What is the recommended dosing of Tadalafil (phosphodiesterase type 5 inhibitor) for patients with World Health Organization (WHO) group 2 pulmonary hypertension?

Tadalafil Dosing for WHO Group 2 Pulmonary Hypertension

Tadalafil is not recommended for patients with WHO Group 2 pulmonary hypertension as it lacks evidence for efficacy in this population and is only approved for WHO Group 1 pulmonary arterial hypertension (PAH). 1

Understanding WHO Classification of Pulmonary Hypertension

WHO classification of pulmonary hypertension includes five distinct groups:

• Group 1: Pulmonary Arterial Hypertension (PAH)
• Group 2: Pulmonary Hypertension due to left heart disease
• Group 3: Pulmonary Hypertension due to lung disease
• Group 4: Chronic thromboembolic pulmonary hypertension
• Group 5: Pulmonary Hypertension with unclear/multifactorial mechanisms

Evidence for Tadalafil Use in PAH (WHO Group 1)

For WHO Group 1 PAH patients, the evidence supports:

• Recommended dose: 40 mg once daily 1, 2
• This dosage has been shown to:
  • Improve 6-minute walk distance (6MWD) by 33m (placebo-corrected) 2, 3
  • Delay time to clinical worsening 3
  • Improve quality of life measures 4
  • Improve cardiopulmonary hemodynamics 1

The 2014 CHEST guideline specifically suggests tadalafil to improve 6MWD in WHO FC II and III patients with PAH 1. The 2019 update to these guidelines reinforces this recommendation 1.

Important Considerations for WHO Group 2 Pulmonary Hypertension

WHO Group 2 pulmonary hypertension is characterized by:

• Elevated pulmonary pressures due to left heart disease
• Elevated left ventricular filling pressure/pulmonary venous pressure
• Different pathophysiology from WHO Group 1 PAH

Why Tadalafil is Not Recommended for WHO Group 2:

1. Lack of evidence: Clinical trials of tadalafil (like PHIRST) specifically enrolled patients with WHO Group 1 PAH 3

2. Potential harm: Vasodilators like PDE5 inhibitors may worsen pulmonary edema in patients with left heart disease by increasing pulmonary blood flow without addressing the underlying left heart dysfunction

3. Regulatory approval: Tadalafil is FDA-approved only for WHO Group 1 PAH

Clinical Approach for WHO Group 2 Pulmonary Hypertension

Instead of tadalafil, management should focus on:

• Treating the underlying left heart disease (heart failure, valvular disease)
• Optimizing volume status
• Managing systemic hypertension if present
• Considering diuretics for symptom relief

Pitfalls to Avoid

1. Misclassification: Ensure accurate hemodynamic assessment with right heart catheterization to confirm WHO Group 2 classification (elevated PAWP/LVEDP >15 mmHg)

2. Off-label use: Using PAH-specific therapies like tadalafil in WHO Group 2 patients without evidence of benefit and potential for harm

3. Overlooking the primary problem: Focusing on pulmonary hypertension without adequately addressing the underlying left heart disease

If a patient has features of both WHO Group 1 and Group 2 (mixed phenotype), referral to a specialized pulmonary hypertension center is recommended for comprehensive evaluation and management.