From the Guidelines
Nitrates are not recommended for the management of pulmonary hypertension due to their potential to worsen outcomes by causing systemic hypotension without adequately reducing pulmonary pressures. The use of nitrates in pulmonary hypertension is limited and potentially dangerous, as they predominantly affect systemic circulation rather than pulmonary vessels, creating a mismatch that can compromise hemodynamic stability 1. In patients with pulmonary arterial hypertension (PAH), nitrates can cause significant systemic hypotension without adequately reducing pulmonary pressures, leading to decreased cardiac output and worsened symptoms. For patients with PH due to left heart disease, nitrates might occasionally help reduce pulmonary congestion by decreasing left ventricular filling pressures, but this approach requires careful monitoring.
According to the 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure, routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or quality of life in patients with heart failure with preserved ejection fraction (HFpEF) is ineffective 1. The NEAT-HFpEF trial randomized 110 patients with EF ≥50% on stable HF therapy, not including nitrates, and with activity limited by dyspnea, fatigue, or chest pain, to either isosorbide mononitrate or placebo and found no beneficial effects on activity levels, quality of life, exercise tolerance, or NT-proBNP levels.
Instead of nitrates, FDA-approved medications specifically for PAH include phosphodiesterase-5 inhibitors (sildenafil, tadalafil), endothelin receptor antagonists (bosentan, ambrisentan), prostacyclin analogs (epoprostenol, treprostinil), and soluble guanylate cyclase stimulators (riociguat), which more selectively target pulmonary vasculature and work through pathways that specifically address the pathophysiology of pulmonary hypertension rather than causing generalized vasodilation. The 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension also do not recommend the use of PAH-approved therapies in patients with PH due to left heart disease, emphasizing the importance of optimizing the treatment of the underlying condition and identifying other causes of PH before considering assessment of PH-LHD 2.
Key points to consider in the management of pulmonary hypertension include:
- Optimization of the treatment of the underlying condition
- Identification of other causes of PH and treatment when appropriate
- Invasive assessment of PH in patients on optimized volume status
- Referral to an expert PH centre for a complete diagnostic workup and individual treatment decision in patients with PH-LHD and a severe pre-capillary component.
- Avoidance of routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or quality of life in patients with HFpEF.
From the Research
Role of Nitrates in Pulmonary Hypertension Management
- Nitrates, such as nitroglycerin, have been shown to be effective in reducing pulmonary artery pressures and improving hemodynamics in patients with pulmonary hypertension 3, 4.
- The use of nitrates in combination with other vasodilators, such as phosphodiesterase-5 inhibitors, may lead to a potentiation of vasodilation that is relatively selective for the pulmonary vasculature 5.
- Inhaled nitrates, such as sodium nitrite, have also been shown to be safe and effective in reducing pulmonary artery pressures and improving cardiac output in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction 6.
- Nitrates may exert their effects by dilating venous capacitance vessels, reducing pulmonary vascular resistance, and improving right ventricular function 3, 4.
Benefits and Risks of Nitrate Therapy
- The benefits of nitrate therapy in pulmonary hypertension include improved hemodynamics, reduced symptoms, and potentially improved exercise tolerance 3, 5, 4.
- However, nitrate therapy may also be associated with risks such as hypotensive events, systemic hypoxemia, and decreased cardiac output 3, 5.
- The use of nitrates in combination with other vasodilators may increase the risk of adverse effects, and careful monitoring of patients is necessary to minimize these risks 5.
Comparison with Other Therapies
- Nitrates may be used in combination with other selective pulmonary vasodilators, such as phosphodiesterase inhibitors, prostacyclins, and endothelin receptor antagonists, to achieve optimal management of pulmonary hypertension 5, 7.
- The choice of therapy will depend on the individual patient's condition, the severity of their pulmonary hypertension, and their response to treatment 7.