Cardiovascular effect of discontinuing statins for primary prevention at the age of 75 years: a nationwide population-based cohort study in France

Abstract

Aims: The role of statin therapy in primary prevention of cardiovascular disease in persons older than 75 years remains a subject of debate with little evidence to support or exclude the benefit of this treatment. We assessed the effect of statin discontinuation on cardiovascular outcomes in previously adherent 75-year-olds treated for primary prevention.

Methods and results: A population-based cohort study using French national healthcare databases was performed, studying all subjects who turned 75 in 2012-14, with no history of cardiovascular disease and with a statin medication possession ratio ≥80% in each of the previous 2 years. Statin discontinuation was defined as three consecutive months without exposure. The outcome was hospital admission for cardiovascular event. The hazard ratio comparing statin discontinuation with continuation was estimated using a marginal structural model adjusting for both baseline and time-varying covariates (cardiovascular drug use, comorbidities, and frailty indicators). A total of 120 173 subjects were followed for an average of 2.4 years, of whom 17 204 (14.3%) discontinued statins and 5396 (4.5%) were admitted for a cardiovascular event. The adjusted hazard ratios for statin discontinuation were 1.33 [95% confidence interval (CI) 1.18-1.50] (any cardiovascular event), 1.46 (95% CI 1.21-1.75) (coronary event), 1.26 (95% CI 1.05-1.51) (cerebrovascular event), and 1.02 (95% CI 0.74-1.40) (other vascular event).

Conclusion: Statin discontinuation was associated with a 33% increased risk of admission for cardiovascular event in 75-year-old primary prevention patients. Future studies, including randomized studies, are needed to confirm these findings and support updating and clarification of guidelines on the use of statins for primary prevention in the elderly.

Keywords: Cardiovascular disease; Elderly; Primary prevention; Statins; Treatment discontinuation.

Figure 1

Diagram of the study design. Patients with an outcome or censoring event before the start of follow-up at month m = 3 were excluded. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker.

Take home figure

In 75-year-old primary prevention patients previously adherent to statin therapy for at least 2 years, discontinuation of statins was associated with an increased risk of admission for a cardiovascular event. Cumulative incidence functions were adjusted for confounding due to baseline and time-varying covariates using inverse probability of treatment and censoring weighting. 95% confidence intervals are indicated by hatched curves. Under the assumptions required by this method (see Supplementary material online, Table S2), the cumulative incidence estimated for statin discontinuation represents the experience of the entire study population had all individuals discontinued statins right from the beginning of follow-up. The cumulative incidence estimated for statin continuation represents the experience of the entire study population had no individuals discontinued statins during follow-up.

Figure 2

Patient selection flow chart. ^aMedication possession ratio, calculated as the sum of the days with exposure to statins over the period considered divided by the total number of days in this period. Statin exposure was determined as indicated in the text. ^bAt least one of the following therapies: (i) combined use of aspirin and another antiplatelet agent (prescriptions filled on the same day), (ii) combined use of antiplatelet agent, β-blocker, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker or aliskiren (prescriptions filled on the same day), (iii) long-term treatment by an antiplatelet agent other than aspirin (at least three prescriptions filled during at least one of the 6 years before the 75th birthday). Time was divided into calendar months. Month m = 0 refers to the month of the 75th birthday.

Figure 3

Adjusted cumulative incidence of hospital admission for cardiovascular events according to statin use. Follow-up started at month 3 after the month of the 75th birthday. Cumulative incidence functions were adjusted for confounding due to all baseline and time-varying covariates listed in Table 1 and Supplementary material online, Table S4 (except for the use of other lipid-lowering agents during follow-up), plus the year of the 75th birthday, using inverse probability of treatment and censoring weighting. 95% confidence intervals are indicated by hatched curves. Under the assumptions required by this method (see Supplementary material online, Table S2), the cumulative incidence estimated for statin discontinuation represents the experience of the entire study population had all individuals discontinued statins right from the beginning of follow-up. The cumulative incidence estimated for statin continuation represents the experience of the entire study population had no individuals discontinued statins during follow-up. CI, confidence interval; HR, hazard ratio.

Figure 4

Estimated effect of statin discontinuation in patient subgroups. ^aLow intensity: fluvastatin 20–40 mg, pravastatin 10–20 mg, simvastatin 5–10 mg; moderate intensity: atorvastatin 10–20 mg, rosuvastatin 5–10 mg, fluvastatin 80 mg, pravastatin 40 mg, simvastatin 20–40 mg; high intensity: atorvastatin 40–80 mg, rosuvastatin 20 mg (rosuvastatin 40 mg and simvastatin 80 mg are not available in France). The outcome was hospital admission for cardiovascular event. All patient subgroups were defined at baseline. The estimated effects were adjusted for confounding due to all baseline and time-varying covariates listed in Table 1 and Supplementary material online, Table S4 (except for the use of other lipid-lowering agents during follow-up), plus the year of the 75th birthday. The result for the fluvastatin subgroup was omitted due to the small sample size of this subgroup (a total of 6345 patients with 11 and 277 events on statin discontinuation and continuation, respectively). CI confidence interval; HR, hazard ratio.