Hypertension Treatment Combinations

First-Line Combination Therapy

The European Society of Cardiology recommends combination therapy with a RAS blocker (ACE inhibitor or ARB) plus either a dihydropyridine calcium channel blocker (CCB) or thiazide/thiazide-like diuretic as initial therapy for most patients with confirmed hypertension (BP ≥140/90 mmHg), preferably as a single-pill combination 1, 2, 3
Combination therapy is more effective than monotherapy for blood pressure control in most hypertensive patients, with a preferred initial combination of ACE inhibitor + dihydropyridine CCB, ACE inhibitor + thiazide/thiazide-like diuretic, ARB + dihydropyridine CCB, or ARB + thiazide/thiazide-like diuretic 1, 2, 3, 4
Fixed-dose single-pill combinations are strongly recommended to improve adherence 1, 2, 3

For most patients with confirmed hypertension (BP ≥140/90 mmHg), start with a two-drug combination of a RAS blocker (ACE inhibitor or ARB) with either a dihydropyridine CCB or thiazide/thiazide-like diuretic 1, 2, 3
If BP remains uncontrolled on a two-drug combination, increase to a three-drug combination: RAS blocker + dihydropyridine CCB + thiazide/thiazide-like diuretic, preferably as a single-pill combination 1, 2, 3
If BP remains uncontrolled on maximally tolerated triple therapy, add spironolactone 2, 5

For patients with stable angina and hypertension, the American Heart Association recommends a regimen including a beta-blocker with either an ACE inhibitor/ARB, CCB, or thiazide diuretic 7
For patients with heart failure with reduced ejection fraction (HFrEF), treatment should include an ACE inhibitor/ARB, beta-blocker, diuretic, and/or mineralocorticoid receptor antagonist, according to the European Society of Cardiology 5
RAS blockers are more effective at reducing albuminuria and are recommended as part of the treatment strategy in hypertensive patients with microalbuminuria or proteinuria, as suggested by the European Society of Cardiology 5

Single-pill combinations improve adherence by reducing pill burden, allow for lower doses of individual components, potentially reducing side effects, and provide more rapid blood pressure control, according to the European Society of Cardiology 1, 2, 8
Single-pill combinations are associated with better cardiovascular outcomes in observational studies, as reported by the European Society of Cardiology 2

For most adults, target systolic BP should be 120-129 mmHg, provided treatment is well tolerated, as recommended by the European Society of Cardiology 1, 3
If BP-lowering treatment is poorly tolerated, target a systolic BP level that is "as low as reasonably achievable" (ALARA principle), according to the European Society of Cardiology 1, 3