What is the preferred second antihypertensive agent for a patient with carotid atherosclerosis, coronary artery disease, peripheral arterial disease, ischemic heart disease, prior myocardial infarction, and prior transient ischemic attack?

Preferred Second Antihypertensive Agent for Multi-Territory Atherosclerotic Disease

A thiazide-like diuretic (preferably chlorthalidone) is the preferred second agent for blood pressure control in this patient with extensive atherosclerotic disease, assuming a beta-blocker and ACE inhibitor/ARB are already in use.

Rationale Based on Guidelines

First-Line Foundation

Your patient with prior MI, TIA, CAD, carotid atherosclerosis, and PAD requires a multi-drug regimen. The foundation should include:

• Beta-blocker (Class 1 recommendation) for secondary prevention post-MI, especially within the first 3 years, and for angina management 1
• ACE inhibitor or ARB (Class 1 recommendation) for patients with prior MI, stroke/TIA, carotid artery disease, and PAD to reduce cardiovascular events 1

Second Agent Selection: Thiazide-Like Diuretic

Chlorthalidone is specifically preferred over other thiazides as the second-line agent for this patient 1. The 2015 AHA/ACC/ASH Scientific Statement explicitly designates diuretics as "drug of choice" (labeled as "1") for stable angina and post-MI patients, while other agents are classified as "add-on" or "alternative" (labeled as "2") 1.

Supporting Evidence:

• ALLHAT trial demonstrated thiazide-type diuretics were superior to calcium channel blockers and ACE inhibitors in preventing major cardiovascular disease forms, including lower rates of heart failure 2
• Chlorthalidone specifically is the preferred thiazide formulation in guideline recommendations 1
• For patients with post-MI, stroke/TIA, carotid artery disease, and PAD, the BP target is <130/80 mmHg (Class IIb/B), which typically requires 2+ agents 1

Alternative Consideration: Calcium Channel Blockers

Dihydropyridine calcium channel blockers (DHP-CCB) like amlodipine are reasonable alternatives if diuretics are contraindicated or not tolerated 1:

• Classified as "add-on" agents for stable angina and post-MI 1
• CAMELOT trial showed amlodipine reduced hospitalizations for angina and revascularization procedures in CAD patients 3
• The 2024 ESC Guidelines support ACE inhibitors/ARBs as first-line with consideration for adding calcium channel blockers in combination therapy for PAD patients 1
• Particularly useful in carotid atherosclerosis management 1, 4

Critical caveat: Non-dihydropyridine CCBs (diltiazem, verapamil) should be used cautiously if combining with beta-blockers due to additive negative chronotropic effects 1

Why Not Other Agents?

• Aldosterone antagonists are reserved for patients with left ventricular dysfunction, heart failure, or diabetes—not routine second-line therapy 1
• Additional beta-blocker or ACE inhibitor/ARB: Never combine two drugs from the same class (e.g., two ACE inhibitors or ACE inhibitor + ARB), as this increases adverse effects without cardiovascular benefit 1, 5

Blood Pressure Target

Target BP <130/80 mmHg for this patient with post-MI, TIA, carotid artery disease, and PAD (Class IIb/B recommendation) 1. The 2024 ESC Guidelines recommend targeting SBP 120-129 mmHg if tolerated in patients with peripheral and aortic disease 1.

Monitoring Caution:

• Avoid excessive diastolic BP lowering (<60 mmHg), particularly in patients >60 years or with diabetes, as this may worsen myocardial ischemia 1
• Monitor renal function and potassium within 1-2 weeks after initiating or adjusting ACE inhibitor/ARB therapy 5

Practical Implementation

1. If already on beta-blocker + ACE inhibitor/ARB: Add chlorthalidone 12.5-25 mg daily 1, 2
2. If diuretic contraindicated: Add amlodipine 5-10 mg daily 1, 3
3. Monitor: BP response, renal function, electrolytes, and symptoms within 2-4 weeks 5
4. Titrate: Adjust doses to achieve BP <130/80 mmHg while avoiding excessive diastolic lowering 1