What antihypertensive should be added to candesartan and felodipine in a patient with impaired renal function, ischaemia, and elevated systolic blood pressure, who is intolerant to statins and on ezetimibe?

Add a Beta-Blocker as the Next Antihypertensive Agent

In this patient with ischemic heart disease, renal impairment, and uncontrolled hypertension on candesartan and felodipine, a beta-blocker—specifically bisoprolol or carvedilol—should be added immediately as the next antihypertensive agent. This recommendation prioritizes mortality reduction in patients with ischemia while providing additional blood pressure control.

Rationale for Beta-Blocker Selection

Mortality Benefit in Ischemic Heart Disease

• Beta-blockers are Class I indicated for all patients with ischemic heart disease and should be continued long-term unless contraindications exist 1
• The American Heart Association specifically recommends beta-blockers for patients with ongoing ischemia or refractory hypertension, which applies to this patient averaging 149 mmHg systolic 1
• Beta-blockers reduce cardiovascular mortality and recurrent ischemic events in patients with coronary artery disease 1

Safety in Renal Impairment

• Bisoprolol is the preferred beta-blocker in renal impairment due to its balanced clearance (50% renal, 50% hepatic), preventing drug accumulation even in severe renal dysfunction 2
• In severe renal failure, bisoprolol elimination half-life increases only by a factor of 1.96, with no dose adjustment needed for mild-to-moderate dysfunction 2
• Maximum dose should not exceed 10 mg once daily in severe or end-stage renal failure 2
• Carvedilol is an alternative with proven mortality benefit in heart failure and ischemic disease 1

Specific Dosing Recommendations

Bisoprolol (Preferred)

• Start with 1.25 mg once daily 1
• Titrate gradually to target dose of 10 mg once daily as tolerated 1
• No dose adjustment needed for mild-to-moderate renal impairment; cap at 10 mg daily in severe renal dysfunction 2

Carvedilol (Alternative)

• Start with 3.125 mg twice daily 1
• Titrate to target dose of 25 mg twice daily as tolerated 1

Why Not Other Options?

Avoid Adding Another Diuretic First

• The patient is already on felodipine 10 mg (maximum dose), and adding a thiazide to candesartan in renal impairment significantly increases hyperkalemia risk 1
• Loop diuretics are less effective for blood pressure control than thiazides and should be reserved for volume overload 1

Avoid Aldosterone Antagonists at This Stage

• Spironolactone or eplerenone would be appropriate for resistant hypertension, but only after optimizing the current three-drug regimen 1
• Combining aldosterone antagonists with candesartan in renal impairment creates unacceptable hyperkalemia risk 1
• These agents should be considered only if blood pressure remains uncontrolled after adding a beta-blocker, with close monitoring of potassium and renal function 1, 3

Cannot Intensify Current Regimen

• Felodipine is already at maximum dose (10 mg daily) 1
• Candesartan dose is not specified, but adding another RAS blocker (ACE inhibitor) is contraindicated and increases adverse events without benefit 1

Monitoring Requirements

Before Initiating Beta-Blocker

• Assess for contraindications: active asthma, reactive airways disease, second- or third-degree heart block, or PR interval >0.24 seconds 1
• Check baseline heart rate and blood pressure 1

During Titration

• Monitor heart rate (target 50-60 bpm at rest), blood pressure, and symptoms of heart failure 1
• Reassess renal function and potassium within 1-2 weeks, then at 1,3, and 6 months 1
• Watch for signs of worsening heart failure, bradycardia, or hypotension 1

Target Blood Pressure and Next Steps

• Target blood pressure is <130/80 mmHg in this high-risk patient with ischemia and renal impairment 1, 3
• If blood pressure remains uncontrolled after optimizing beta-blocker dose, consider adding a thiazide-like diuretic (chlorthalidone 12.5-25 mg or indapamide 1.25-2.5 mg) with close monitoring of renal function and electrolytes 1, 3
• Spironolactone 25 mg daily can be added as a fourth agent for resistant hypertension, but only with intensive monitoring of potassium (target <5.5 mmol/L) and creatinine 1, 3

Critical Pitfalls to Avoid

• Do not combine ACE inhibitors with the existing ARB (candesartan)—this increases adverse events without additional benefit 1
• Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) if adding a beta-blocker due to increased risk of bradycardia and heart block 1
• Do not use alpha-blockers (doxazosin) except as last resort, as they increase heart failure risk 1
• Monitor closely for hyperkalemia when combining RAS blockade with any additional agent in renal impairment 1