Hypertension

• Start medication: Average SBP ≥140 or DBP ≥90 mmHg; or SBP ≥130 or DBP ≥80 mmHg with CVD, prior stroke, diabetes, CKD, or PREVENT 10-year total CVD risk ≥7.5%.
• Lower-risk stage 1 HTN: Add medication if BP remains ≥130/80 mmHg after 3–6 months of lifestyle intervention.
• Target: Generally <130/80 mmHg, with encouragement toward SBP <120 mmHg when appropriate and tolerated, particularly with increased CVD risk. Individualize for frailty, limited life expectancy, institutional care, and tolerability; pregnancy and acute stroke require separate guidance.

The second and third agents usually come from the same first-line classes; comorbidities and tolerability determine the combination.

• Stage 1 requiring medication: Usually start one first-line agent.
• Stage 2: Start two complementary first-line agents, preferably in a single pill: an angiotensin-converting enzyme inhibitor (ACE inhibitor) or angiotensin II receptor blocker (ARB) plus a long-acting dihydropyridine calcium channel blocker (CCB) or thiazide-type diuretic.

• Above goal: Confirm home averages, adherence, tolerability, and effective dosing; add a complementary class. A usual three-drug foundation is an ACE inhibitor or ARB + dihydropyridine CCB + diuretic.
• Follow-up: Reassess generally monthly until controlled, using home averages and class-specific renal function and electrolyte monitoring.

BP above goal on three complementary drugs, including a diuretic at maximally tolerated doses—or control requiring four or more—suggests resistant HTN. Exclude measurement error, white-coat effect, nonadherence, and interfering substances before escalation.

• Preferred fourth drug when appropriate: Spironolactone, a mineralocorticoid receptor antagonist (MRA). Assess eGFR and potassium before and after initiation or titration; hyperkalemia or significant kidney dysfunction may preclude use.
• Further options: Seek specialist evaluation of secondary causes and individualized add-ons. Beta-blockers, alpha-blockers, central agents, and direct vasodilators have distinct indications and adverse effects.
• Aprocitentan: An add-on option for adults inadequately controlled on other drugs. Monitor fluid retention, anemia, and liver function; it is contraindicated in pregnancy.
• Renal denervation (RDN): An adjunct for selected patients after confirmation of uncontrolled HTN and optimization of care; refer for specialist evaluation.

• Albuminuric CKD: Favor an ACE inhibitor or ARB for kidney protection when indicated; diabetes alone does not require these classes.
• HF with reduced ejection fraction (HFrEF): Prioritize outcome-directed therapy: an angiotensin receptor–neprilysin inhibitor (ARNI) or ACE inhibitor/ARB, an evidence-based beta-blocker, MRA, and sodium-glucose cotransporter-2 inhibitor (SGLT2 inhibitor) as appropriate. Avoid nondihydropyridine CCBs.
• Angina, selected settings after myocardial infarction (MI), or rate control: A beta-blocker may be indicated earlier; it is not routine first-line therapy for uncomplicated HTN.
• Pregnancy or pregnancy planning: Use pregnancy-specific thresholds and drug selection; ACE inhibitors and ARBs are contraindicated in pregnancy.

• Acute target-organ injury: Requires monitored hospital management, often intravenous (IV) therapy. The affected organ and clinical syndrome determine the BP-lowering strategy.
• Without acute injury: Nonpregnant adults with SBP >180 or DBP >120 mmHg generally need timely oral therapy adjustment and follow-up. Avoid reflex rapid lowering of isolated asymptomatic inpatient readings.