What is the initial medication recommendation for a patient with hypertension, considering potential comorbid conditions such as heart failure or chronic kidney disease?

Initial Medication Recommendation for Hypertension

For most patients with hypertension, initiate treatment with a thiazide-type diuretic (preferably chlorthalidone 12.5-25 mg daily), as this class has the strongest evidence for reducing cardiovascular mortality, stroke, and heart failure. 1, 2

Treatment Algorithm Based on Blood Pressure Stage

Stage 1 Hypertension (140-159/90-99 mmHg)

• Start with monotherapy using a thiazide-type diuretic for most patients 3, 1
• Chlorthalidone is preferred over hydrochlorothiazide due to superior 24-hour blood pressure control, particularly overnight, and stronger cardiovascular outcomes data 2
• Alternative first-line options include ACE inhibitors, ARBs, or long-acting calcium channel blockers if diuretics are not tolerated 3, 1

Stage 2 Hypertension (≥160/100 mmHg)

• Initiate dual therapy immediately with two first-line agents from different classes 3
• Preferred combinations: thiazide diuretic + ACE inhibitor/ARB, or thiazide diuretic + calcium channel blocker 1
• Single-pill combinations improve adherence and should be used when possible 1

Comorbidity-Specific Recommendations

Heart Failure (Reduced Ejection Fraction)

• First-line: ACE inhibitor (lisinopril 5 mg daily) or ARB plus beta-blocker 3, 4
• Add thiazide diuretic for volume management 3
• Avoid non-dihydropyridine calcium channel blockers 3

Heart Failure (Preserved Ejection Fraction)

• First-line: Thiazide diuretic for volume overload 3
• Add ACE inhibitor or ARB for additional blood pressure control 3

Chronic Kidney Disease

• With albuminuria (≥30 mg/g creatinine): ACE inhibitor or ARB is mandatory first-line therapy to reduce progressive kidney disease 3, 1
• Without albuminuria: Any first-line agent (thiazide, ACE inhibitor, ARB, or calcium channel blocker) is appropriate 3
• Target blood pressure <130/80 mmHg 3

Diabetes Mellitus

• With albuminuria: ACE inhibitor or ARB first-line 3, 1
• Without albuminuria: Thiazide diuretic, ACE inhibitor, ARB, or calcium channel blocker are all appropriate 3
• Target blood pressure <130/80 mmHg 3

Coronary Artery Disease or Post-Myocardial Infarction

• First-line: Beta-blocker plus ACE inhibitor or ARB 3, 1
• These agents provide cardioprotection beyond blood pressure lowering 3

Stable Angina

• First-line: Beta-blocker 3
• Add dihydropyridine calcium channel blocker (amlodipine) for additional blood pressure control 3

Race-Specific Considerations

Black Patients Without Comorbidities

• First-line: Thiazide diuretic or calcium channel blocker 1, 2
• ACE inhibitors are significantly less effective than thiazide diuretics and calcium channel blockers for stroke and heart failure prevention in this population 1, 2
• If ACE inhibitor is needed for a compelling indication (CKD, diabetes with albuminuria), combine with thiazide or calcium channel blocker 1

Specific Dosing Recommendations

Thiazide Diuretics

• Chlorthalidone: 12.5-25 mg once daily (preferred agent) 2
• Hydrochlorothiazide: 12.5-25 mg once daily (maximum 50 mg daily) 2, 4

ACE Inhibitors

• Lisinopril: 10 mg once daily for uncomplicated hypertension 4
• Reduce to 5 mg once daily if already on diuretic therapy 4
• For heart failure: Start 5 mg once daily, titrate to maximum 40 mg daily 4

Calcium Channel Blockers

• Amlodipine: 5 mg once daily, titrate to 10 mg as needed 2

Critical Pitfalls to Avoid

• Never use beta-blockers as first-line therapy for uncomplicated hypertension - they are 36% less effective than calcium channel blockers and 30% less effective than thiazides for stroke prevention 2
• Avoid underdosing ACE inhibitors - low doses have the same potency but shorter duration of action, causing blood pressure fluctuations that worsen cardiovascular outcomes 1
• Do not combine ACE inhibitors with ARBs - this provides no added benefit and increases adverse events 2
• Monitor potassium and renal function within 7-14 days after initiating ACE inhibitors, ARBs, or diuretics 3, 2
• Use caution with dual therapy in patients at risk for orthostatic hypotension 3

Blood Pressure Targets

• General population: <130/80 mmHg 3, 1
• Diabetes or chronic kidney disease: <130/80 mmHg 3
• Adults ≥65 years: Systolic <130 mmHg if tolerated 1

Monitoring Schedule

• Monthly follow-up after initiation or medication changes until blood pressure target is achieved 1
• Home blood pressure monitoring target: <135/85 mmHg 1
• Titrate to maximum tolerated dose before adding additional agents 1