Inhaled therapies and cardiovascular risk in patients with chronic obstructive pulmonary disease

ABSTRACT

Introduction: Chronic obstructive pulmonary disease (COPD) therapy includes a multi-dimensional approach, taking into account both symptoms of the patient and the number of acute exacerbations of COPD (AECOPDs). There are three main pharmaceutical classes currently available including long-acting muscarinic antagonists (LAMA), long-acting β₂-agonists (LABA) and inhaled corticosteroids (ICS). COPD is a major risk factor for most cardiovascular diseases, and cardiac comorbidities are very common in COPD patients. Both LAMA and LABA have a considerable impact on cardiac function by stimulating cardiac β2-adrenergic receptors or inhibiting the heart M₂ muscarinic receptors. ICS alone or in combination has never been associated with a real cardiovascular risk.

Areas covered: This review explores the data published on the safety of COPD therapy and the implications for current pharmacotherapy.

Expert opinion: Several studies have confirmed the good safety profile of bronchodilators available both in monotherapy and in association with other bronchodilators of different classes or with ICS despite the device used. Cardiovascular events in clinical trials are generally low and balanced between groups. The actual cardiovascular risk of fixed-dose combinations (FDCs) in an unselected COPD population will need to be investigated through post-marketing surveillance studies and observational studies.

KEYWORDS:

• COPD
• LAMA
• LABA
• ICS/LABA
• LABA/LAMA
• triple therapy
• cardiovascular safety
• mortality

Article highlights

• To date several concerns remains concerning the safety profile of bronchodilator therapy in COPD patients.

• Long acting bronchodilators (LAMA and LABA) administered in monotherapy have shown a high safety profile in COPD patients.

• Dual bronchodilation therapy (LAMA/LABA combination) seems to not increase cardiovascular adverse events in COPD patients.

• ICS and ICS/LABA combinations are not associated with increased CV risk, although some ICSs seem to increase the risk of pneumonia.

• The main data on the cardiovascular safety profile of bronchodilator agents came from randomized controlled trials, ad-hoc post-marketing and observation studies may provide more robust findings.

This box summarizes key points contained in the article.

Declaration of interest

P Rogliani has participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Mundipharma, and Novartis. Her department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. L Calzetta has participated as advisor in scientific meetings under the sponsorship of Boehringer Ingelheim and Novartis, has received non-financial support by AstraZeneca and has received a research grant partially funded by Boehringer Ingelheim, Novartis and Almirall, and is or has been a consultant to Edmond Pharma, Zambon and Verona Pharma. His department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. MG Matera has participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline and Novartis, and has been a consultant to Chiesi Farmaceutici. M Cazzola has participated as a lecturer, speaker, and advisor in scientific meetings and courses under the sponsorship of Almirall, AstraZeneca, Biofutura, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Menarini Group, Lallemand, Mundipharma, Novartis, Pfizer, Verona Pharma, and Zambon. He is or has been a consultant to Chiesi Farmaceutici, Edmond Pharma Lallemand, Novartis, Verona Pharma, and Zambon. His department was funded by Almirall, Boehringer Ingelheim, Novartis, and Zambon. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This study has been supported by the University of Rome "Tor Vergata".