What is the first line treatment for a patient with hypertension (HTN) and elevated brain natriuretic peptide (BNP)?

First-Line Treatment for Hypertension with Elevated BNP

For a patient with hypertension and elevated BNP (indicating heart failure or left ventricular dysfunction), initiate an ACE inhibitor or ARB combined with a diuretic as first-line therapy, targeting a blood pressure <130/80 mmHg. 1

Treatment Algorithm Based on Heart Failure Status

If Elevated BNP Indicates HFrEF (Heart Failure with Reduced Ejection Fraction)

Start with guideline-directed medical therapy (GDMT) that simultaneously treats both hypertension and heart failure:

• First-line agents include: ACE inhibitors, ARBs, angiotensin receptor-neprilysin inhibitors (ARNIs), mineralocorticoid receptor antagonists, diuretics, and GDMT beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) 1

• ACE inhibitors are preferred over ARBs for reducing cardiovascular events and mortality in HFrEF, unless the patient cannot tolerate ACEis (typically due to cough or angioedema) 1, 2

• Add a diuretic (thiazide or thiazide-like such as chlorthalidone) to control volume overload and achieve blood pressure targets 1

• Target systolic BP <130 mmHg based on extrapolation from the SPRINT trial, though this specific target has not been tested in randomized trials of HFrEF patients 1

• Avoid non-dihydropyridine calcium channel blockers (verapamil, diltiazem) as they have myocardial depressant activity and worsen outcomes in HFrEF 1

If Elevated BNP Indicates HFpEF (Heart Failure with Preserved Ejection Fraction)

Prioritize volume management first, then blood pressure control:

• Diuretics are mandatory for symptom control in patients with volume overload 1

• After volume optimization, use ACE inhibitors or ARBs plus beta-blockers titrated to achieve systolic BP <130 mmHg 1

• Consider adding a mineralocorticoid receptor antagonist (spironolactone) in patients with elevated BNP/NT-proBNP or recent HF hospitalization to reduce hospitalizations 1

• Thiazide/thiazide-like diuretics are preferred over loop diuretics for chronic blood pressure control unless significant renal impairment exists 1, 3

Specific Drug Selection Rationale

Why ACE Inhibitors Are First Choice

• Superior cardiovascular outcomes compared to other antihypertensive classes in high-risk patients with or without hypertension 1

• Proven mortality benefit in HFrEF when compared to ARBs 1

• Reduce risk of myocardial infarction more effectively than ARBs 2

• The cough side effect is often overestimated and can be mitigated by using lipophilic ACE inhibitors or combining with calcium channel blockers 2

Why Diuretics Are Essential

• Thiazide-like diuretics (chlorthalidone, indapamide) have the strongest evidence for reducing heart failure events compared to other antihypertensive classes 4

• In the ALLHAT trial, chlorthalidone reduced HFrEF risk more than amlodipine and doxazosin, and similarly to lisinopril 1

• BNP itself promotes natriuresis and diuresis, suggesting that elevated BNP reflects compensatory mechanisms that diuretics can support 5, 6

• Combination therapy with RAS blockers plus diuretics is recommended as initial therapy for most patients with confirmed hypertension 1

Practical Implementation

Initial Regimen

• Start ACE inhibitor (e.g., lisinopril 10 mg daily, ramipril 2.5 mg daily) 1
• Add thiazide-like diuretic (chlorthalidone 12.5-25 mg daily or indapamide 1.25 mg daily) 1
• Monitor renal function and potassium within 1-2 weeks of initiation 1

If Two-Drug Combination Inadequate

• Escalate to triple therapy: RAS blocker + dihydropyridine calcium channel blocker + thiazide/thiazide-like diuretic, preferably as a single-pill combination 1, 3

If Triple Therapy Inadequate

• Add spironolactone 25 mg daily after confirming normal potassium and adequate renal function 1, 3

Critical Caveats

• Never combine ACE inhibitor + ARB + renin inhibitor as this is potentially harmful 1

• Beta-blockers alone are not first-line for uncomplicated hypertension but should be added when there are compelling indications (post-MI, angina, rate control in atrial fibrillation) 1

• Elevated BNP in hypertension often indicates left ventricular hypertrophy even before overt heart failure develops, making early aggressive treatment essential 7

• Target BP achievement within 3 months to maintain patient confidence and reduce cardiovascular risk 1