Hypertension (High Blood Pressure) β Symptoms, Causes & Treatment
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HYPERTENSION β INDIA
COMPREHENSIVE CLINICAL MANAGEMENT GUIDELINE
For Healthcare Professionals Only | Not for Public Use
Scope: Screening | Diagnosis | Risk Stratification | Pharmacotherapy | Special Populations | Emergencies | Long-term Management
Applicable Settings: Primary Care → Secondary Care → Tertiary Care → ICU
Version: 3.0
Last Updated: July 2025
Last Updated: July 2025
SYMBOL LEGEND
| Symbol | Meaning |
| β | Recommended / First-line / Strong evidence |
| β οΈ | Use with caution / Monitor closely / Conditional |
| β | Contraindicated / Avoid |
| π | Drug name |
| π | Clinical pearl / Key point |
| π¬ | Evidence-based recommendation |
| β±οΈ | Time-critical action |
| π¨ | Emergency / Life-threatening |
SECTION 1: DEFINITION, CLASSIFICATION & DIAGNOSIS
1.1 CLASSIFICATION OF BLOOD PRESSURE
Office BP Classification (ESC/ESH 2023, ISH 2020)
| Category | SBP (mmHg) | DBP (mmHg) | |
| Optimal | < 120 | and | < 80 |
| Normal | 120β129 | and/or | 80β84 |
| High Normal | 130β139 | and/or | 85β89 |
| Grade 1 HTN (Mild) | 140β159 | and/or | 90β99 |
| Grade 2 HTN (Moderate) | 160β179 | and/or | 100β109 |
| Grade 3 HTN (Severe) | ≥ 180 | and/or | ≥ 110 |
| Isolated Systolic HTN | ≥ 140 | and | < 90 |
π When SBP and DBP fall into different categories, classify by the higher category.
1.2 BLOOD PRESSURE MEASUREMENT
Patient Preparation
- Patient seated comfortably for ≥ 5 minutes
- Back supported, feet flat on floor, legs uncrossed
- Arm supported at heart level on table or armrest
- Empty bladder
- No caffeine, exercise, or smoking in preceding 30 minutes
- No talking during measurement
- Remove clothing from upper arm β do not measure over rolled-up tight sleeves
Cuff Selection
| Arm Circumference | Cuff Size |
| 22β26 cm | Small adult (12 × 22 cm) |
| 27β34 cm | Standard adult (16 × 30 cm) |
| 35β44 cm | Large adult (16 × 36 cm) |
| 45β52 cm | Adult thigh cuff (16 × 42 cm) |
π Incorrect cuff size is the most common source of measurement error. A cuff that is too small overestimates BP by 5β15 mmHg. A cuff that is too large underestimates BP by 3β10 mmHg.
Measurement Protocol
- Place cuff bladder centre over brachial artery
- Lower edge of cuff 2β3 cm above antecubital fossa
- Take ≥ 2 readings, 1β2 minutes apart
- Record the average of the last 2 readings
- On first visit: measure in both arms
-
- If persistent inter-arm difference > 15 mmHg → use the higher arm for all subsequent measurements
- If persistent inter-arm difference > 20 mmHg → investigate for subclavian stenosis, coarctation, or aortic disease
- In elderly, diabetics, and patients on treatment: check standing BP at 1 and 3 minutes
-
- Orthostatic hypotension = SBP drop ≥ 20 mmHg or DBP drop ≥ 10 mmHg on standing
Device
- Validated oscillometric (automated) upper arm device preferred
- Wrist devices are not recommended for clinical use
- Calibrate devices annually
- Mercury sphygmomanometers are being phased out (Minamata Convention on Mercury)
1.3 OUT-OF-OFFICE BLOOD PRESSURE MEASUREMENT
Diagnostic Thresholds
| Measurement Method | SBP (mmHg) | DBP (mmHg) |
| Office BP | ≥ 140 | ≥ 90 |
| Home BP (HBPM) | ≥ 135 | ≥ 85 |
| ABPM β daytime mean | ≥ 135 | ≥ 85 |
| ABPM β night-time mean | ≥ 120 | ≥ 70 |
| ABPM β 24-hour mean | ≥ 130 | ≥ 80 |
π Home and ambulatory thresholds are approximately 5 mmHg lower than office thresholds.
Home BP Monitoring (HBPM) Protocol
- Use validated upper arm device
- Measure in the morning (before medication, before breakfast) AND evening
- Perform for 7 consecutive days (minimum 3 days)
- Take 2 readings each session, 1 minute apart
- Discard all Day 1 readings
- Calculate the average of the remaining readings
- Hypertension confirmed if average ≥ 135/85 mmHg
BP Phenotypes
| Phenotype | Office BP | Out-of-Office BP | CV Risk | Management |
| Sustained Normotension | Normal (< 140/90) | Normal (< 135/85) | Low | Reassure; periodic screening |
| White Coat HTN | Elevated (≥ 140/90) | Normal (< 135/85) | Slightly above normal | Lifestyle; annual monitoring; do NOT routinely start drug therapy |
| Masked HTN | Normal (< 140/90) | Elevated (≥ 135/85) | Similar to sustained HTN | Treat as sustained hypertension |
| Sustained HTN | Elevated (≥ 140/90) | Elevated (≥ 135/85) | High | Full treatment per guideline |
π White coat hypertension has a prevalence of 15β30% among patients with elevated office BP. These patients should not be labelled hypertensive or started on drug therapy based on office readings alone.
π Masked hypertension is the most dangerous phenotype β office BP appears normal, but the patient sustains organ damage. Suspect when target organ damage is present despite normal office readings.
Indications for ABPM
- Suspected white coat hypertension
- Suspected masked hypertension
- Resistant hypertension
- Assessment of nocturnal BP and dipping status
- Episodic or labile BP
- Autonomic dysfunction
- Pregnancy with borderline readings
Nocturnal BP and Dipping Status (from ABPM)
| Pattern | Night-time SBP Dip |
| Normal dipper | 10β20% decline |
| Non-dipper | 0β10% decline |
| Reverse dipper | Nocturnal BP rise |
| Extreme dipper | > 20% decline |
Non-dipping and reverse dipping patterns are associated with increased CV risk and target organ damage. They are common in CKD, diabetes, OSA, and secondary hypertension. Consider evening dosing of at least one antihypertensive if non-dipping is confirmed.
1.4 CONFIRMING THE DIAGNOSIS
Diagnostic Pathway
ELEVATED OFFICE BP DETECTED
(≥ 140/90 mmHg)
β
βββββββββββββββ΄ββββββββββββββ
β β
GRADE 2β3 HTN GRADE 1 HTN
(≥ 160/100) OR (140β159/90β99)
evidence of HMOD β
β β
βΌ βΌ
Confirm with repeat Offer ABPM or HBPM
same-visit reading to confirm diagnosis
→ Diagnosis confirmed β
→ Start treatment βββββββ΄ββββββ
β β
ABPM/HBPM ABPM/HBPM
confirms does NOT
(≥ 135/85) confirm
β β
βΌ βΌ
Diagnosis White Coat HTN
confirmed → Lifestyle
→ Treat → Annual
monitoring
Number of Readings Required
| Scenario | Readings Required |
| Grade 2β3 HTN (≥ 160/100) | Confirm with second reading same visit; can diagnose same day |
| Grade 1 HTN (140β159/90β99) | Confirm with ABPM or HBPM (preferred) OR repeat office readings on ≥ 2 separate occasions |
| Grade 1 HTN + HMOD or high CV risk | Can diagnose and start treatment sooner |
| Hypertensive emergency (any level + acute organ damage) | Single reading sufficient; treat immediately |
1.5 PATHOPHYSIOLOGY β MECHANISM-TO-DRUG RATIONALE
Major Mechanisms and Corresponding Drug Targets
| Mechanism | Pathways | Targeted By |
| RAAS Activation | ↑ Angiotensin II → Vasoconstriction + NaβΊ retention + Aldosterone release | ACE-I, ARB, ARNI, MRA, Direct Renin Inhibitors |
| Sympathetic Overactivity | ↑ Heart rate, ↑ Cardiac output, ↑ Vascular tone | Beta-blockers, Central agents (Clonidine, Methyldopa) |
| Volume Expansion | ↑ NaβΊ and water retention | Thiazide diuretics, Loop diuretics |
| Vascular Stiffness | Arterial wall changes, ↓ Compliance | CCBs, Nitrates |
| Endothelial Dysfunction | ↓ Nitric oxide, ↑ Endothelin | CCBs, ACE-I, ARB |
Age and Ethnicity Affect Predominant Mechanism
| Patient Group | Predominant Mechanism | Best Initial Drug |
| Young (< 55 years) | High renin, RAAS-driven | ACE-I or ARB |
| Elderly (≥ 55 years) | Low renin, volume/stiffness | CCB or Thiazide |
| Black/African ethnicity (any age) | Low renin, salt-sensitive | CCB or Thiazide |
| Obese | RAAS activation + volume | ACE-I/ARB + Diuretic |
| Diabetes | RAAS activation | ACE-I or ARB |
π¬ This physiological basis underpins the age-based drug selection algorithm in Section 6.3.
SECTION 2: CLINICAL EVALUATION
2.1 ROUTINE INVESTIGATIONS (ALL HYPERTENSIVE PATIENTS)
| Test | Purpose | Key Interpretation |
| Haemoglobin / CBC | Anaemia (CKD), Polycythaemia (OSA, renal tumour) | Hb < 12 g/dL (F) or < 13 g/dL (M) suggests anaemia |
| Fasting Glucose | Diabetes screening | ≥ 126 mg/dL = DM; 100β125 = prediabetes |
| HbA1c | Diabetes screening/control | ≥ 6.5% = DM; 5.7β6.4% = prediabetes |
| Lipid Profile | CV risk assessment | LDL, HDL, TG; calculate non-HDL-C |
| Serum Creatinine | Renal function | Elevated suggests CKD |
| eGFR | CKD staging | Use CKD-EPI equation |
| Serum NaβΊ, KβΊ | Baseline electrolytes; secondary HTN clues | KβΊ < 3.5 unprovoked → screen for primary aldosteronism |
| Serum Uric Acid | Baseline before diuretics; CV risk marker | Diuretics elevate uric acid |
| Urinalysis | Proteinuria, haematuria, casts | Simple but informative |
| Urine ACR (spot) | Microalbuminuria β HMOD marker | > 30 mg/g = abnormal; > 300 mg/g = overt proteinuria |
| 12-Lead ECG | LVH, ischaemia, arrhythmia, prior MI | All hypertensive patients |
2.2 ECG INTERPRETATION IN HYPERTENSION
| Finding | Criteria | Significance |
| LVH (voltage) | Sokolow-Lyon: S(V1) + R(V5/V6) ≥ 35 mm | Left ventricular hypertrophy |
| Cornell: R(aVL) + S(V3) > 28 mm (M), > 20 mm (F) | More specific | |
| LVH with strain | ST depression + T inversion in lateral leads | Worse prognosis |
| Left atrial enlargement | P mitrale (notched P in II, biphasic in V1) | Diastolic dysfunction |
| Ischaemia | ST depression, T wave changes | CAD |
| Atrial fibrillation | Irregularly irregular, absent P waves | ↑ Stroke risk |
| Prior MI | Pathological Q waves | Established CVD |
π ECG has low sensitivity (~50%) for LVH. If clinical suspicion is high and ECG is negative, order echocardiography.
2.3 ADDITIONAL INVESTIGATIONS (BY CLINICAL INDICATION)
| Test | When to Order | Purpose |
| Echocardiography | Suspected LVH, HF, murmur, abnormal ECG | LVMI, LVEF, diastolic function, valve disease |
| Renal Ultrasound | Elevated creatinine, abnormal urinalysis, family history PKD | Size, asymmetry, cysts, obstruction |
| Renal Artery Doppler | Resistant HTN, abdominal bruit, flash pulmonary oedema, renal impairment on ACE-I/ARB | Renal artery stenosis |
| CT/MR Angiography | Suspected RAS, coarctation, adrenal mass | Detailed anatomy |
| Fundoscopy | Grade 2β3 HTN, diabetes, visual symptoms | Retinopathy grading |
| Carotid Ultrasound | Carotid bruit, high CV risk | Plaque, IMT, stenosis |
| ABI | Suspected PAD, claudication | < 0.9 = PAD |
| NT-proBNP / BNP | Suspected HF | Elevated in HF |
| Chest X-ray | Suspected HF, coarctation, aortic disease | Cardiomegaly, pulmonary congestion, rib notching |
2.4 SECONDARY HYPERTENSION: WHEN TO SCREEN AND HOW
When to Screen
| Red Flag | Action |
| Age < 30 years without obesity or family history | Screen |
| Sudden onset of HTN | Screen |
| Acute worsening of previously controlled HTN | Screen |
| Resistant HTN (uncontrolled on ≥ 3 drugs including diuretic) | Screen |
| Grade 3 HTN with acute HMOD | Screen |
| Unprovoked hypokalaemia (KβΊ < 3.5) or severe diuretic-induced hypokalaemia | Screen |
| Abdominal bruit | Screen |
| Labile BP with paroxysmal symptoms (sweating, palpitations, headache) | Screen |
| Features of specific syndrome (Cushing, thyroid, acromegaly) | Screen |
| > 30% rise in creatinine after starting ACE-I/ARB | Screen |
| Flash pulmonary oedema with preserved LV function | Screen |
Screening and Confirmatory Tests by Cause
| Suspected Cause | Screening Test | Confirmatory Test |
| Primary Aldosteronism | Aldosterone-to-Renin Ratio (ARR) | Salt loading test; Adrenal CT; Adrenal vein sampling |
| Renovascular Disease | Renal artery Doppler | CT/MR angiography |
| Phaeochromocytoma | Plasma free metanephrines (preferred) OR 24-hr urine metanephrines/catecholamines | CT/MRI abdomen; MIBG scan |
| Cushing Syndrome | 24-hr urine free cortisol OR overnight 1 mg dexamethasone suppression test OR late-night salivary cortisol | ACTH level; Pituitary MRI; Adrenal CT |
| Thyroid Dysfunction | TSH | Free T4, Free T3 |
| Obstructive Sleep Apnoea | STOP-BANG questionnaire; Epworth Sleepiness Scale | Polysomnography |
| Coarctation of Aorta | Arm-leg BP gradient > 20 mmHg; CXR (rib notching, β3β sign) | CT/MR angiography; Echocardiography |
| Renal Parenchymal Disease | Creatinine, eGFR, Urinalysis, Urine ACR, Renal ultrasound | Renal biopsy if indicated |
SECTION 3: RISK STRATIFICATION
3.1 HYPERTENSION-MEDIATED ORGAN DAMAGE (HMOD)
| Organ | Marker | Detection |
| Heart | LVH | ECG (Sokolow-Lyon, Cornell); Echo (LVMI: M > 115, F > 95 g/m²) |
| Diastolic dysfunction | Echo (E/eβ ratio, LA volume) | |
| Arteries | Carotid IMT ≥ 0.9 mm or plaque | Carotid ultrasound |
| Aortic stiffness (PWV > 10 m/s) | Pulse wave velocity | |
| ABI < 0.9 | Ankle-brachial index | |
| Kidney | eGFR 30β59 (CKD Stage 3) | Serum creatinine calculation |
| Microalbuminuria (ACR 30β300 mg/g) | Spot urine ACR | |
| Eye | Retinopathy (Grade IIIβIV) | Fundoscopy |
| Brain | White matter lesions, silent infarcts | MRI (not routine) |
3.2 ESTABLISHED CARDIOVASCULAR/RENAL DISEASE
| Category | Examples |
| Cerebrovascular | Ischaemic stroke, Haemorrhagic stroke, TIA |
| Coronary | MI, Angina, PCI, CABG |
| Heart Failure | HFrEF, HFpEF |
| Peripheral Arterial | Symptomatic PAD, revascularisation, amputation |
| Renal | CKD Stage 4β5 (eGFR < 30), ESKD, Transplant |
| Retinal | Advanced retinopathy (Grade IIIβIV) |
| Aortic | Aneurysm, Prior dissection |
3.3 RISK STRATIFICATION MATRIX
| BP Category | No Other RF | 1β2 RF | ≥ 3 RF | HMOD, CKD 3, or DM without HMOD | CVD, CKD ≥ 4, or DM with HMOD |
| High Normal (130β139/85β89) | Low | Low | LowβMod | ModβHigh | Very High |
| Grade 1 (140β159/90β99) | Low | Mod | ModβHigh | High | Very High |
| Grade 2 (160β179/100β109) | Mod | ModβHigh | High | High | Very High |
| Grade 3 (≥ 180/110) | High | High | High | Very High | Very High |
Interpretation
| Risk Category | 10-Year CV Risk | Action |
| Low | < 5% | Lifestyle; drug if HTN persists |
| Moderate | 5β10% | Lifestyle + consider drug |
| High | 10β20% | Lifestyle + drug |
| Very High | > 20% | Lifestyle + drug urgently |
3.4 CARDIOVASCULAR RISK CALCULATORS
| Calculator | Population | Notes |
| WHO/ISH Risk Charts | Global including SEAR-D (India) | Free, simple; uses age, sex, BP, DM, smoking, cholesterol |
| QRISK3 | UK population | Includes South Asian ethnicity adjustment |
| SCORE2 / SCORE2-OP | European | Age-specific; updated |
| ASCVD Risk Estimator | US population | ACC/AHA |
| Framingham Risk Score | US population | Original; may underestimate in South Asians |
π WHO/ISH charts (SEAR-D region) or QRISK3 (with South Asian ethnicity adjustment) are reasonable choices for Indian patients.
SECTION 4: TREATMENT TARGETS
4.1 EVIDENCE FOR BP TARGETS
π¬ Key Trials:
- SPRINT (2015): Intensive (< 120 mmHg) vs Standard (< 140 mmHg) in non-diabetics reduced CV events by 25% and all-cause mortality by 27%, but with more adverse events (hypotension, syncope, AKI, electrolyte disturbances)
- ACCORD-BP (2010): In Type 2 diabetics, intensive SBP target (< 120) vs standard (< 140) did not reduce the primary composite CV endpoint, but did significantly reduce stroke. Increased adverse effects.
- Meta-analyses (Ettehad et al., Lancet 2016): Every 10 mmHg SBP reduction → 20% reduction in major CV events, 28% reduction in HF, 27% reduction in stroke, 13% reduction in all-cause mortality.
Balancing Benefits and Risks
| Target | Benefits | Risks |
| < 120/80 | Maximum CV risk reduction | More hypotension, syncope, AKI, electrolyte disturbances |
| < 130/80 | Significant CV benefit with acceptable risk profile | Mild increase in adverse effects |
| < 140/90 | Clear benefit, fewer side effects | Suboptimal protection in high-risk patients |
4.2 TARGET BP β QUICK REFERENCE
| Population | SBP Target | DBP Target | Lower Limit | Key Notes |
| General < 65 years | < 130 | < 80 | > 110/70 | If tolerated |
| General 65β79 years | < 140 (ideal < 130 if tolerated) | < 80 | > 110/70 | Individualise; check orthostatic BP |
| ≥ 80 years | < 150 (< 140 if fit) | < 90 | > 110/70 | Avoid overtreatment; function over numbers |
| Diabetes | < 130 | < 80 | > 110/70 | ACE-I/ARB preferred |
| CKD (no proteinuria) | < 140 | < 90 | > 110/70 | Any agent acceptable |
| CKD (proteinuria present) | < 130 (< 120 SBP if tolerated) | < 80 | > 110/70 | ACE-I/ARB mandatory; KDIGO 2021 |
| CAD / Post-MI | < 130 | 70β80 | DBP > 60β70 | J-curve concern |
| Heart Failure | < 130 | < 80 | Tolerate SBP 100β110 | Use GDMT |
| Post-Stroke (chronic) | < 130 | < 80 | > 110/70 | After acute phase |
| Pregnancy | < 140 | < 90 | > 110/70 | Avoid hypoperfusion |
| Frail elderly | Individualise | β | Avoid falls, syncope | Function over numbers |
SECTION 5: NON-PHARMACOLOGICAL MANAGEMENT
π Every patient with hypertension β regardless of BP level, risk category, or drug treatment β should receive structured lifestyle advice.
5.1 LIFESTYLE INTERVENTIONS β SUMMARY OF EVIDENCE
| Intervention | Recommendation | Expected SBP Reduction |
| Salt restriction | < 5 g/day (< 2 g sodium/day) | 5β6 mmHg |
| Dietary pattern (DASH-style) | Rich in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat | 8β14 mmHg |
| Potassium intake | Increase dietary potassium to 3.5β5 g/day (fruits, vegetables); avoid supplements if on ACE-I/ARB/MRA | 2β4 mmHg |
| Weight loss | Target BMI 18.5β22.9 (Asian cut-offs); waist < 90 cm (M), < 80 cm (F) | ~1 mmHg per kg lost |
| Aerobic exercise | ≥ 150 min/week moderate intensity OR ≥ 75 min/week vigorous | 4β9 mmHg |
| Resistance exercise | 2β3 days/week, moderate intensity | 2β4 mmHg |
| Alcohol reduction | ≤ 2 standard drinks/day (men); ≤ 1 standard drink/day (women) | 2β4 mmHg |
| Smoking cessation | Complete cessation of all tobacco | Minimal direct BP effect; major CV risk reduction |
| Stress management | Meditation, yoga, relaxation techniques | Variable |
π Combined lifestyle modifications can reduce SBP by 10β20 mmHg β equivalent to one antihypertensive drug.
π Central obesity (waist circumference) is more important than BMI for cardiovascular risk assessment in South Asians.
Exercise Cautions
| If Patient Has | Precaution |
| BP > 180/110 | Control BP before commencing vigorous exercise |
| CAD | Graded exercise; consider stress test if new to exercise |
| Orthopaedic limitations | Low-impact activities |
| Autonomic dysfunction | Avoid sudden position changes |
SECTION 6: PHARMACOLOGICAL MANAGEMENT
6.1 WHEN TO START DRUG THERAPY
Decision Matrix
| BP Grade | LowβModerate CV Risk | High CV Risk (or DM, CKD, CVD, HMOD) |
| High Normal (130β139/85β89) | Lifestyle only | Consider drugs (especially if CAD, DM with HMOD, HFrEF) |
| Grade 1 (140β159/90β99) | Lifestyle × 3β6 months → Drug if not controlled | Lifestyle + Drug immediately |
| Grade 2 (160β179/100β109) | Lifestyle + Drug immediately | Lifestyle + Drug immediately |
| Grade 3 (≥ 180/110) | Lifestyle + Drug immediately | Lifestyle + Drug immediately |
Start Drug Therapy Immediately If:
- BP ≥ 160/100 mmHg (Grade 2 or 3)
- BP ≥ 140/90 mmHg + Diabetes Mellitus
- BP ≥ 140/90 mmHg + CKD (eGFR < 60 or albuminuria)
- BP ≥ 140/90 mmHg + Established CVD (CAD, stroke, PAD, HF)
- BP ≥ 140/90 mmHg + HMOD (LVH, retinopathy, microalbuminuria)
- BP ≥ 140/90 mmHg + High 10-year CV risk (> 10%)
- Any hypertensive emergency
Trial Lifestyle First If:
- Grade 1 HTN (140β159/90β99) AND
- Lowβmoderate CV risk AND
- No diabetes, CKD, CVD, or HMOD AND
- Patient is motivated and close follow-up is possible
- Duration: 3β6 months with regular monitoring
6.2 FIRST-LINE DRUG CLASSES
Overview
| Class | Letter | Key Drugs | Mechanism | Key Advantage |
| ACE Inhibitors | A | Ramipril, Enalapril, Perindopril, Lisinopril | Block ACE → ↓ Angiotensin II | Renoprotection; HF benefit |
| ARBs | A | Telmisartan, Losartan, Olmesartan, Valsartan, Azilsartan, Candesartan | Block ATβ receptor | Like ACE-I but no cough |
| CCBs (DHP) | C | Amlodipine, Cilnidipine, Nifedipine ER | Block L-type Ca²βΊ channels | Potent; metabolically neutral |
| Thiazide-like Diuretics | D | Chlorthalidone, Indapamide | Inhibit Na-Cl cotransporter | Volume control; inexpensive |
π¬ All four classes reduce CV events and mortality comparably. Choice depends on compelling indications, contraindications, and patient characteristics.
Comparison of First-Line Classes
| Feature | ACE-I | ARB | CCB | Thiazide-like |
| Efficacy | +++ | +++ | ++++ | +++ |
| Renoprotection | ++++ | ++++ | + | + |
| HF benefit | ++++ | +++ | ± | ++ |
| Metabolic neutrality | +++ | +++ | ++++ | + |
| Cough | 5β20% | Rare | No | No |
| Peripheral oedema | No | No | Yes | No |
| Hypokalaemia | No (↑ KβΊ) | No (↑ KβΊ) | No | Yes |
6.3 INITIAL DRUG SELECTION
Age/Ethnicity-Based Selection (No Compelling Indication)
NO COMPELLING INDICATION
β
ββββββββββββββββ΄βββββββββββββββ
β β
AGE < 55 YEARS AGE ≥ 55 YEARS
β or Black/African
β ethnicity
βΌ βΌ
ββββββββββββ ββββββββββββ
β ACE-I β β CCB β
β or β β or β
β ARB β βThiazide β
ββββββββββββ ββββββββββββ
6.4 COMPELLING INDICATIONS β MASTER TABLE
| Condition | β Preferred | β οΈ Caution | β Avoid |
| Diabetes (no albuminuria) | ACE-I/ARB | High-dose thiazide | β |
| DM + Albuminuria | ACE-I/ARB (mandatory) | β | β |
| CKD | ACE-I/ARB | Monitor KβΊ, Cr | β |
| CKD (eGFR < 30) | Loop diuretic | ACE-I/ARB (with caution) | Thiazides (less effective) |
| HFrEF (EF ≤ 40%) | ACE-I/ARB → ARNI, BB, MRA, SGLT2i | β | Non-DHP CCB (Verapamil, Diltiazem) |
| HFpEF | Any agent; SGLT2i; consider MRA | β | β |
| Post-MI | ACE-I, BB | β | β |
| CAD (stable) | ACE-I, BB, CCB | β | β |
| Post-Stroke (chronic) | ACE-I + Thiazide | β | β |
| Atrial Fibrillation (rate control) | BB or Non-DHP CCB | β | β |
| Aortic aneurysm | BB | β | β |
| Pregnancy | Methyldopa, Labetalol, Nifedipine ER | β | ACE-I, ARB, ARNI, MRA |
| Asthma | CCB, ACE-I, ARB, Thiazide | Cardioselective BB only if compelling cardiac indication and no alternative; specialist supervision | Non-selective BB (Propranolol, Carvedilol, Labetalol) |
| COPD (without reversible airway disease) | Any; cardioselective BB generally safe | β | β |
| Gout / Hyperuricaemia | Losartan (uricosuric) | β | Thiazides |
| BPH | Alpha-blocker (add-on, not first-line) | Orthostatic hypotension | β |
| Osteoporosis | Thiazide (↓ urinary Ca²βΊ) | β | β |
| Bradycardia / Heart block | DHP CCB, ACE-I, ARB | β | BB, Non-DHP CCB |
| Bilateral renal artery stenosis | CCB, Thiazide | β | ACE-I, ARB |
| Prior ACE-I angioedema | ARB (with caution), CCB, others | β | ACE-I (absolute) |
| Hyperkalaemia (KβΊ > 5.5) | CCB, Thiazide | β | ACE-I, ARB, MRA (until KβΊ corrected) |
Compelling Indications β Expanded Notes
Diabetes Mellitus:
- Target: < 130/80 mmHg
- ACE-I/ARB mandatory if any degree of albuminuria
- Consider SGLT2 inhibitor for combined cardiorenal benefit (see Section 8.1)
- Consider Finerenone if albuminuria persists on maximal ACE-I/ARB (see Section 8.1)
Heart Failure (HFrEF):
- Guideline-directed medical therapy: ACE-I/ARB → ARNI + BB + MRA + SGLT2i ± diuretic
- ARNI (Sacubitril/Valsartan) is preferred over ACE-I/ARB once stable (PARADIGM-HF: 20% reduction in CV death/HF hospitalisation vs enalapril)
- β Never combine ARNI with ACE-I; 36-hour washout required when switching from ACE-I to ARNI
CAD / Post-MI:
- β οΈ J-curve: Keep DBP > 60β70 mmHg in CAD patients to maintain coronary perfusion
Post-Stroke/TIA:
- Acute ischaemic stroke: do NOT lower BP unless > 220/120 (or > 185/110 if thrombolysis planned)
- Chronic secondary prevention: ACE-I + Thiazide preferred (PROGRESS trial); target < 130/80
6.5 MONOTHERAPY VS COMBINATION THERAPY
π¬ Evidence:
- Monotherapy controls BP in only 30β50% of patients
- Low-dose combination is more effective than high-dose monotherapy
- Combination therapy reaches target faster with fewer side effects
- Single-pill combinations (SPC) improve adherence by 20β30%
When to Use Monotherapy
- Grade 1 HTN (140β159/90β99) with low CV risk
- BP within 20/10 mmHg of target
- Very elderly or frail (risk of hypotension)
When to Start with Dual Combination
- Grade 2β3 HTN (≥ 160/100)
- BP > 20/10 mmHg above target
- High or very high CV risk
- Diabetes mellitus
- CKD
- Established CVD
- HMOD
- Most patients (default strategy in modern practice)
Recommended Combinations
| Combination | Suitability | Notes |
| ACE-I/ARB + CCB | β Preferred for most patients | Reduces CCB-induced oedema; metabolically neutral; strong evidence (ACCOMPLISH) |
| ACE-I/ARB + Thiazide-like | β Preferred | Good for volume-related HTN; HF |
| CCB + Thiazide-like | β Acceptable | When ACE-I/ARB intolerant |
| CCB + BB | β Acceptable | Especially if tachycardia or angina |
| BB + Diuretic | β οΈ Limited use | HF or post-MI; not first-line for uncomplicated HTN |
Combinations to AVOID
| β Combination | Reason |
| ACE-I + ARB | No added benefit; ↑ hyperkalaemia, ↑ AKI (ONTARGET) |
| ACE-I/ARB + Aliskiren | ↑ Hyperkalaemia, AKI |
| Non-DHP CCB + BB | Risk of severe bradycardia and heart block |
| Two drugs of the same class | No added benefit |
6.6 STEP-BY-STEP TREATMENT PROTOCOL
STEP 1: Initial Therapy
Select drug(s) based on compelling indications (Section 6.4) or age-based algorithm (Section 6.3). Start with monotherapy or dual combination per Section 6.5. Reassess in 4β6 weeks.
STEP 2: If Not at Target
| Current Therapy | If NOT at Full Dose | If AT Full Dose |
| Monotherapy | Uptitrate to full dose | Add 2nd drug → Dual combination |
| Dual combination | Uptitrate both to full doses | Add 3rd drug → Triple combination |
STEP 3: Triple Combination
Standard triple therapy:
- ACE-I or ARB (full dose) + CCB (full dose) + Thiazide-like diuretic (Chlorthalidone or Indapamide)
Use single-pill triple combination if available.
STEP 4: Resistant Hypertension
See Section 8.5. Key steps:
- Rule out pseudo-resistance (adherence, white coat, measurement error, interfering drugs)
- Optimise diuretic: switch to Chlorthalidone 25 mg or Indapamide 2.5 mg
- Screen for secondary causes (especially primary aldosteronism, OSA)
- Add Spironolactone 25β50 mg as 4th drug (PATHWAY-2)
- Specialist referral if still uncontrolled
STEP 5: Refractory Hypertension
Uncontrolled on ≥ 5 drugs at optimal doses including chlorthalidone and spironolactone → mandatory specialist referral.
6.7 COMPLETE TREATMENT ALGORITHM
HYPERTENSION CONFIRMED
β
βΌ
ββββββββββ COMPELLING INDICATION? ββββββββββ
β β
YES NO
β β
βΌ βΌ
USE INDICATED DRUG(S) AGE-BASED SELECTION
β’ DM/CKD → ACE-I/ARB β’ < 55 → ACE-I/ARB
β’ HF → ACE-I→ARNI+BB+MRA β’ ≥ 55 → CCB/Thiazide
β’ CAD → ACE-I+BB
β’ Pregnancy → Methyldopa/Labetalol
β β
ββββββββββββββββββ¬ββββββββββββββββββββββββββ
β
βΌ
βββββββ GRADE & RISK? βββββββ
β β
Grade 1 + Low Risk Grade 2-3 or High Risk
β β
βΌ βΌ
MONOTHERAPY DUAL COMBINATION
(ACE-I/ARB or CCB) (ACE-I/ARB + CCB preferred)
β β
βββββββββββββββ¬ββββββββββββββ
β
βΌ
REASSESS 4β6 WEEKS
β
ββββββββββββββ΄βββββββββββββ
β β
AT TARGET NOT AT TARGET
β β
βΌ βΌ
Continue; UPTITRATE or ADD DRUG
F/U 3β6 months β
ββββββββββββββ΄βββββββββββββ
β β
On Monotherapy On Dual Therapy
β β
βΌ βΌ
DUAL THERAPY TRIPLE THERAPY
(ACE-I/ARB + CCB) (ACE-I/ARB + CCB + Thiazide)
β β
ββββββββββββββ¬βββββββββββββ
β
βΌ
REASSESS 4β6 WEEKS
β
ββββββββββββββ΄βββββββββββββ
β β
AT TARGET NOT AT TARGET
β β
βΌ βΌ
Continue RESISTANT HTN WORKUP
β
βΌ
β’ Confirm adherence
β’ ABPM (rule out white coat)
β’ Screen secondary causes
β’ Optimise diuretic
β
βΌ
ADD SPIRONOLACTONE 25β50 mg
β
βΌ
REASSESS 4β6 WEEKS
β
ββββββββββββββββββ΄ββββββββββββββββ
β β
AT TARGET NOT AT TARGET
β β
βΌ βΌ
Continue SPECIALIST REFERRAL
6.8 DRUG DOSING β COMPLETE REFERENCE
ACE Inhibitors
| Drug | Starting Dose | Target Dose | Maximum Dose | Frequency | Notes |
| π Ramipril | 2.5 mg | 10 mg | 10 mg | OD | Most evidence (HOPE trial); preferred |
| π Perindopril erbumine | 4 mg | 8 mg | 8 mg | OD | EUROPA, ADVANCE. Note: Perindopril arginine 5 mg ≈ erbumine 4 mg |
| π Enalapril | 5 mg | 20 mg | 40 mg | BD | BD dosing usually required for 24-hour coverage |
| π Lisinopril | 5 mg | 20β40 mg | 40 mg | OD | No hepatic metabolism |
Class side effects:
- Dry cough (5β20%; higher in Asians) → switch to ARB
- Hyperkalaemia → monitor KβΊ
- Angioedema (rare but serious) → discontinue permanently; avoid rechallenge
- First-dose hypotension → start low in elderly, volume-depleted patients
- AKI → check creatinine at 1β2 weeks after initiation
ARBs
| Drug | Starting Dose | Target Dose | Maximum Dose | Frequency | Notes |
| π Telmisartan | 40 mg | 80 mg | 80 mg | OD | Longest half-life (24 hrs); PPARγ activity; metabolically neutral |
| π Olmesartan | 20 mg | 40 mg | 40 mg | OD | Potent BP reduction |
| π Azilsartan | 40 mg | 80 mg | 80 mg | OD | Most potent ARB in head-to-head comparisons |
| π Losartan | 50 mg | 100 mg | 100 mg | OD | Unique uricosuric effect; shortest half-life |
| π Valsartan | 80 mg | 160β320 mg | 320 mg | OD | Strong HF evidence (Val-HeFT) |
| π Candesartan | 8 mg | 32 mg | 32 mg | OD | Strong HF evidence (CHARM) |
π Telmisartan and Azilsartan provide the best 24-hour BP coverage. Losartan is preferred when hyperuricaemia or gout is present.
ARNI (Angiotensin Receptor-Neprilysin Inhibitor)
| Drug | Starting Dose | Target Dose | Maximum Dose | Frequency | Notes |
| π Sacubitril/Valsartan | 24/26 mg | 97/103 mg | 97/103 mg | BD | Preferred over ACE-I/ARB in HFrEF (PARADIGM-HF) |
Key prescribing rules:
- β Indicated for HFrEF; replaces ACE-I/ARB once patient is stable
- β Potent antihypertensive effect
- β Never combine with ACE-I (risk of angioedema)
- β οΈ Requires 36-hour washout after stopping ACE-I before starting ARNI
- β οΈ No washout needed when switching from ARB
- β οΈ Can cause hypotension β start low, uptitrate gradually
- Monitor KβΊ and renal function as with ACE-I/ARB
CCBs β Dihydropyridines
| Drug | Starting Dose | Target Dose | Maximum Dose | Frequency | Notes |
| π Amlodipine | 5 mg | 10 mg | 10 mg | OD | Most widely used; ankle oedema common at higher doses |
| π S-Amlodipine | 2.5 mg | 5 mg | 5 mg | OD | Purified S-isomer; may have less oedema |
| π Cilnidipine | 10 mg | 20 mg | 20 mg | OD | N+L type blockade; less reflex tachycardia, less oedema |
| π Nifedipine ER | 30 mg | 60 mg | 90 mg | OD | Extended-release formulation ONLY |
| π Felodipine | 5 mg | 10 mg | 10 mg | OD | Alternative |
β Never use immediate-release Nifedipine capsules for hypertension management. Causes unpredictable precipitous BP drops with risk of stroke and MI. This formulation should not be stocked for antihypertensive use.
CCBs β Non-Dihydropyridines
| Drug | Starting Dose | Target Dose | Maximum Dose | Frequency | Notes |
| π Diltiazem SR | 90 mg | 180β240 mg | 360 mg | ODβBD | Rate control in AF; constipation |
| π Verapamil SR | 120 mg | 240 mg | 480 mg | ODβBD | Rate control; constipation; negative inotropy |
β Do NOT combine non-DHP CCBs with beta-blockers (risk of severe bradycardia and heart block).
β Avoid Verapamil and Diltiazem in HFrEF (negative inotropy).
β Avoid Verapamil and Diltiazem in HFrEF (negative inotropy).
Thiazide and Thiazide-like Diuretics
| Drug | Starting Dose | Target Dose | Maximum Dose | Frequency | Notes |
| π Chlorthalidone | 12.5 mg | 25 mg | 50 mg | OD | Preferred; longer acting; greater potency per mg |
| π Indapamide | 1.5 mg | 2.5 mg | 2.5 mg | OD | Preferred; fewer metabolic effects than other thiazides |
| π Hydrochlorothiazide | 12.5 mg | 25 mg | 50 mg | OD | Shorter acting; less potent; widely available |
π Chlorthalidone and Indapamide are preferred over HCTZ based on longer duration, greater potency, and superior outcome data (ALLHAT, SHEP). However, the DCP Trial (NEJM 2022) showed no significant difference in CV outcomes between chlorthalidone and HCTZ. HCTZ is acceptable when preferred agents are unavailable.
Class side effects:
- Hypokalaemia β combine with ACE-I/ARB or KβΊ-sparing diuretic
- Hyponatraemia β especially in elderly women; monitor NaβΊ at 1β2 weeks after starting
- Hyperuricaemia / gout precipitation β use Losartan if gout co-exists; avoid in severe gout
- Glucose intolerance β use low doses; prefer Indapamide
- Hypercalcaemia β usually mild; beneficial if osteoporosis co-exists
Beta-Blockers
| Drug | Starting Dose | Target Dose | Maximum Dose | Frequency | Notes |
| π Bisoprolol | 2.5β5 mg | 10 mg | 20 mg | OD | Cardioselective; HF evidence |
| π Metoprolol Succinate XL | 25β50 mg | 200 mg | 400 mg | OD | Extended-release; HF evidence (MERIT-HF) |
| π Nebivolol | 5 mg | 10 mg | 40 mg | OD | Vasodilating; less fatigue, less erectile dysfunction |
| π Carvedilol | 6.25 mg BD | 25 mg BD | 25 mg BD (50 mg/day) | BD | α + β blocker; HF evidence. For HF: start 3.125 mg BD |
| π Atenolol | 25β50 mg | 100 mg | 100 mg | OD | Less preferred; inferior stroke prevention (LIFE trial) |
| π Propranolol | 40 mg | 160 mg | 320 mg | BDβTID | Non-selective; migraine, tremor, thyrotoxicosis |
| π Labetalol | 100 mg | 200β400 mg | 1200 mg | BD | α + β; pregnancy-safe; hypertensive emergencies |
π Metoprolol formulations are NOT interchangeable:
- Succinate (XL/ER): Once daily; smooth BP control; HF mortality evidence (MERIT-HF). Preferred.
- Tartrate (IR): Twice daily; peaks and troughs; NO HF mortality evidence. Not preferred for HTN or HF.
π Beta-blockers are NOT first-line for uncomplicated HTN. Indicated for:
- Heart failure (HFrEF)
- Post-MI
- Coronary artery disease
- Arrhythmias (AF, SVT)
- Aortic aneurysm
- Hyperkinetic states (anxiety, thyrotoxicosis)
- Migraine prophylaxis, essential tremor
MRAs (Mineralocorticoid Receptor Antagonists)
| Drug | Starting Dose | Target Dose | Maximum Dose | Frequency | Notes |
| π Spironolactone | 12.5β25 mg | 25β50 mg | 100 mg | OD | Best 4th-line agent for resistant HTN (PATHWAY-2); gynecomastia in males |
| π Eplerenone | 25 mg | 50 mg | 50 mg | OD | Selective MRA; much less gynecomastia; more expensive |
β οΈ Monitor KβΊ closely, especially when combined with ACE-I/ARB. Avoid if KβΊ > 5.0 mmol/L or eGFR < 30.
Non-Steroidal MRA
| Drug | Starting Dose | Target Dose | Maximum Dose | Frequency | Notes |
| π Finerenone | 10 mg | 20 mg | 20 mg | OD | Indicated specifically for diabetic kidney disease with albuminuria; modest BP lowering; renal and CV benefit (FIDELIO-DKD, FIGARO-DKD) |
Other Antihypertensive Agents
| Drug | Dose Range | Frequency | Indication | Key Cautions |
| π Doxazosin | 4β8 mg | OD (bedtime) | Resistant HTN; BPH | First-dose hypotension |
| π Prazosin | 1β5 mg | BDβTID | Resistant HTN; BPH | First-dose syncope; start 1 mg at bedtime |
| π Clonidine | 0.1β0.3 mg | BDβTID | Resistant HTN | Rebound HTN on sudden withdrawal |
| π Methyldopa | 250β500 mg | BDβTID | Pregnancy (first-line) | Sedation; depression |
| π Hydralazine | 25β100 mg | TIDβQID | HF; pregnancy; resistant HTN | Reflex tachycardia; lupus-like syndrome at high doses |
| π Minoxidil | 5β40 mg | ODβBD | Severe resistant HTN | Hirsutism; fluid retention; pericardial effusion; must combine with BB + diuretic |
6.9 DRUG COMBINATIONS β SINGLE-PILL COMBINATIONS (SPCs)
π SPCs improve adherence by 20β30%, reach target faster, reduce pill burden, and are often more cost-effective than separate pills.
Dual SPCs
| Combination | Commonly Available Strengths (mg) |
| Telmisartan + Amlodipine | 40/5, 80/5, 40/10, 80/10 |
| Olmesartan + Amlodipine | 20/5, 40/5, 20/10, 40/10 |
| Losartan + Amlodipine | 50/5, 100/5, 50/10 |
| Ramipril + Amlodipine | 2.5/5, 5/5, 5/10, 10/5 |
| Perindopril + Amlodipine | 4/5, 8/5, 4/10, 8/10 |
| Telmisartan + Chlorthalidone | 40/12.5, 80/12.5 |
| Telmisartan + HCTZ | 40/12.5, 80/12.5, 80/25 |
| Losartan + HCTZ | 50/12.5, 100/25 |
| Amlodipine + Atenolol | 5/25, 5/50 |
| Cilnidipine + Telmisartan | 10/40, 10/80 |
| Azilsartan + Cilnidipine | 40/10, 80/10 |
Triple SPCs
| Combination | Commonly Available Strengths (mg) |
| Telmisartan + Amlodipine + HCTZ | 40/5/12.5, 80/5/12.5 |
| Olmesartan + Amlodipine + HCTZ | 20/5/12.5, 40/5/12.5 |
| Losartan + Amlodipine + HCTZ | 50/5/12.5 |
6.10 ASPIRIN AND STATIN CO-PRESCRIPTION IN HYPERTENSION
Aspirin
| Indication | Recommendation |
|
Primary prevention (HTN without established CVD)
|
β Do NOT use aspirin routinely. Risk of major bleeding exceeds benefit. (ARRIVE 2018; ASPREE 2018) |
|
Secondary prevention (established CVD: prior MI, stroke/TIA, PCI, CABG, PAD)
|
β Aspirin 75β150 mg OD |
β οΈ If prescribing aspirin, ensure BP is controlled first. Uncontrolled hypertension + aspirin increases bleeding risk, particularly intracranial haemorrhage.
Statin
| Indication | Statin Intensity |
| Established ASCVD (MI, stroke, PAD, PCI, CABG) | High-intensity (Atorvastatin 40β80 mg or Rosuvastatin 20β40 mg) |
| Diabetes mellitus, age 40β75 | Moderate-intensity (Atorvastatin 10β20 mg or Rosuvastatin 5β10 mg); high-intensity if additional risk factors |
| LDL ≥ 190 mg/dL | High-intensity |
| 10-year CV risk > 10%, age 40β75 | Moderate-to-high intensity |
| 10-year CV risk 7.5β10% with risk enhancers | Consider moderate-intensity |
π South Asian ethnicity is recognised as a cardiovascular risk enhancer; a lower threshold for statin initiation is appropriate.
β οΈ Drug interaction: Simvastatin β avoid with Diltiazem or Verapamil (CYP3A4 inhibition → ↑ statin levels → myopathy risk). Use ≤ 10 mg simvastatin, or switch to Atorvastatin or Rosuvastatin.
6.11 SIDE EFFECT SUMMARY TABLE
| Drug Class | Side Effect | Frequency | Management |
| ACE-I | Dry cough | 5β20% | Switch to ARB |
| Angioedema | < 1% | Stop permanently; avoid rechallenge; use ARB with caution | |
| Hyperkalaemia | 2β5% | Check KβΊ; reduce dose; avoid KβΊ supplements | |
| First-dose hypotension | Variable | Start low; caution in volume-depleted | |
| AKI | Variable | Check Cr at 1β2 weeks; accept ≤ 30% rise if stable | |
| ARB | Similar to ACE-I but cough rare | β | β |
| DHP CCB | Ankle oedema | 10β25% | Add ACE-I/ARB; switch to Cilnidipine; switch class |
| Headache, flushing | 5β10% | Usually transient | |
| Gum hyperplasia | Rare | Dental hygiene; switch | |
| Non-DHP CCB | Constipation | 10β20% | Fibre; switch |
| Bradycardia | Variable | Reduce dose; never combine with BB | |
| Thiazides | Hypokalaemia | 10β40% | Combine with ACE-I/ARB or KβΊ-sparing agent |
| Hyponatraemia | 5β10% | Monitor NaβΊ at 1β2 weeks; reduce dose or switch | |
| Hyperuricaemia/gout | 5β10% | Losartan; avoid in severe gout | |
| Hyperglycaemia | 2β5% | Use low doses; prefer Indapamide | |
| BB | Fatigue | 10β20% | Switch to Nebivolol or Carvedilol |
| Bradycardia | Variable | Reduce dose; switch | |
| Sexual dysfunction | 5β15% | Switch to Nebivolol | |
| Bronchospasm | Variable | Avoid in asthma; generally safe in COPD | |
| Masking of hypoglycaemia | β | Caution in insulin-treated DM | |
| MRA | Hyperkalaemia | 5β15% | Monitor KβΊ; reduce dose |
| Gynecomastia (Spironolactone) | 10β20% in males | Switch to Eplerenone | |
| Alpha-blockers | First-dose hypotension | Variable | Start low; give at bedtime |
| Orthostatic hypotension | 5β15% | Caution in elderly |
π CCB-induced ankle oedema is NOT fluid retention β it is caused by precapillary vasodilation increasing capillary hydrostatic pressure. Diuretics do NOT help. Adding ACE-I/ARB (postcapillary venodilation) counteracts this effect.
6.12 DRUG INTERACTIONS
Clinically Important Interactions
| Drug | Interacts With | Effect | Action |
| ACE-I/ARB | NSAIDs | ↓ Antihypertensive effect; ↑ AKI risk | Minimise NSAID use |
| KβΊ-sparing diuretics / supplements | ↑ Hyperkalaemia | Monitor KβΊ | |
| Lithium | ↑ Lithium levels | Monitor levels | |
| Other ACE-I/ARB | No added benefit; ↑ AKI, hyperkalaemia | Never combine | |
| Aliskiren | ↑ Hyperkalaemia, AKI | Avoid combination | |
| Thiazides | NSAIDs | ↓ Diuretic effect; ↑ AKI risk | Minimise NSAIDs |
| Lithium | ↑ Lithium toxicity | Monitor levels | |
| Digoxin | Hypokalaemia → ↑ Digoxin toxicity | Monitor KβΊ | |
| BB | Non-DHP CCBs | Severe bradycardia, heart block | Avoid combination |
| Digoxin | ↑ Bradycardia | Monitor HR | |
| Insulin/Sulfonylureas | Masks hypoglycaemia symptoms | Caution; educate patient | |
| Clonidine | Rebound HTN if clonidine withdrawn | Stop BB first, then clonidine | |
| Non-DHP CCB | BB | Severe bradycardia, heart block | Avoid combination |
| Simvastatin | ↑ Statin levels (CYP3A4) | Use ≤ 10 mg simvastatin; or switch statin | |
| Digoxin | ↑ Digoxin levels | Monitor levels | |
| All antihypertensives | NSAIDs | ↓ BP-lowering effect | Minimise chronic NSAID use |
| Alcohol (excess) | ↑ Hypotensive effect acutely | Moderate alcohol | |
| PDE5 inhibitors | ↑ Hypotension | Caution; contraindicated with nitrates |
The βTriple Whammyβ
ACE-I/ARB + Diuretic + NSAID = significantly increased risk of AKI
- Mechanism: NSAID blocks prostaglandin-mediated afferent arteriolar dilation + ACE-I/ARB causes efferent dilation + diuretic causes volume depletion → marked reduction in GFR
- Action: Avoid chronic NSAIDs in patients on ACE-I/ARB + diuretic. If unavoidable, monitor creatinine closely and ensure adequate hydration.
π Self-prescribed NSAID use is extremely common. Ask about over-the-counter analgesic use at every visit.
6.13 ADHERENCE
- Assess adherence at every visit using non-judgemental questioning
- Use once-daily dosing whenever possible
- Use single-pill combinations to reduce pill burden
- Proactively manage side effects β they are the most common reason for discontinuation
- Confirm adherence before diagnosing resistant hypertension
π Non-adherence affects 30β50% of hypertensive patients and is the most common cause of apparent treatment failure.
SECTION 7: HYPERTENSIVE CRISES
7.1 DEFINITIONS
| Term | Definition | Key Feature | Management Setting |
| Hypertensive Emergency | Severe HTN (usually > 180/120) WITH acute target organ damage | Organ damage present | ICU; IV therapy |
| Hypertensive Urgency | Severe HTN (usually > 180/120) WITHOUT acute target organ damage | Organ damage absent | Outpatient/observation; oral therapy |
π¨ The presence of acute organ damage β NOT the absolute BP number β defines an emergency.
7.2 TARGET ORGAN DAMAGE IN HYPERTENSIVE EMERGENCY
| Organ | Condition | Key Features | Key Investigations |
| Brain | Hypertensive encephalopathy | Headache, confusion, visual changes, seizures, coma | CT head |
| Ischaemic stroke | Focal neurological deficits | CT head (initially normal); MRI | |
| Haemorrhagic stroke (ICH) | Sudden severe headache, focal deficits, ↓ consciousness | CT head (hyperdense lesion) | |
| PRES | Headache, visual changes, seizures, altered mental status | MRI (posterior white matter oedema) | |
| Heart | Acute Coronary Syndrome | Chest pain, dyspnoea, diaphoresis | ECG, Troponin |
| Acute Pulmonary Oedema | Severe dyspnoea, orthopnoea, pink frothy sputum, crackles | CXR, BNP | |
| Aortic Dissection | Tearing chest/back pain, pulse deficit, inter-arm BP difference | CT aortogram | |
| Kidney | Acute Kidney Injury | Oliguria, rising creatinine | Creatinine, Urinalysis |
| Eye | Acute severe retinopathy | Visual changes | Fundoscopy (haemorrhages, exudates, papilloedema) |
| Vascular | MAHA | Haemolysis | Peripheral smear (schistocytes), ↑ LDH, ↓ haptoglobin |
| Pregnancy | Eclampsia | Seizures in pregnant/postpartum woman with HTN | Clinical diagnosis |
| HELLP Syndrome | RUQ pain, nausea, vomiting | ↑ LFTs, ↓ Platelets, Haemolysis |
7.3 INITIAL RAPID EVALUATION
The First 15 Minutes
| Step | Action |
| 1 | Confirm BP β both arms; proper technique; repeat if very high |
| 2 | Focused history β headache? Chest pain? Dyspnoea? Visual changes? Neurological symptoms? Pregnancy? Medication adherence? Drug use (cocaine, amphetamines)? |
| 3 | Focused examination β GCS, focal neurological deficits; Fundoscopy; Cardiac (JVP, S3, murmurs); Lungs (crackles); Peripheral pulses |
| 4 |
Determine: Emergency (organ damage) vs Urgency (no organ damage)
|
| 5 | Act accordingly |
Urgent Investigations
| Test | Purpose |
| 12-lead ECG | Ischaemia, LVH, arrhythmia |
| Troponin | ACS |
| BNP / NT-proBNP | Heart failure |
| Serum Creatinine, Electrolytes | Renal function, KβΊ |
| CBC with peripheral smear | Anaemia, MAHA (schistocytes) |
| Urinalysis | Proteinuria, haematuria, casts |
| Chest X-ray | Pulmonary oedema, aortic contour, cardiomegaly |
| CT Head (non-contrast) | If neurological symptoms β stroke, haemorrhage |
| CT Aortogram | If aortic dissection suspected |
| Urine pregnancy test | All women of childbearing age |
7.4 BP REDUCTION GOALS
General Principles
β οΈ Do NOT normalise BP rapidly in hypertensive emergencies. Chronic hypertensives have shifted cerebral autoregulation curves. Rapid normalisation risks watershed ischaemia (stroke, MI, AKI).
| Timeframe | Goal |
| First 1 hour | Reduce MAP by 20β25% OR reduce DBP to 100β110 mmHg |
| Next 2β6 hours | Reduce to approximately 160/100β110 mmHg |
| Next 24β48 hours | Gradual further reduction toward target |
Condition-Specific Targets
| Condition | Target | Timeframe | Key Notes |
|
Aortic Dissection π¨
|
SBP < 120 mmHg AND HR < 60/min | Within 20 minutes | Beta-blocker FIRST before vasodilator |
|
Acute Ischaemic Stroke (thrombolysis candidate)
|
< 185/110 before tPA; < 180/105 for 24h after | Before tPA administration | |
|
Acute Ischaemic Stroke (no thrombolysis)
|
Do NOT lower unless > 220/120 | β | Permissive hypertension |
|
Haemorrhagic Stroke (ICH) β presenting SBP 150β220
|
Target SBP ~140 mmHg | Within 1 hour | INTERACT2: reduced haematoma expansion. Do NOT target < 130 (ATACH-2: no benefit, more renal AEs) |
|
Haemorrhagic Stroke (ICH) β presenting SBP > 220
|
Target SBP 140β160 mmHg | β | Aggressive lowering reasonable; limited evidence |
|
Hypertensive Encephalopathy
|
↓ MAP by 20β25% | Over 1β2 hours | |
|
Acute Pulmonary Oedema
|
Reduce gradually with therapy | β | Preload reduction key |
|
ACS
|
Reduce gradually; avoid hypotension | β | DBP > 60 mmHg for coronary perfusion |
|
Eclampsia / Severe Preeclampsia
|
< 160/110 mmHg | Immediately | MgSOβ for seizure prophylaxis/treatment |
|
Phaeochromocytoma Crisis
|
Reduce gradually | β | Alpha-blocker first, then beta-blocker |
7.5 IV ANTIHYPERTENSIVES
First-Line Agents
| Drug | Mechanism | Dose | Onset | Duration | Best For | Avoid In |
| π Labetalol | α + β blocker | 20 mg IV bolus; repeat 20β80 mg q10min OR 0.5β2 mg/min infusion | 5β10 min | 3β6 hrs | Most emergencies; Aortic dissection; Eclampsia | HF, Asthma, Bradycardia, Heart block |
| π Nicardipine | DHP CCB | 5β15 mg/hr infusion | 5β15 min | 30β40 min | Most emergencies; Stroke; Post-operative | Severe aortic stenosis |
| π Nitroglycerin | Venodilator (+ coronary vasodilator) | 5β200 mcg/min infusion | 2β5 min | 5β10 min | ACS; Pulmonary oedema | RV infarct; Concomitant PDE5 inhibitors |
| π Nitroprusside | Arterial + venous dilator | 0.25β10 mcg/kg/min infusion | Immediate | 1β2 min | Severe emergency; last resort | Prolonged use > 24β48 hrs (cyanide toxicity); hepatic/renal impairment; ↑ ICP. Monitor thiocyanate if > 24 hrs or > 2 mcg/kg/min |
| π Esmolol | Cardioselective ultra-short β-blocker | 500 mcg/kg bolus → 50β200 mcg/kg/min infusion | 1β2 min | 10β20 min | Aortic dissection; Perioperative | HF, Asthma, Bradycardia |
Second-Line / Specific Agents
| Drug | Mechanism | Dose | Indication |
| π Hydralazine | Direct vasodilator | 10β20 mg IV q4β6h | Eclampsia; Pregnancy |
| π Phentolamine | α-blocker | 5β15 mg IV bolus | Phaeochromocytoma; Cocaine/amphetamine crisis |
| π Fenoldopam | Dopamine-1 agonist | 0.1β0.3 mcg/kg/min | AKI; Renal protection desired |
| π Clevidipine | Ultra-short DHP CCB | 1β16 mg/hr infusion | Perioperative |
| π Enalaprilat | IV ACE-I | 1.25β5 mg IV q6h | HF with HTN (avoid in AKI) |
Drug Selection by Clinical Scenario
| Scenario | First Choice | Alternative | Avoid |
| Aortic Dissection | Esmolol or Labetalol (HR control first) ± Nitroprusside | β | Vasodilators before beta-blockade |
| ACS | Nitroglycerin ± Esmolol/Labetalol | β | Nitroprusside (coronary steal); Hydralazine (reflex tachycardia) |
| Acute Pulmonary Oedema | Nitroglycerin + Furosemide | Nitroprusside | β |
| Hypertensive Encephalopathy | Nicardipine or Labetalol | Nitroprusside (with caution) | β |
| Ischaemic Stroke | Labetalol or Nicardipine | β | Excessive lowering |
| Haemorrhagic Stroke | Nicardipine or Labetalol | β | β |
| Eclampsia | Labetalol or Hydralazine + MgSOβ | Nicardipine | ACE-I, ARB, Nitroprusside |
| Phaeochromocytoma | Phentolamine | Nicardipine | Beta-blockers before alpha-blockade |
| Cocaine/Amphetamine | Phentolamine or Nicardipine + Benzodiazepines | β | Pure beta-blockers (unopposed alpha stimulation) |
7.6 SPECIFIC EMERGENCY PROTOCOLS
π¨ AORTIC DISSECTION
β±οΈ Mortality increases 1β2% per hour if untreated.
| Priority | Action | Details |
| 1 | Pain control | π Morphine 2β4 mg IV (pain drives sympathetic activation) |
| 2 | HR control FIRST |
π Esmolol 500 mcg/kg bolus → 50β200 mcg/kg/min OR π Labetalol 20 mg IV bolus → infusion. Target: HR < 60/min
|
| 3 | Then BP control |
Add π Nitroprusside 0.25β0.5 mcg/kg/min if needed after HR controlled. Target: SBP < 120 mmHg
|
| 4 | Imaging | CT aortogram |
| 5 | Surgical consult | Cardiothoracic / Vascular surgery β STAT |
- Type A (Ascending): Usually surgical emergency
- Type B (Descending): Medical management; surgery/endovascular if complicated
β NEVER give vasodilators BEFORE beta-blocker in aortic dissection. Reflex tachycardia increases aortic shear stress and propagates the dissection.
π¨ ACUTE PULMONARY OEDEMA
| Priority | Action | Details |
| 1 | Position | Sit upright; legs dangling |
| 2 | Oxygen | High-flow Oβ; NIV (CPAP/BiPAP) if needed |
| 3 | Preload reduction | π Furosemide 40β80 mg IV + π Nitroglycerin 10β200 mcg/min infusion |
| 4 | Afterload reduction | π Nitroprusside if severe and refractory |
| 5 | Morphine | 2β4 mg IV (use cautiously; may worsen respiratory depression) |
| 6 | Treat underlying cause | ACS? Arrhythmia? Valvular disease? |
β οΈ Avoid beta-blockers acutely in decompensated HF.
π¨ HYPERTENSIVE ENCEPHALOPATHY
| Step | Action |
| 1 | CT head β rule out stroke/haemorrhage before aggressive BP lowering |
| 2 | Reduce MAP by 20β25% over 1β2 hours |
| 3 | π Nicardipine 5β15 mg/hr OR π Labetalol infusion |
| 4 | Avoid Nitroprusside if possible (may ↑ ICP) |
| 5 | Symptoms should improve as BP lowers β if not, reconsider diagnosis |
7.7 HYPERTENSIVE URGENCY β OUTPATIENT MANAGEMENT
Principles
- Severe HTN (> 180/120) WITHOUT acute organ damage
- Goal: gradual BP reduction over 24β48 hours
- Oral therapy; restart or intensify existing regimen
Oral Agents
| Drug | Dose | Onset | Notes |
| π Captopril | 12.5β25 mg PO | 15β30 min | Avoid if bilateral RAS, hyperkalaemia |
| π Labetalol | 200β400 mg PO | 30β120 min | Avoid if asthma, bradycardia |
| π Clonidine | 0.1β0.2 mg PO; repeat q1h (max 0.6 mg) | 30β60 min | Sedation; rebound on withdrawal |
| π Amlodipine | 5β10 mg PO | 1β2 hrs | Gradual onset |
| π Telmisartan | 40β80 mg PO | 1β2 hrs | Long-acting |
| π Furosemide | 20β40 mg PO | 30β60 min | If volume overload |
β Do NOT use sublingual Nifedipine. Causes unpredictable precipitous BP drops with risk of stroke and myocardial infarction.
Disposition
| Step | Details |
| Observe | 2β6 hours |
| Goal | BP trending down (does not need to normalise) |
| Medications | Restart or intensify oral regimen |
| Follow-up | Within 24β72 hours |
SECTION 8: SPECIAL POPULATIONS
8.1 HYPERTENSION IN DIABETES MELLITUS
Key Principles
- 70β80% of patients with T2DM have co-existing hypertension
- HTN + DM confers 2β4× cardiovascular risk
- HTN accelerates diabetic nephropathy
- Target: < 130/80 mmHg
- Achieving BP target is as important as glycaemic control for preventing complications
Treatment Approach
| Step | Recommendation |
| 1 | Lifestyle: salt restriction, dietary modification, exercise, weight management |
| 2 | ACE-I or ARB β mandatory if any degree of albuminuria; preferred in all diabetic hypertensives |
| 3 | Add CCB (Amlodipine) if not at target |
| 4 | Add Thiazide-like diuretic if still not at target |
| 5 | Add SGLT2 inhibitor for cardiorenal benefit (see below) |
| 6 | Consider Finerenone if albuminuria persists despite maximally tolerated ACE-I/ARB (see below) |
SGLT2 Inhibitors in Diabetic Hypertension
| Drug | BP Effect | Key CV/Renal Evidence |
| π Empagliflozin 10 mg OD | ↓ 3β5 mmHg SBP | EMPA-REG OUTCOME: ↓ CV death; ↓ HF hospitalisation; ↓ renal progression |
| π Dapagliflozin 10 mg OD | ↓ 3β5 mmHg SBP | DECLARE-TIMI 58: ↓ HF hospitalisation. DAPA-HF: ↓ CV death/HF. DAPA-CKD: ↓ renal progression |
| π Canagliflozin 100 mg OD | ↓ 3β5 mmHg SBP | CANVAS: ↓ MACE. CREDENCE: ↓ renal progression |
π SGLT2 inhibitors are now considered foundational therapy in T2DM with HTN, particularly if co-existing CVD, HF, or CKD.
Finerenone in Diabetic Kidney Disease
- π Finerenone 10β20 mg OD β non-steroidal MRA
- Indicated for DKD with persistent albuminuria despite maximal ACE-I/ARB
- FIDELIO-DKD: 18% reduction in renal composite endpoint
- FIGARO-DKD: 13% reduction in CV composite endpoint
- β οΈ Monitor KβΊ closely; do not initiate if KβΊ > 5.0 mmol/L
8.2 HYPERTENSION IN CHRONIC KIDNEY DISEASE
BP Targets in CKD
| Guideline | Target | Notes |
| KDIGO 2021 | < 120 mmHg SBP (if tolerated) | Based on SPRINT; requires standardised office measurement |
| Practical target | < 130/80 mmHg | Especially if proteinuria present |
| Conservative | < 140/90 mmHg | If intolerant to lower targets |
Drug Selection by CKD Stage
| eGFR (mL/min/1.73m²) | ACE-I/ARB | Diuretic | CCB | Notes |
| > 45 | β First-line | Thiazide-like β | β | Standard approach |
| 30β44 | β (monitor KβΊ, Cr) | Thiazide-like still effective | β | More frequent monitoring |
| 15β29 | β (with caution) | Loop diuretic (thiazides less effective) | β | Close monitoring |
| < 15 / Dialysis | Variable; often held | Loop diuretic | β | Individualise |
SGLT2 Inhibitors in CKD (With or Without Diabetes)
| Drug | Evidence | Indication |
| π Dapagliflozin 10 mg OD | DAPA-CKD: 39% reduction in renal composite; benefit regardless of diabetes status | eGFR 20β90 + UACR ≥ 200 mg/g |
| π Empagliflozin 10 mg OD | EMPA-KIDNEY: 28% reduction in renal progression; includes non-diabetic CKD | eGFR 20β90 (with or without albuminuria) |
Key points:
- β Can be initiated down to eGFR 20 mL/min/1.73m²
- β Continue even if eGFR falls below 20 (unless dialysis or transplant)
- β οΈ Expected initial eGFR dip of 3β5 mL/min (haemodynamic; not harmful; recovers)
- β οΈ Risk of genital mycotic infections; counsel on hygiene
- β οΈ May cause volume depletion β consider reducing diuretic dose
π SGLT2 inhibitors are now considered foundational therapy in CKD with significant albuminuria, alongside ACE-I/ARB, regardless of diabetes status.
Monitoring ACE-I/ARB in CKD
| When | What to Check | Action |
| Baseline | Cr, KβΊ | Document |
| 1β2 weeks after starting or uptitrating | Cr, KβΊ | If Cr ↑ ≤ 30% and stable → continue. If Cr ↑ > 30% or KβΊ > 5.5 → hold and investigate |
| Stable | Every 3β6 months | Ongoing monitoring |
When to Refer to Nephrology
- eGFR < 30 (CKD Stage 4β5)
- Rapid eGFR decline (> 5 mL/min/year)
- Significant proteinuria (ACR > 300 mg/g)
- Refractory hyperkalaemia
- Suspected renovascular disease
- Uncertain aetiology of CKD
8.3 HYPERTENSION IN THE ELDERLY (≥ 65 YEARS)
Key Considerations
| Issue | Implication |
| White coat HTN common | Confirm with HBPM/ABPM before treatment |
| Isolated Systolic HTN predominates | Treat based on SBP; CCB/Thiazide most effective |
| Orthostatic hypotension | Check standing BP before and after starting treatment |
| Polypharmacy | Review interactions; simplify regimen |
| Frailty | Individualise targets; function over numbers |
| Falls risk | Avoid excessive lowering; caution with alpha-blockers |
BP Targets
| Age | Target | Notes |
| 65β79 years | < 140/90 (< 130/80 if tolerated) | Individualise based on fitness |
| ≥ 80 years | < 150/90 (< 140/90 if fit) | HYVET trial |
| Frail elderly | Individualise | Prioritise functional status over numerical targets |
Drug Selection
| Preferred | Notes |
| CCB (Amlodipine) | Effective for ISH; well-tolerated |
| Thiazide-like (Indapamide, Chlorthalidone) | Effective; watch for hyponatraemia |
| ACE-I / ARB | If CKD, DM, or HF |
| Use with Caution | Reason |
| Beta-blockers (unless CAD/HF) | Less effective for ISH |
| Alpha-blockers | Orthostatic hypotension; falls |
| High-dose diuretics | Volume depletion; electrolyte disturbance |
Practical Principles
- Start low, go slow
- Check orthostatic BP before and after starting/changing therapy
- Monitor for hyponatraemia, especially with thiazides
- Avoid DBP < 70 mmHg (J-curve risk)
- Use SPCs to reduce pill burden
- Reassess targets periodically β goals may change with increasing frailty
8.4 HYPERTENSION IN PREGNANCY
Classification
| Type | Definition |
| Chronic HTN | HTN present before pregnancy or diagnosed before 20 weeks |
| Gestational HTN | New HTN after 20 weeks WITHOUT proteinuria or end-organ dysfunction |
| Preeclampsia | New HTN after 20 weeks WITH proteinuria (≥ 300 mg/24h or ACR ≥ 30 mg/mmol) OR end-organ dysfunction |
| Eclampsia | Preeclampsia + seizures |
| Chronic HTN + Superimposed Preeclampsia | Chronic HTN with new/worsening proteinuria or end-organ features |
| HELLP Syndrome | Haemolysis + Elevated Liver enzymes + Low Platelets |
Preeclampsia β End-Organ Features
| Organ | Features |
| Renal | Proteinuria ≥ 300 mg/24h; Cr > 1.1 mg/dL |
| Hepatic | Transaminases > 2× ULN; RUQ/epigastric pain |
| Neurological | Severe headache; visual disturbances; altered mental status; seizures |
| Haematological | Platelets < 100,000; haemolysis (HELLP) |
| Fetal | IUGR; oligohydramnios |
BP Targets in Pregnancy
| Scenario | Target |
| Chronic / Gestational HTN | < 140/90 mmHg |
| Severe HTN (≥ 160/110) | < 160/110 mmHg urgently |
| Lower limit | Do NOT lower below 110/70 mmHg (uteroplacental perfusion) |
Safe Antihypertensives in Pregnancy
| Drug | Dose | Notes |
| π Methyldopa | 250β500 mg BDβTID (max 3 g/day) | First-line; longest safety record; may cause sedation, depression |
| π Labetalol | 100β400 mg BDβTID (max 2.4 g/day) | First-line; avoid in asthma |
| π Nifedipine ER | 30β60 mg OD (max 120 mg/day) | Safe; extended-release formulation only |
| π Hydralazine | 25β50 mg TIDβQID | Add-on; reflex tachycardia |
Contraindicated in Pregnancy
| β Drug | Reason |
| ACE-I | Fetal renal dysgenesis, oligohydramnios, IUGR, neonatal renal failure |
| ARB | Same teratogenic risks as ACE-I |
| ARNI | Contains ARB component |
| MRA (Spironolactone, Eplerenone) | Anti-androgen effects on fetus |
| Atenolol | IUGR, neonatal bradycardia |
| Nitroprusside | Fetal cyanide toxicity |
Postpartum Considerations
- BP may rise in the first 3β5 days postpartum β monitor closely
- Can switch to ACE-I, ARB, CCB, most beta-blockers (safe in breastfeeding)
- Avoid Atenolol if breastfeeding (concentrated in breast milk)
- Methyldopa may worsen postpartum depression β consider switching
- Monitor for postpartum preeclampsia (can occur up to 6 weeks after delivery)
Preeclampsia Prevention
| High-Risk Women | Recommendation |
| Prior preeclampsia, chronic HTN, DM, CKD, autoimmune disease, multiple gestation | π Low-dose Aspirin 75β150 mg OD, started at ≤ 16 weeks gestation (ideally by 12 weeks for maximum benefit), continued until 36 weeks |
8.5 RESISTANT AND REFRACTORY HYPERTENSION
Definitions
| Term | Definition |
| Resistant HTN | BP above target despite ≥ 3 drugs at optimal doses, including a diuretic |
| Controlled Resistant HTN | BP at target but requiring ≥ 4 drugs |
| Refractory HTN | BP above target despite ≥ 5 drugs at optimal doses, including chlorthalidone and spironolactone |
Prevalence
- Resistant HTN: 10β15% of treated hypertensives
- Refractory HTN: ~5% of resistant HTN cases
Exclude Pseudo-Resistance Before Diagnosing
| Cause | How to Address |
| Non-adherence | Pill counts, pharmacy refill records, directly observed therapy, drug levels |
| White coat effect | ABPM or HBPM |
| Improper BP measurement | Verify technique, cuff size |
| Suboptimal doses | Review; uptitrate to maximum tolerated |
| Inadequate diuretic | Switch HCTZ to Chlorthalidone or Indapamide |
| Interfering drugs | NSAIDs, corticosteroids, OCP, decongestants, liquorice |
| Excess salt or alcohol intake | Dietary assessment |
Causes of True Resistant HTN
| Primary | Secondary (Screen For) |
| Advanced vascular disease | Primary aldosteronism (most common secondary cause in resistant HTN) |
| Obstructive sleep apnoea | |
| Renal artery stenosis | |
| CKD | |
| Phaeochromocytoma | |
| Cushing syndrome |
Management of Confirmed Resistant HTN
| Step | Action |
| 1 | Confirm true resistance (adherence, ABPM, technique, interfering drugs) |
| 2 | Optimise diuretic: Chlorthalidone 25 mg or Indapamide 2.5 mg |
| 3 | Screen for primary aldosteronism (ARR) and OSA (STOP-BANG) |
| 4 | Add π Spironolactone 25β50 mg OD as 4th drug |
| 5 | If spironolactone not tolerated: π Eplerenone 50 mg OD, OR π Amiloride 10β20 mg OD, OR π Bisoprolol 5β10 mg OD |
| 6 | Specialist referral if uncontrolled on 4 drugs |
| 7 | Consider renal denervation in selected cases at specialised centres |
π¬ PATHWAY-2 trial: Spironolactone was the most effective 4th-line agent for resistant HTN, reducing SBP by an additional 8β10 mmHg compared to placebo, bisoprolol, and doxazosin.
Fourth-Line Drug Options
| Drug | Dose | Evidence Level | Key Consideration |
| π Spironolactone | 25β50 mg OD | β β Strongest (PATHWAY-2) | Gynecomastia; monitor KβΊ |
| π Eplerenone | 50 mg OD | β Good | Less gynecomastia; more expensive |
| π Amiloride | 10β20 mg OD | β Moderate | KβΊ-sparing |
| π Bisoprolol | 5β10 mg OD | β Moderate | If not already on beta-blocker |
| π Doxazosin | 4β8 mg OD (bedtime) | β Moderate | Orthostatic hypotension |
| π Clonidine | 0.1β0.3 mg BD | β οΈ Limited | Rebound HTN on withdrawal |
Refractory Hypertension
- Mandatory specialist referral
- Confirm adherence with supervised drug intake or drug levels
- Re-evaluate for rare secondary causes
- Consider renal denervation (selected cases; specialised centres)
- Consider bariatric surgery referral if obese
Renal Denervation
- Sham-controlled trials (SPYRAL HTN-ON MED, RADIANCE-HTN TRIO, RADIANCE II) demonstrate SBP reduction of 4β9 mmHg
- Not first-line; reserve for confirmed resistant/refractory HTN or documented persistent non-adherence
- Available only at select specialised centres
- Long-term (> 5 year) durability data still emerging
SECTION 9: MONITORING AND FOLLOW-UP
9.1 FOLLOW-UP SCHEDULE
| Phase | Frequency | Purpose |
| Initial (titration) | Every 2β4 weeks | Adjust drugs until BP at target |
| Newly at target | Every 3 months × 2 visits | Confirm stability |
| Stable | Every 3β6 months | Maintain control; adherence; side effects |
| Annual | Yearly | Comprehensive review; labs; CV risk reassessment |
9.2 PARAMETERS AT EACH VISIT
| Parameter | Action |
| Blood pressure | Office BP (proper technique); review home BP log if available |
| Symptoms | Side effects? New symptoms? |
| Adherence | Non-judgemental assessment |
| Lifestyle | Salt, weight, exercise, alcohol, smoking |
| Medications | Any changes? New prescriptions? OTC drugs (especially NSAIDs)? |
9.3 PERIODIC INVESTIGATIONS
Routine Monitoring
| Test | Frequency | Notes |
| Creatinine, eGFR | Every 6β12 months | Renal function |
| KβΊ, NaβΊ | Every 6β12 months | Drug effects (diuretics, ACE-I/ARB, MRA) |
| Fasting glucose / HbA1c | Annually | Diabetes screening |
| Lipid profile | Annually | CV risk assessment |
| Urine ACR | Annually | Nephropathy screening |
| ECG | Every 1β2 years | LVH, arrhythmia |
| Body weight / BMI | Every visit | Weight management tracking |
Accelerated Monitoring
| Situation | What to Check | When |
| Starting or uptitrating ACE-I/ARB | Cr, KβΊ | 1β2 weeks |
| Starting or uptitrating diuretic | KβΊ, NaβΊ, Cr | 1β4 weeks |
| Starting or uptitrating MRA | KβΊ, Cr | 1 week, then 4 weeks |
| CKD Stage 3β5 | Cr, KβΊ, eGFR | More frequently per CKD stage |
| Elderly on thiazides | NaβΊ | 1β2 weeks after starting; periodically |
9.4 WHEN TO REFER
To Hypertension Specialist / Cardiologist
- Resistant HTN (uncontrolled on ≥ 3 drugs including diuretic)
- Suspected secondary HTN
- Hypertensive emergency requiring ICU management
- Complex comorbidities (HF, advanced CKD, multiple CV events)
- Young-onset HTN (< 30 years)
To Nephrologist
- CKD Stage 4β5 (eGFR < 30)
- Rapidly declining eGFR (> 5 mL/min/year)
- Significant proteinuria (ACR > 300 mg/g)
- Suspected renovascular disease
- Refractory hyperkalaemia
To Endocrinologist
- Suspected primary aldosteronism (for confirmation and subtyping)
- Phaeochromocytoma
- Cushing syndrome
- Acromegaly
To Sleep Specialist
- Suspected OSA (loud snoring, witnessed apnoeas, daytime somnolence)
- Resistant HTN with elevated STOP-BANG score
To Obstetrician (High-Risk)
- Pregnancy with hypertension (any classification)
- Preeclampsia or HELLP syndrome
SECTION 10: QUICK REFERENCE TABLES
10.1 BP TARGETS
| Population | Target |
| General < 65 years | < 130/80 |
| General 65β79 years | < 140/90 (< 130/80 if tolerated) |
| ≥ 80 years | < 150/90 (< 140/90 if fit) |
| Diabetes | < 130/80 |
| CKD | < 130/80 (< 120 SBP if tolerated) |
| CAD | < 130/80 (DBP > 60β70) |
| Post-Stroke | < 130/80 |
| Heart Failure | < 130/80 |
| Pregnancy | < 140/90 (> 110/70) |
10.2 DRUG SELECTION
| Situation | First Choice |
| Age < 55, no comorbidity | ACE-I or ARB |
| Age ≥ 55 or Black/African ethnicity, no comorbidity | CCB or Thiazide-like |
| Diabetes | ACE-I or ARB |
| CKD with proteinuria | ACE-I or ARB |
| Heart Failure (HFrEF) | ACE-I/ARB → ARNI + BB + MRA + SGLT2i |
| Post-MI | ACE-I + BB |
| CAD (stable) | ACE-I + BB (± CCB) |
| Pregnancy | Methyldopa or Labetalol or Nifedipine ER |
| Resistant HTN (4th drug) | Spironolactone |
10.3 COMBINATIONS
| β Recommended | β Avoid |
| ACE-I/ARB + CCB | ACE-I + ARB |
| ACE-I/ARB + Thiazide-like | Non-DHP CCB + BB |
| CCB + Thiazide-like | Two drugs from same class |
| Triple: ACE-I/ARB + CCB + Thiazide-like | ACE-I/ARB + Aliskiren |
10.4 EMERGENCY DRUG SELECTION
| Scenario | First-Line IV Drug | Target |
| Aortic Dissection | Esmolol or Labetalol | SBP < 120, HR < 60 |
| ACS | Nitroglycerin | Gradual reduction; DBP > 60 |
| Pulmonary Oedema | Nitroglycerin + Furosemide | Gradual reduction |
| Encephalopathy | Nicardipine or Labetalol | ↓ MAP 20β25% in 1β2 hrs |
| ICH (SBP 150β220) | Nicardipine or Labetalol | SBP ~140 within 1 hr |
| Eclampsia | Labetalol or Hydralazine + MgSOβ | < 160/110 |
| Phaeochromocytoma | Phentolamine | Gradual reduction |
| Cocaine/Amphetamine | Phentolamine or Nicardipine + Benzodiazepine | Gradual reduction |
10.5 NEVER / ALWAYS TABLE
| β NEVER | β ALWAYS |
| Combine ACE-I + ARB | Check Cr and KβΊ after starting ACE-I/ARB |
| Use sublingual Nifedipine for BP lowering | Use appropriate cuff size for BP measurement |
| Give vasodilators before BB in aortic dissection | Control HR before BP in aortic dissection |
| Lower BP too rapidly in chronic hypertensives | Reduce gradually (20β25% MAP in first hour for emergencies) |
| Use ACE-I/ARB/ARNI in pregnancy | Use Methyldopa, Labetalol, or Nifedipine ER in pregnancy |
| Combine Non-DHP CCB + BB | Choose one or the other |
| Ignore orthostatic hypotension in elderly | Check standing BP in elderly before and after treatment changes |
| Use thiazides if eGFR < 30 | Switch to loop diuretics in advanced CKD |
| Assume non-adherence without checking | Confirm adherence before adding drugs or diagnosing resistance |
| Forget to ask about NSAIDs | Ask about OTC analgesic use at every visit |
| Use aspirin for primary prevention in HTN | Reserve aspirin for secondary prevention (established CVD only) |
| Use immediate-release Nifedipine for HTN | Use only extended-release formulations for chronic BP management |
ABBREVIATIONS
| Abbreviation | Full Form |
| ABPM | Ambulatory Blood Pressure Monitoring |
| ABI | Ankle-Brachial Index |
| ACE-I | Angiotensin-Converting Enzyme Inhibitor |
| ACR | Albumin-to-Creatinine Ratio |
| ACS | Acute Coronary Syndrome |
| AKI | Acute Kidney Injury |
| ARB | Angiotensin Receptor Blocker |
| ARNI | Angiotensin Receptor-Neprilysin Inhibitor |
| ARR | Aldosterone-to-Renin Ratio |
| BB | Beta-Blocker |
| BNP | B-type Natriuretic Peptide |
| BP | Blood Pressure |
| BPH | Benign Prostatic Hyperplasia |
| CABG | Coronary Artery Bypass Grafting |
| CAD | Coronary Artery Disease |
| CCB | Calcium Channel Blocker |
| CKD | Chronic Kidney Disease |
| COPD | Chronic Obstructive Pulmonary Disease |
| CV | Cardiovascular |
| CVD | Cardiovascular Disease |
| CXR | Chest X-Ray |
| CT | Computed Tomography |
| DBP | Diastolic Blood Pressure |
| DHP | Dihydropyridine |
| DKD | Diabetic Kidney Disease |
| DM | Diabetes Mellitus |
| ECG | Electrocardiogram |
| eGFR | Estimated Glomerular Filtration Rate |
| ESKD | End-Stage Kidney Disease |
| GDMT | Guideline-Directed Medical Therapy |
| GCS | Glasgow Coma Scale |
| HBPM | Home Blood Pressure Monitoring |
| HELLP | Haemolysis, Elevated Liver enzymes, Low Platelets |
| HF | Heart Failure |
| HFpEF | Heart Failure with Preserved Ejection Fraction |
| HFrEF | Heart Failure with Reduced Ejection Fraction |
| HMOD | Hypertension-Mediated Organ Damage |
| HTN | Hypertension |
| HCTZ | Hydrochlorothiazide |
| HR | Heart Rate |
| ICH | Intracerebral Haemorrhage |
| ICP | Intracranial Pressure |
| IMT | Intima-Media Thickness |
| ISH | Isolated Systolic Hypertension |
| IUGR | Intrauterine Growth Restriction |
| IV | Intravenous |
| JVP | Jugular Venous Pressure |
| LVH | Left Ventricular Hypertrophy |
| LVMI | Left Ventricular Mass Index |
| MAHA | Microangiopathic Haemolytic Anaemia |
| MAP | Mean Arterial Pressure |
| MI | Myocardial Infarction |
| MRA | Mineralocorticoid Receptor Antagonist |
| MRI | Magnetic Resonance Imaging |
| NIV | Non-Invasive Ventilation |
| Non-DHP | Non-Dihydropyridine |
| NSAID | Non-Steroidal Anti-Inflammatory Drug |
| OCP | Oral Contraceptive Pills |
| OD | Once Daily |
| BD | Twice Daily |
| TID | Three Times Daily |
| QID | Four Times Daily |
| OSA | Obstructive Sleep Apnoea |
| OTC | Over-The-Counter |
| PAD | Peripheral Artery Disease |
| PCI | Percutaneous Coronary Intervention |
| PDE5 | Phosphodiesterase Type 5 |
| PO | Per Oral |
| PRES | Posterior Reversible Encephalopathy Syndrome |
| PWV | Pulse Wave Velocity |
| RAS | Renal Artery Stenosis |
| RF | Risk Factor |
| SBP | Systolic Blood Pressure |
| SGLT2i | Sodium-Glucose Cotransporter-2 Inhibitor |
| SPC | Single-Pill Combination |
| T2DM | Type 2 Diabetes Mellitus |
| TIA | Transient Ischaemic Attack |
| UACR | Urine Albumin-to-Creatinine Ratio |
| ULN | Upper Limit of Normal |
REFERENCES
| Source | Year |
| ESC/ESH Guidelines for the Management of Arterial Hypertension | 2018 (with 2023 focused update) |
| ESC Guidelines on Elevated Blood Pressure and Hypertension | 2024 |
| ISH Global Hypertension Practice Guidelines | 2020 |
| ACC/AHA High Blood Pressure Clinical Practice Guideline | 2017 |
| NICE Hypertension in Adults: Diagnosis and Management (NG136) | 2022 (updated) |
| KDIGO Clinical Practice Guideline for Blood Pressure Management in CKD | 2021 |
| SPRINT Trial (Systolic Blood Pressure Intervention Trial) | 2015 |
| ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes β Blood Pressure) | 2010 |
| PATHWAY-2 (Prevention and Treatment of Hypertension With Algorithm-based Therapy) | 2015 |
| PARADIGM-HF (Sacubitril/Valsartan in Heart Failure) | 2014 |
| DAPA-CKD (Dapagliflozin in CKD) | 2020 |
| EMPA-KIDNEY (Empagliflozin in CKD) | 2022 |
| FIDELIO-DKD (Finerenone in Diabetic Kidney Disease) | 2020 |
| FIGARO-DKD (Finerenone in Diabetic Kidney Disease β CV Outcomes) | 2021 |
| HOPE Trial (Heart Outcomes Prevention Evaluation) | 2000 |
| PROGRESS Trial (Perindopril Protection Against Recurrent Stroke Study) | 2001 |
| HYVET Trial (Hypertension in the Very Elderly Trial) | 2008 |
| ACCOMPLISH Trial (Avoiding Cardiovascular Events in Combination Therapy) | 2008 |
| INTERACT2 (Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial) | 2013 |
| ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage) | 2016 |
| DCP Trial (Diuretic Comparison Project) | 2022 |
| ONTARGET (Telmisartan, Ramipril, or Both in Patients at High Risk) | 2008 |
| ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) | 2018 |
| ASPREE (Aspirin in Reducing Events in the Elderly) | 2018 |
| SPYRAL HTN-ON MED (Renal Denervation) | 2020 |
| RADIANCE-HTN TRIO (Renal Denervation in Resistant HTN) | 2022 |
| API Textbook of Medicine | 11th Edition |
| Harrisonβs Principles of Internal Medicine | 21st Edition |
For Healthcare Professionals Only
Disclaimer: This guideline provides evidence-based recommendations for clinical decision-making. Individual clinical judgement must be exercised for each patient. Local protocols, drug availability, and patient-specific factors should guide management. Always verify doses and indications before prescribing.
End of Guideline
π‘οΈ
Medical Advisory
Clinical guidelines are subject to change. Physicians should exercise their regular clinical judgment. This protocol does not replace individual institutional policies. Verified for Q1 2026.
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