How do I choose the best antihypertensive regimen considering age, race, renal function, diabetes mellitus, coronary artery disease, heart failure, stroke history, and contraindications such as pregnancy or severe asthma?

Choosing the Best Antihypertensive Regimen

For most patients, start with an ACE inhibitor or ARB combined with a calcium channel blocker or thiazide diuretic, then add the third class if needed; tailor initial selection based on race (calcium channel blocker or thiazide for Black patients), compelling indications (ACE inhibitor/ARB for diabetes, chronic kidney disease, heart failure, post-MI; beta-blocker for angina, post-MI, heart failure), and avoid contraindications (ACE inhibitor/ARB in pregnancy, beta-blocker in severe asthma). 1, 2

Initial Drug Selection by Patient Characteristics

Race-Based Considerations

• Black patients: Start with a calcium channel blocker or thiazide diuretic as first-line therapy, as ACE inhibitors and ARBs are less effective as monotherapy in this population due to lower renin activity. 1, 2
• Non-Black patients: ACE inhibitor, ARB, calcium channel blocker, or thiazide diuretic are all appropriate first-line options. 1, 2
• When combining agents in Black patients, the interracial differences in blood pressure lowering with ACE inhibitors/ARBs are abolished when combined with a diuretic. 1

Age-Based Selection

• Elderly patients (≥60 years) or isolated systolic hypertension: Thiazide diuretics or calcium channel blockers are preferred as they provide superior stroke prevention and cardiovascular event reduction. 1
• Elderly patients derive substantial reductions in stroke and coronary events from antihypertensive therapy, making aggressive treatment appropriate despite advanced age. 1

Compelling Indications (Organ-Specific)

Diabetes Mellitus:

• Start with ACE inhibitor or ARB as first-line therapy. 1, 2
• Target blood pressure <130/80 mmHg. 2, 3
• The combination of ACE inhibitor with amlodipine has demonstrated superior blood pressure control in patients with diabetes. 4

Chronic Kidney Disease or Proteinuria:

• ACE inhibitor or ARB is mandatory as first-line therapy to slow progression of nephropathy. 1, 2, 3
• Target blood pressure <130/80 mmHg; if proteinuria ≥1 gram, aim for systolic blood pressure approaching 115 mmHg. 3
• Loop diuretics are preferred over thiazides when estimated glomerular filtration rate is significantly reduced. 1

Heart Failure:

• Use diuretics (thiazide or loop depending on severity), beta-blockers (carvedilol, metoprolol succinate, or bisoprolol), ACE inhibitors or ARBs, and aldosterone antagonists (spironolactone or eplerenone). 1, 5
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) due to negative inotropic effects. 1, 2, 5
• Target blood pressure <120/80 mmHg if tolerated. 5

Coronary Artery Disease or Post-Myocardial Infarction:

• Beta-blockers and ACE inhibitors (or ARBs if ACE inhibitor not tolerated) form the foundation of therapy. 1, 5
• If additional blood pressure lowering is needed, add a thiazide diuretic and/or a dihydropyridine calcium channel blocker (amlodipine, not verapamil or diltiazem). 5
• Beta-blockers reduce mortality by 28% in patients after acute myocardial infarction. 1

Angina Pectoris:

• Beta-blockers or calcium channel blockers are preferred. 1
• If beta-blocker is contraindicated or not tolerated, diltiazem or verapamil can be substituted. 5

Previous Stroke or Transient Ischemic Attack:

• Any blood pressure-lowering agent is appropriate; the primary goal is achieving target blood pressure. 1

Atrial Fibrillation:

• For recurrent atrial fibrillation: ARB or ACE inhibitor. 1
• For permanent atrial fibrillation requiring rate control: Beta-blocker or non-dihydropyridine calcium channel blocker. 1

Left Ventricular Hypertrophy:

• ACE inhibitors, calcium channel blockers, or ARBs are preferred as they effectively reduce left ventricular hypertrophy. 1

Metabolic Syndrome:

• ACE inhibitors, ARBs, or calcium channel blockers are preferred. 1
• Avoid or use beta-blockers cautiously as they may worsen glucose metabolism and lipid profiles. 1

Peripheral Artery Disease:

• Calcium channel blockers are preferred. 1

Critical Contraindications to Avoid

Absolute Contraindications:

• Pregnancy: ACE inhibitors and ARBs are absolutely contraindicated; use calcium channel blockers (nifedipine), methyldopa, or beta-blockers (labetalol). 1, 2
• Severe asthma or A-V block (grade 2 or 3): Beta-blockers are contraindicated. 1
• Bilateral renal artery stenosis: ACE inhibitors and ARBs are contraindicated. 1
• History of angioedema: ACE inhibitors are contraindicated. 1
• Gout: Thiazide diuretics are contraindicated. 1
• Renal failure or hyperkalemia: Aldosterone antagonists (spironolactone, eplerenone) are contraindicated. 1

Relative Contraindications (Use with Caution):

• Chronic obstructive pulmonary disease: Beta-blockers should be avoided unless compelling indication exists; calcium channel blockers are safe. 1
• Metabolic syndrome or glucose intolerance: Thiazide diuretics and beta-blockers may worsen metabolic parameters. 1
• Peripheral artery disease: Beta-blockers may worsen symptoms. 1
• Athletes and physically active patients: Beta-blockers may limit exercise capacity. 1

Combination Therapy Algorithm

When to Start Combination Therapy

• Stage 2 hypertension (≥160/100 mmHg): Start with two antihypertensive agents immediately or use a single-pill combination. 1, 2
• Stage 1 hypertension (140-159/90-99 mmHg): Start with monotherapy, then add a second agent if blood pressure remains ≥140/90 mmHg after 2-4 weeks. 2

Preferred Combinations

• First-line dual therapy: ACE inhibitor or ARB + calcium channel blocker or ACE inhibitor or ARB + thiazide diuretic. 1, 4, 2
• Triple therapy (if dual therapy fails): ACE inhibitor or ARB + calcium channel blocker + thiazide diuretic. 1, 4, 2
• Adding a thiazide diuretic to amlodipine is particularly effective for volume-dependent hypertension, elderly patients, or Black patients. 4

Fourth-Line Agent for Resistant Hypertension

• Spironolactone 25-50 mg daily is the preferred fourth-line agent, providing additional reductions of 20-25/10-12 mmHg systolic/diastolic when added to triple therapy. 4
• Alternative fourth-line agents include amiloride, doxazosin, eplerenone, or clonidine if spironolactone is contraindicated. 4

Combinations to Avoid

• Never combine ACE inhibitor + ARB: This dual renin-angiotensin system blockade increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1, 2, 5
• Avoid beta-blocker as second or third agent unless compelling indication exists (angina, post-MI, heart failure, atrial fibrillation), as beta-blockers are less effective than calcium channel blockers or diuretics for stroke prevention. 1, 2

Blood Pressure Targets

• Standard target: <140/90 mmHg for most patients. 2, 5
• Intensive target (<130/80 mmHg): For patients with diabetes, chronic kidney disease, established cardiovascular disease, or 10-year cardiovascular risk ≥10%. 2, 5, 3
• Heart failure with left ventricular dysfunction: <120/80 mmHg if tolerated. 5

Monitoring Schedule

• After initiation or dose change: Recheck blood pressure in 2-4 weeks. 2
• When adding ACE inhibitor, ARB, or diuretic: Check serum potassium and creatinine 2-4 weeks after initiation. 4, 2
• Goal: Achieve target blood pressure within 3 months of therapy modification. 4, 2
• Once stable: Monitor blood pressure monthly until target achieved, then every 3-6 months. 2

Common Pitfalls to Avoid

• Do not delay treatment intensification: Most patients require 2-3 medications to achieve target blood pressure; waiting too long increases cardiovascular risk. 2
• Do not uptitrate a single agent to maximum dose before adding a second drug class; combination therapy is more effective than monotherapy dose escalation. 4
• Do not assume treatment failure without first confirming medication adherence (the most common cause of apparent treatment resistance) and excluding white-coat hypertension with home or ambulatory monitoring. 4, 2
• Do not add a beta-blocker for uncomplicated hypertension when calcium channel blockers or diuretics are more effective for stroke prevention. 1