Recent trends in incidence, survival and treatment of multiple myeloma in Finland - a nationwide cohort study.

This study aimed to determine the incidence and prevalence of multiple myeloma (MM) in Finland in 2015-2019, to characterize adult patients newly diagnosed with MM, and to follow-up their overall survival (OS) and treatment patterns until the end of 2020. We sourced the data on inpatient and outpatient diagnoses, outpatient medication use, and date of death from comprehensive, nationwide registers. We identified 2037 incident patients with MM in 2015-2019. On average, the annual crude incidence was 8.8 and the age-standardized incidence (World Standard Population) was 3.3 per 100,000. The crude prevalence at the end of 2019 was 32.7 cases per 100,000 inhabitants ≥ 18 years of age. Median age of the patients at first diagnosis (index date) was 71 years, and 48% were female, the median follow-up being 2.4 years. The median OS was estimated at 4.5 years. The proportion of the patients receiving autologous stem cell transplantation (ASCT) within one year since the index date was 24%, with little variation across study years. Conversely, the proportion of all patients receiving lenalidomide within one year since the index date increased from 27 to 48% overall, and from 39 to 81% among ASCT recipients. The estimated median relapse-free survival after ASCT was 2.9 years. Information on in-hospital MM medication administrations was available for a subset of the study cohort. In this subset, 85.8% of the patients received immunomodulatory drugs and/or proteasome inhibitors within the first year after the index date.

The changing pattern of statin use in people with dementia: A population-based study.

BACKGROUND: After a dementia diagnosis, goals of care are often reassessed, including the use of preventive medications like statins. OBJECTIVE: To examine changes in statin use after initiating medication for managing dementia. METHODS: A case-crossover study utilizing medication dispensing data from the Australian Pharmaceutical Benefits Scheme (PBS) 10% random sample was conducted. Use of statins was compared in the 12 months pre- and post-initiation (pre-period and post-period) of anti-dementia medications or risperidone for behavioural symptoms of dementia. Individuals aged ≥65 years who had their first dispensing of anti-dementia medication or risperidone between July 2006 and June 2017 and survived ≥12 months after their first supply were included. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for change in statin use in the discordant pairs. RESULTS: The cohort (n = 19,809) had a median age of 81 years and 61% were female. Statins were less likely to be used after initiating anti-dementia medication or risperidone (OR 0.50; 95%CI 0.45-0.55). The OR for statin use in the post-period versus the pre-period decreased annually over the 11 years from 1.21; 95%CI 0.84-1.75 in 2006-7 to 0.31; 95%CI 0.24-0.41 in 2016-17 (p for interaction <0.05). CONCLUSION: Statins are more likely to be ceased than started after initiating medication for dementia. This may reflect changes in goals of care, or changes in the interpretation of the available evidence for the safety and efficacy of statins in older people living with dementia.

Real-world adherence, persistence, and in-class switching during use of dipeptidyl peptidase-4 inhibitors: a systematic review and meta-analysis involving 594,138 patients with type 2 diabetes.

AIMS: Medication adherence and persistence are important determinants of treatment success in type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis evaluated the real-world adherence, persistence, and in-class switching among patients with T2DM prescribed dipeptidyl peptidase-4 (DPP4) inhibitors. METHODS: MEDLINE, EMBASE, Cochrane Library, PsychINFO, and CINAHL were searched for relevant observational studies published in the English language up to 20 December 2019. This was supplemented by manual screening of the references of included papers. Random-effects meta-analysis was performed. RESULTS: Thirty-four cohort studies involving 594,138 patients with T2DM prescribed DPP4 inhibitors from ten countries were included. The pooled proportion adherent (proportion of days covered (PDC) or medication possession ratio (MPR) ≥ 0.80) was 56.9% (95% confidence interval [CI] 49.3-64.4) at one year and 44.2% (95% CI 36.4-52.1) at two years. The proportion persistent with treatment decreased from 75.6% (95% CI 71.5-79.5) at six months to 52.8% (95% CI 51.6-59.8) at two years. No significant differences in adherence and persistence were observed between individual DPP4 inhibitors. At one year, just 3.2% (95% CI 3.1-3.3) of patients switched from one DPP4 inhibitor to another. Switching from saxagliptin and alogliptin to others was commonest. CONCLUSIONS: Adherence to and persistence with DPP4 inhibitors is suboptimal but similar across all medications within the class. While in-class switching is uncommon, saxagliptin and alogliptin are the DPP4 inhibitors most commonly switched. Interventions to improve treatment adherence and persistence among patients with T2DM prescribed DPP4 inhibitors may be warranted.

Prevalence and incidence of prescription opioid analgesic use in Australia.

AIMS: The aims of the current study were to determine the prevalence and incidence of prescription opioid analgesic use in Australia and compare the characteristics of people with and without cancer initiating prescription opioid analgesics. METHODS: A retrospective population-based study was conducted using the random 10% sample of adults who were dispensed prescription opioid analgesics in Australia between July 2013 and June 2017 through the Pharmaceutical Benefits Scheme. Poisson regression was used to calculate rate ratios (RR) for opioid prevalence and incidence. The characteristics of people initiating opioids, including type of opioid initiated, total oral morphine equivalents dispensed, prescriber speciality, medical comorbidities, and past analgesic and benzodiazepine use, were compared for people with and without cancer. RESULTS: Opioid prevalence increased {RR = 1.006 [95% confidence interval (CI) 1.004, 1.008]}, while incidence decreased [RR = 0.977 (95% CI 0.975,0.979)] from 2013/2014 to 2016/2017. There were between 287 677 and 307 772 prevalent users each year. In total, 769 334 adults initiated opioids between 2013/2014 and 2016/2017, and half of these initiations were by general practitioners. Initiation with a strong opioid occurred in 55.8% of those with cancer and 28.2% of those without cancer. CONCLUSION: Rates of opioid use have remained high since 2013, with approximately 3 million adults using opioids and over 1.9 million adults initiating opioids each year. Between 2013 and 2017, opioid prevalence has slightly increased but incidence has decreased. People without cancer account for the majority of opioid use and are more likely to be initiated on short-acting and weak opioids. Initiation of strong opioids has increased over time, reinforcing concerns about increased use and the harms associated with strong opioids in the community.

Demographic, clinical and lifestyle factors associated with high-intensity statin therapy in Australia: the AusDiab study.

PURPOSE: Clinical guidelines specify who should receive high-intensity statins; however, it is unclear how high-intensity statins are used in Australia. Our objective was to determine the demographic, clinical, and lifestyle factors associated with high-intensity statin therapy in Australia. METHODS: Data from the Australian Diabetes, Obesity and Lifestyle study collected in 2011-2012 were analyzed. High-, moderate-, and low-intensity statins were defined as use of statins at doses demonstrated to reduce low-density lipoprotein cholesterol levels by > 50, 30-50, and < 30%, respectively. Logistic regression was used to estimate adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for factors associated with high- versus low-to-moderate-intensity statin therapy. RESULTS: Overall, 1108 (24%) study participants used a statin. Data on statin intensity were available for 1072 participants. The proportions of high-, moderate-, and low-intensity statin therapy were 32 (n = 341), 65 (n = 696), and 3% (n = 35), respectively. Overall, 51% of people with prior cardiovascular disease (CVD) used a high-intensity statin. In addition to prior CVD (OR = 3.34, 95% CI = 1.95-5.73), no (OR = 1.84, 95%CI 1.02-3.31) or insufficient physical activity (OR = 1.51, 95% CI = 1.01-2.25), obesity (OR = 1.87, 95% CI = 1.13-3.10), and consuming > 2 alcoholic drinks daily (OR = 1.66, 95% CI = 1.08-2.55) were associated with high versus low-to-moderate-intensity statin therapy. Conversely, age 65-74 vs. < 65 years was inversely associated with high-intensity statin therapy (OR = 0.62, 95% CI = 0.41-0.94). CONCLUSIONS: Prior CVD was the strongest factor associated with high-intensity statin therapy. Although the prevalence of CVD increases with age, older people were less likely to be treated with high-intensity statins.

Statins do not Increase the Rate of Bleeding Among Warfarin Users.

Clinical significance of potential interaction between warfarin and statins is unclear. Our objective was to determine whether use of statins as a class or use of simvastatin modulates the rate of bleeding requiring hospitalization among new warfarin users. Using Finnish healthcare databases, we identified a cohort of 101,588 warfarin initiators between 1 January 2009 and 30 June 2012. By the end of 2012, these patients accumulated 92,695 person-years of exposure to warfarin-only and 60,253 years of exposure to warfarin-with-statin. The outcome was a composite of gastrointestinal, intracranial or other bleeding leading to hospitalization. A Poisson generalized estimating equation model was employed to estimate rate ratios (RR) and their 95% confidence intervals (CI) for exposure to warfarin-with-statin compared to warfarin-only and to allow multiple episodes per patient and time-dependent covariates. In multivariable models, we found no difference in the bleeding rate in association with exposure to any statin (multivariable-adjusted RR = 0.98, 95% CI 0.89-1.07) or to simvastatin (RR = 1.01, 95% CI 0.91-1.11) with warfarin compared to exposure to warfarin-only. We conclude that concomitant use of statins and warfarin was not associated with an increased rate of bleeding requiring hospitalization.

Predictors of persistent prescription opioid analgesic use among people without cancer in Australia.

AIMS: To identify patterns of opioid analgesic use and determine predictors of persistent opioid use among people without cancer. METHODS: A population-based cohort study of Australians initiating prescription opioids from July 2013 to December 2015 was conducted using data from a random 10% sample of people who accessed medicines through Australia's Pharmaceutical Benefits Scheme. A 12-month retrospective period was used to define opioid initiation, exclude people with cancer and determine comorbidities. Persistent use over 12 months since initiation was identified through group-based trajectory modelling. Odds ratios (OR) and 95% confidence intervals (CIs) for predictors of opioid persistence were estimated using logistic regression. RESULTS: The cohort consisted of 431 963 people without cancer who initiated opioids. A total of 11 323 (2.6%) persistent opioid users were identified. Predictors of persistence included initiation with transdermal formulations (OR 4.2, 95% CI 3.9-4.5), or initiation with total oral morphine equivalents (OME) ≥ 750 mg (3.7, 3.3-4.1), having depression (1.6, 1.5-1.7) or psychotic illness (2.0, 1.9-2.2). Previous dispensing of paracetamol (2.0, 1.9-2.1), pregabalin (2.0, 1.8-2.1) and benzodiazepines (1.53, 1.4-1.6) predicted persistence. Compared to people aged 18-44 years, those ≥75 years were 2.5 (2.3-2.6) times more likely to be persistent users. CONCLUSIONS: Patient-specific characteristics (older age, prior history of mental health comorbidities and use of non-opioid analgesics) and prescriber choice of initial opioid (transdermal formulation and higher total OMEs) were found to strongly predict persistent use. This information may help prescribers target monitoring and early intervention efforts in order to prevent harms associated with the long-term use of opioids.

Adherence and Persistence Among Statin Users Aged 65 Years and Over: A Systematic Review and Meta-analysis.

Background: Older people (aged ≥ 65 years) have distinctive challenges with medication adherence. However, adherence and persistence patterns among older statin users have not been comprehensively reviewed. Methods: As part of a broader systematic review, we searched Medline, Embase, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects, CENTRAL, and the National Health Service Economic Evaluation Database through December 2016 for English articles reporting adherence and/or persistence among older statin users. Data were analyzed via descriptive methods and meta-analysis using random-effect modeling. Results: Data from more than 3 million older statin users in 82 studies conducted in over 40 countries were analyzed. At 1-year follow-up, 59.7% (primary prevention 47.9%; secondary prevention 62.3%) of users were adherent (medication possession ratio [MPR] or proportion of days covered [PDC] ≥ 80%). For both primary and secondary prevention subjects, 1-year adherence was worse among individuals aged more than 75 years than those aged 65-75 years. At 3 and ≥10 years, 55.3% and 28.4% of users were adherent, respectively. The proportion of users persistent at 1-year was 76.7% (primary prevention 76.0%; secondary prevention 82.6%). Additionally, 68.1% and 61.2% of users were persistent at 2 and 4 years, respectively. Among new statin users, 48.2% were nonadherent and 23.9% discontinued within the first year. The proportion of statin users who were adherent based on self-report was 85.5%. Conclusions: There is poor short and long term adherence and persistence among older statin users. Strategies to improve adherence and reduce discontinuation are needed if the intended cardiovascular benefits of statin treatment are to be realized.

Changes in Statin Adherence Following an Acute Myocardial Infarction Among Older Adults: Patient Predictors and the Association With Follow-Up With Primary Care Providers and/or Cardiologists.

BACKGROUND: Hospitalizations for acute myocardial infarctions (AMIs) are associated with changes in statin adherence. It is unclear to what extent adherence changes, which patients are likely to change, and how post-discharge follow-up is associated with statin adherence change. METHODS AND RESULTS: This retrospective study used Medicare data for all fee-for-service beneficiaries 66 years and older with an AMI hospitalization in 2008-2010 and statin use before their index AMI. Multivariable multinomial logistic regression models (odds ratio [OR] and 99% confidence interval [CI]) were applied to assess associations between both patient characteristics and follow-up with a primary care provider and/or cardiologist with the outcome of statin adherence change (increase or decrease) from the 6-month pre- to 6-month post-AMI periods. Of 113 296 patients, 64.0% had no change in adherence, while 19.7% had increased and 16.3% had decreased adherence after AMI hospitalization. Black and Hispanic patients were more likely to have either increased or decreased adherence than white patients. Patients who required coronary artery bypass graft surgery (OR, 1.34; 99% CI, 1.21-1.49) or percutaneous transluminal coronary angioplasty/stent procedure (OR, 1.25; 99% CI, 1.17-1.32) during their index hospitalization were more likely to have increased adherence. Follow-up with a primary care provider was only mildly associated with increased adherence (OR, 1.08; 99% CI, 1.00-1.16), while follow-up with a cardiologist (OR, 1.15; 99% CI, 1.05-1.25) or both provider types (OR, 1.21; 99% CI, 1.12-1.30) had stronger associations with increased adherence. CONCLUSIONS: Post-AMI changes in statin adherence varied by patient characteristics, and improved adherence was associated with post-discharge follow-up care, particularly with a cardiologist or both a primary care provider and a cardiologist.

Potential contribution of lifestyle and socioeconomic factors to healthy user bias in antihypertensives and lipid-lowering drugs.

OBJECTIVES: Healthy user bias arises when users of preventive medications such as lipid-lowering drugs (LLDs), hormone replacement therapy and antihypertensive (AH) medications are healthier than non-users due to factors other than medication effects, making the medications appear more beneficial in observational studies of effectiveness and safety. The purpose of the study is to examine factors contributing to healthy user effect in patients taking AHs or LLDs. METHODS: Among patients with hypertension or hyperlipidaemia in a population-based sample from the National Health and Nutrition Examination Survey (1999-2010), we assessed the association between socioeconomic and lifestyle factors and the use of AHs/LLDs by logistic regression with adjustment for demographics and comorbidities in a cross-sectional study. RESULTS: When 9715 AH/LLD users were compared with 3725 non-users, AH/LLD users were more likely to be: highly educated (OR 1.2, 95% CI 1.2 to 1.3), non-impoverished (OR 1.3, 95% CI 1.2 to 1.4), current non-smokers (OR 1.2, 95% CI 1.1 to 1.4), physically active (OR 1.1, 95% CI 1.0 to 1.2) and consume more calcium (OR 1.1, 95% CI 1.0 to 1.3) but less likely to have normal body mass index (OR 0.6, 95% CI 0.6 to 0.7) or to meet dietary sodium recommendations (OR 0.8, 95% CI 0.7 to 0.9). CONCLUSIONS: We identified several salutary lifestyle factors associated with AH/LLD use in a representative US population. Healthy user effect may be partly explained by better socioeconomic profiles and lifestyles in AH/LLD users compared with non-users.

Statin adherence and risk of acute cardiovascular events among women: a cohort study accounting for time-dependent confounding affected by previous adherence.

OBJECTIVES: Previous studies on the effect of statin adherence on cardiovascular events in the primary prevention of cardiovascular disease have adjusted for time-dependent confounding, but potentially introduced bias into their estimates as adherence and confounders were measured simultaneously. We aimed to evaluate the effect when accounting for time-dependent confounding affected by previous adherence as well as time sequence between factors. DESIGN: Retrospective cohort study. SETTING: Finnish healthcare registers. PARTICIPANTS: Women aged 45-64 years initiating statin use for primary prevention of cardiovascular disease in 2001-2004 (n=42 807). OUTCOMES: Acute cardiovascular event defined as a composite of acute coronary syndrome and acute ischaemic stroke was our primary outcome. Low-energy fractures were used as a negative control outcome to evaluate the healthy-adherer effect. RESULTS: During the 3-year follow-up, 474 women experienced the primary outcome event and 557 suffered a low-energy fracture. The causal HR estimated with marginal structural model for acute cardiovascular events for all the women who remained adherent (proportion of days covered ≥80%) to statin therapy during the previous adherence assessment year was 0.78 (95% CI: 0.65 to 0.94) when compared with everybody remaining non-adherent (proportion of days covered <80%). The result was robust against alternative model specifications. Statin adherers had a potentially reduced risk of experiencing low-energy fractures compared with non-adherers (HR 0.90, 95% CI 0.76 to 1.07). CONCLUSIONS: Our study, which took into account the time dependence of adherence and confounders, as well as temporal order between these factors, is support for the concept that adherence to statins in women in primary prevention decreases the risk of acute cardiovascular events by about one-fifth in comparison to non-adherence. However, part of the observed effect of statin adherence on acute cardiovascular events may be due to the healthy-adherer effect.

Somatic symptoms of anxiety and nonadherence to statin therapy.

BACKGROUND: The association between anxiety and nonadherence to preventive therapies remains unclear. We investigated whether somatic symptoms of anxiety predict statin nonadherence. METHODS: This is a prospective cohort study of 1924 individuals who responded to a questionnaire survey on health status and initiated statin therapy after the survey during 2008-2010. We followed the cohort for nonadherence, defined as the proportion of days covered <80%, during the 365days since the first dispensation after the survey. We used log-binomial regression to estimate the predictors of nonadherence. RESULTS: 18% of participants reported no experience of the eight somatic symptoms of anxiety (palpitation without exercise, irregular heartbeat, chest pain upon anger or emotion, sweating without exercise, flushing, tremor of hands or voice, muscle twitching) before the statin initiation, and 16% had experienced at least one symptom on average weekly to daily. 49% of respondents were nonadherent. Weekly to daily occurrence of these symptoms predicted a 33% increase in the risk of nonadherence (risk ratio [RR] 1.33, 95% confidence interval, CI, 1.13-1.57) compared to no symptoms when adjusted for sociodemographics, lifestyle risks, cardiovascular comorbidities, and depression. Particularly, chest pain upon anger or emotion (RR 1.21, 95% CI 1.01-1.46) and muscle twitching (RR 1.24, 95% CI 1.08-1.42) predicted an increased risk of nonadherence to statin therapy. Psychological symptoms of anxiety were not associated with nonadherence when adjusted for somatic symptoms. CONCLUSIONS: Somatic anxiety-related symptoms predicted nonadherence to statin therapy. Information on pre-existing somatic symptoms may help identifying patients at increased risk of statin nonadherence.

Natural history of bleeding and characteristics of early bleeders among warfarin initiators - a cohort study in Finland.

AIMS: The demand for oral anticoagulant therapy will continue to increase in the future along with the aging of the population. This study aimed to determine the rate of bleeding requiring hospitalization and to characterize early bleeders among persons initiating warfarin therapy. Characterization of those most susceptible to early bleeding is important in order to increase the safety of warfarin initiation. PATIENTS AND METHODS: Using data from nationwide health registers, we identified persons initiating warfarin therapy between January 1, 2009 and June 30, 2012, n=101,588, and followed them until hospitalization for bleeding, death, or administrative end of the study (December 31, 2012). We defined early bleeders as persons with a bleeding requiring hospitalization within 30 days since warfarin initiation. RESULTS: The rate of hospitalization for bleeding during a median follow-up of 1.9 years was 2.6% per person-year (95% confidence interval [CI] 2.5%-2.7%), with a peak within the first 30 days of warfarin initiation (6.5% per person-year, 95% CI 6.0%-7.1%). In a multivariable Cox proportional hazards regression analysis, early bleeders were characterized by prior bleeding (<180 days before initiation, hazard ratio [HR] =13.7, 95% CI 10.9-17.1; during 180 days-7 years before initiation, HR =1.48, 95% CI 1.15-1.90), male sex (HR =1.32, 95% CI 1.10-1.57), older age (HR =1.13, 95% CI 1.04-1.22, per 10-year increase), venous thrombosis (HR =1.83, 95% CI 1.44-2.34), pulmonary embolism (HR =1.46, 95% CI 1.11-1.91), alcohol abuse (HR =1.59, 95% CI 1.08-2.35), rheumatic disease (HR =1.40, 95% CI 1.07-1.83), and exposure to drugs with dynamic interaction mechanism with warfarin (HR =1.43, 95% CI 1.20-1.71). In age-adjusted models, Charlson comorbidity index and number of drugs predicted a graded increase in the hazard of early bleeding. CONCLUSION: The rate of hospitalizations for bleeding peaked in the beginning of warfarin therapy. Early bleeders were characterized by venous thrombosis, pulmonary embolism, and factors that increase bleeding risk without affecting the international normalized ratio.

Cardiovascular risk profile and use of statins at the age of 70 years: a comparison of two Finnish birth cohorts born 20 years apart.

OBJECTIVE: to compare cardiovascular morbidity and risk factor profiles of two 70-year-old cohorts of Finns examined in 1991 and 2011 and to describe prevalence of statin use according to cardiovascular risk in the later cohort. METHODS: 1920-born cohort of community-dwelling 70-year-old persons (n = 1032) participated in comprehensive health surveys, physical and laboratory examinations in the Turku Elderly Study (TUVA) during 1991-92. In 2011, identical examination pattern was performed, in a 1940-born cohort of 70-year-old persons (n = 956) from the same area. Prevalence of cardiovascular diseases (CVD) and risk factors in the two cohorts was compared. Further, each cohort was divided into three cardiovascular risk groups (high, moderate and low) based on their estimated risk. Prevalence of statin use was calculated among each risk group in the 1940 cohort. RESULTS: coronary heart disease (25 versus 11%) and peripheral artery disease (9 versus 2%) were more common in the 1920 than 1940 cohort, respectively. Lipid profile was worse and blood pressure higher in the earlier cohort, whereas use of statins and antihypertensives was more common in the later cohort. Forty-two per cent of the 1920 cohort and 29% of the 1940 cohort were estimated to have high cardiovascular risk. In the 1940 cohort, a total of 36% used statins. Statin use was most common among high-risk persons. CONCLUSIONS: seventy-year olds examined in 2011 had less CVD morbidity than their counterparts 20 years earlier, and their cardiovascular risk factors were better controlled which is reflected in higher use of preventive medications, such as statins and antihypertensives.

Adherence to statin therapy and the incidence of ischemic stroke in patients with diabetes.

PURPOSE: We aimed to quantify for the first time the relationship between statin adherence and ischemic stroke (IS) in patients with diabetes. METHODS: Using Finnish health registers, we assembled a cohort of 52 868 statin initiators with diabetes in 1995-2006. We conducted a nested case-control analysis matching cases with IS with up to four controls for age, sex, date of statin initiation and follow-up duration. Adjusted rate ratios for IS were estimated with conditional logistic regression. Additional potential confounders were considered with inverse probability weighting and the role of unmeasured confounding using external adjustment. Statin adherence was measured as the proportion of days covered (PDC). RESULTS: Among 1703 cases and 6799 controls, good adherence to statins (PDC ≥ 80%) was associated with a 23% decreased incidence of IS (95%CI 14-32%) compared with poor adherence (PDC < 80%). This association remained broadly unchanged when stratified by sex, age, history of atherosclerotic cardiovascular disease or IS. There was a dose-response relationship between adherence level and the risk of IS (RR 0.63 [0.53-0.75] for PDC ≥ 80% versus PDC < 20%, P for trend <0.0001). Among patients with good adherence, those initiating with low intensity statin therapy had a 15% lower incidence (95%CI 2-27%) and those initiating with moderate intensity therapy a 29% lower incidence (16-41%) of IS compared with those with poor adherence who initiated with low intensity therapy. Our sensitivity analyses supported the robustness of the results. CONCLUSIONS: In diabetes, poor statin adherence may considerably increase the risk of IS both in primary and secondary prevention of IS.

Impact of Statin Adherence on Cardiovascular Morbidity and All-Cause Mortality in the Primary Prevention of Cardiovascular Disease: A Population-Based Cohort Study in Finland.

OBJECTIVES: To assess the extent to which adherence to statins is associated with the incidence of cardiovascular (CV) events and all-cause mortality in the primary prevention of CV diseases and whether different analytical approaches influence the observed associations. METHODS: This population-based cohort study used data from Finnish registers. The cohort included 97,575 new statin users aged 45 to 75 years in 2001 to 2004 with no CV diseases at baseline. Exposure was defined as adherence to statins (proportion of days covered [PDC]). The primary outcome was any CV event or death during a 3-year follow-up. Different analytical approaches, including multivariable-adjusted Cox regression, inverse probability weighting with time-varying adherence, and propensity score calibration, were used. RESULTS: During the first year of follow-up, 53% displayed good (PDC ≥80%), 26% had intermediate (PDC 40%-79%), and 21% exhibited poor (PDC <40%) adherence. After adjustment for sociodemographic and clinical covariates, a 25% relative risk reduction (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.71-0.79) was observed in the rate of any CV event or death among good versus poor adherers. Good adherers also had a lower incidence than poor adherers of acute coronary syndrome (HR 0.56; 95% CI 0.49-0.65) and acute cerebrovascular disease events (HR 0.67; 95% CI 0.60-0.76). The different analytical approaches achieved comparable results for all the outcomes. CONCLUSIONS: The incidence of CV events and mortality was higher in poor versus good adherers. Different analytical methods that took into account changes in adherence and confounding at baseline did not appreciably affect the results.

Influence of Retirement on Adherence to Statins in the Insurance Medicine All-Sweden Total Population Data Base.

BACKGROUND: Retirement has been suggested to reduce medication adherence, but no evidence is available for statins. We investigated changes in adherence to statins among Swedish adults after retirement. METHODS: A prospective cohort study was carried out on all individuals living in Sweden on 31 December 2004, alive in 2010, having purchased statins in the second half of 2005, and retired in 2008 (n=11 718). We used prescription dispensing data in 2006-2010 to determine nonadherence (defined as <80% of days covered by filled prescriptions) before and after old-age or disability retirement. Using multiple repeat measurements of filled statin prescriptions, we calculated the annual prevalence rates of nonadherence for those who continued therapy. Discontinuation was defined as no statin dispensations during a calendar year. RESULTS: After adjustment for age at retirement, the prevalence ratio (PR) of nonadherence after retirement in comparison with those before retirement was 1.23 [95% confidence interval (CI) 1.17-1.29] for the men and 1.19 (95% CI 1.13-1.26) for the women. A post-retirement increase in nonadherence was consistently observed across the strata of age at retirement, marital status, education, income, type of retirement, and participants with and without cardiovascular disease, the largest increases being observed for statin use in secondary prevention (men: PR 1.38, 95% CI 1.26-1.54; women: PR 1.43, 1.18-1.72). For primary prevention, the corresponding prevalence ratios were 1.18 (95% CI 1.13‒1.25) and 1.18 (95% CI 1.11-1.24), respectively. INTERPRETATION: Retirement appears to be associated with increased nonadherence to statin therapy among Swedish men and women.

Childhood adversity as a predictor of non-adherence to statin therapy in adulthood.

PURPOSE: To investigate whether adverse experiences in childhood predict non-adherence to statin therapy in adulthood. METHODS: A cohort of 1378 women and 538 men who initiated statin therapy during 2008-2010 after responding to a survey on childhood adversities, was followed for non-adherence during the first treatment year. Log-binomial regression was used to estimate predictors of non-adherence, defined as the proportion of days covered by dispensed statin tablets <80%. In fully adjusted models including age, education, marital status, current smoking, heavy alcohol use, physical inactivity, obesity, presence of depression and cardiovascular comorbidity, the number of women ranged from 1172 to 1299 and that of men from 473 to 516, because of missing data on specific adversities and covariates. RESULTS: Two in three respondents reported at least one of the following six adversities in the family: divorce/separation of the parents, long-term financial difficulties, severe conflicts, frequent fear, severe illness, or alcohol problem of a family member. 51% of women and 44% of men were non-adherent. In men, the number of childhood adversities predicted an increased risk of non-adherence (risk ratio [RR] per adversity 1.11, 95% confidence interval [CI] 1.01-1.21], P for linear trend 0.013). Compared with those reporting no adversities, men reporting 3-6 adversities had a 1.44-fold risk of non-adherence (95% CI 1.12-1.85). Experiencing severe conflicts in the family (RR 1.27, 95% CI 1.03-1.57]) and frequent fear of a family member (RR 1.27, 95% CI 1.00-1.62]) in particular, predicted an increased risk of non-adherence. In women, neither the number of adversities nor any specific type of adversity predicted non-adherence. CONCLUSIONS: Exposure to childhood adversity may predict non-adherence to preventive cardiovascular medication in men. Usefulness of information on childhood adversities in identification of adults at high risk of non-adherence deserves further research.