7.2 Cardiovascular & Gastrointestinal Therapeutics

7.2 Cardiovascular & Gastrointestinal Therapeutics

Cardiovascular and gastrointestinal disorders represent a major proportion of primary care presentation and inpatient pharmacotherapy. This section provides an in-depth review of evidence-based management for hypertension, heart failure with reduced ejection fraction (HFrEF), atrial fibrillation (AF), peptic ulcer disease (PUD), gastro-oesophageal reflux disease (GERD), and inflammatory bowel disease (IBD).

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Hypertension Management (ESC & NICE Guidelines)

Diagnosis and treatment of hypertension depend on accurate Blood Pressure (BP) classification across clinic and ambulatory/home settings.

BP Thresholds & Definitions

• Stage 1 Hypertension: Clinic BP >=140/90 mmHg AND Subsequent ABPM/HBPM average >=135/85 mmHg.
• Stage 2 Hypertension: Clinic BP >=160/100 mmHg AND Subsequent ABPM/HBPM average >=150/95 mmHg.
• Stage 3 (Severe) Hypertension: Clinic SBP >=180 mmHg OR Clinic DBP >=110 mmHg.

                  NICE HYPERTENSION TREATMENT ALGORITHM
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   Step 1: Patient Selection
   ├── Aged < 55 years OR Type 2 Diabetes ───────> ACEi or ARB (Step 1 A)
   └── Aged >= 55 years OR Black African/Carib ─> CCB (Step 1 C)
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   Step 2: Combination Therapy
   └── Combine A + C  (ACEi/ARB + CCB)
       OR Combine A + D (ACEi/ARB + Thiazide-like Diuretic, e.g., Indapamide)
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   Step 3: Triple Therapy
   └── Combine A + C + D (ACEi/ARB + CCB + Thiazide-like Diuretic)
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   Step 4: Resistant Hypertension (Confirm with ABPM)
   ├── Check Serum Potassium (K+)
   ├── K+ <= 4.5 mmol/L ──> Add Low-Dose Spironolactone (25 mg daily)
   └── K+ > 4.5 mmol/L  ──> Add Alpha-blocker (Doxazosin) or Beta-blocker

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Heart Failure with Reduced Ejection Fraction (HFrEF)

HFrEF is defined as symptomatic heart failure with Left Ventricular Ejection Fraction (LVEF) <=40%. Pharmacotherapy centers on mortality reduction via neurohormonal blockade.

The Four Foundational Pillars of HFrEF Therapy

All four drug classes should be initiated and uptitrated rapidly to target doses as tolerated:

1. ARNI / ACEi / ARB:
   • Angiotensin Receptor-Neprilysin Inhibitor (ARNI): Sacubitril/Valsartan is preferred over ACEi/ARB to reduce mortality and hospitalizations.
   • CRITICAL SAFETY RULE: When switching a patient from an ACE inhibitor to Sacubitril/Valsartan, a mandatory 36-hour washout period must be observed to avoid accumulation of bradykinin causing fatal angioedema.
2. Evidence-Based Beta-Blockers: Bisoprolol, Carvedilol, or Nebivolol. Start low and titrate slowly once the patient is hemodynamically stable.
3. Mineralocorticoid Receptor Antagonists (MRAs): Spironolactone or Eplerenone. Requires monitoring of serum potassium and eGFR (risk of hyperkalemia).
4. SGLT2 Inhibitors: Dapagliflozin or Empagliflozin. Provides mortality benefit independent of glycemic status.

Symptomatic Relief: Loop Diuretics (e.g., Furosemide 20-80 mg daily) are added to control congestion and volume overload, but do not directly confer mortality reduction.

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Atrial Fibrillation (AF) & Anticoagulation

AF management requires dual focus: stroke prevention and symptom control (rate vs. rhythm control).

Stroke Risk Stratification: CHA2DS2-VASc Score

• Anticoagulation Guidance:
  • Score >= 2 in Males or >= 3 in Females: Oral Anticoagulation Strongly Recommended.
  • Score = 1 in Males or = 2 in Females: Consider Oral Anticoagulation.
  • Score = 0 in Males or = 1 in Females: No Anticoagulation required.

Direct Oral Anticoagulants (DOACs) vs. Warfarin

DOACs (Apixaban, Rivaroxaban, Edoxaban, Dabigatran) are first-line over Warfarin due to superior safety profiles (lower intracranial hemorrhage risk) and lack of routine INR monitoring.

Exception: Warfarin remains mandatory (DOACs contraindicated) in patients with mechanical heart valves or moderate-to-severe mitral stenosis.

Rate vs. Rhythm Control

• Rate Control (First-Line for Most): Target resting HR <110 bpm. First-line agents: Beta-blockers (Bisoprolol) or Non-dihydropyridine CCBs (Diltiazem/Verapamil). Contraindication: Non-dihydropyridine CCBs are strictly contraindicated in HFrEF due to negative inotropic effects.
• Rhythm Control: Indicated for symptomatic AF despite rate control. Agents include Flecainide (contraindicated in structural/ischemic heart disease) and Amiodarone.

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Gastro-Oesophageal Reflux (GERD) & Peptic Ulcer Disease (PUD)

GERD Step-Wise Escalation & Red Flags

GERD management steps: Lifestyle modification -> Antacids/Alginates -> H2-Receptor Antagonists (Famotidine) -> Proton Pump Inhibitors (PPIs: Omeprazole, Lansoprazole).

PPI Long-Term Risks: Clostridioides difficile infection, hypomagnesaemia, vitamin B12 deficiency, acute interstitial nephritis, and osteoporotic fractures.

                  ALARM RED FLAGS FOR URGENT ENDOSCOPY
                  ===================================

   A ──> Anemia (iron deficiency)
   L ──> Loss of weight (unintentional)
   A ──> Anorexia
   R ──> Recent onset of progressive dyspepsia in patients aged > 55 years
   M ──> Melaena or Hematemesis
   D ──> Dysphagia or Odynophagia

Peptic Ulcer Disease & H. pylori Eradication

Helicobacter pylori infection is a major cause of PUD. Eradication requires high-dose triple therapy for 7-14 days.

• First-Line Standard Triple Therapy:
  • PPI (e.g., Omeprazole 20 mg b.i.d.) + Amoxicillin 1 g b.i.d. + Clarithromycin 500 mg b.i.d.
• Penicillin-Allergic Regimen:
  • PPI b.i.d. + Metronidazole 400 mg b.i.d. + Clarithromycin 500 mg b.i.d.
• High Clarithromycin Resistance Area / Second-Line: Bismuth Quadruple Therapy (PPI + Bismuth Subsalicylate + Metronidazole + Tetracycline).

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Inflammatory Bowel Disease (IBD)

Safety Check: Prior to starting Azathioprine or Mercaptopurine, test for Thiopurine S-methyltransferase (TPMT) activity. Deficiency of TPMT leads to severe, potentially fatal bone marrow toxicity due to toxic thioguanine metabolite accumulation.