Statin intolerance – a question of definition

ABSTRACT

Introduction: Statin therapy is the backbone of pharmacologic therapy for low-density lipoproteins cholesterol lowering and plays a pivotal role in cardiovascular disease prevention. Statin intolerance is understood as the inability to continue using a statin to reduce individual cardiovascular risk sufficiently, due to the development of symptoms or laboratory abnormalities attributable to the initiation or dose escalation of a statin. Muscle symptoms are the most common side effects observed.

Areas covered: The main aim of this article is to present a review on published definitions of statin intolerance. In addition, a brief review on clinical aspects and risk factors of statin intolerance is provided and features for a common definition for statin intolerance are suggested.

Expert opinion: A definition of statin intolerance by major drug regulatory agencies is not available. In clinical studies, different definitions are chosen and results are not comparable; different medical associations do not agree on one common definition. There is an unmet need to establish a common definition of statin intolerance to ensure an appropriate clinical use of this important drug class. Further work is required to develop a consensus definition on statin intolerance that could have significant positive impact on both research and clinical management.

KEYWORDS:

• HMG-CoA reductase inhibitors
• hypercholesterolemia
• myopathy
• PCSK9 inhibitors
• statin adverse effects
• statin discontinuation

Article highlights

• Statins are well tolerated by the majority of patients but they are associated with some AE among which muscle-related symptoms are the most commonly observed effects, especially at higher doses.

• Statin intolerance is generally understood as the inability to use a statin to reduce individual cardiovascular risk sufficiently due to emergence of significant clinical symptoms and/or laboratory abnormalities.

• Statin intolerance is a major cause of discontinuation of statin therapy with a frequency as high as 25% in patients treated in clinical practice and could result from any statin-related AE.

• There are currently no uniform, standardized definitions or diagnostic criteria available for statin intolerance and published definitions are not comparable.

• There is an unmet need to establish a robust and clear definition of statin intolerance especially since the availability of an alternative treatment approach provided by the novel drug class of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

• Important aspects that should be integrated in a consensus definition include temporal association between symptoms and therapy, exclusion of predisposing factors, consideration of all statin-related side effects, drug rechallenge and the use of different statins.

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Declaration of interest

S Rosenfeld is an employee of Sanofi-Aventis Deutschland GmbH. 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.

Additional information

Funding

This project was funded by Sanofi-Aventis Deutschland GmbH.