Effects of lipid-lowering treatment intensity and adherence on cardiovascular outcomes in patients with a recent myocardial infarction: a Swedish register-based study.

Background: Oral lipid-lowering treatment (LLT) is the standard of care for patients with cardiovascular disease (CVD). However, insufficient treatment intensity and poor adherence can lead to suboptimal treatment benefit, rendering patients at increased risk of CVD. Aims: The objective of this study was to evaluate trends in LLT intensity and adherence in Sweden over time, and their association with major adverse cardiovascular events (MACE) after recent myocardial infarction (MI), and also to assess the impact of transition from secondary to primary care on intensity and adherence. Methods and results: This retrospective observational cohort study used data from Swedish nationwide patient registers and included patients on LLT after an MI in the years 2010-2016 (n = 50,298; mean age, 68 years; 69% men). LLT intensity was evaluated over time (overall, for 2010-2013 and for 2014-2016) as the proportion of patients prescribed low-, moderate-, and high-intensity LLT. Adherence was assessed as the proportion of days covered. A combined measure of intensity and adherence was also considered. Differences in treatment patterns and MACE were assessed. Initiation of high-intensity LLT increased over the two time periods studied (2010-2013, 32%; 2014-2016, 91%). Adherence varied by LLT intensity and was highest in patients receiving high-intensity LLT (>80%), especially during the first time period. Little change in treatment intensity or the combined measure of intensity and adherence was observed after transition to primary care. There was a significant association between the combined measure of intensity and adherence and MACE reduction (hazard ratio [95% confidence interval] per 10% increase in the combined measure: 0.84 [0.82-0.86]; P < 0.01). Conclusion: The proportion of post-MI patients with high LLT intensity and adherence has increased in recent years, with little change after transfer from specialist to primary care. The combination of LLT intensity and adherence is important for preventing future cardiovascular events.

Achieving Lower LDL-C Levels After a Recent Myocardial Infarction Might Be Associated with Lower Healthcare Resource Use and Costs in Spain.

INTRODUCTION: There is little evidence on the relationship between achieved low-density lipoprotein cholesterol (LDL-C) levels and costs in patients on lipid-lowering therapy (LLT). We described healthcare resource use and costs (direct and indirect) by achieved LDL-C in patients receiving LLT after a recent myocardial infarction (MI) in Spain. METHODS: This was a retrospective observational study of anonymized electronic medical records from seven regions in Spain (BIG-PAC® database; n = 1.9 million). Eligible patients were adults (≥ 18 years) hospitalized for an MI between January 2015 and December 2017, treated with a statin and/or ezetimibe, and having recorded LDL-C values at baseline and during follow-up. Healthcare resource use and direct and indirect costs (in 2018, €) were described by achieved LDL-C levels during a follow-up of 18 months. RESULTS: Of 6025 patients (mean age, 69.7 years; 77% male), only 11% achieved LDL-C goals as defined in the 2016 ESC/EAS guidelines (< 70 mg/dL), and just 1% reached the lower target (< 55 mg/dL) in the current 2019 guidelines. Achieving lower LDL-C levels translated to lower healthcare resource use and costs. Mean total (direct and indirect) costs ranged from €5044 for patients with LDL-C < 55 mg/dL to €7567 for patients with LDL-C ≥ 130 mg/dL. CONCLUSION: Very few patients achieved recommended LDL-C goals despite using LLT. Achieving lower LDL-C levels after an MI might be associated with lower healthcare resource use and costs. Use of more intensive LLT, leading to greater reductions in LDL-C, could therefore be beneficial both from a clinical and an economic perspective.

Non-statin lipid-lowering therapy over time in very-high-risk patients: effectiveness of fixed-dose statin/ezetimibe compared to separate pill combination on LDL-C.

BACKGROUND: Many patients at very-high atherosclerotic cardiovascular disease risk do not reach guideline-recommended targets for LDL-C. There is a lack of data on real-world use of non-statin lipid-lowering therapies (LLT) and little is known on the effectiveness of fixed-dose combinations (FDC). We therefore studied prescription trends in oral non-statin LLT and their effects on LDL-C. METHODS: A retrospective analysis was conducted of electronic medical records of outpatients at very-high cardiovascular risk treated by general practitioners (GPs) and cardiologists, and prescribed LLT in Germany between 2013 and 2018. RESULTS: Data from 311,242 patients were analysed. Prescriptions for high-potency statins (atorvastatin and rosuvastatin) increased from 10.4% and 25.8% of patients treated by GPs and cardiologists, respectively, in 2013, to 34.7% and 58.3% in 2018. Prescription for non-statin LLT remained stable throughout the period and low especially for GPs. Ezetimibe was the most prescribed non-statin LLT in 2018 (GPs, 76.1%; cardiologists, 92.8%). Addition of ezetimibe in patients already prescribed a statin reduced LDL-C by an additional 23.8% (32.3 ± 38.4 mg/dL), with a greater reduction with FDC [reduction 28.4% (40.0 ± 39.1 mg/dL)] as compared to separate pills [19.4% (27.5 ± 33.8 mg/dL)]; p < 0.0001. However, only a small proportion of patients reached the recommended LDL-C level of < 70 mg/dL (31.5% with FDC and 21.0% with separate pills). CONCLUSIONS: Prescription for high-potency statins increased over time. Non-statin LLT were infrequently prescribed by GPs. The reduction in LDL-C when statin and ezetimibe were prescribed in combination was considerably larger for FDC; however, a large proportion of patients still remained with uncontrolled LDL-C levels.

Cardiovascular Event Rates After Myocardial Infarction or Ischaemic Stroke in Patients with Additional Risk Factors: A Retrospective Population-Based Cohort Study.

INTRODUCTION: The impact of additional risk factors on major cardiovascular event (MACE) rates in patients with a history of myocardial infarction (MI) or ischaemic stroke (IS) treated with statins is not well defined. METHODS: In this retrospective population-based cohort study, patients with a history of MI or IS treated with moderate- or high-intensity statins were identified using Swedish national register data. Patients were incident (index event between July 2006 and December 2014 and followed from diagnosis) or prevalent (MI or IS before July 2006 and followed thereafter). Four subgroups were defined on the basis of additional risk factors associated with increased cardiovascular risk: diabetes mellitus with target organ damage; chronic kidney disease stages 3-4; index event within 2 years after prior MI or IS; and polyvascular disease. First and total MACE rates (i.e. MI, IS, or cardiovascular death) were calculated, and first MACE 10-year risks (prevalent cohort only) were predicted. RESULTS: Numerically, MACE rates in subgroups were 1.5-3 times higher than in overall populations, and were highest in the 2 years after the index event. First MACE rates in the additional risk factor subgroups were 17.2-33.5 per 100 person-years for the incident cohorts and 9.9-13.2 per 100 person-years for the prevalent cohorts. Total MACE rates per 100 person-years were 20.1-39.8 per 100 person-years and 12.4-17.6 per 100 person-years, respectively. CONCLUSION: Despite previous use of moderate- or high-intensity statins, patients with a history of MI or IS, and additional risk factors remain at very high cardiovascular risk.

Patient characteristics, treatment patterns, and adherence to lipid-lowering therapies following an acute coronary syndrome.

Despite dyslipidaemia management guidelines, many patients do not reach low-density lipoprotein cholesterol targets due to insufficiently intensive regimens or lack of adherence to their medication. This was a retrospective cohort study on the Pharmacoepidemiologic General Research eXtension (PGRx)-acute coronary syndrome (ACS) registry. Patients included were ≥ 18 years old who suffered an ACS between 2013 and 2016, and treated with lipid-lowering therapy (LLT) at hospital discharge or within 92 days. Patients were followed up to 12 months' post index ACS, a new cardiovascular event, loss to follow-up or death. Treatment intensity (high, moderate and low intensity statins ± ezetimibe) and adherence (proportion of days covered > 80%) are described. A total of 2,695 patients were included; mean age [SD] was 63.1 [12.8] years, and 77% were men. High, moderate and low intensity statins were started in 56% (1,520), 36% (971), and 3% (86) of patients, respectively. A further 2% (46) were on statin/ezetimibe combination, 2% (42) on other LLT and 1% (30) on ezetimibe alone. At follow-up, around 70% of patients were adherent to LLT, with those on moderate intensity treatments showing better adherence (76%) than those on low (63%) or high (67%) intensity treatments. Despite guideline recommendations, many patients following an ACS are not treated with high intensity statins, and adherence remains far from optimal. Effort should be made to increase the proportion of patients treated with high intensity statins following an ACS and to further improve treatment adherence.

A systematic literature review comparing methods for the measurement of patient persistence and adherence.

OBJECTIVES: A systematic literature review was conducted comparing different approaches estimating persistence and adherence in chronic diseases with polypharmacy of oral and subcutaneous treatments. METHODS: This work followed published guidance on performing systematic reviews. Twelve electronic databases and grey literature sources were used to identify studies and guidelines for persistence and adherence of oral and subcutaneous therapies in hypercholesterolemia, type 2 diabetes, hypertension, osteoporosis and rheumatoid arthritis. Outcomes of interest of each persistence and adherence data collection and calculation method included pros: accurate, easy to use, inexpensive; and cons: inaccurate, difficult to use, expensive. RESULTS: A total of 4158 records were retrieved up to March 2017. We included 16 observational studies, 5 systematic reviews and 7 guidelines, in patients with hypercholesterolemia (n = 8), type 2 diabetes (n = 4), hypertension (n = 2), rheumatoid arthritis (n = 1) and mixed patient populations (n = 13). Pharmacy and medical records offer an accurate, easy and inexpensive data collection method. Pill count, medication event monitoring systems (MEMs), self-report questionnaires and observer report are easy to use. MEMS and biochemical monitoring tests can be expensive. Proportion of days covered (PDC) was recommended as a gold standard calculation method for long-term treatments. PDC avoids use of days' supply in calculation, hence is more accurate compared to medication possession ratio (MPR) to assess adherence to treatments in chronic diseases. CONCLUSIONS: Decisions on what method to use should be based on considerations of the route of medication administration, the resources available, setting and aim of the assessment. Combining different methods may provide wider insights into adherence and persistence, including patient behavior.

Cost-utility of denosumab for the treatment of postmenopausal osteoporosis in Spain.

BACKGROUND: The objective of this study was to estimate the cost-effectiveness of denosumab for fracture prevention compared with no treatment, generic bisphosphonates, and strontium ranelate in a cohort of osteoporotic postmenopausal women in Spain. METHODS: A Markov model represented the possible health state transitions of Spanish postmenopausal women from initiation of fracture prevention treatment until age 100 years or death. The perspective was that of the Spanish National Health System. Fracture efficacy data for denosumab were taken from a randomized controlled trial. Fracture efficacy data for alendronate, ibandronate, risedronate, and strontium ranelate were taken from an independent meta-analysis. Data on the incidence of fractures in Spain were either taken from the published literature or derived from Swedish data after applying a correction factor based on the reported incidence from each country. Resource use in each health state was obtained from the literature, or where no data had been published, conservative assumptions were made. Utility values for the various fracture health states were taken from published sources. The primary endpoints of the model were life-years gained, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios for denosumab against the comparators. RESULTS: Denosumab reduced the risk of fractures compared with either no treatment or the other active interventions, and produced the greatest gains in life-years and QALYs. With an annual acquisition cost of €417.34 for denosumab, the incremental cost-effectiveness ratios for denosumab versus no treatment, alendronate, risedronate, and ibandronate were estimated at €6,823, €16,294, €4,895, and €2,205 per QALY gained, respectively. Denosumab dominated strontium ranelate. Sensitivity analyses confirmed the robustness of these findings. CONCLUSION: Our analyses show that denosumab is a cost-effective intervention for fracture prevention in osteoporotic postmenopausal women in Spain compared with alendronate and risedronate, and is a dominant treatment option compared with strontium ranelate.