What is the next step in managing a 52-year-old female patient with uncontrolled Hypertension (HTN) despite being on metoprolol (Beta Blocker), lisinopril (Angiotensin-Converting Enzyme Inhibitor), and Hydrochlorothiazide (HCTZ) (Diuretic)?

Management of Uncontrolled Hypertension on Triple Therapy

Add spironolactone 25-50mg daily as the fourth antihypertensive agent, as this patient has resistant hypertension (uncontrolled BP despite three-drug therapy including an ACE inhibitor, beta-blocker, and thiazide diuretic). 1, 2

Confirming Resistant Hypertension

Before adding a fourth agent, verify the following:

• Confirm medication adherence through direct questioning and pharmacy refill records, as non-adherence is the most common cause of apparent treatment resistance 3, 4
• Obtain out-of-office BP measurements (home BP monitoring or 24-hour ambulatory monitoring) to exclude white coat hypertension—home BP ≥135/85 mmHg or 24-hour ambulatory BP ≥130/80 mmHg confirms true hypertension 1
• Screen for secondary hypertension causes, particularly obstructive sleep apnea given her age and sex, as OSA is a common contributor to resistant hypertension 4
• Review medications that may interfere with BP control, including NSAIDs for her psoriatic arthritis and shoulder pain 2

Optimizing Current Regimen First

The current three-drug regimen (metoprolol, lisinopril, HCTZ) is not the guideline-recommended triple therapy:

• The preferred triple therapy is ACE inhibitor/ARB + calcium channel blocker + thiazide diuretic 1, 3, 2
• Beta-blockers are not first-line agents and should typically be reserved as fourth or fifth-line therapy unless there are specific indications (heart failure, coronary disease, arrhythmia) 1
• Consider replacing metoprolol with a dihydropyridine calcium channel blocker (amlodipine 5-10mg) to create the guideline-concordant triple therapy of lisinopril + amlodipine + HCTZ 1, 3
• Ensure all medications are at optimal doses: lisinopril up to 40mg, HCTZ 25mg (or preferably chlorthalidone 12.5-25mg for longer duration of action), and amlodipine up to 10mg 3, 5

Adding Fourth-Line Agent

If BP remains uncontrolled after optimizing to the preferred triple therapy:

• Spironolactone 25-50mg daily is the preferred fourth-line agent based on the PATHWAY-2 trial demonstrating superior efficacy in resistant hypertension 1, 2
• Monitor serum potassium and creatinine within 1 week of adding spironolactone, as hyperkalemia risk is significant when combined with ACE inhibitors 3, 4
• Alternative fourth-line agents if spironolactone is contraindicated or not tolerated include: amiloride, doxazosin, eplerenone, clonidine, or beta-blockers 1, 2

Monitoring and Targets

• Target BP is <140/90 mmHg minimum, ideally <130/80 mmHg for this patient 1, 3
• Reassess BP within 2-4 weeks after any medication adjustment 3
• Achieve target BP within 3 months of initiating or modifying therapy 1, 3

Lifestyle Modifications

Reinforce the following to provide additive BP reduction of 10-20 mmHg:

• Sodium restriction to <2g/day 3
• Weight loss if overweight 3
• Regular aerobic exercise 3
• Limit alcohol consumption 3

Referral Considerations

• Refer to a hypertension specialist if BP remains uncontrolled despite four-drug therapy or if secondary hypertension is suspected 1, 3, 4

Special Consideration for Psoriatic Arthritis

• Avoid NSAIDs if possible, as they can significantly impair BP control and reduce the efficacy of antihypertensive medications 2
• Coordinate with rheumatology regarding NSAID use for her psoriatic arthritis and shoulder pain, considering alternative pain management strategies 2