What is the preferred initial antihypertensive agent in patients with hypertension and various comorbidities, such as heart failure, diabetes, chronic kidney disease, or geriatric patients?

Preferred Initial Antihypertensive Agents by Clinical Condition

For most patients with uncomplicated hypertension, initiate treatment with a thiazide-type diuretic, ACE inhibitor/ARB, or long-acting calcium channel blocker (such as amlodipine), with specific selection guided by race, comorbidities, and blood pressure severity. 1, 2, 3

Heart Failure

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Start with guideline-directed medical therapy (GDMT) beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) as the preferred initial antihypertensive agent. 1
• Add ACE inhibitors or ARBs for additional blood pressure control and mortality benefit. 1
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) due to negative inotropic effects. 1, 2
• Amlodipine can be added as a third-line agent if blood pressure remains uncontrolled after ACE inhibitors/ARBs, beta-blockers, and diuretics. 2

Heart Failure with Preserved Ejection Fraction (HFpEF)

• Initiate diuretics for volume overload as first-line therapy. 1
• Add ACE inhibitors or ARBs and beta-blockers for incremental blood pressure control. 1
• Consider angiotensin receptor-neprilysin inhibitors and mineralocorticoid receptor antagonists. 1

Diabetes Mellitus

With Albuminuria (≥30 mg/g creatinine)

• Start with an ACE inhibitor or ARB as mandatory first-line therapy to reduce progressive kidney disease. 1, 2, 3
• This recommendation applies regardless of blood pressure level if albuminuria is present. 2

Without Albuminuria

• Use any of the four first-line drug classes: thiazide diuretic, ACE inhibitor, ARB, or calcium channel blocker. 3
• The 2020 ACC/AHA guidelines recommend a blood pressure target of <140/90 mmHg (revised from the previous <130/80 mmHg target). 1

With Established Coronary Artery Disease

• Prioritize ACE inhibitors or ARBs as first-line therapy, then add amlodipine if needed for blood pressure control. 2

Chronic Kidney Disease (CKD)

CKD with Any Stage

• Initiate an ACE inhibitor or ARB as first-line therapy. 1, 3
• Use ARB if ACE inhibitor is not tolerated. 1
• Blood pressure target is <140/90 mmHg for all age groups with CKD. 1

CKD with Severely Increased Albuminuria

• ACE inhibitors or ARBs are mandatory as they reduce the risk of kidney endpoints including rate of eGFR decline, 50% decline in eGFR, and incident kidney failure. 1

Advanced CKD (eGFR <30 mL/min/1.73 m²)

• ACE inhibitors or ARBs remain appropriate but require close monitoring of potassium and creatinine. 1
• Thiazide diuretics can still be effective in advanced CKD despite common misconceptions about lack of efficacy. 1

Post-Kidney Transplant

• Start with a calcium channel blocker as first-line therapy to improve kidney graft survival and GFR. 1
• Use ACE inhibitors with caution. 1
• Target blood pressure <160/90 mmHg in the first month post-transplant to avoid hypotension-induced graft thrombosis. 1

Geriatric Patients (≥60 Years)

General Elderly Population

• Initiate treatment with a thiazide-type diuretic or calcium channel blocker as preferred first-line agents. 1
• Blood pressure target is <150/90 mmHg for patients >60 years according to JNC-8. 1
• For fit elderly patients <80 years, consider a systolic blood pressure target of <140 mmHg. 1

Frail Elderly

• Use clinical discretion with individualized blood pressure targets, typically more conservative (systolic 140-150 mmHg). 1
• Start with low medication doses and uptitrate slowly. 1

Elderly with Isolated Systolic Hypertension

• Thiazide diuretics or dihydropyridine calcium channel blockers are the preferred initial agents. 1

Race-Specific Considerations

Black Patients Without Heart Failure or CKD

• Start with either a thiazide-type diuretic or calcium channel blocker as these are more effective as monotherapy in this population. 1, 2, 3
• Calcium channel blockers are more effective than ACE inhibitors in preventing heart failure and stroke in black patients. 2

Non-Black Patients

• Any of the four first-line classes can be used: ACE inhibitor, ARB, thiazide-type diuretic, or calcium channel blocker. 1

Additional Comorbid Conditions

Stable Ischemic Heart Disease

• Initiate GDMT beta-blockers with ACE inhibitor or ARB. 1

Angina

• Start with GDMT beta-blockers, then add dihydropyridine calcium channel blockers for additional blood pressure control. 1

Post-Myocardial Infarction or Acute Coronary Syndrome

• GDMT beta-blockers are the preferred initial agents. 1

Secondary Stroke Prevention

• Use thiazide diuretics, ACE inhibitors, ARBs, or thiazide + ACE inhibitor combination. 1
• If previously treated, restart drugs a few days post-event; if not previously treated, start drug treatment a few days post-event if blood pressure ≥140/90 mmHg. 1

Atrial Fibrillation

• ARBs are favored as they may reduce atrial fibrillation recurrence. 1

Aortic Disease (Thoracic)

• Beta-blockers are the preferred agents for patients with thoracic aorta disease. 1, 3

Aortic Stenosis (Asymptomatic)

• Initiate treatment with low medication doses and uptitrate slowly; no specific drug class preference. 1

Aortic Insufficiency

• Avoid beta-blockers and non-dihydropyridine calcium channel blockers as they slow heart rate. 1

Benign Prostatic Hypertrophy

• Alpha-blockers are a compelling indication. 1

Asthma or Chronic Obstructive Pulmonary Disease

• Avoid beta-blockers as they are contraindicated. 1
• ARBs are more likely to be selected as initial treatment in these patients. 4

Critical Pitfalls to Avoid

• Never combine an ACE inhibitor, ARB, and/or renin inhibitor simultaneously as this is potentially harmful. 1
• Do not use beta-blockers as first-line therapy without specific cardiac indications, as they are less effective for stroke prevention. 1, 3
• Avoid underdosing medications before adding additional agents; titrate to maximum tolerated dose first. 3
• Do not discontinue medications just because blood pressure falls below target without adverse effects. 1
• Monitor potassium and creatinine within 7-14 days when initiating or changing doses of ACE inhibitors or ARBs. 3

Combination Therapy Considerations

When to Initiate Combination Therapy

• Start with two-drug combination therapy if blood pressure is ≥150/90 mmHg or stage 2 hypertension (≥160/100 mmHg). 1, 3
• Use single-pill combinations when possible to improve medication adherence. 3

Preferred Two-Drug Combinations

• Thiazide diuretic + ACE inhibitor or ARB 3
• Calcium channel blocker + ACE inhibitor or ARB 3
• Calcium channel blocker + thiazide diuretic 3