/day 2
• Increase dietary potassium to 3500-5000 mg/day 2
• Weight loss if overweight (target at least 1 kg reduction) 2
• Physical activity: 90-150 min/week of aerobic exercise or 3 sessions/week of isometric resistance 2
• Alcohol moderation: ≤2 drinks/day for men, ≤1 drink/day for women 2
• DASH diet: rich in fruits, vegetables, whole grains, low-fat dairy with reduced saturated fat 2, 3

When to Start Drug Therapy

Grade 1 Hypertension (140-159/90-99 mmHg):

• Start drug treatment immediately if high-risk (CVD, CKD, diabetes, organ damage, or age 50-80 years) 2
• For low-moderate risk patients, start drug treatment if BP remains elevated after 3-6 months of lifestyle intervention 2

Grade 2 Hypertension (≥160/100 mmHg):

• Start drug treatment immediately regardless of risk level 2

Initial Drug Selection Algorithm

For Non-Black Patients:

Start with low-dose ACE inhibitor or ARB + dihydropyridine calcium channel blocker as single-pill combination 1

• Example: Lisinopril 10 mg + Amlodipine 5 mg once daily 4, 5
• This combination therapy is more effective than sequential monotherapy titration 1

For Black Patients:

Start with low-dose ARB + dihydropyridine calcium channel blocker OR calcium channel blocker + thiazide-like diuretic 2, 1

• This combination is more effective than monotherapy in Black patients 1

Exception - Consider Monotherapy Only:

• Low-risk Grade 1 hypertension 2
• Patients aged >80 years or frail 2
• In these cases, start with a single agent at low dose and titrate up 2

Comorbidity-Specific Drug Selection

When specific comorbidities are present, tailor your initial drug choice: 2

• Chronic kidney disease: ACEI or ARB (use ARB if ACEI not tolerated) 2
• Diabetes with albuminuria: ACEI or ARB 2
• Heart failure (reduced EF): Beta blockers (avoid non-DHP calcium antagonists) 2
• Heart failure (preserved EF): Diuretics for volume overload, add ACEI/ARB and beta blocker for BP control 2
• Stable ischemic heart disease or post-MI: Beta blockers + ACEI or ARB 2
• Atrial fibrillation: ARB (may reduce AF recurrence) 2
• Post-kidney transplant: Calcium antagonist (use ACEI with caution) 2

Blood Pressure Targets

Target BP <130/80 mmHg for most adults 1, 3

• Initial goal: reduce BP by at least 20/10 mmHg 2, 1
• Achieve target within 3 months of initiating treatment 2, 1
• Individualize for elderly based on frailty 2

Monitoring and Titration

• Schedule follow-up within 2-4 weeks initially to assess response and tolerability 1
• Check serum creatinine and potassium 7-14 days after starting or adjusting ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists 1
• Patients initiating drug therapy should be followed approximately monthly for drug titration until BP is controlled 2
• Use home BP monitoring to track progress and improve adherence 1

Dose Titration Steps

If BP remains uncontrolled after initial combination therapy: 2

1. Increase to full doses of both agents (e.g., Lisinopril 40 mg + Amlodipine 10 mg) 4, 5
2. Add thiazide-like diuretic as third agent 2
3. Add spironolactone or, if not tolerated/contraindicated, amiloride, doxazosin, eplerenone, clonidine, or beta-blocker 2

Critical Pitfalls to Avoid

• Never combine two RAS blockers (ACE inhibitor + ARB) as this is potentially harmful 1
• Avoid clinical inertia: immediate combination therapy is more effective than sequential monotherapy titration 1
• Do not discontinue lifestyle modifications once drug therapy starts—they are complementary and may reduce medication requirements 1
• Do not use inadequate doses: titrate to full doses before adding additional agents 2
• Avoid non-DHP calcium antagonists in heart failure with reduced ejection fraction 2

Special Populations

Renal Impairment:

• Creatinine clearance >30 mL/min: no dose adjustment needed 4
• Creatinine clearance 10-30 mL/min: reduce initial lisinopril dose to 5 mg 4
• Hemodialysis or CrCl <10 mL/min: start lisinopril at 2.5 mg once daily 4

Elderly or Frail Patients:

• May start amlodipine at 2.5 mg once daily 5
• Consider monotherapy initially 2
• Individualize BP targets based on frailty 2