Pharmacological Combinations to Avoid in Hypertension

Combinations of Antihypertensive Agents

The American College of Cardiology recommends avoiding the combination of two blockers of the renin-angiotensin-aldosterone system (RAAS), specifically ACE inhibitors + ARB, due to the lack of additional benefits and increased risk of adverse events such as hyperkalemia, syncope, and acute kidney injury 1, 2, 3
The combination of ACE inhibitors or ARB with direct renin inhibitors (such as aliskiren) is also not recommended, as it increases the risk of hyperkalemia, syncope, and acute kidney injury without providing additional cardiovascular benefits 1, 4
Combinations of drugs with similar mechanisms of action or similar clinical effects should be avoided, such as two beta-blockers, two ACE inhibitors, or two non-dihydropyridine calcium channel blockers 3, 4

Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the efficacy of antihypertensive agents, particularly ACE inhibitors and ARB, and may cause sodium and water retention, increasing blood pressure 5

The European Heart Journal recommends combination therapy as initial treatment for most patients with confirmed hypertension (≥140/90 mmHg), with a preferred combination of a RAAS blocker (ACE inhibitor or ARB) with a dihydropyridine calcium channel blocker or a diuretic 2, 6
If blood pressure is not controlled with a combination of two drugs, a combination of three drugs is recommended, typically a RAAS blocker + a dihydropyridine calcium channel blocker + a thiazide or thiazide-like diuretic 2

In patients with renal impairment, careful monitoring of renal function and electrolytes is recommended when using ACE inhibitors or ARB, especially in combination with diuretics 5
The European Heart Journal recommends avoiding renal denervation in patients with moderately to severely impaired renal function (eGFR <40 mL/min/1.73 m²) 2
In patients requiring NSAID therapy, the lowest effective dose of NSAID should be used for the shortest possible duration, and alternative antihypertensive strategies that may be less affected by NSAIDs should be considered 5