How should I adjust antihypertensive therapy in a patient aged 65 years or older with hypertension and chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m²), possibly with diabetes or coronary artery disease, who is not at blood pressure goal?

Adjusting Antihypertensive Therapy in Older Adults with CKD

In a patient ≥65 years with hypertension, CKD (eGFR <60 mL/min/1.73 m²), and possibly diabetes or coronary artery disease who is not at blood pressure goal, intensify therapy by adding a third agent from a complementary drug class—specifically a calcium channel blocker if currently on an ACE inhibitor/ARB plus diuretic, or a thiazide-like diuretic if on an ACE inhibitor/ARB plus calcium channel blocker—targeting a systolic BP of 120–129 mmHg if eGFR >30 mL/min/1.73 m² and tolerated, or 130–139 mmHg in those ≥65 years with lower eGFR or frailty. 1

Blood Pressure Targets in This Population

For CKD with eGFR >30 mL/min/1.73 m²

• Target systolic BP to 120–129 mmHg if tolerated in adults with moderate-to-severe CKD receiving BP-lowering drugs 1
• This intensive target is supported by SPRINT data showing reduced cardiovascular events and mortality in non-diabetic adults with CKD, without accelerating CKD progression 1, 2
• The minimum acceptable target remains <140/90 mmHg for all patients with CKD 1

For Older Adults (≥65 years)

• Target systolic BP to 130–139 mmHg in older people with diabetes or CKD 1
• For community-dwelling older adults ≥65 years, aim for <130/80 mmHg when tolerated, with mandatory orthostatic BP monitoring at each visit 3
• Evidence from SPRINT and HYVET demonstrates that intensive BP control safely reduces cardiovascular risk even in older adults living independently 3

Special Considerations for Diabetes

• In people with diabetes ≥65 years, target systolic BP to 130–139 mmHg 1
• For younger adults with diabetes, target systolic BP to 130 mmHg and <130 mmHg if tolerated, but not <120 mmHg 1

Medication Adjustment Algorithm

Step 1: Verify Current Regimen and Adherence

• Confirm medication adherence first—non-adherence is the most common cause of apparent treatment resistance 1
• Review for interfering medications: NSAIDs, decongestants, oral contraceptives, systemic corticosteroids 1
• Confirm true hypertension with home BP monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) 1

Step 2: Optimize Current Medications Before Adding

• If on dual therapy (e.g., ACE inhibitor + diuretic), ensure doses are optimized before adding a third agent 1
• For ACE inhibitors: lisinopril 40 mg, enalapril 20 mg, or ramipril 10 mg daily are maximum doses 4
• For thiazide-like diuretics: chlorthalidone 25 mg or indapamide 2.5 mg are optimal doses (hydrochlorothiazide 25 mg is less effective) 1

Step 3: Add Third Agent from Complementary Class

If currently on ACE inhibitor/ARB + thiazide diuretic:

• Add amlodipine 5–10 mg once daily to create the guideline-recommended triple therapy (RAS blocker + diuretic + calcium channel blocker) 1
• This combination targets three mechanisms: renin-angiotensin blockade, volume reduction, and vasodilation 1

If currently on ACE inhibitor/ARB + calcium channel blocker:

• Add chlorthalidone 12.5–25 mg once daily (preferred over hydrochlorothiazide due to superior 24-hour BP control and cardiovascular outcomes) 1
• Alternative: indapamide 1.25–2.5 mg once daily 1

If currently on calcium channel blocker + thiazide diuretic:

• Add an ACE inhibitor (e.g., lisinopril 10–40 mg) or ARB (e.g., losartan 50–100 mg) 1
• RAS blockers are particularly important in CKD with albuminuria (≥30 mg/g) or proteinuria 1

Step 4: Monitor After Medication Addition

• Check serum potassium and creatinine 2–4 weeks after adding any agent, especially when combining RAS blockers with diuretics or spironolactone 1, 3
• Reassess BP within 2–4 weeks, aiming to achieve target within 3 months of therapy modification 1
• Monitor for orthostatic hypotension at every visit in older adults—measure BP seated and after standing 1–3 minutes 3

Step 5: Fourth-Line Agent for Resistant Hypertension

If BP remains ≥140/90 mmHg despite optimized triple therapy:

• Add spironolactone 25–50 mg daily as the preferred fourth-line agent 1, 3
• Spironolactone provides additional reductions of approximately 20–25/10–12 mmHg systolic/diastolic 1
• Monitor potassium closely: check at 3 days, 1 week, then monthly for 3 months after initiation 3
• Alternative fourth-line agents if spironolactone contraindicated: eplerenone, amiloride, doxazosin, or beta-blocker (only if compelling indication) 1

Drug Selection Nuances in CKD

RAS Blockers (ACE Inhibitors or ARBs)

• RAS blockers are recommended as part of the treatment strategy in CKD with microalbuminuria or proteinuria because they are more effective at reducing albuminuria than other agents 1
• In CKD stage 3 or higher with albuminuria ≥300 mg/d, treatment with an ACE inhibitor is reasonable to slow kidney disease progression 1
• If ACE inhibitor not tolerated (cough, angioedema), an ARB may be used 1
• Never combine an ACE inhibitor with an ARB—dual RAS blockade increases hyperkalemia and acute kidney injury without cardiovascular benefit 1, 4

Diuretic Selection in CKD

• Thiazide-like diuretics (chlorthalidone, indapamide) are preferred over hydrochlorothiazide for superior efficacy and outcomes 1, 3
• In CKD with eGFR <30 mL/min/1.73 m², loop diuretics (furosemide 40–80 mg daily) may be more effective than thiazides for volume control 5
• Nephrologists preferentially prescribe furosemide at higher doses (47 mg/d) compared to primary care (28 mg/d) in CKD patients 5

Calcium Channel Blockers

• Dihydropyridine calcium channel blockers (amlodipine, nifedipine) are safe and effective in CKD 1, 6
• Amlodipine 5–10 mg daily is the most commonly used, evidence-based CCB 6
• Non-dihydropyridine CCBs (diltiazem, verapamil) should be avoided in heart failure with reduced ejection fraction 1

Special Populations and Comorbidities

Diabetes + CKD

• Target systolic BP to 130–139 mmHg in older adults (≥65 years) with diabetes 1
• Initiate pharmacological treatment when BP ≥130/80 mmHg after maximum 3 months of lifestyle intervention 1
• RAS blockers are particularly beneficial in diabetic CKD with albuminuria 1

Coronary Artery Disease + CKD

• In patients with confirmed BP ≥130/80 mmHg and history of TIA or stroke, target systolic BP to 120–129 mmHg if tolerated 1
• Beta-blockers may be appropriate as part of the regimen if there is angina, post-MI, or heart failure with reduced ejection fraction 1

Black Patients with CKD

• Initial therapy should include a diuretic or calcium channel blocker, either in combination or with a RAS blocker 1
• The combination of CCB + thiazide diuretic may be more effective than CCB + RAS blocker in Black patients 1

Critical Pitfalls to Avoid

Do Not Delay Intensification

• Stage 2 hypertension (≥160/100 mmHg) requires prompt action within 2–4 weeks to reduce cardiovascular risk 1
• Do not withhold intensive BP treatment based solely on age—no trial has shown harm from BP lowering in adults >65 years 3, 7

Do Not Use Inappropriate Drug Combinations

• Avoid dual RAS blockade (ACE inhibitor + ARB)—increases hyperkalemia and acute kidney injury without benefit 1, 4
• Do not add a beta-blocker as third agent unless compelling indication (angina, post-MI, heart failure, atrial fibrillation) exists 1
• Beta-blockers are less effective than CCBs or diuretics for stroke prevention in uncomplicated hypertension 1, 6

Do Not Ignore Monitoring Requirements

• Orthostatic hypotension assessment is mandatory at every visit in older adults on antihypertensive therapy 3
• Check serum potassium and creatinine 2–4 weeks after any medication change, especially when combining RAS blockers with diuretics or adding spironolactone 1, 3, 4
• Monitor for acute kidney injury—occurs at similar rates as in younger adults but requires vigilance 3

Do Not Assume Treatment Failure Prematurely

• Verify adherence, exclude white-coat hypertension, and rule out secondary causes before assuming treatment resistance 1
• Screen for secondary hypertension if BP remains severely elevated (≥180/110 mmHg) or resistant to triple therapy 1

Lifestyle Modifications (Essential Adjunct)

• Sodium restriction to <2 g/day provides 5–10 mmHg systolic reduction and enhances efficacy of all antihypertensives 1
• Weight loss (≈10 kg) reduces BP by approximately 6/4.6 mmHg systolic/diastolic 1
• DASH dietary pattern lowers BP by roughly 11.4/5.5 mmHg 1
• Regular aerobic exercise (≥150 minutes/week moderate intensity) reduces BP by ≈4/3 mmHg 1
• Limit alcohol to ≤2 drinks/day for men, ≤1 drink/day for women 1

Monitoring Timeline

• 2–4 weeks: Recheck BP, serum potassium, and creatinine after any medication change 1, 3
• 3 months: Achieve target BP within this timeframe of therapy modification 1
• 3–6 months: Ongoing monitoring for hypertension-mediated organ damage (renal function, proteinuria, left ventricular hypertrophy) 1
• Every visit: Assess orthostatic BP in older adults 3