What is the recommended approach to initiating antihypertensive therapy in a patient with peripheral vascular disease?

Antihypertensive Management in Peripheral Vascular Disease

In patients with peripheral vascular disease (PVD) and hypertension, target a systolic blood pressure of 120-129 mmHg if tolerated, and initiate therapy with ACE inhibitors or ARBs as first-line agents to reduce cardiovascular events and mortality. 1

Blood Pressure Targets

• The most recent 2024 ESC guidelines recommend targeting systolic blood pressure towards 120-129 mmHg in patients with peripheral arterial and aortic diseases (PAAD) and hypertension, if tolerated. 1

• This represents a significant shift from older guidelines that recommended <140/90 mmHg for non-diabetics or <130/80 mmHg for diabetics. 1

• For patients who cannot tolerate lower targets (age ≥85 years, residential care settings, symptomatic orthostatic hypotension, or severe frailty), a more lenient goal of <140/90 mmHg remains acceptable. 2

First-Line Medication Selection

ACE inhibitors or ARBs should be considered as first-line antihypertensive therapy in all patients with PVD, regardless of baseline blood pressure levels, in the absence of contraindications. 1, 2

Evidence Supporting ACE Inhibitors/ARBs:

• The HOPE trial demonstrated that ramipril reduced the risk of myocardial infarction, stroke, or vascular death by 25% in patients with PVD, with similar efficacy in both symptomatic disease and asymptomatic low ankle-brachial index (ABI). 1, 2

• The ONTARGET trial confirmed that telmisartan had equivalent efficacy to ramipril in reducing cardiovascular events in the PVD subgroup, establishing ARBs as a valid alternative to ACE inhibitors. 1, 2

• ACE inhibitors/ARBs may be considered in all patients with PAD to reduce cardiovascular events, regardless of blood pressure levels, in the absence of contraindications. 1

Strength of Recommendation:

• For symptomatic PAD: Class IIa recommendation (reasonable to use ACE inhibitors/ARBs). 1

• For asymptomatic PAD: Class IIb recommendation (may be considered). 1

Other Antihypertensive Agents

Beta-Blockers:

• Beta-blockers are NOT contraindicated in PVD and can be safely prescribed when indicated for other conditions (coronary artery disease, heart failure). 1

• Multiple studies have demonstrated that beta-blockers do not worsen claudication symptoms, walking distance, or functional status in patients with PVD. 1, 2

• Historical concerns about peripheral vasoconstriction have been disproven by recent evidence. 1

Calcium Channel Blockers:

• No specific advantage or disadvantage in PVD patients for blood pressure control. 3

• In patients with concurrent carotid atherosclerosis, calcium channel blockers combined with ACE inhibitors are recommended. 3

• In renal artery stenosis-related hypertension, the combination of ACE inhibitors/ARBs with diuretics and/or calcium channel blockers should be considered. 2

Diuretics:

• Thiazide or thiazide-like diuretics are effective antihypertensive agents in elderly patients and those with isolated systolic hypertension. 1

• No specific contraindications in PVD, though conventional diuretics may show some disadvantages. 4

Critical Caveats and Monitoring

Renal Artery Stenosis:

• In patients with bilateral renal artery stenosis, ACE inhibitors/ARBs may be considered only if close monitoring of renal function is feasible. 2

• Renovascular hypertension should be strongly considered in PVD patients if blood pressure is uncontrolled. 1

Gradual Blood Pressure Reduction:

• In patients with critical limb ischemia (rest pain or necrosis), cautious and gradual blood pressure lowering is recommended to avoid compromising poststenotic perfusion pressure. 4

• Avoid aggressive blood pressure reduction that may decrease limb perfusion pressure and potentially exacerbate claudication symptoms, though most patients tolerate therapy without worsening symptoms. 1

Comprehensive Cardiovascular Risk Management

Antihypertensive therapy is only one component of guideline-directed medical therapy (GDMT) for PVD patients. 1

Additional Essential Therapies:

• Antiplatelet therapy: Aspirin 75-325 mg daily or clopidogrel 75 mg daily to reduce MI, stroke, and vascular death. 1, 2

• Statin therapy: Indicated for all patients with PAD to improve both cardiovascular and limb outcomes, targeting LDL-C <1.4 mmol/L (55 mg/dL) with >50% reduction from baseline. 1, 2

• Smoking cessation: Advised at every visit with pharmacotherapy (varenicline, bupropion, nicotine replacement) and/or referral to cessation programs. 1, 5

• Supervised exercise therapy: Recommended for symptomatic PAD to improve walking distance and quality of life. 1, 2, 5

Key Clinical Pitfall

The most common error is withholding beta-blockers or being overly cautious with blood pressure lowering in PVD patients due to outdated concerns about worsening claudication. Modern evidence clearly demonstrates that appropriate antihypertensive therapy, including beta-blockers, does not worsen limb symptoms and is essential for reducing cardiovascular mortality. 1, 2