6.3: Cardiovascular Therapeutics (Hypertension, Heart Failure, Dyslipidemia)

Cardiovascular Therapeutics (Hypertension, Heart Failure, Dyslipidemia)

Cardiovascular therapeutics represents a major clinical focus of the OPRA exam, aligning with its 45% weighting on Therapeutics & Patient Care. Pharmacists in Australia play a critical role in managing risk, optimising drug regimens, and monitoring for key adverse effects in accordance with Australian national guidelines.

1. Hypertension Management

Australian guidelines (National Heart Foundation of Australia) emphasise treating hypertension based on absolute cardiovascular risk rather than blood pressure numbers in isolation. For uncomplicated hypertension, first-line drug classes are similarly effective at lowering blood pressure:

• ACE Inhibitors (ACEIs): (e.g., perindopril, ramipril)
• Angiotensin II Receptor Blockers (ARBs): (e.g., irbesartan, candesartan, telmisartan)
• Dihydropyridine Calcium Channel Blockers (CCBs): (e.g., amlodipine, lercanidipine)
• Thiazide-like Diuretics: (e.g., indapamide, chlorthalidone)

Clinical Selection Criteria

• Chronic Kidney Disease (CKD) or Diabetes with Proteinuria: An ACEI or ARB is preferred first-line due to renal protective actions (efferent arteriole vasodilation, reducing intraglomerular pressure).
• Elderly or Isolated Systolic Hypertension: Dihydropyridine CCBs or thiazide-like diuretics are highly effective and preferred.
• Pregnancy: ACEIs, ARBs, and diuretics are contraindicated (teratogenic risk). Safe alternatives include methyldopa, labetalol, and nifedipine.

Key Clinical Safety Monitoring & Interactions

• Renal Function and Potassium: ACEIs, ARBs, and diuretics require assessment of serum creatinine/eGFR and potassium at baseline, 1–2 weeks after initiation or dose escalation, and annually thereafter.
  • ACEIs/ARBs: Can cause hyperkalaemia and acute kidney injury. A transient increase in creatinine of up to 30% is acceptable, but larger increases warrant drug cessation or dose reduction.
  • Thiazide-like Diuretics: Can cause hypokalaemia, hyponatremia, and hyperuricaemia (precipitating gout).
• Verapamil/Diltiazem (Non-dihydropyridine CCBs) + Beta-blockers: This combination is contraindicated in primary care due to synergistic negative inotropic and chronotropic effects, posing a severe risk of bradycardia and heart block.
• ACEI + ARB Combination: Contraindicated. Combining these classes does not provide clinical benefit but significantly increases the risk of renal failure and hyperkalaemia.

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2. Heart Failure with Reduced Ejection Fraction (HFrEF)

Modern management of chronic heart failure (Left Ventricular Ejection Fraction $\le 40%$) focuses on the rapid implementation of the 'Four Pillars' of therapy to reduce hospitalisation and mortality. These agents should be introduced and titrated to target clinical trial doses as tolerated by the patient.

Crucial Safety Warning: The 36-Hour Washout Period

When switching a patient from an ACE inhibitor (e.g., ramipril, perindopril) to the ARNI sacubitril/valsartan, a washout period of 36 hours is mandatory. Both classes inhibit the breakdown of bradykinin; co-administration or rapid switching can result in life-threatening angioedema. Note: No washout period is required when switching from an ARB to sacubitril/valsartan.

Clinical Counselling & Patient Care

• Fluid Balance: Patients must monitor their weight daily (first thing in the morning after voiding, before breakfast). A weight gain of >2 kg in 2 days indicates fluid accumulation, requiring temporary upregulation of loop diuretics (e.g., frusemide) in consultation with their heart failure action plan.
• Beta-blocker Initiation: Beta-blockers must only be initiated in stable patients when they are euvolaemic (no signs of acute congestion or fluid overload). A temporary worsening of symptoms can occur upon starting or increasing the dose.

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3. Dyslipidemia & Absolute Cardiovascular Risk

In 2023, Australia released updated guidelines for assessing absolute cardiovascular disease (CVD) risk. The 2023 Australian Cardiovascular Risk Calculator estimates the 5-year probability of a primary cardiovascular event using parameters including age, sex, blood pressure, lipid fractions, smoking status, kidney function, and diabetes status.

Target LDL-Cholesterol (LDL-C) Levels

• High Risk (\ge 10% 5-year risk): Target LDL-C is <1.8 mmol/L.
• Very High Risk / Secondary Prevention (Established CVD): Target LDL-C is <1.4 mmol/L.

Pharmacological Interventions

1. Statins (HMG-CoA Reductase Inhibitors): First-line therapy.
   • High-Intensity: Atorvastatin (40–80 mg) and Rosuvastatin (20–40 mg) have long half-lives and can be taken at any time of day.
   • Moderate-Intensity: Simvastatin (20–40 mg) and Pravastatin (20–40 mg). Simvastatin has a short half-life and must be taken at night to match diurnal cholesterol synthesis.
2. Ezetimibe: Inhibits intestinal cholesterol absorption. Often added if target LDL-C is not achieved on maximally tolerated statin doses.
3. PCSK9 Inhibitors (Evolocumab, Alirocumab): Subcutaneous monoclonal antibodies reserved for patients at very high risk who fail to reach targets despite maximal oral therapy.

Clinical Counselling & Side Effect Management

• Statin-Associated Muscle Symptoms (SAMS): Ranges from mild myalgia to rare, life-threatening rhabdomyolysis. If muscle pain occurs, check serum Creatine Kinase (CK).
  • If CK is $<10 \times$ Upper Limit of Normal (ULN) and symptoms are tolerable: Hold statin temporarily to determine if pain resolves. Re-trial at a lower dose or switch to a different statin.
  • If CK is $\ge 10 \times$ ULN: Discontinue the statin immediately and monitor renal function (risk of myoglobinuria and acute kidney injury).
• CYP3A4 Interactions: Simvastatin and atorvastatin are metabolised by CYP3A4. Concomitant use of strong CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, itraconazole, amiodarone, grapefruit juice) increases systemic exposure, raising myotoxicity risks. Rosuvastatin and pravastatin are not metabolised by CYP3A4 and are safer choices.