Statin Discontinuation Associated with Excess MACE Events in Older Patients

Wade Thompson, PharmD, PhD

A new study of more than 65,000 statin users in Denmark is providing an overview of the increased risk of major adverse cardiovascular events (MACE) associated with discontinuation of statin therapy among primary and secondary prevention patients.

A staple of guideline-directed management for lowering cholesterol and primary prevention, results of the study detail an increase in events associated with statin discontinuation among older patients, which translated to 1 excess event per 112 persons per year in a primary prevention cohort and 1 excess event per 77 persons per year in a secondary prevention cohort.

“Our results provide important evidence on statin discontinuation in people receiving long-term statin treatment for both primary and secondary prevention. Clinicians and policymakers should be aware of a possible increased risk of MACE associated with discontinuation of long-term statin treatment. This finding may be of clinical and public health importance because of the magnitude of excess risk,” wrote investigators.

With statin therapy common among older patients, a team of investigators from institutions across Europe sought to assess the effects of discontinuing statin therapy on rate of MACE among patients 75 years or older receiving long-term statin therapy. To do so, the current cohort study was designed as an analysis of data obtained from the Danish Health Data Authority, which included data from the Danish National Prescription Registry, National Patient Registry, Population Registry, and Register of Causes of Death.

After excluding those younger than 75 years, those who did not have at least 1 statin prescription filled annually from 2006-2010, and those with a medication possession ratio below 70%, investigators identified a cohort of 67,418 statin users for inclusion in their final analyses. This cohort included 27,463 primary prevention patients and 39,955 secondary prevention patients. The primary prevention cohort had a median age of 79 (IQR, 77-83) years, had a median duration of follow-up of 5.5 (IQR, 2.8-5.5) years, and was 66% (n=18,134) female. The secondary prevention cohort had a median age of 80 (IQR, 77-84) years, had a median duration of follow-up of 4.2 (IQR, 1.8-5.5) years, and was 47% (n=18,717) female.

The discontinuation rate of statin therapy during the follow-up period was 30% (89,311 of 279,463) in the primary prevention cohort and 25% (9,853 of 39,955) in the secondary prevention cohort. Investigators noted 3085 discontinuers from the primary prevention cohort and 3541 discontinuers from the secondary prevention cohort were censored for restarting statin therapy.

The primary outcome of interest for the study was the rate of MACE and its components in those continuing statins versus those who discounted statin therapy. For the purpose of analysis, MACE components included myocardial infarction, ischemic stroke or transient ischemic attack, coronary revascularization, and death due to myocardial infarction or ischemic stroke. Investigators noted separate analyses were conducted for primary and secondary prevention cohorts and confounding adjustment was done performed through inverse probability of treatment weighting.

Upon analysis, results indicated the rate of MACE was greater among those who discontinued statins compared to those who continued statin therapy in both the primary and secondary prevention cohorts. In the primary prevention cohort, weighted analyses indicated the rate difference was 9 (95% CI, 5-12) per 1000 person-years and the adjusted sub-hazard ratio was 1.32 (95% CI, 1.18-1.48), which corresponded to 1 excess MACE per 112 persons who discontinued statins per year. In the secondary prevention cohort, weighted analyses indicated the rate of difference was 13 (95% CI, 8-17) per 1000 person-years and the adjusted sub-hazard ratio was 1.28 (95% CI, 1.18-1.39), which corresponded to 1 excess MACE per 77 persons who discontinued statins per years.

“Among older Danes receiving long-term statin treatment, discontinuation was associated with a higher rate of MACE compared with statin continuation. Although the relative effect of statin discontinuation was similar in the primary and secondary prevention cohorts, the rate difference was larger in the secondary prevention cohort. These findings suggest a need for further evidence from RCTs on this topic to inform shared decision-making in clinical practice,” wrote investigators in their conclusion.

This study, “Statin Discontinuation and Cardiovascular Events Among Older People in Denmark,” was published in JAMA Network Open.