What are the first-line treatment options for managing hypertension (high blood pressure) with medications such as Angiotensin-Converting Enzyme (ACE) inhibitors?

First-Line Treatment Options for Managing Hypertension

For most patients with confirmed hypertension (BP ≥140/90 mmHg), a combination of two first-line antihypertensive medications is recommended as initial therapy, preferably a RAS blocker (ACE inhibitor or ARB) with either a dihydropyridine calcium channel blocker or a thiazide/thiazide-like diuretic in a single-pill combination. 1

First-Line Medication Classes

• ACE inhibitors, ARBs, dihydropyridine calcium channel blockers (CCBs), and diuretics (thiazides and thiazide-like drugs such as chlorthalidone and indapamide) have demonstrated the most effective reduction of blood pressure and cardiovascular disease events and are therefore recommended as first-line treatments 1
• These four major drug classes can be used either alone or in combination, with the exception that two RAS blockers (ACE inhibitor and ARB) should not be combined 1
• Single-pill combinations are preferred when using combination therapy to improve adherence 1

Initial Treatment Approach Based on Blood Pressure Level

• For patients with elevated BP (120-139/70-89 mmHg), treatment with lifestyle measures for 3 months is recommended prior to considering medications 1
• For patients with BP 140/90-159/99 mmHg, combination therapy is recommended as initial treatment 1
• For patients with BP ≥160/100 mmHg, prompt initiation and timely titration of two drugs or a single-pill combination is strongly recommended 1, 2

Preferred Combinations

• The preferred two-drug combination is a RAS blocker (either an ACE inhibitor or an ARB) with a dihydropyridine CCB or diuretic 1
• If BP is not controlled with a two-drug combination, increasing to a three-drug combination is recommended, usually a RAS blocker with a dihydropyridine CCB and a thiazide/thiazide-like diuretic, preferably in a single-pill combination 1
• If BP is not controlled with a three-drug combination, adding spironolactone should be considered 1

Special Populations and Comorbidities

• For patients with diabetes and albuminuria (UACR ≥30 mg/g), an ACE inhibitor or ARB is recommended as first-line therapy 1, 2
• For patients with established coronary artery disease, ACE inhibitors or ARBs are recommended as first-line agents 1, 2
• Beta-blockers are recommended when there are other compelling indications for their use, such as angina, post-myocardial infarction, heart failure with reduced ejection fraction, or for heart rate control 1
• For patients aged ≥85 years, those with symptomatic orthostatic hypotension, moderate-to-severe frailty, or elevated BP with increased CVD risk, consider initiating with monotherapy, slower up-titration, and lower dosing 1

Monitoring and Follow-up

• For patients on ACE inhibitors, ARBs, or diuretics, serum creatinine/eGFR and potassium levels should be monitored at least annually 1
• Ideally, BP should be treated to target within 3 months to retain patient confidence, ensure long-term adherence, and reduce cardiovascular disease risk 1
• The target BP recommended in routine practice is 120-129/70-79 mmHg 1

Common Pitfalls to Avoid

• Combining two RAS blockers (ACE inhibitor and ARB) is not recommended due to increased risk of adverse effects without additional benefit 1
• Using beta-blockers as first-line therapy in uncomplicated hypertension is not recommended 2
• Delaying initiation of pharmacological therapy in patients with significantly elevated blood pressure can lead to poor outcomes 2
• Inadequate monitoring of renal function and electrolytes in patients on ACE inhibitors, ARBs, or diuretics can lead to complications such as hyperkalemia or acute kidney injury 1

Evidence Quality Considerations

• The recommendation for combination therapy as initial treatment is based on observational studies showing better BP control and adherence, though there are no outcomes data from prospective trials that prove superiority over monotherapy 1
• Low-dose thiazide diuretics have shown high-quality evidence for reducing mortality, total cardiovascular events, stroke, and coronary heart disease 3
• ACE inhibitors have demonstrated efficacy in reducing mortality, stroke, coronary heart disease, and total cardiovascular events 3
• While the 2007 ESH/ESC guidelines suggested monotherapy as a potential first approach 1, more recent guidelines (2018-2024) have shifted toward recommending combination therapy as initial treatment for most patients with hypertension 1