Adherence to lipid-lowering medications and cardiovascular disease prevention in type 2 diabetes mellitus

Background and aims: Globally, cardiovascular disease (CVD) is the major cause of death among patients with type 2 diabetes mellitus (T2DM). Improved control of LDL cholesterol with lipid-lowering medications and patients’ adherence to such medications have been shown associate with lower risk of CV events and mortality among T2DM patients. The impact of healthcare providers’ adherence to guidelines regarding prescription for lipid-lowering medications is unclear. This thesis aimed to assess and compare i) patients’ adherence to lipid-lowering medications, ii) healthcare providers’ adherence to lipid-lowering prescription guidelines, and iii) risk of CV events and mortality in relation to patients’ adherence to lipidlowering medication and healthcare providers’ guideline adherence among patients with T2DM. Patients and methods: This thesis is based on four observational studies where individualized data were linked between Swedish National Registers. All studies included data about patients with T2DM of at least 18 years of age. To assess patients’ adherence, our studies used information about new users of lipidlowering medications from pharmacy claims data in the Swedish Prescribed Drug Register. Using data from the Swedish National Diabetes Register, guideline adherence was assessed for healthcare providers who treated patients with T2DM and LDL cholesterol above the recommended target values. We used information about cause of death and completed admissions of in and out-patients care to analyze risk of CV events and mortality, adjusted for sex, age, socioeconomic status, and concurrent medications as well as health-related and clinical characteristics. Results: On average, patients’ adherence to lipid-lowering medications was higher among secondary prevention patients, smokers and those with concurrent cardioprotective medications, compared to lower adherence among patients born outside of Sweden. Healthcare providers’ adherence to lipid-lowering prescription guidelines was higher among patients attributed to secondary prevention and the odds of receiving a prescription associated with patients’ individual risk of CV events. Adjusted for potential confounders, risk of CV events was higher among patients with less than complete adherence to lipidlowering medications and that risk gradually increased as patient adherence declined, independent of prevention group. Healthcare providers’ adherence to guidelines had little or no impact on patients’ risk of CV events and mortality. Conclusions: Patients’ adherence to lipid-lowering medications among patients with T2DM had greater impact on risk of CV events and mortality compared to healthcare providers’ adherence to prescription guidelines for such medications. This thesis emphasizes the value of individualized diabetes care among T2DM patients

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/hypothesisDyslipidemia 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. MethodA 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.  ResultsMean 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/InterpretationIn 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

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

Abstract 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