What is the next antihypertensive to add to a 67yo smoker with PAD and uncontrolled hypertension on Hydrochlorothiazide (HCTZ)?

Optimal Second Antihypertensive for a 67-Year-Old Smoker with PAD on HCTZ

An ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) should be added as the second antihypertensive medication for this patient with PAD and uncontrolled hypertension on HCTZ. 1

Rationale for ACEI/ARB Selection

The choice of second-line antihypertensive in this patient is guided by:

1. Presence of PAD: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure specifically addresses hypertension management in PAD patients, noting that ACEIs or ARBs are appropriate choices 1.

2. Avoidance of Beta-Blockers: Beta-blockers were historically avoided in PAD due to concerns about peripheral vasoconstriction, though recent evidence suggests they may be used cautiously if needed for other indications 1.

3. Combination Therapy Evidence: When adding to HCTZ, an ACEI or ARB provides complementary mechanisms of action and has demonstrated efficacy in blood pressure reduction 2.

Treatment Algorithm

1. First step: Add an ACEI (e.g., lisinopril, ramipril) or ARB (e.g., losartan, valsartan) to the current HCTZ regimen

   • Start at a moderate dose and titrate as needed
   • Monitor renal function and potassium within 2-4 weeks of initiation

2. If inadequate response after 3-4 weeks:

   • Increase the dose of the ACEI/ARB to maximum tolerated dose
   • If still inadequate, consider adding a calcium channel blocker (CCB) as a third agent

3. Blood pressure target: Aim for SBP 120-129 mmHg if tolerated 1

Supporting Evidence

Multiple guidelines support this approach:

• The JNC-7 report specifically addresses PAD patients with hypertension, noting that ACEIs are appropriate choices and can reduce cardiovascular events 1.

• The 2024 ESC guidelines for peripheral arterial and aortic diseases recommend a target SBP of 120-129 mmHg if tolerated in patients with PAAD and hypertension 1.

• Research evidence shows that ACE inhibitors reduce cardiovascular events in PAD patients, with one study showing a significant 13% reduction in the primary endpoint of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction 3.

Medication-Specific Considerations

ACE Inhibitors

• Advantages: Reduce cardiovascular events in PAD patients, improve endothelial function
• Monitoring: Check renal function and potassium within 2-4 weeks of initiation
• Common side effects: Dry cough, risk of angioedema

ARBs

• Alternative if ACEI not tolerated (e.g., due to cough)
• Similar cardiovascular benefits to ACEIs
• Better tolerated than ACEIs in some patients

Important Precautions

1. Monitor for renal deterioration: Check creatinine and potassium within 2-4 weeks of starting therapy

2. Smoking cessation: Strongly encourage smoking cessation as it may be the most important factor in PAD progression 1

3. Additional PAD management:

   • Consider antiplatelet therapy
   • Statin therapy for lipid management
   • Structured exercise program 1

By adding an ACEI or ARB to this patient's regimen, you address both the hypertension and provide additional cardiovascular protection specifically beneficial for a patient with PAD, targeting the reduction of morbidity and mortality in this high-risk individual.