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Hypertension (High Blood Pressure) – 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

SYMBOL LEGEND

Symbol Meaning
βœ… Recommended / First-line / Strong evidence
⚠️ Use with caution / Monitor closely / Conditional
❌ Contraindicated / Avoid
πŸ’Š Drug name
πŸ“Œ Clinical pearl / Key point
πŸ”¬ Evidence-based recommendation
⏱️ Time-critical action
🚨 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 120–129 and/or 80–84
High Normal 130–139 and/or 85–89
Grade 1 HTN (Mild) 140–159 and/or 90–99
Grade 2 HTN (Moderate) 160–179 and/or 100–109
Grade 3 HTN (Severe) ≥ 180 and/or ≥ 110
Isolated Systolic HTN ≥ 140 and < 90
πŸ“Œ 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
22–26 cm Small adult (12 × 22 cm)
27–34 cm Standard adult (16 × 30 cm)
35–44 cm Large adult (16 × 36 cm)
45–52 cm Adult thigh cuff (16 × 42 cm)
πŸ“Œ Incorrect cuff size is the most common source of measurement error. A cuff that is too small overestimates BP by 5–15 mmHg. A cuff that is too large underestimates BP by 3–10 mmHg.
Measurement Protocol
  • Place cuff bladder centre over brachial artery
  • Lower edge of cuff 2–3 cm above antecubital fossa
  • Take ≥ 2 readings, 1–2 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
πŸ“Œ 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
πŸ“Œ White coat hypertension has a prevalence of 15–30% among patients with elevated office BP. These patients should not be labelled hypertensive or started on drug therapy based on office readings alone.
πŸ“Œ 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 10–20% decline
Non-dipper 0–10% 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”‚
β”Œβ”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”΄β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”
β”‚ β”‚
GRADE 2–3 HTN GRADE 1 HTN
(≥ 160/100) OR (140–159/90–99)
evidence of HMOD β”‚
β”‚ β”‚
β–Ό β–Ό
Confirm with repeat Offer ABPM or HBPM
same-visit reading to confirm diagnosis
→ Diagnosis confirmed β”‚
→ Start treatment β”Œβ”€β”€β”€β”€β”€β”΄β”€β”€β”€β”€β”€β”
β”‚ β”‚
ABPM/HBPM ABPM/HBPM
confirms does NOT
(≥ 135/85) confirm
β”‚ β”‚
β–Ό β–Ό
Diagnosis White Coat HTN
confirmed → Lifestyle
→ Treat → Annual
monitoring
Number of Readings Required
Scenario Readings Required
Grade 2–3 HTN (≥ 160/100) Confirm with second reading same visit; can diagnose same day
Grade 1 HTN (140–159/90–99) 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 + Na⁺ 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 ↑ Na⁺ 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
πŸ”¬ 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; 100–125 = prediabetes
HbA1c Diabetes screening/control ≥ 6.5% = DM; 5.7–6.4% = 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 Na⁺, K⁺ Baseline electrolytes; secondary HTN clues K⁺ < 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
πŸ“Œ 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 2–3 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 (K⁺ < 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, ”3β€œ 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/e’ 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 30–59 (CKD Stage 3) Serum creatinine calculation
Microalbuminuria (ACR 30–300 mg/g) Spot urine ACR
Eye Retinopathy (Grade III–IV) 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 4–5 (eGFR < 30), ESKD, Transplant
Retinal Advanced retinopathy (Grade III–IV)
Aortic Aneurysm, Prior dissection

3.3 RISK STRATIFICATION MATRIX

BP Category No Other RF 1–2 RF ≥ 3 RF HMOD, CKD 3, or DM without HMOD CVD, CKD ≥ 4, or DM with HMOD
High Normal (130–139/85–89) Low Low Low–Mod Mod–High Very High
Grade 1 (140–159/90–99) Low Mod Mod–High High Very High
Grade 2 (160–179/100–109) Mod Mod–High 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 5–10% Lifestyle + consider drug
High 10–20% 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
πŸ“Œ 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

πŸ”¬ 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 65–79 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 70–80 DBP > 60–70 J-curve concern
Heart Failure < 130 < 80 Tolerate SBP 100–110 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


πŸ“Œ 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) 5–6 mmHg
Dietary pattern (DASH-style) Rich in fruits, vegetables, whole grains, low-fat dairy; low in saturated fat 8–14 mmHg
Potassium intake Increase dietary potassium to 3.5–5 g/day (fruits, vegetables); avoid supplements if on ACE-I/ARB/MRA 2–4 mmHg
Weight loss Target BMI 18.5–22.9 (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 4–9 mmHg
Resistance exercise 2–3 days/week, moderate intensity 2–4 mmHg
Alcohol reduction ≤ 2 standard drinks/day (men); ≤ 1 standard drink/day (women) 2–4 mmHg
Smoking cessation Complete cessation of all tobacco Minimal direct BP effect; major CV risk reduction
Stress management Meditation, yoga, relaxation techniques Variable
πŸ“Œ Combined lifestyle modifications can reduce SBP by 10–20 mmHg β€” equivalent to one antihypertensive drug.
πŸ“Œ 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 Low–Moderate CV Risk High CV Risk (or DM, CKD, CVD, HMOD)
High Normal (130–139/85–89) Lifestyle only Consider drugs (especially if CAD, DM with HMOD, HFrEF)
Grade 1 (140–159/90–99) Lifestyle × 3–6 months → Drug if not controlled Lifestyle + Drug immediately
Grade 2 (160–179/100–109) 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 (140–159/90–99) AND
  • Low–moderate CV risk AND
  • No diabetes, CKD, CVD, or HMOD AND
  • Patient is motivated and close follow-up is possible
  • Duration: 3–6 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 AT₁ receptor Like ACE-I but no cough
CCBs (DHP) C Amlodipine, Cilnidipine, Nifedipine ER Block L-type Ca²βΊ channels Potent; metabolically neutral
Thiazide-like Diuretics D Chlorthalidone, Indapamide Inhibit Na-Cl cotransporter Volume control; inexpensive
πŸ”¬ 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 5–20% Rare No No
Peripheral oedema No No Yes No
Hypokalaemia No (↑ K⁺) No (↑ K⁺) No Yes

6.3 INITIAL DRUG SELECTION

Age/Ethnicity-Based Selection (No Compelling Indication)
NO COMPELLING INDICATION
β”‚
β”Œβ”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”΄β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”
β”‚ β”‚
AGE < 55 YEARS AGE ≥ 55 YEARS
β”‚ or Black/African
β”‚ ethnicity
β–Ό β–Ό
β”Œβ”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β” β”Œβ”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”
β”‚ ACE-I β”‚ β”‚ CCB β”‚
β”‚ or β”‚ β”‚ or β”‚
β”‚ ARB β”‚ β”‚Thiazide β”‚
β””β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”˜ β””β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”˜

6.4 COMPELLING INDICATIONS β€” MASTER TABLE

Condition βœ… Preferred ⚠️ Caution ❌ Avoid
Diabetes (no albuminuria) ACE-I/ARB High-dose thiazide β€”
DM + Albuminuria ACE-I/ARB (mandatory) β€” β€”
CKD ACE-I/ARB Monitor K⁺, 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 Ca²βΊ) 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 (K⁺ > 5.5) CCB, Thiazide β€” ACE-I, ARB, MRA (until K⁺ 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)
  • ❌ Never combine ARNI with ACE-I; 36-hour washout required when switching from ACE-I to ARNI
CAD / Post-MI:
  • ⚠️ J-curve: Keep DBP > 60–70 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

πŸ”¬ Evidence:
  • Monotherapy controls BP in only 30–50% 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 20–30%
When to Use Monotherapy
  • Grade 1 HTN (140–159/90–99) 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 2–3 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 βœ… Preferred for most patients Reduces CCB-induced oedema; metabolically neutral; strong evidence (ACCOMPLISH)
ACE-I/ARB + Thiazide-like βœ… Preferred Good for volume-related HTN; HF
CCB + Thiazide-like βœ… Acceptable When ACE-I/ARB intolerant
CCB + BB βœ… Acceptable Especially if tachycardia or angina
BB + Diuretic ⚠️ Limited use HF or post-MI; not first-line for uncomplicated HTN
Combinations to AVOID
❌ 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 4–6 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:
  1. Rule out pseudo-resistance (adherence, white coat, measurement error, interfering drugs)
  2. Optimise diuretic: switch to Chlorthalidone 25 mg or Indapamide 2.5 mg
  3. Screen for secondary causes (especially primary aldosteronism, OSA)
  4. Add Spironolactone 25–50 mg as 4th drug (PATHWAY-2)
  5. 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”‚
β–Ό
β”Œβ”€β”€β”€β”€β”€β”€β”€β”€β”€ COMPELLING INDICATION? ─────────┐
β”‚ β”‚
YES NO
β”‚ β”‚
β–Ό β–Ό
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”‚
β””β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”¬β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”˜
β”‚
β–Ό
β”Œβ”€β”€β”€β”€β”€β”€ GRADE & RISK? ──────┐
β”‚ β”‚
Grade 1 + Low Risk Grade 2-3 or High Risk
β”‚ β”‚
β–Ό β–Ό
MONOTHERAPY DUAL COMBINATION
(ACE-I/ARB or CCB) (ACE-I/ARB + CCB preferred)
β”‚ β”‚
β””β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”¬β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”˜
β”‚
β–Ό
REASSESS 4–6 WEEKS
β”‚
β”Œβ”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”΄β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”
β”‚ β”‚
AT TARGET NOT AT TARGET
β”‚ β”‚
β–Ό β–Ό
Continue; UPTITRATE or ADD DRUG
F/U 3–6 months β”‚
β”Œβ”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”΄β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”
β”‚ β”‚
On Monotherapy On Dual Therapy
β”‚ β”‚
β–Ό β–Ό
DUAL THERAPY TRIPLE THERAPY
(ACE-I/ARB + CCB) (ACE-I/ARB + CCB + Thiazide)
β”‚ β”‚
β””β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”¬β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”˜
β”‚
β–Ό
REASSESS 4–6 WEEKS
β”‚
β”Œβ”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”΄β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”
β”‚ β”‚
AT TARGET NOT AT TARGET
β”‚ β”‚
β–Ό β–Ό
Continue RESISTANT HTN WORKUP
β”‚
β–Ό
β€’ Confirm adherence
β€’ ABPM (rule out white coat)
β€’ Screen secondary causes
β€’ Optimise diuretic
β”‚
β–Ό
ADD SPIRONOLACTONE 25–50 mg
β”‚
β–Ό
REASSESS 4–6 WEEKS
β”‚
β”Œβ”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”΄β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”€β”
β”‚ β”‚
AT TARGET NOT AT TARGET
β”‚ β”‚
β–Ό β–Ό
Continue SPECIALIST REFERRAL

6.8 DRUG DOSING β€” COMPLETE REFERENCE

ACE Inhibitors
Drug Starting Dose Target Dose Maximum Dose Frequency Notes
πŸ’Š Ramipril 2.5 mg 10 mg 10 mg OD Most evidence (HOPE trial); preferred
πŸ’Š Perindopril erbumine 4 mg 8 mg 8 mg OD EUROPA, ADVANCE. Note: Perindopril arginine 5 mg ≈ erbumine 4 mg
πŸ’Š Enalapril 5 mg 20 mg 40 mg BD BD dosing usually required for 24-hour coverage
πŸ’Š Lisinopril 5 mg 20–40 mg 40 mg OD No hepatic metabolism
Class side effects:
  • Dry cough (5–20%; higher in Asians) → switch to ARB
  • Hyperkalaemia → monitor K⁺
  • Angioedema (rare but serious) → discontinue permanently; avoid rechallenge
  • First-dose hypotension → start low in elderly, volume-depleted patients
  • AKI → check creatinine at 1–2 weeks after initiation
ARBs
Drug Starting Dose Target Dose Maximum Dose Frequency Notes
πŸ’Š Telmisartan 40 mg 80 mg 80 mg OD Longest half-life (24 hrs); PPARγ activity; metabolically neutral
πŸ’Š Olmesartan 20 mg 40 mg 40 mg OD Potent BP reduction
πŸ’Š Azilsartan 40 mg 80 mg 80 mg OD Most potent ARB in head-to-head comparisons
πŸ’Š Losartan 50 mg 100 mg 100 mg OD Unique uricosuric effect; shortest half-life
πŸ’Š Valsartan 80 mg 160–320 mg 320 mg OD Strong HF evidence (Val-HeFT)
πŸ’Š Candesartan 8 mg 32 mg 32 mg OD Strong HF evidence (CHARM)
πŸ“Œ 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
πŸ’Š Sacubitril/Valsartan 24/26 mg 97/103 mg 97/103 mg BD Preferred over ACE-I/ARB in HFrEF (PARADIGM-HF)
Key prescribing rules:
  • βœ… Indicated for HFrEF; replaces ACE-I/ARB once patient is stable
  • βœ… Potent antihypertensive effect
  • ❌ Never combine with ACE-I (risk of angioedema)
  • ⚠️ Requires 36-hour washout after stopping ACE-I before starting ARNI
  • ⚠️ No washout needed when switching from ARB
  • ⚠️ Can cause hypotension β€” start low, uptitrate gradually
  • Monitor K⁺ and renal function as with ACE-I/ARB
CCBs β€” Dihydropyridines
Drug Starting Dose Target Dose Maximum Dose Frequency Notes
πŸ’Š Amlodipine 5 mg 10 mg 10 mg OD Most widely used; ankle oedema common at higher doses
πŸ’Š S-Amlodipine 2.5 mg 5 mg 5 mg OD Purified S-isomer; may have less oedema
πŸ’Š Cilnidipine 10 mg 20 mg 20 mg OD N+L type blockade; less reflex tachycardia, less oedema
πŸ’Š Nifedipine ER 30 mg 60 mg 90 mg OD Extended-release formulation ONLY
πŸ’Š Felodipine 5 mg 10 mg 10 mg OD Alternative
❌ 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
πŸ’Š Diltiazem SR 90 mg 180–240 mg 360 mg OD–BD Rate control in AF; constipation
πŸ’Š Verapamil SR 120 mg 240 mg 480 mg OD–BD Rate control; constipation; negative inotropy
❌ Do NOT combine non-DHP CCBs with beta-blockers (risk of severe bradycardia and heart block).
❌ Avoid Verapamil and Diltiazem in HFrEF (negative inotropy).
Thiazide and Thiazide-like Diuretics
Drug Starting Dose Target Dose Maximum Dose Frequency Notes
πŸ’Š Chlorthalidone 12.5 mg 25 mg 50 mg OD Preferred; longer acting; greater potency per mg
πŸ’Š Indapamide 1.5 mg 2.5 mg 2.5 mg OD Preferred; fewer metabolic effects than other thiazides
πŸ’Š Hydrochlorothiazide 12.5 mg 25 mg 50 mg OD Shorter acting; less potent; widely available
πŸ“Œ 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 K⁺-sparing diuretic
  • Hyponatraemia β€” especially in elderly women; monitor Na⁺ at 1–2 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
πŸ’Š Bisoprolol 2.5–5 mg 10 mg 20 mg OD Cardioselective; HF evidence
πŸ’Š Metoprolol Succinate XL 25–50 mg 200 mg 400 mg OD Extended-release; HF evidence (MERIT-HF)
πŸ’Š Nebivolol 5 mg 10 mg 40 mg OD Vasodilating; less fatigue, less erectile dysfunction
πŸ’Š 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
πŸ’Š Atenolol 25–50 mg 100 mg 100 mg OD Less preferred; inferior stroke prevention (LIFE trial)
πŸ’Š Propranolol 40 mg 160 mg 320 mg BD–TID Non-selective; migraine, tremor, thyrotoxicosis
πŸ’Š Labetalol 100 mg 200–400 mg 1200 mg BD α + β; pregnancy-safe; hypertensive emergencies
πŸ“Œ 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.
πŸ“Œ 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
πŸ’Š Spironolactone 12.5–25 mg 25–50 mg 100 mg OD Best 4th-line agent for resistant HTN (PATHWAY-2); gynecomastia in males
πŸ’Š Eplerenone 25 mg 50 mg 50 mg OD Selective MRA; much less gynecomastia; more expensive
⚠️ Monitor K⁺ closely, especially when combined with ACE-I/ARB. Avoid if K⁺ > 5.0 mmol/L or eGFR < 30.
Non-Steroidal MRA
Drug Starting Dose Target Dose Maximum Dose Frequency Notes
πŸ’Š 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
πŸ’Š Doxazosin 4–8 mg OD (bedtime) Resistant HTN; BPH First-dose hypotension
πŸ’Š Prazosin 1–5 mg BD–TID Resistant HTN; BPH First-dose syncope; start 1 mg at bedtime
πŸ’Š Clonidine 0.1–0.3 mg BD–TID Resistant HTN Rebound HTN on sudden withdrawal
πŸ’Š Methyldopa 250–500 mg BD–TID Pregnancy (first-line) Sedation; depression
πŸ’Š Hydralazine 25–100 mg TID–QID HF; pregnancy; resistant HTN Reflex tachycardia; lupus-like syndrome at high doses
πŸ’Š Minoxidil 5–40 mg OD–BD Severe resistant HTN Hirsutism; fluid retention; pericardial effusion; must combine with BB + diuretic

6.9 DRUG COMBINATIONS β€” SINGLE-PILL COMBINATIONS (SPCs)

πŸ“Œ SPCs improve adherence by 20–30%, 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)
❌ 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)
βœ… Aspirin 75–150 mg OD
⚠️ 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 40–80 mg or Rosuvastatin 20–40 mg)
Diabetes mellitus, age 40–75 Moderate-intensity (Atorvastatin 10–20 mg or Rosuvastatin 5–10 mg); high-intensity if additional risk factors
LDL ≥ 190 mg/dL High-intensity
10-year CV risk > 10%, age 40–75 Moderate-to-high intensity
10-year CV risk 7.5–10% with risk enhancers Consider moderate-intensity
πŸ“Œ South Asian ethnicity is recognised as a cardiovascular risk enhancer; a lower threshold for statin initiation is appropriate.
⚠️ 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 5–20% Switch to ARB
Angioedema < 1% Stop permanently; avoid rechallenge; use ARB with caution
Hyperkalaemia 2–5% Check K⁺; reduce dose; avoid K⁺ supplements
First-dose hypotension Variable Start low; caution in volume-depleted
AKI Variable Check Cr at 1–2 weeks; accept ≤ 30% rise if stable
ARB Similar to ACE-I but cough rare β€” β€”
DHP CCB Ankle oedema 10–25% Add ACE-I/ARB; switch to Cilnidipine; switch class
Headache, flushing 5–10% Usually transient
Gum hyperplasia Rare Dental hygiene; switch
Non-DHP CCB Constipation 10–20% Fibre; switch
Bradycardia Variable Reduce dose; never combine with BB
Thiazides Hypokalaemia 10–40% Combine with ACE-I/ARB or K⁺-sparing agent
Hyponatraemia 5–10% Monitor Na⁺ at 1–2 weeks; reduce dose or switch
Hyperuricaemia/gout 5–10% Losartan; avoid in severe gout
Hyperglycaemia 2–5% Use low doses; prefer Indapamide
BB Fatigue 10–20% Switch to Nebivolol or Carvedilol
Bradycardia Variable Reduce dose; switch
Sexual dysfunction 5–15% Switch to Nebivolol
Bronchospasm Variable Avoid in asthma; generally safe in COPD
Masking of hypoglycaemia β€” Caution in insulin-treated DM
MRA Hyperkalaemia 5–15% Monitor K⁺; reduce dose
Gynecomastia (Spironolactone) 10–20% in males Switch to Eplerenone
Alpha-blockers First-dose hypotension Variable Start low; give at bedtime
Orthostatic hypotension 5–15% Caution in elderly
πŸ“Œ 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
K⁺-sparing diuretics / supplements ↑ Hyperkalaemia Monitor K⁺
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 K⁺
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 ”Triple Whammyβ€œ
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.
πŸ“Œ 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
πŸ“Œ Non-adherence affects 30–50% 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
🚨 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, K⁺
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
⚠️ 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 20–25% OR reduce DBP to 100–110 mmHg
Next 2–6 hours Reduce to approximately 160/100–110 mmHg
Next 24–48 hours Gradual further reduction toward target
Condition-Specific Targets
Condition Target Timeframe Key Notes
Aortic Dissection 🚨
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 150–220
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 140–160 mmHg β€” Aggressive lowering reasonable; limited evidence
Hypertensive Encephalopathy
↓ MAP by 20–25% Over 1–2 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
πŸ’Š Labetalol α + β blocker 20 mg IV bolus; repeat 20–80 mg q10min OR 0.5–2 mg/min infusion 5–10 min 3–6 hrs Most emergencies; Aortic dissection; Eclampsia HF, Asthma, Bradycardia, Heart block
πŸ’Š Nicardipine DHP CCB 5–15 mg/hr infusion 5–15 min 30–40 min Most emergencies; Stroke; Post-operative Severe aortic stenosis
πŸ’Š Nitroglycerin Venodilator (+ coronary vasodilator) 5–200 mcg/min infusion 2–5 min 5–10 min ACS; Pulmonary oedema RV infarct; Concomitant PDE5 inhibitors
πŸ’Š Nitroprusside Arterial + venous dilator 0.25–10 mcg/kg/min infusion Immediate 1–2 min Severe emergency; last resort Prolonged use > 24–48 hrs (cyanide toxicity); hepatic/renal impairment; ↑ ICP. Monitor thiocyanate if > 24 hrs or > 2 mcg/kg/min
πŸ’Š Esmolol Cardioselective ultra-short β-blocker 500 mcg/kg bolus → 50–200 mcg/kg/min infusion 1–2 min 10–20 min Aortic dissection; Perioperative HF, Asthma, Bradycardia
Second-Line / Specific Agents
Drug Mechanism Dose Indication
πŸ’Š Hydralazine Direct vasodilator 10–20 mg IV q4–6h Eclampsia; Pregnancy
πŸ’Š Phentolamine α-blocker 5–15 mg IV bolus Phaeochromocytoma; Cocaine/amphetamine crisis
πŸ’Š Fenoldopam Dopamine-1 agonist 0.1–0.3 mcg/kg/min AKI; Renal protection desired
πŸ’Š Clevidipine Ultra-short DHP CCB 1–16 mg/hr infusion Perioperative
πŸ’Š Enalaprilat IV ACE-I 1.25–5 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

🚨 AORTIC DISSECTION
⏱️ Mortality increases 1–2% per hour if untreated.
Priority Action Details
1 Pain control πŸ’Š Morphine 2–4 mg IV (pain drives sympathetic activation)
2 HR control FIRST
πŸ’Š Esmolol 500 mcg/kg bolus → 50–200 mcg/kg/min OR πŸ’Š Labetalol 20 mg IV bolus → infusion. Target: HR < 60/min
3 Then BP control
Add πŸ’Š Nitroprusside 0.25–0.5 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
❌ NEVER give vasodilators BEFORE beta-blocker in aortic dissection. Reflex tachycardia increases aortic shear stress and propagates the dissection.
🚨 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 πŸ’Š Furosemide 40–80 mg IV + πŸ’Š Nitroglycerin 10–200 mcg/min infusion
4 Afterload reduction πŸ’Š Nitroprusside if severe and refractory
5 Morphine 2–4 mg IV (use cautiously; may worsen respiratory depression)
6 Treat underlying cause ACS? Arrhythmia? Valvular disease?
⚠️ Avoid beta-blockers acutely in decompensated HF.
🚨 HYPERTENSIVE ENCEPHALOPATHY
Step Action
1 CT head β€” rule out stroke/haemorrhage before aggressive BP lowering
2 Reduce MAP by 20–25% over 1–2 hours
3 πŸ’Š Nicardipine 5–15 mg/hr OR πŸ’Š 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 24–48 hours
  • Oral therapy; restart or intensify existing regimen
Oral Agents
Drug Dose Onset Notes
πŸ’Š Captopril 12.5–25 mg PO 15–30 min Avoid if bilateral RAS, hyperkalaemia
πŸ’Š Labetalol 200–400 mg PO 30–120 min Avoid if asthma, bradycardia
πŸ’Š Clonidine 0.1–0.2 mg PO; repeat q1h (max 0.6 mg) 30–60 min Sedation; rebound on withdrawal
πŸ’Š Amlodipine 5–10 mg PO 1–2 hrs Gradual onset
πŸ’Š Telmisartan 40–80 mg PO 1–2 hrs Long-acting
πŸ’Š Furosemide 20–40 mg PO 30–60 min If volume overload
❌ Do NOT use sublingual Nifedipine. Causes unpredictable precipitous BP drops with risk of stroke and myocardial infarction.
Disposition
Step Details
Observe 2–6 hours
Goal BP trending down (does not need to normalise)
Medications Restart or intensify oral regimen
Follow-up Within 24–72 hours


SECTION 8: SPECIAL POPULATIONS


8.1 HYPERTENSION IN DIABETES MELLITUS

Key Principles
  • 70–80% of patients with T2DM have co-existing hypertension
  • HTN + DM confers 2–4× 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
πŸ’Š Empagliflozin 10 mg OD ↓ 3–5 mmHg SBP EMPA-REG OUTCOME: ↓ CV death; ↓ HF hospitalisation; ↓ renal progression
πŸ’Š Dapagliflozin 10 mg OD ↓ 3–5 mmHg SBP DECLARE-TIMI 58: ↓ HF hospitalisation. DAPA-HF: ↓ CV death/HF. DAPA-CKD: ↓ renal progression
πŸ’Š Canagliflozin 100 mg OD ↓ 3–5 mmHg SBP CANVAS: ↓ MACE. CREDENCE: ↓ renal progression
πŸ“Œ SGLT2 inhibitors are now considered foundational therapy in T2DM with HTN, particularly if co-existing CVD, HF, or CKD.
Finerenone in Diabetic Kidney Disease
  • πŸ’Š Finerenone 10–20 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
  • ⚠️ Monitor K⁺ closely; do not initiate if K⁺ > 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 βœ… First-line Thiazide-like βœ… βœ… Standard approach
30–44 βœ… (monitor K⁺, Cr) Thiazide-like still effective βœ… More frequent monitoring
15–29 βœ… (with caution) Loop diuretic (thiazides less effective) βœ… Close monitoring
< 15 / Dialysis Variable; often held Loop diuretic βœ… Individualise
SGLT2 Inhibitors in CKD (With or Without Diabetes)
Drug Evidence Indication
πŸ’Š Dapagliflozin 10 mg OD DAPA-CKD: 39% reduction in renal composite; benefit regardless of diabetes status eGFR 20–90 + UACR ≥ 200 mg/g
πŸ’Š Empagliflozin 10 mg OD EMPA-KIDNEY: 28% reduction in renal progression; includes non-diabetic CKD eGFR 20–90 (with or without albuminuria)
Key points:
  • βœ… Can be initiated down to eGFR 20 mL/min/1.73m²
  • βœ… Continue even if eGFR falls below 20 (unless dialysis or transplant)
  • ⚠️ Expected initial eGFR dip of 3–5 mL/min (haemodynamic; not harmful; recovers)
  • ⚠️ Risk of genital mycotic infections; counsel on hygiene
  • ⚠️ May cause volume depletion β€” consider reducing diuretic dose
πŸ“Œ 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, K⁺ Document
1–2 weeks after starting or uptitrating Cr, K⁺ If Cr ↑ ≤ 30% and stable → continue. If Cr ↑ > 30% or K⁺ > 5.5 → hold and investigate
Stable Every 3–6 months Ongoing monitoring
When to Refer to Nephrology
  • eGFR < 30 (CKD Stage 4–5)
  • 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
65–79 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
πŸ’Š Methyldopa 250–500 mg BD–TID (max 3 g/day) First-line; longest safety record; may cause sedation, depression
πŸ’Š Labetalol 100–400 mg BD–TID (max 2.4 g/day) First-line; avoid in asthma
πŸ’Š Nifedipine ER 30–60 mg OD (max 120 mg/day) Safe; extended-release formulation only
πŸ’Š Hydralazine 25–50 mg TID–QID Add-on; reflex tachycardia
Contraindicated in Pregnancy
❌ 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 3–5 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 πŸ’Š Low-dose Aspirin 75–150 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: 10–15% 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 πŸ’Š Spironolactone 25–50 mg OD as 4th drug
5 If spironolactone not tolerated: πŸ’Š Eplerenone 50 mg OD, OR πŸ’Š Amiloride 10–20 mg OD, OR πŸ’Š Bisoprolol 5–10 mg OD
6 Specialist referral if uncontrolled on 4 drugs
7 Consider renal denervation in selected cases at specialised centres
πŸ”¬ PATHWAY-2 trial: Spironolactone was the most effective 4th-line agent for resistant HTN, reducing SBP by an additional 8–10 mmHg compared to placebo, bisoprolol, and doxazosin.
Fourth-Line Drug Options
Drug Dose Evidence Level Key Consideration
πŸ’Š Spironolactone 25–50 mg OD βœ…βœ… Strongest (PATHWAY-2) Gynecomastia; monitor K⁺
πŸ’Š Eplerenone 50 mg OD βœ… Good Less gynecomastia; more expensive
πŸ’Š Amiloride 10–20 mg OD βœ… Moderate K⁺-sparing
πŸ’Š Bisoprolol 5–10 mg OD βœ… Moderate If not already on beta-blocker
πŸ’Š Doxazosin 4–8 mg OD (bedtime) βœ… Moderate Orthostatic hypotension
πŸ’Š Clonidine 0.1–0.3 mg BD ⚠️ 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 4–9 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 2–4 weeks Adjust drugs until BP at target
Newly at target Every 3 months × 2 visits Confirm stability
Stable Every 3–6 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 6–12 months Renal function
K⁺, Na⁺ Every 6–12 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 1–2 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, K⁺ 1–2 weeks
Starting or uptitrating diuretic K⁺, Na⁺, Cr 1–4 weeks
Starting or uptitrating MRA K⁺, Cr 1 week, then 4 weeks
CKD Stage 3–5 Cr, K⁺, eGFR More frequently per CKD stage
Elderly on thiazides Na⁺ 1–2 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 4–5 (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 65–79 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 > 60–70)
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

βœ… Recommended ❌ 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 20–25% in 1–2 hrs
ICH (SBP 150–220) 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 βœ… ALWAYS
Combine ACE-I + ARB Check Cr and K⁺ 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 (20–25% 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
Harrison’s 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
πŸ›‘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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