What antihypertensive to add in a patient with stroke, Type 2 Diabetes Mellitus, Obstructive Sleep Apnea, reduced ejection fraction, and uncontrolled hypertension on Hydrochlorothiazide, Spironolactone, and Prazosin?

Recommended Antihypertensive Addition

Add an ACE inhibitor or ARB (angiotensin receptor blocker) immediately as the next agent for this patient with resistant hypertension, heart failure with reduced ejection fraction (EF 30%), diabetes, and prior stroke. 1, 2

Rationale for RAS Blockade Priority

This patient has resistant hypertension (BP 190/90 on three agents including a diuretic, aldosterone antagonist, and alpha-blocker) with multiple compelling indications for renin-angiotensin system (RAS) blockade 1:

• Heart failure with reduced ejection fraction (EF 30%): RAS blockers are Class I indicated for mortality reduction in HFrEF 1
• Type 2 diabetes mellitus: ARBs/ACE inhibitors provide superior renal protection and reduce proteinuria progression 1, 3
• Prior cerebrovascular accident: RAS blockers reduce recurrent stroke risk by approximately 30% 1

The absence of an ACE inhibitor or ARB in this regimen is a critical gap that must be addressed before adding additional agents 1

Specific Drug Selection

Preferred option: Start losartan 50 mg daily or equivalent ARB 4, 3:

• ARBs demonstrate superiority over ACE inhibitors in diabetic patients for cardiovascular and renal protection 3
• Losartan specifically reduces stroke risk by 25% compared to beta-blockers in hypertensive patients with left ventricular hypertrophy 4
• Better tolerated than ACE inhibitors (no cough) 3

Alternative: ACE inhibitor (e.g., enalapril 10-20 mg daily) if ARB contraindicated or cost prohibitive 1, 5

Current Regimen Assessment

Your patient's current medications have significant limitations 1, 2:

• Dytor (torasemide): Appropriate loop diuretic given likely volume overload with HFrEF 2
• Aldactone (spironolactone): Correct choice for resistant hypertension and HFrEF, but insufficient alone 1, 2
• Prazosin (alpha-blocker): Should be used cautiously as it increases heart failure risk and is typically a 4th-5th line agent 1, 2

The regimen lacks the foundational triple therapy: RAS blocker + calcium channel blocker + thiazide/thiazide-like diuretic 1

Subsequent Steps After RAS Blocker Addition

If BP remains uncontrolled after optimizing RAS blocker dosing 1:

1. Add amlodipine 5-10 mg daily (dihydropyridine calcium channel blocker) 1, 3
2. Consider adding/optimizing thiazide-like diuretic (chlorthalidone 12.5-25 mg or indapamide 1.5-2.5 mg) in addition to loop diuretic 1, 2
3. Optimize spironolactone dose to 50 mg if potassium and renal function permit 1, 2
4. Consider beta-blocker (bisoprolol or carvedilol) given HFrEF indication, which also provides additional BP lowering 1

Critical Monitoring Requirements

Monitor closely for hyperkalemia when combining RAS blocker with spironolactone, especially with reduced renal function 2, 3:

• Check potassium and creatinine within 1-2 weeks of initiation 2
• Target potassium <5.5 mEq/L 2

Assess for obstructive sleep apnea contribution to resistant hypertension 6:

• OSA is a major contributor to treatment-resistant hypertension 7, 6
• CPAP therapy provides modest additional BP reduction 6
• Beta-blockers and RAS blockers are particularly effective in OSA-related hypertension 6

Common Pitfalls to Avoid

Do not combine ACE inhibitor with ARB - this increases adverse events without additional benefit 1

Verify medication adherence before escalating therapy, as pseudo-resistance from non-adherence is common 7, 8

Ensure adequate diuretic therapy first - volume overload is the most common cause of apparent resistance in HFrEF patients 2, 7

Avoid NSAIDs which interfere with all antihypertensive classes and worsen heart failure 7, 8

Target BP <130/80 mmHg in this high-risk patient with diabetes, stroke history, and HFrEF 1