What additional medications can be added to lisinopril (Angiotensin-Converting Enzyme inhibitor) 50mg for a patient with hypertension who is also seeing a pulmonologist?

Additional Antihypertensive Therapy for Uncontrolled Hypertension on Lisinopril 50mg

Add a thiazide-like diuretic (hydrochlorothiazide 12.5-25 mg daily) or a calcium channel blocker (amlodipine 5-10 mg daily) to the current lisinopril regimen, with the diuretic being the preferred first addition based on guideline recommendations. 1

Primary Add-On Options

First Choice: Thiazide Diuretic

• Hydrochlorothiazide 12.5-25 mg once daily is the recommended first add-on agent when blood pressure remains uncontrolled on an ACE inhibitor alone 1, 2
• The combination of lisinopril plus hydrochlorothiazide provides complementary mechanisms: the diuretic stimulates the renin-angiotensin-aldosterone system, which is then blocked by the ACE inhibitor, resulting in additive blood pressure lowering 1
• After adding a diuretic, it may be possible to reduce the lisinopril dose if needed 2
• Research demonstrates that in patients not controlled on amlodipine plus lisinopril, adding bendrofluazide (a thiazide) produces significantly greater blood pressure reduction than adding a beta-blocker 3

Second Choice: Calcium Channel Blocker

• Amlodipine 5-10 mg once daily is an effective alternative add-on if diuretics are contraindicated or not tolerated 1, 4
• The combination of an ACE inhibitor and calcium channel blocker has synergistic effects through complementary vasodilation mechanisms 1, 3
• Amlodipine is well-tolerated in patients with mild left ventricular dysfunction and does not affect heart rate or cardiovascular reflexes 1, 4
• Clinical trials show the amlodipine plus ACE inhibitor combination achieves blood pressure control in the majority of patients with stage 2 hypertension 5

Target Blood Pressure Goals

• For patients with confirmed hypertension and 10-year ASCVD risk ≥10%, target blood pressure is <130/80 mmHg 1
• For patients without additional cardiovascular risk markers, a target of <130/80 mmHg may be reasonable 1
• If the patient has chronic kidney disease or diabetes, the target remains <130/80 mmHg 1

Pulmonology Considerations

Critical Drug Interactions to Avoid

• Do not use non-dihydropyridine calcium channel blockers (verapamil, diltiazem) if the patient has pulmonary edema or severe left ventricular dysfunction 1
• If the patient is on pulmonary arterial hypertension medications (endothelin antagonists, phosphodiesterase inhibitors, prostacyclins), be aware of potential interactions 1:
  • Bosentan can decrease simvastatin levels by 50% through CYP2C9 induction 1
  • Sildenafil levels may be affected by concurrent medications metabolized through CYP3A4 1
• Avoid combining two drugs from the same class (e.g., two ACE inhibitors, ACE inhibitor plus ARB) as this increases cardiovascular and renal risk without additional benefit 1

Safe Options for Pulmonary Comorbidities

• Amlodipine and other dihydropyridine calcium channel blockers are safe in patients with pulmonary conditions as they primarily cause peripheral vasodilation without affecting pulmonary vascular resistance significantly 1
• Thiazide diuretics are generally safe but monitor for volume depletion if the patient has concurrent respiratory infections requiring antibiotics 6

Dosing Algorithm

If Adding Hydrochlorothiazide:

1. Start hydrochlorothiazide 12.5 mg once daily 1, 2
2. Continue lisinopril at current dose initially 2
3. Recheck blood pressure after 2-4 weeks 1
4. If blood pressure remains >130/80 mmHg, increase hydrochlorothiazide to 25 mg daily 1
5. Monitor serum potassium and creatinine within 2-4 weeks of initiation 1

If Adding Amlodipine:

1. Start amlodipine 5 mg once daily 4, 5
2. Continue lisinopril at current dose 5
3. Recheck blood pressure after 2 weeks 1
4. If blood pressure remains >130/80 mmHg, increase amlodipine to 10 mg daily 4, 5
5. Monitor for peripheral edema, which occurs in 5-10% of patients 4

Important Monitoring Parameters

• Check orthostatic vital signs to assess for volume depletion, especially if adding a diuretic 6
• Monitor serum creatinine and electrolytes within 2-4 weeks after adding any new antihypertensive, particularly with diuretics or in patients with baseline renal impairment 1, 7
• Assess for hyperkalemia if the patient is on potassium-sparing agents or has chronic kidney disease 1
• Recheck blood pressure every 2-4 weeks until target is achieved, then every 3-6 months 1

Critical Pitfalls to Avoid

• Never combine lisinopril with an ARB or direct renin inhibitor (aliskiren) as this increases cardiovascular and renal adverse events without additional benefit 1
• Do not use rapid-release, short-acting nifedipine as it increases adverse cardiovascular outcomes 1
• Avoid abrupt discontinuation of any antihypertensive, particularly clonidine if used, as this can cause rebound hypertension 1
• Do not overlook medication adherence as the primary cause of uncontrolled hypertension before adding additional agents 1
• If the patient develops symptomatic hypotension after adding a second agent, temporarily hold or reduce the diuretic dose first, then reassess 6, 2