What is the best medication combination for a patient with newly diagnosed arterial hypertension and severe hypertension?

Initial Combination Therapy for Severe Hypertension (Systolic BP 180 mmHg)

For a patient with newly diagnosed severe hypertension (systolic BP 180 mmHg), you should initiate combination therapy immediately with a RAS blocker (ACE inhibitor or ARB) plus a dihydropyridine calcium channel blocker, preferably as a fixed-dose single-pill combination. 1

Why Combination Therapy is Mandatory

• With a systolic BP of 180 mmHg, this patient has Grade 2-3 hypertension, which requires immediate combination therapy rather than monotherapy 1
• Monotherapy achieves target BP in only a limited number of hypertensive patients, and when BP is in the Grade 2 or 3 range, a combination of two drugs at low doses should be preferred as first-step treatment 1
• In higher-risk hypertensives, goal blood pressure should be achieved more promptly, which favors initial combination therapy and quicker adjustment of doses 1
• The 2024 ESC guidelines explicitly recommend combination BP-lowering treatment for most patients with confirmed hypertension (BP ≥140/90 mmHg) as initial therapy, with exceptions only for patients aged ≥85 years, symptomatic orthostatic hypotension, or moderate-to-severe frailty 1

Preferred First-Line Combinations

The optimal two-drug combinations are:

• ACE inhibitor + dihydropyridine calcium channel blocker (e.g., lisinopril + amlodipine) 1
• ARB + dihydropyridine calcium channel blocker (e.g., valsartan + amlodipine) 1
• ACE inhibitor + thiazide/thiazide-like diuretic (e.g., lisinopril + hydrochlorothiazide) 1
• ARB + thiazide/thiazide-like diuretic 1

The RAS blocker (ACE inhibitor or ARB) combined with a dihydropyridine calcium channel blocker is particularly effective because these drug classes have complementary mechanisms of action and the combination has been proven to reduce cardiovascular events 1

Practical Implementation

Start with low doses in a fixed-dose single-pill combination:

• Lisinopril 10 mg + amlodipine 5 mg once daily 2, 3
• OR Valsartan 160 mg + amlodipine 5-10 mg once daily 2
• Fixed-dose single-pill combinations are strongly recommended as they simplify the treatment schedule, improve compliance, and reduce the number of tablets 1

Timing of medication:

• Administer at the most convenient time of day for the patient to establish a habitual pattern and improve adherence 1
• Current evidence does not show benefit of specific diurnal timing on cardiovascular outcomes 1

Escalation Strategy if Target Not Achieved

If BP is not controlled after 2-4 weeks with the two-drug combination:

• Increase to a three-drug combination: RAS blocker + dihydropyridine calcium channel blocker + thiazide/thiazide-like diuretic, preferably in a single-pill combination 1
• If still uncontrolled with three drugs, add spironolactone 1
• If spironolactone is not effective or tolerated, consider eplerenone, beta-blocker (if not already indicated), centrally acting agent, alpha-blocker, hydralazine, or potassium-sparing diuretic 1

Target Blood Pressure

Aim for a systolic BP of 120-129 mmHg if well tolerated 1

• The 2024 ESC guidelines recommend targeting systolic BP values of 120-129 mmHg in most adults to reduce cardiovascular risk 1
• If this target is poorly tolerated, use the "as low as reasonably achievable" (ALARA) principle 1
• The WHO recommends a target of <140/90 mmHg for patients without comorbidities, but <130 mmHg systolic for those with known cardiovascular disease 1

Critical Pitfalls to Avoid

Do NOT combine two RAS blockers (ACE inhibitor + ARB) - this is explicitly not recommended due to lack of benefit and increased risk of adverse events 1

Avoid beta-blocker + thiazide diuretic combination in patients with metabolic syndrome or high risk of incident diabetes, as these drugs have dysmetabolic effects that are more pronounced when administered together 1

Do not delay treatment - with a BP of 180 mmHg, this patient requires prompt initiation of combination therapy to reduce cardiovascular risk 1

Follow-Up Schedule

• Monthly follow-up after initiation until target BP is reached 1
• Once controlled, follow-up every 3-5 months 1
• Maintain BP-lowering drug treatment lifelong, even beyond age 85 years, if well tolerated 1