Association between refill adherence to lipid-lowering medications and the risk of cardiovascular disease and mortality in Swedish patients with type 2 diabetes mellitus: a nationwide cohort study

Abstract

ObjectivesTo analyse the association between refill adherence to lipid-lowering medications, and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes mellitus.DesignCohort study.SettingNational population-based cohort of Swedish patients with type 2 diabetes mellitus.Participants86 568 patients aged ≥18 years, registered with type 2 diabetes mellitus in the Swedish National Diabetes Register, who filled at least one prescription for lipid-lowering medication use during 2007–2010, 87% for primary prevention.Exposure and outcome measuresRefill adherence of implementation was assessed using the medication possession ratio (MPR), representing the proportion of days with medications on hand during an 18-month exposure period. MPR was categorised by five levels (≤20%, 21%–40%, 41%–60%, 61%–80% and >80%). Patients without medications on hand for ≥180 days were defined as non-persistent. Risk of CVD (myocardial infarction, ischaemic heart disease, stroke and unstable angina) and mortality by level of MPR and persistence was analysed after the exposure period using Cox proportional hazards regression and Kaplan-Meier, adjusted for demographics, socioeconomic status, concurrent medications and clinical characteristics.ResultsThe hazard ratios for CVD ranged 1.33–2.36 in primary prevention patients and 1.19–1.58 in secondary prevention patients, for those with MPR ≤80% (p<0.0001). The mortality risk was similar regardless of MPR level. The CVD risk was 74% higher in primary prevention patients and 33% higher in secondary prevention patients, for those who were non-persistent (p<0.0001). The mortality risk was 6% higher in primary prevention patients and 18% higher in secondary prevention patients, for non-persistent patients (p<0.0001).ConclusionsHigher refill adherence to lipid-lowering medications was associated with lower risk of CVD in primary and secondary prevention patients with type 2 diabetes mellitus.

Risk of cardiovascular event and mortality in relation to refill and guideline adherence to lipid-lowering medications among patients with type 2 diabetes mellitus in Sweden

“…Patients who filled prescriptions for a lipid-lowering combination therapy or lipid-lowering extemporaneous preparation that lacked information about package size were also excluded. Combination therapy has been described elsewhere 6 28. Patients who experienced CVD prior to or on the index date were classified as prescribed lipid-lowering secondary prevention; all other patients were defined as primary prevention.…”

“…The supply of each prescription was calculated by dividing the number of tablets filled by the daily dosage stated as a free-text variable by the prescriber. Interpretation of the free-text variable to obtain the daily dosage has been described elsewhere 6 28. Overlapping supplies for the same substance and strength were added to the latter supply.…”

“…Adherence is defined as the extent to which individuals follow agreed recommendations 11. Previous studies have shown that patients with T2DM with adherence of at least 80% to lipid-lowering medications face a lower risk of CVD and mortality than those with adherence below 80% 5 6 8 12 13. Among multiple levels of adherence to lipid-lowering medications, a gradual increase in CVD risk was observed with declining adherence by patients with T2DM 6…”

“…Despite declining mortality rates among Swedish patients with T2DM, the risk is still higher than among patients without diabetes mellitus, and CVD remains the major cause of death 4. Improved control of low-density lipoprotein (LDL) cholesterol with lipid-lowering medications has been shown to reduce the risk of CVD and mortality among patients with T2DM 5–8. Thus, national9 and international1 10 treatment guidelines recommended lipid-lowering medications to patients with T2DM to lower LDL cholesterol below 2.5 mmol/L.…”

Adherence and diabetes

“…What of lipid‐lowering treatment? Adherence to lipid‐lowering medication in people with T2DM has been shown to be associated with a reduction in cardiovascular events and mortality, both in primary and secondary prevention . So‐called statin intolerance may be a factor, brought about, in part, by patient beliefs about side effects, both varying to a large degree from country to country and tracking with each other .…”