Discontinuing statins or not in the elderly? Study protocol for a randomized controlled trial

Abstract

Background: The risk/benefit ratio of using statins for primary prevention of cardiovascular (CV) events in elderly people has not been established. The main objectives of the present study are to assess the cost-effectiveness of statin cessation and to examine the non-inferiority of statin cessation in terms of mortality in patients aged 75 years and over, treated with statins for primary prevention of CV events. Methods: The "Statins in the elderly" (SITE) study is an ongoing 3-year follow-up, open-label comparative multicentre, randomized clinical trial that is being conducted in two parallel groups in outpatient primary care offices. Participants meeting the following criteria are included: people aged 75 years and older being treated with statins as primary prevention for CV events, who provide informed consent. After randomization, patients in the statincessation strategy are instructed to withdraw their treatment. In the comparison strategy, patients continue their statin treatment at the usual dosage. The cost-effectiveness of the statin-cessation strategy compared to continuing statins will be estimated through the incremental cost per quality-adjusted life years (QALYs) gained at 36 months, from the perspective of the French healthcare system. Overall mortality will be the primary clinical endpoint. We assumed that the mortality rate at 3 years will be 15%. The sample size was computed to achieve 90% power in showing the non-inferiority of statin cessation, assuming a non-inferiority margin of 5% of the between-group difference in overall mortality. In total, the SITE study will include 2430 individuals. Discussion: There is some debate on the value of statins in people over 75 years old, especially for primary prevention of CV events, due to a lack of evidence of their efficacy in this population, potential compliance-related events, drug-drug interactions and side effects that could impair quality of life. Data from clinical trials guide the initiation of medication therapy for primary or secondary prevention of CV disease but do not define the timing, safety, or risks of discontinuing the agents. The SITE study is one of the first to examine whether treatment cessation is a cost-effective and a safe strategy in people of 75 years and over, formerly treated with statins.

Sex-Differences in Discontinuation of Statin Treatment in Cancer Patients the Year before Death

“…In addition, cost effectiveness is an issue to consider when continuing preventive medicine. This issue is currently studied in an ongoing study on statin cessation [ 26 ].…”

“…In the future there is a need for prospective studies to confirm our result and to clarify how deprescribing affect the QoL in palliative patients and the risk of cardiovascular events. There is one ongoing randomized controlled trial on statin discontinuation in elderly >75 years [ 26 ]. However, in the previously mentioned randomized study performed by Kutner, more than 30% of the patients allocated to discontinuation restarted their treatment with statin [ 12 ].…”

Deprescribing statins, considerations for informed decision making

“…The ongoing SITE study will hopefully provide data on the timing of events after statin discontinuation. 39 There are several caveats to our conclusions. The outcomes above ranged from mortality to composite "events."…”

“…There is evidence that relatively brief cessation of statins (6 week washout phase of TNT study) may have minimal risk in patients with stable coronary artery disease 38 . Finally, there is an ongoing large randomized trial of withdrawal of statins given for primary prevention in those over 75 (SITE study) to help clarify this question further 39 …”

“…38 Finally, there is an ongoing large randomized trial of withdrawal of statins given for primary prevention in those over 75 (SITE study) to help clarify this question further. 39 The timing of events after statin withdrawal may be provided by data from Giral et al 34 Over the interval from 3 to 7 months after stopping statins, there were 34 events in 1138 (0.03 events/patient) which decreased to 0.011 events/patient (39 events in 3456; over the next 5 month interval; months 8-12). 34 These data may suggest there is a window of heightened risk after stopping statins, and that the risk is reduced with time.…”