What is the best course of action for a 41-year-old male with severe hypertension and chest pain, non-compliant with newly prescribed Lisinopril, and experiencing uncontrolled hypertension for three weeks?

Management of Non-Compliance with Newly Prescribed Lisinopril in Severe Hypertension

Address medication non-compliance immediately through direct patient education about the serious cardiovascular risks of untreated severe hypertension, simplify the regimen if possible, and verify adherence before any medication changes—non-compliance is the most common cause of treatment failure and must be resolved first. 1

Immediate Priority: Address Non-Compliance

• Non-compliance with antihypertensive therapy occurs in approximately 50% of patients and is the single most important barrier to blood pressure control. 1, 2
• Verify medication adherence through direct questioning, pill counts, or pharmacy refill records before making any changes to the treatment regimen. 1, 3
• Lisinopril 20mg once daily is an appropriate starting dose for severe hypertension, but it requires 2-4 weeks to achieve maximal blood pressure reduction—the patient may not have given adequate time for the medication to work. 4, 3

Strategies to Improve Adherence

• Educate the patient about the immediate cardiovascular risks of uncontrolled severe hypertension, including stroke, myocardial infarction, heart failure, and kidney damage—patients who understand treatment benefits have significantly better compliance. 5, 2
• Simplify the dosing regimen by using once-daily medications like lisinopril, which improves adherence compared to multiple daily dosing. 1, 5
• Establish a partnership with the patient by addressing their concerns about side effects, costs, or beliefs about medication necessity—poor patient-physician communication is a major factor in non-compliance. 5, 2
• Consider single-pill combination therapy once adherence is established, as this further improves persistence with treatment. 1, 3

Clinical Assessment Before Medication Changes

• Confirm elevated blood pressure readings with home blood pressure monitoring (≥135/85 mmHg) or 24-hour ambulatory monitoring (≥130/80 mmHg) to exclude white coat hypertension. 1, 3
• Screen for secondary causes of hypertension given the severity and recent onset, including primary aldosteronism, renal artery stenosis, obstructive sleep apnea, and medication interference (NSAIDs, decongestants, stimulants). 1, 3
• Review for contraindications to ACE inhibitors, including pregnancy, angioedema history, bilateral renal artery stenosis, and hyperkalemia. 1

If Adherence is Confirmed and Blood Pressure Remains Uncontrolled

• Increase lisinopril to 40mg once daily (maximum dose) before adding a second agent, as dose optimization is required before combination therapy. 6, 3
• If blood pressure remains ≥140/90 mmHg after 2-4 weeks on maximum-dose lisinopril, add a dihydropyridine calcium channel blocker (amlodipine 5-10mg daily) as the preferred second agent for non-Black patients. 1, 7, 3
• For Black patients, either a calcium channel blocker or thiazide-like diuretic (chlorthalidone 12.5-25mg or hydrochlorothiazide 25mg daily) is appropriate as the second agent. 1, 3
• The combination of ACE inhibitor + calcium channel blocker provides complementary mechanisms (renin-angiotensin system blockade and vasodilation) with superior blood pressure control compared to monotherapy. 7, 3

Target Blood Pressure and Monitoring

• Target blood pressure is <140/90 mmHg minimum, with an optimal target of <130/80 mmHg for this high-risk patient with severe hypertension and chest pain. 1, 3
• See the patient within 1-2 weeks to reassess adherence, blood pressure response, and side effects—frequent follow-up is essential until control is achieved. 3
• Aim to achieve target blood pressure within 3 months of treatment initiation. 3

Critical Pitfalls to Avoid

• Do not add or switch medications without first confirming adherence—this is the most common error in managing apparent treatment-resistant hypertension. 1
• Do not delay treatment intensification once adherence is confirmed, as severe hypertension (especially with chest pain) requires urgent blood pressure reduction to prevent cardiovascular events. 1
• Monitor for hyperkalemia and acute kidney injury 1-4 weeks after starting or increasing ACE inhibitor doses, particularly in patients with chronic kidney disease or diabetes. 1, 3
• Be aware of potential drug interactions with lisinopril, including NSAIDs (which reduce efficacy) and potassium supplements or potassium-sparing diuretics (which increase hyperkalemia risk). 1, 8

If Triple Therapy is Eventually Required

• Add a thiazide-like diuretic (chlorthalidone preferred over hydrochlorothiazide due to longer duration and superior cardiovascular outcomes) as the third agent if blood pressure remains uncontrolled on ACE inhibitor + calcium channel blocker. 1, 7, 3
• If blood pressure remains ≥140/90 mmHg despite optimal triple therapy, add spironolactone 25-50mg daily as the preferred fourth-line agent for resistant hypertension. 1, 3