JOURNAL ARTICLE
REVIEW
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Pulmonary Arterial Hypertension: Combination Therapy in Practice.

Combination therapy is now regarded as the standard of care in pulmonary arterial hypertension (PAH) and is becoming widely used in clinical practice. Given the inherent complexities of combining medications, there is a need for practical advice on implementing this treatment strategy in the clinic. Drawing on our experience and expertise, within this review, we discuss some of the challenges associated with administration of combination therapy in PAH and how these can be addressed in the clinic. Despite their differing modes of action, all of the currently available classes of PAH therapy induce systemic vasodilation. In initial combination therapy regimens in particular, this may lead to additive side effects and reduced tolerability compared with monotherapy. However, approaches such as staggered treatment initiation and careful up-titration may reduce the risk of additive side effects and have been used successfully in clinical practice, as well as in clinical trials and registry studies. When combination therapy regimens are initiated, it is important that patients are monitored regularly for the presence of any side effects and that these are then managed promptly and appropriately. For patients to attain the best outcomes, the treatment regimen must be tailored to the individual's specific needs, including consideration of PAH etiology, the presence of comorbidities and concomitant medications beyond PAH therapy, and patient lifestyle and preference. It is also vital that individuals are managed at expert care centers, where multidisciplinary teams have a wealth of specialist experience in treating PAH patients. Adherence to therapy can be a concern in a chronic disease such as PAH, and as treatment regimens become increasingly complex, maintaining good treatment adherence may become more challenging. It is essential that patients are educated on the importance of treatment adherence, and this is a key role for the PAH nurse specialist. For patients who are managed carefully in expert centers with combination therapy regimens that are tailored to their specific needs, a favorable benefit-risk ratio can be achieved. With individual and carefully managed approaches, the excellent results observed with combination therapy in clinical trials can be obtained by patients in a real-world setting.

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