In a 67-year-old man with peripheral arterial disease, uncontrolled systolic hypertension (145-155 mm Hg) and heart rate 80-90 bpm who is already on a statin and aspirin, which second antihypertensive agent is preferred: an ACE inhibitor, an angiotensin‑II receptor blocker, a selective β‑blocker, a dihydropyridine calcium‑channel blocker, or a potassium‑sparing diuretic?

ACE Inhibitor or ARB is the Preferred Second Antihypertensive Agent

For this 67-year-old man with peripheral arterial disease (PAD) and uncontrolled hypertension, an ACE inhibitor or angiotensin receptor blocker (ARB) should be added as the second blood pressure medication. The 2024 ESC Guidelines for peripheral arterial and aortic diseases specifically recommend ACE inhibitors or ARBs as first-line antihypertensive therapy in patients with PAD and hypertension 1.

Rationale for ACE Inhibitor/ARB Selection

The evidence strongly supports renin-angiotensin system (RAS) blockade in this clinical scenario for several compelling reasons:

• Guideline-directed recommendation: The 2024 ESC PAD guidelines give a Class IIa, Level B recommendation that "ACEIs or ARBs should be considered as first-line antihypertensive therapy" in patients with PAAD and hypertension 1

• Cardiovascular risk reduction beyond blood pressure lowering: ACE inhibitors (particularly ramipril and perindopril) reduce cardiovascular events beyond their blood pressure-lowering effects in PAD patients 2

• Limb-specific benefits: ACE inhibitors may improve perfusion to the diseased leg and are recommended even in critical limb ischemia 3

• Comprehensive secondary prevention: Adherence to guideline-recommended therapy including ACE inhibitors is associated with decreased major adverse cardiovascular events (MACE) and major adverse limb events (MALE) 4

Blood Pressure Target Considerations

This patient's systolic blood pressure of 145-155 mmHg requires treatment toward a target of 120-129 mmHg if tolerated 1, 5. However, critical caveats apply:

• Avoid excessive lowering: Systolic BP <120 mmHg may worsen oxygen delivery to the diseased leg and is associated with higher cardiovascular event rates, creating a J-shaped relationship 3

• Monitor carefully: With an ankle-brachial index of 0.6 (indicating moderate-to-severe PAD), aggressive BP lowering could compromise limb perfusion

Why Not the Other Options?

Selective beta-blocker: While beta-blockers do not worsen walking capacity or limb events and can be prescribed if necessary 1, they are not first-line for hypertension in PAD. They should be reserved for compelling indications like post-MI or heart failure 5

Dihydropyridine calcium channel blocker: This is a reasonable alternative and part of recommended combination therapy (RAS blocker + CCB + diuretic for three-drug regimens) 5, but ACE inhibitors/ARBs have superior evidence for cardiovascular risk reduction in PAD specifically

Potassium-sparing diuretic: Not recommended as monotherapy. Thiazide or thiazide-like diuretics are preferred diuretic choices when needed 5

Implementation Strategy

Start with either:

• ACE inhibitor (e.g., ramipril or perindopril based on evidence 2)
• ARB if ACE inhibitor is not tolerated (cough, angioedema)

Monitor renal function closely given his PAD, as these patients may have concurrent renal artery stenosis. If bilateral renal artery stenosis is suspected, ACE inhibitors/ARBs may still be considered with close monitoring 1.

Common Pitfalls to Avoid

• Do not withhold ACE inhibitors/ARBs due to concerns about beta-blocker use in PAD - this is an outdated contraindication
• Do not target BP <120 mmHg aggressively - risk of compromising limb perfusion with ABI of 0.6
• Do not use combination of ACE inhibitor + ARB - this is explicitly not recommended 5
• Do not forget the comprehensive approach: This patient also needs smoking cessation support (most critical), optimization of his statin to achieve LDL <55 mg/dL, and consideration of supervised exercise therapy 1