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cardio.htn.resistant.v1PRODUCTION
cardio.htn.resistant.v1

Resistant hypertension (≥3 meds at max + diuretic)

cardiologychronicadult
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Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Confirm true resistant HTN — BP ≥130/80 on ≥3 max-dose antihypertensives including thiazide-like diuretic + ACEi/ARB + CCB, OR controlled on ≥4 (ACC/AHA 2017; Carey AHA 2018)

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Actions
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Advance rule
Set
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definition met or refuted

Patient inputs (23)

PA screen — mandatory in resistant HTN (Carey AHA 2018; ACC/AHA 2017)

OSA dominant in resistant HTN — STOP-BANG + sleep study (Carey AHA 2018)

Age-specific secondary HTN differential — PA peaks 30-60; renovascular in elderly + atherosclerosis (Carey AHA 2018)

Office + ABPM/HBPM SBP defines true vs pseudo-resistant (ACC/AHA 2017; ESC/ESH 2023)

Diastolic component for grading (ACC/AHA 2017)

BB / non-DHP CCB titration; pheo screen (Carey AHA 2018)

HBPM ≥7 days excludes white-coat resistance (ACC/AHA 2017; ESC/ESH 2023)

eGFR for chlorthalidone/loop crossover; ACEi/ARB titration; CKD modifier (ACC/AHA 2017)

Hypokalaemia → screen primary aldo; baseline before spironolactone (Williams Lancet 2015 PATHWAY-2; Carey AHA 2018)

Non-adherence is the most common cause of pseudo-resistant HTN (Carey AHA 2018; ACC/AHA 2017)

High Na, alcohol, NSAIDs, sympathomimetics, OCP, COCs reverse with removal (ACC/AHA 2017; ESC/ESH 2023)

AVOID ACEi/ARB/spironolactone; use labetalol / methyldopa / nifedipine ER (ACC/AHA 2017; ESC/ESH 2023)

Verify true 3+ antihypertensives at max dose with diuretic; flag drug-induced HTN — NSAIDs, decongestants, COCs, stimulants, glucocorticoids, VEGF inhibitors (ACC/AHA 2017; Carey AHA 2018)

24-h ABPM gold standard — excludes white-coat resistance (ACC/AHA 2017; ESC/ESH 2023)

CKD/HTN end-organ damage; risk-stratification (ACC/AHA 2017; ESC/ESH 2023)

LVH / ischemia / arrhythmia screen (ACC/AHA 2017; ESC/ESH 2023)

Pheo screen — paroxysmal symptoms / labile BP / family history (Carey AHA 2018)

Cushing screen — features of weight gain, central obesity, easy bruising, glucose intolerance (Carey AHA 2018)

Renovascular screen — atherosclerotic vs FMD (Carey AHA 2018)

Volume status + spironolactone monitoring (ACC/AHA 2017)

Hyper/hypothyroidism reversible HTN driver (ACC/AHA 2017)

DM target <130/80; comorbid driver (ACC/AHA 2017)

LVH severity, LVEF, valvular HD (ESC/ESH 2023)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (7)

7 need judgement
  • informationallife_threateningbp_180_120_with_end_organ
    BP ≥180/120 + neuro deficit, CP, ACS, pulm edema, AKI, vision change, or eclampsia (ACC/AHA 2017)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverebp_180_120_no_end_organ
    BP ≥180/120 with no end-organ damage (ACC/AHA 2017)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverek_above_5_5_on_mra
    K ≥5.5 on spironolactone / eplerenone / finerenone (Williams Lancet 2015 PATHWAY-2)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereaki_on_RAS_or_diuretic
    Cr rise >0.3 mg/dL or 50% on ACEi / ARB / diuretic / MRA (ACC/AHA 2017)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepheo_screen_positive
    Plasma free metanephrines ≥3x ULN or 24-h urine fractionated metanephrines elevated (Carey AHA 2018)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatearr_positive
    ARR ≥20-30 with aldosterone ≥15 ng/dL — primary aldosteronism positive screen (Carey AHA 2018)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateosa_high_risk
    STOP-BANG ≥3 in resistant HTN (Carey AHA 2018)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

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Recommended regimen

Resistant HTN backbone — confirm 3-drug max-dose regimen (ACEi/ARB + CCB + thiazide-like diuretic)
axis: resistant_htn_backbone
Selected axis "Resistant HTN backbone — confirm 3-drug max-dose regimen (ACEi/ARB + CCB + thiazide-like diuretic)" by default fallback (first axis)
  • chlorthalidone
    first line
    thiazide_like_diuretic
    12.5 mg • PO • once daily (max: 25 mg/day)
    triggers: eGFR>=30
    Thiazide-like > thiazide — longer t1/2, more potent; preferred (ACC/AHA 2017; ALLHAT)
    rxcui 2409
  • indapamide
    first line
    thiazide_like_diuretic
    1.25–2.5 mg • PO • once daily (max: 5 mg/day)
    triggers: eGFR>=30
    Alternative thiazide-like; Beckett Lancet 2008 HYVET evidence in elderly
    rxcui 5764
  • furosemide
    comorbidity specific
    loop_diuretic
    20–40 mg • PO • BID
    triggers: eGFR<30, HF_with_volume_overload
    Crossover to loop when eGFR <30 — thiazide-like loses efficacy (ACC/AHA 2017)
    rxcui 4603
  • lisinopril
    first line
    ACEi
    10 mg • PO • once daily (max: 40 mg/day)
    triggers: no_pregnancy, no_angioedema
    RAS blockade Class I (ACC/AHA 2017; ESC/ESH 2023)
    rxcui 29046
  • losartan
    first line
    ARB
    50 mg • PO • once daily (max: 100 mg/day)
    triggers: ACEi_intolerant
    RAS blockade Class I; switch from ACEi for cough/angioedema (ACC/AHA 2017)
    rxcui 52175
  • amlodipine
    first line
    DHP_CCB
    5 mg • PO • once daily (max: 10 mg/day)
    CCB backbone — long-acting (ACC/AHA 2017; ALLHAT)
    rxcui 17767

outpatient playbook — drug actions (6)

  1. 1. optimise backbone
    chlorthalidone 12.5–25 mg + ACEi/ARB at max + amlodipine 10 mg • PO • daily
    trigger: Confirm 3-drug max-dose regimen
    ACC/AHA 2017 Class I — true resistance requires verified 3-drug regimen with thiazide-like diuretic
  2. 2. spironolactone
    12.5–25 → 50 mg • PO • daily
    trigger: Confirmed resistant + K <5.0 + eGFR ≥30
    Superior 4th drug; ACC/AHA 2017 Class I (Williams Lancet 2015 PATHWAY-2)
  3. 3. eplerenone
    25 → 50 mg • PO • BID
    trigger: Gynecomastia on spironolactone
    Selective MRA (ACC/AHA 2017; ESC/ESH 2023)
  4. 4. doxazosin / carvedilol / labetalol
    doxazosin 1 → 16 mg HS; carvedilol 6.25 → 25 BID; labetalol 100 → 1200 BID • PO • BID/HS
    trigger: MRA intolerant/insufficient
    Alternative agents (Williams Lancet 2015 PATHWAY-2; Brown Lancet 2016 PATHWAY-3)
  5. 5. clonidine / hydralazine / minoxidil
    clonidine 0.1 BID; hydralazine 25 TID; minoxidil 2.5 BID (with BB + loop) • PO • BID-TID
    trigger: Refractory after 5 drugs at max
    Refractory HTN ladder — specialist-level (Carey AHA 2018)
  6. 6. pregnancy alternatives
    labetalol / methyldopa / nifedipine ER • PO • BID-TID
    trigger: Pregnancy
    AVOID ACEi/ARB/spironolactone (ACC/AHA 2017; ESC/ESH 2023)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Resistant HTN — referred from primary HTN engine (ACC/AHA 2017; Carey AHA 2018); Office BP above target on ≥3 antihypertensives at max dose (ACC/AHA 2017; ESC/ESH 2023); BP controlled on ≥4 antihypertensives (ACC/AHA 2017; ESC/ESH 2023).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Resistant hypertension (≥3 meds at max + diuretic)** (cardio.htn.resistant.v1).
Phenotype framing: Categorise: pseudo-resistant (non-adherence/white-coat/inadequate regimen) vs true resistant (apparent / refractory) vs secondary — PA, pheo, renovascular, OSA, CKD, Cushing, coarctation, drug-induced (Carey AHA 2018)
Scope: Confirm true resistant HTN — BP ≥130/80 on ≥3 max-dose antihypertensives including thiazide-like diuretic + ACEi/ARB + CCB, OR controlled on ≥4 (ACC/AHA 2017; Carey AHA 2018)

No severity triggers fired against current inputs.

Plan

Regimen axis: **Resistant HTN backbone — confirm 3-drug max-dose regimen (ACEi/ARB + CCB + thiazide-like diuretic)**.
1. chlorthalidone 12.5 mg PO once daily (thiazide_like_diuretic, first line) — Thiazide-like > thiazide — longer t1/2, more potent; preferred (ACC/AHA 2017; ALLHAT)
2. indapamide 1.25–2.5 mg PO once daily (thiazide_like_diuretic, first line) — Alternative thiazide-like; Beckett Lancet 2008 HYVET evidence in elderly
3. furosemide 20–40 mg PO BID (loop_diuretic, comorbidity specific) — Crossover to loop when eGFR <30 — thiazide-like loses efficacy (ACC/AHA 2017)
4. lisinopril 10 mg PO once daily (ACEi, first line) — RAS blockade Class I (ACC/AHA 2017; ESC/ESH 2023)
5. losartan 50 mg PO once daily (ARB, first line) — RAS blockade Class I; switch from ACEi for cough/angioedema (ACC/AHA 2017)
6. amlodipine 5 mg PO once daily (DHP_CCB, first line) — CCB backbone — long-acting (ACC/AHA 2017; ALLHAT)

Setting playbook (outpatient) — Achieve BP <130/80 by (1) confirming true resistance with ABPM, (2) excluding secondary HTN, (3) optimising backbone, (4) adding spironolactone, (5) considering renal denervation
7. optimise backbone chlorthalidone 12.5–25 mg + ACEi/ARB at max + amlodipine 10 mg PO daily — Confirm 3-drug max-dose regimen (ACC/AHA 2017 Class I — true resistance requires verified 3-drug regimen with thiazide-like diuretic)
8. spironolactone 12.5–25 → 50 mg PO daily — Confirmed resistant + K <5.0 + eGFR ≥30 (Superior 4th drug; ACC/AHA 2017 Class I (Williams Lancet 2015 PATHWAY-2))
9. eplerenone 25 → 50 mg PO BID — Gynecomastia on spironolactone (Selective MRA (ACC/AHA 2017; ESC/ESH 2023))
10. doxazosin / carvedilol / labetalol doxazosin 1 → 16 mg HS; carvedilol 6.25 → 25 BID; labetalol 100 → 1200 BID PO BID/HS — MRA intolerant/insufficient (Alternative agents (Williams Lancet 2015 PATHWAY-2; Brown Lancet 2016 PATHWAY-3))
11. clonidine / hydralazine / minoxidil clonidine 0.1 BID; hydralazine 25 TID; minoxidil 2.5 BID (with BB + loop) PO BID-TID — Refractory after 5 drugs at max (Refractory HTN ladder — specialist-level (Carey AHA 2018))
12. pregnancy alternatives labetalol / methyldopa / nifedipine ER PO BID-TID — Pregnancy (AVOID ACEi/ARB/spironolactone (ACC/AHA 2017; ESC/ESH 2023))

Non-pharmacologic actions:
- DASH diet, Na <1.5-2 g/day (ACC/AHA 2017)
- Alcohol limit <=2 drinks/day men, <=1 women (ACC/AHA 2017)
- Weight loss if BMI >25; aerobic + resistance exercise (ACC/AHA 2017)
- Pharmacist-led adherence intervention if non-adherence (ACC/AHA 2017; Carey AHA 2018)
- CPAP if AHI ≥15 (TIPTOP, HIPARCO)
- Renal denervation referral — Class IIa (2025 AHA + 2024 ESC/ESH) for true resistant despite ≥3 drugs at max + spironolactone tried/failed

AVOID / contraindication checks:
- Acei arb block in pregnancy (ACC/AHA 2017)
- Acei arb pause if AKI or K gt 5.5 (ACC/AHA 2017)
- Thiazide like monitor Na K uric acid (ACC/AHA 2017)
- Loop electrolyte monitoring (ACC/AHA 2017)

Monitoring

Regimen monitoring:
- BMP q1-2w after diuretic or ACEi change (ACC/AHA 2017)
- HBPM weekly during titration (ACC/AHA 2017)
- ABPM at 6 months (ACC/AHA 2017; ESC/ESH 2023)

Setting (outpatient) monitoring:
- BMP at 1-2 wks after spironolactone start; q1m during titration; q3m steady state (Williams Lancet 2015 PATHWAY-2)
- HBPM weekly during titration (ACC/AHA 2017)
- ABPM at 6 mo to confirm BP control (ACC/AHA 2017; ESC/ESH 2023)
- Adherence reassessed at every visit (ACC/AHA 2017; Carey AHA 2018)

Follow-up plan: q3 mo until controlled, then q6 mo; ASCVD prevention bundle; reassess adherence at every visit (ACC/AHA 2017; ESC/ESH 2023)
- Close-out criterion: follow-up scheduled

Monitoring phase: BMP within 1-2 wks of spironolactone start; HBPM weekly during titration; ABPM at 6 months (Williams Lancet 2015 PATHWAY-2; ACC/AHA 2017)

Disposition

Current setting: outpatient — Achieve BP <130/80 by (1) confirming true resistance with ABPM, (2) excluding secondary HTN, (3) optimising backbone, (4) adding spironolactone, (5) considering renal denervation

Disposition criteria:
- Continue chronic management if at goal (ACC/AHA 2017)
- Refer HTN specialist if refractory (Carey AHA 2018)
- Refer endocrine if PA / pheo / Cushing confirmed (Carey AHA 2018)
- Refer interventional / vascular if renal denervation candidate or RAS confirmed (ACC/AHA 2017; ESC/ESH 2023)

Escalation triggers (move to higher acuity):
- BP >=180/120 with end-organ damage → ED (ACC/AHA 2017)
- New AKI / hyperkalemia on spironolactone → pause + reassess (Williams Lancet 2015 PATHWAY-2)
- Refractory after 5 drugs at max → HTN specialist (Carey AHA 2018)

Patient Action Plan

**Resistant HTN home BP action plan**
Personalised values: target_bp_systolic, target_bp_diastolic, home_diuretic, rescue_meds_per_provider.

**At goal — home BP <130/80 average** (green):
Triggers:
- 7-day average home BP <130/80 (ACC/AHA 2017)
- No headache, vision change, chest pain, or shortness of breath (ACC/AHA 2017)
Actions:
- Take all BP meds exactly as prescribed every day at the same time (ACC/AHA 2017)
- Continue DASH-style diet; <2 g sodium/day (ACC/AHA 2017)
- Continue exercise plan (ACC/AHA 2017)
- Daily home BP at same time, after voiding, both arms initially (ACC/AHA 2017)
- Bring BP log to every clinic visit (ACC/AHA 2017)

**Caution — home BP 140–159 / 90–99 OR symptoms** (yellow):
Triggers:
- Several home readings >=140/90 over 3-5 days (ACC/AHA 2017)
- New mild headache, dizziness, leg swelling (ACC/AHA 2017)
- New irregular pulse / palpitations (ACC/AHA 2017)
- Missed doses recently (ACC/AHA 2017)
Actions:
- Recheck BP technique cuff size, arm at heart level, 5 min rest, no caffeine/exercise 30 min prior (ACC/AHA 2017)
- Confirm you took all medications today (ACC/AHA 2017)
- Check for OTC meds that raise BP ibuprofen/naproxen, decongestants, herbal stimulants and stop if possible (ACC/AHA 2017; Carey AHA 2018)
- Hold added salt; track sodium for 48 h (ACC/AHA 2017)
- Call HTN clinic / PCP within 24-48 h (ACC/AHA 2017)
Contact provider when:
- Home BP persists >=140/90 despite above (ACC/AHA 2017)
- Any new symptoms headache, vision change, chest pain, shortness of breath (ACC/AHA 2017)

**Medical alert — BP ≥180/120 OR severe symptoms** (red):
Triggers:
- Home BP >=180/120 confirmed by repeat reading 5 minutes later (ACC/AHA 2017)
- Severe headache, blurred vision, chest pain, shortness of breath, weakness or numbness on one side, severe nosebleed, or confusion (ACC/AHA 2017)
Actions:
- Call 911 / emergency services immediately (ACC/AHA 2017)
- Sit down, stay calm, do not drive yourself (ACC/AHA 2017)
- Bring medication list and BP log (ACC/AHA 2017)
- Do not take an extra dose of BP medication unless instructed by your provider (ACC/AHA 2017)
Contact provider when:
- Any red zone reading or symptom — go to ED now, do not wait (ACC/AHA 2017)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] BP ≥180/120 + neuro deficit, CP, ACS, pulm edema, AKI, vision change, or eclampsia (ACC/AHA 2017)
- [SEVERE] BP ≥180/120 with no end-organ damage (ACC/AHA 2017)
- [SEVERE] K ≥5.5 on spironolactone / eplerenone / finerenone (Williams Lancet 2015 PATHWAY-2)

Citations

- 2025 ACC/AHA HTN Guideline + 2024 ESC/ESH HTN Guidelines + KDIGO 2021 BP in CKD + PATHWAY-2 + SPYRAL HTN-ON MED + RADIANCE-HTN [PMID:29133356](https://pubmed.ncbi.nlm.nih.gov/29133356/)
- Cited evidence (PMID 38804483) [PMID:38804483](https://pubmed.ncbi.nlm.nih.gov/38804483/)
- Cited evidence (PMID 26414968) [PMID:26414968](https://pubmed.ncbi.nlm.nih.gov/26414968/)
- Cited evidence (PMID 32360057) [PMID:32360057](https://pubmed.ncbi.nlm.nih.gov/32360057/)
- Cited evidence (PMID 32381182) [PMID:32381182](https://pubmed.ncbi.nlm.nih.gov/32381182/)

Last reconciled with current guidelines: 2026-04-28.
References
  • 2025 ACC/AHA HTN Guideline + 2024 ESC/ESH HTN Guidelines + KDIGO 2021 BP in CKD + PATHWAY-2 + SPYRAL HTN-ON MED + RADIANCE-HTN — PMID:29133356
  • Cited evidence (PMID 38804483) — PMID:38804483
  • Cited evidence (PMID 26414968) — PMID:26414968
  • Cited evidence (PMID 32360057) — PMID:32360057
  • Cited evidence (PMID 32381182) — PMID:32381182