SPIRO-First: A Pragmatic Primary Care-Embedded Pilot Trial of Renin-Guided First-Line Antihypertensive Therapy

The goal of this clinical trial is to determine whether a renin-guided antihypertensive treatment strategy is feasible to implement in community primary care clinics and to explore whether spironolactone improves blood pressure control in adults with low-renin hypertension. The main questions it aims to answer are: Is it feasible to identify, recruit, randomize, and follow adults with low-renin hypertension in a pragmatic primary care-based clinical trial? Does first-line treatment with spironolactone result in greater reductions in ambulatory blood pressure compared with standard first-line antihypertensive therapy among adults with low-renin hypertension? Researchers will compare spironolactone 25 mg daily with standard first-line antihypertensive therapy (candesartan, hydrochlorothiazide, or amlodipine) to determine whether spironolactone provides better blood pressure control in adults with low-renin hypertension. Participants will: Undergo blood pressure assessments, blood tests, and ambulatory blood pressure monitoring (ABPM) to determine eligibility. Be randomly assigned to receive either spironolactone or a standard first-line antihypertensive medication for 12 weeks. Complete follow-up visits and laboratory testing to monitor blood pressure response, kidney function, electrolyte levels, medication adherence, and side effects. Undergo repeat blood pressure measurements and ABPM at the end of the study.

Inclusion Criteria: 1. Age ≥18 years. 2. Under the care of a primary care clinician in Ontario. 3. Standardized office systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg. 4. Mean daytime baseline ABPM systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg. 5. Treating primary care clinician has independently determined that initiation of antihypertensive pharmacotherapy is clinically indicated. 6. Either: * Not currently receiving antihypertensive therapy, OR * Receiving a single antihypertensive medication (ACE inhibitor, ARB, thiazide/thiazide-like diuretic, or calcium channel blocker) which the treating primary care clinician considers safe to discontinue for a 2-week washout period. 7. Suppressed renin defined as direct renin concentration \150 mmHg if receiving one antihypertensive medication. 2. Known diagnosis of PA requiring specialist-directed management. 3. Known secondary hypertension requiring disease-specific therapy. 4. Current use of MR antagonists. 5. Known intolerance or contraindication to spironolactone, candesartan, hydrochlorothiazide, or amlodipine. 6. eGFR \