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Deprescribing statins, considerations for informed decision making

Thomas C, Ellison H, Taffet GE. Deprescribing statins, considerations for informed decision making. J Am Geriatr Soc. 2023 Apr 21. doi: 10.1111/jgs.18362. Epub ahead of print. PMID: 37082816.

To address ongoing uncertainties in deprescribing statins, Thomas et al. authored a commentary that explores key considerations and cautions when stopping these medications. Deprescribing aims to manage risks associated with polypharmacy in older adults. Due to their widespread use, uncertain benefits, and potential adverse effects, statins are a potential target for deprescribing. While statins are effective in reducing cardiovascular events in older patients with preexisting vascular disease, the evidence for primary prevention in older populations is mixed. The decision whether to start a statin is an important one that requires careful consideration.   Thomas et al. highlight the importance of distinguishing between stopping and starting these medications when considering the biologic mechanisms of statin discontinuation. Chronic inhibition of a pathway, as observed with statins, can lead to compensatory upregulation of components within that pathway to maintain homeostasis. Studies have demonstrated profound upregulation of HMG-CoA reductase, cholesterol transporters, and downstream enzymes in response to statin therapy, even as serum cholesterol levels decrease. Discontinuing statins in the presence of upregulated enzymes can have detrimental effects on cholesterol production, inflammation, endothelial function, atherosclerosis, and other pleiotropic processes. Preclinical studies have highlighted a “rebound” effect upon statin discontinuation, resulting in increased activity in previously inhibited pathways. Understanding the dose/response relationship and timing of these adaptive mechanisms, particularly in older adults, is essential for developing optimal strategies for discontinuing statins.

Thomas et al. highlight the findings from several studies investigating the risks of discontinuing statins. Notably, a randomized controlled trial conducted in end-of-life patients did not demonstrate a statistically significant difference in mortality rates between those who ceased statin therapy and those who continued. However, observational studies have provided evidence suggesting an elevated risk of adverse outcomes, including increased hospitalizations for cardiovascular events, heart failure readmissions, emergency room visits, deaths, and overall mortality associated with statin discontinuation. It is crucial to acknowledge the limitations inherent in these studies, such as variations in the assessed outcomes, uncertainties surrounding the circumstances of statin cessation, and the challenges in distinguishing deprescribing from non-adherence.

Further research is needed to develop strategies for identifying patients who would benefit from deprescribing statins, identifying ways to do so safely byminimizing adverse withdrawal effects, and strategies for communication with patients and families.

Senior author George Taffet reflects on how healthcare providers can effectively communicate the risks and benefits of deprescribing statins to older adults, taking into account individual health status, functional abilities, and personal values?

“Deprescribing is a difficult decision, in part because we have such limited evidence of the benefits or harms of withdrawal. With statins we do have some estimate of the harms associated with deprescribing and they are significant but time limited. The harms may in part reflect the body’s adaptations, then de-adaptation to the important changes statins induce. That is why the “would I start the statin today?” is irrelevant to considering which patients may benefit from deprescribing. If a patient has been taking a statin without adverse effects for a long time, we would consider continuing statins as being a preferred option. If discontinuation is desired by the patient, then the increased adverse cardiovascular events following withdrawal need to be part of the risk benefit discussion for shared decision making.

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Authored by Caroline Eskandar

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