Prescription of lipid-lowering medications for patients with type 2 diabetes mellitus and risk-associated LDL cholesterol: a nationwide study of guideline adherence from the Swedish National Diabetes Register.

BACKGROUND: Management of type 2 diabetes mellitus (T2DM) encompasses intensive glycaemic control, along with treatment of comorbidities and complications to handle the increased risk of cardiovascular disease (CVD). Improved control of LDL-cholesterol (LDL-C) with lipid-lowering medications is associated with reduced CVD risk in T2DM patients. Thus, treatment guidelines recommend lipid-lowering medications for T2DM patients with LDL-C above risk-associated thresholds. This study aimed to assess healthcare provider adherence to guidelines regarding lipid-lowering medication prescription among T2DM patients and to analyse factors associated with lipid-lowering medication prescription. METHODS: Observations in 2007 - 2014 for T2DM patients age ≥ 18 were collected from the Swedish National Diabetes Register. Observations were excluded if they lacked information about LDL-C, lipid-lowering medication prescription or CVD. Observations with established CVD were attributed to secondary prevention; remaining observations were attributed to primary prevention. The analyses included primary and secondary prevention observations with LDL-C above risk-associated thresholds (LDL-C ≥ 2.5 mmol/l and LDL-C ≥ 1.8 mmol/l respectively). Guideline adherence was analysed as the probability of prescribing lipid-lowering medications using mixed-effect model regression adjusted for potential confounders. Factors associated with prescribing lipid-lowering medications were analysed for patient and healthcare provider characteristics using mixed-effect model regression and odds ratio. RESULTS: A total of 1,204,376 observations from 322,046 patients reported by 1352 healthcare providers were included. Primary prevention accounted for 63%; 52% were men, mean age was 64 and mean LDL-C was 3.4 mmol/l. For secondary prevention, 60% were men, mean age was 72 and mean LDL-C was 2.7 mmol/l. During 2007-2014, guideline adherence ranged from 36 to 47% for primary prevention and 59 to 69% for secondary prevention. In general, concomitant prescription of diabetes medications, antiplatelets and antihypertensives along with smoking and specialised care were associated with higher prescription of lipid-lowering medications. Patients age ≥ 80 were associated with lower prescription of lipid-lowering medications. Higher prescription was associated with longer diabetes duration in primary prevention and men in secondary prevention. CONCLUSIONS: Adherence to treatment guidelines levelled off after an initial increase in both prevention groups. Lipid-lowering medication prescription was based on individualised CVD risk.

Refill adherence and persistence to lipid-lowering medicines in patients with type 2 diabetes: A nation-wide register-based study.

PURPOSE: This study aimed to describe and compare refill adherence and persistence to lipid-lowering medicines in patients with type 2 diabetes by previous cardiovascular disease (CVD). METHODS: We followed 97 595 patients (58% men; 23% with previous CVD) who were 18 years of age or older when initiating lipid-lowering medicines in 2007-2010 until first fill of multi-dose dispensed medicines, death, or 3 years. Using personal identity numbers, we linked individuals' data from the Swedish Prescribed Drug Register, the Swedish National Diabetes Register, the National Patient Register, the Cause of Death Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. We assessed refill adherence using the medication possession ratio (MPR) and the maximum gap method, and measured persistence from initiation to discontinuation of treatment or until 3 years after initiation. We analyzed differences in refill adherence and persistence by previous CVD in multiple regression models, adjusted for socioeconomic status, concurrent medicines, and clinical characteristics. RESULTS: The mean age of the study population was 64 years, 80% were born in Sweden, and 56% filled prescriptions for diabetes medicines. Mean MPR was 71%, 39% were adherent according to the maximum gap method, and mean persistence was 758 days. Patients with previous CVD showed higher MPR (3%) and lower risk for discontinuing treatment (12%) compared with patients without previous CVD (P < 0.0001). CONCLUSIONS: Patients with previous CVD were more likely to be adherent to treatment and had lower risk for discontinuation compared with patients without previous CVD.

Impact of Socioeconomic Factors and Gender on Refill Adherence and Persistence to Lipid-Lowering Therapy in Type 1 Diabetes.

INTRODUCTION: Lipid-lowering therapy (LLT) reduces the risk of cardiovascular disease (CVD) in patients with type 1 diabetes (T1D). However, socioeconomic factors and gender may have an impact on the adherence to and non-persistence with LLT. METHODS: This was a nationwide register-based cohort study that included 6192 individuals with T1D aged ≥ 18 years who were registered in the Swedish National Diabetes Register and had initiated novel use of LLT. Information on socioeconomic parameters (source: Statistics Sweden) and comorbidity (source: National Patient Register) was collected. The individuals were followed for 36 months, and adherence to LLT was analyzed according to age, socioeconomics and gender. The medication possession ratio (MPR; categorized into ≤ 80% and > 80%) and non-persistence (discontinuation) with medication was calculated after 18 and 36 months. RESULTS: Individuals older than 53 years were more adherent to LLT (MPR > 80%) than those younger than 36 years (odds ratio [(OR] 1.30, p < 0.0001) at 36 months. Women were more adherent and less prone to discontinue LLT at 18 months (OR 1.05, p = 0.0005 and OR 0.95, p = 0.0004, respectively), but not at 36 months. Divorced individuals were less adherent than married ones (OR 0.93, p = 0.0005) and discontinued LLT more often than the latter (OR 1.06, p = 0.003). Education had no impact on adherence, but individuals with higher incomes discontinued LLT less frequently than those with lower incomes. Individuals with a country of origin other than Sweden discontinued LLT more often. CONCLUSION: Lower adherence to LLT in individuals with T1D was associated with male gender, younger age, marital status and country of birth. These factors should be considered when evaluating adherence to LLT in clinical practice, with the aim to help patients achieve full cardioprotective treatment.

Adherence to lipid-lowering therapy and risk for cardiovascular disease and death in type 1 diabetes mellitus: a population-based study from the Swedish National Diabetes Register.

AIMS/HYPOTHESIS: Dyslipidemia is an important modifiable risk factor and lipid-lowering treatment (LLT) is essential to reduce the risk of cardiovascular disease (CVD). Studies in type 2 diabetes indicate that low adherence to statin therapy is a barrier to reach full protective potential, and less is known in type 1 diabetes (T1D). The aim was to assess risk of CVD by adherence and nonpersistence to LLT in T1D.  METHOD: A population-based study with a retrospective longitudinal design was conducted between 2006 and 2010, with follow-up until December 2013. In total, 6192 adult individuals with T1D, initiating LLT between 2006 and 2010, were included. Information on LLT, socioeconomic characteristics, comorbidities and cardiovascular events were collected. After 18 months, refill adherence was estimated by calculating medication possession ratio (MPR). Nonpersistence was defined as being without medicines on hand for at least 180 days. Individuals were thereafter followed until CVD, death or end of follow-up in December 2013. Cox regression analyses were performed to assess adherence level and nonpersistence of LLT as predictor of CVD. Analyses were adjusted for cardiovascular risk factors and socioeconomic status.   RESULTS: Mean MPR was 72%, 52% of the participants had an MPR above 80% and 27% discontinued LLT. There were 637 nonfatal and 58 fatal CVD events, mean follow-up 3.6 and 3.9 years, respectively. MPR above 80% was associated with reduced risk for nonfatal CVD compared with lower MPR, HR 0.78 (95% CI 0.65 to 0.93)). For fatal CVD, results indicated a negative effect of high adherence but the association did not reach statistical significance, HR 1.96 (0.96 to 4.01). Individuals discontinuing LLT had higher risk of nonfatal CVD, HR 1.43 (95% CI 1.18 to 1.73).  CONCLUSIONS/INTERPRETATION: In T1D, the risk for nonfatal CVD was lower among individuals with high adherence and higher among those discontinuing LLT within 18 months. It is important to evaluate and emphasize adherence to prescribed LLT at clinical visits to achieve treatment goals and reduce the risk of CVD.

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.

Objective: To analyze the risk of cardiovascular (CV) events and mortality in relation to adherence to lipid-lowering medications by healthcare centers and patients with type 2 diabetes mellitus (T2DM). Research design and methods: We included 121 914 patients (12% secondary prevention) with T2DM reported by 1363 healthcare centers. Patients initiated lipid-lowering medications between July 2006 and December 2012 and were followed from cessation of the first filled supply until multidose dispensed medications, migration, CV events, death or December 2016. The study period was divided into 4-month intervals through 2014, followed by annual intervals through 2016. Adherence measures were assessed for each interval. Patients' (refill) adherence was measured using the medication possession ratio (MPR). Healthcare centers' (guideline) adherence represented the prescription prevalence of lipid-lowering medications according to guidelines. The risk of CV events and mortality was analyzed for each interval using Cox proportional hazard regression and Kaplan-Meier. Results: Compared with high-adherent patients (MPR >80%), low-adherent primary prevention patients (MPR ≤80%) showed higher risk of all outcomes: 44%-51 % for CV events, doubled for all-cause mortality and 79%-90% for CV mortality. Corresponding risks for low-adherent secondary prevention patients were 17%-19% for CV events, 88%-97% for all-cause and 66%-79% for CV mortality. Primary prevention patients treated by low-adherent healthcare centers (guideline adherence <48%) had a higher risk of CV events and CV mortality. Otherwise, no difference in the risk of CV events or mortality was observed by guideline adherence level. Conclusions: Our results demonstrate the importance of high refill adherence and thus the value of individualized care among patients with T2DM.

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.

OBJECTIVES: To 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. DESIGN: Cohort study. SETTING: National population-based cohort of Swedish patients with type 2 diabetes mellitus. PARTICIPANTS: 86 568 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 MEASURES: Refill 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. RESULTS: The 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). CONCLUSIONS: Higher refill adherence to lipid-lowering medications was associated with lower risk of CVD in primary and secondary prevention patients with type 2 diabetes mellitus.