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.

Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data.

Objective To characterise the determinants, time course, and risks of acute myocardial infarction associated with use of oral non-steroidal anti-inflammatory drugs (NSAIDs).Design Systematic review followed by a one stage bayesian individual patient data meta-analysis.Data sources Studies from Canadian and European healthcare databases.Review methods Eligible studies were sourced from computerised drug prescription or medical databases, conducted in the general or an elderly population, documented acute myocardial infarction as specific outcome, studied selective cyclo-oxygenase-2 inhibitors (including rofecoxib) and traditional NSAIDs, compared risk of acute myocardial infarction in NSAID users with non-users, allowed for time dependent analyses, and minimised effects of confounding and misclassification bias. Exposure and outcomes Drug exposure was modelled as an indicator variable incorporating the specific NSAID, its recency, duration of use, and dose. The outcome measures were the summary adjusted odds ratios of first acute myocardial infarction after study entry for each category of NSAID use at index date (date of acute myocardial infarction for cases, matched date for controls) versus non-use in the preceding year and the posterior probability of acute myocardial infarction.Results A cohort of 446 763 individuals including 61 460 with acute myocardial infarction was acquired. Taking any dose of NSAIDs for one week, one month, or more than a month was associated with an increased risk of myocardial infarction. With use for one to seven days the probability of increased myocardial infarction risk (posterior probability of odds ratio >1.0) was 92% for celecoxib, 97% for ibuprofen, and 99% for diclofenac, naproxen, and rofecoxib. The corresponding odds ratios (95% credible intervals) were 1.24 (0.91 to 1.82) for celecoxib, 1.48 (1.00 to 2.26) for ibuprofen, 1.50 (1.06 to 2.04) for diclofenac, 1.53 (1.07 to 2.33) for naproxen, and 1.58 (1.07 to 2.17) for rofecoxib. Greater risk of myocardial infarction was documented for higher dose of NSAIDs. With use for longer than one month, risks did not appear to exceed those associated with shorter durations.Conclusions All NSAIDs, including naproxen, were found to be associated with an increased risk of acute myocardial infarction. Risk of myocardial infarction with celecoxib was comparable to that of traditional NSAIDS and was lower than for rofecoxib. Risk was greatest during the first month of NSAID use and with higher doses.

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.

[Update on current care guidelines. Pain]. / KÄYPÄ HOITO -SUOSITUS (Tiivistelmä). Kipu.

Management of patients suffering from chronic pain is based on long-term therapeutic relationship. The main objectives of the treatment are pain relief, restoration of function and improvement of quality of life. Interventions for treatment and rehabilitation need to be planned in agreement with the patient. Non-pharmaceutical interventions form the basics of the treatment. If medication is needed, it should be tailored to meet the individual needs of the patient according to the etiology and intensity of pain, comorbidities and psychosocial situation.

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.

Analgesic use before and after oral anticoagulant initiation--a population-based study in Finland.

PURPOSE: Due to potential drug-drug interactions and subsequent bleeding risk, analgesic use should be reviewed when an oral anticoagulant is initiated. The aim of this study was to compare use of non-steroidal anti-inflammatory drugs (NSAIDs) and other analgesics before and after oral anticoagulant initiation. METHODS: All individuals who initiated warfarin, dabigatran, or rivaroxaban between January 2012 and September 2013 were identified from the Finnish Prescription Register. Prevalence of analgesic use during 3 months after oral anticoagulant initiation was compared to analgesic use during 4 months before initiation. Analgesics included were NSAIDs, paracetamol, paracetamol in doses ≥ 2 g/day, tramadol, and other opioids. Conditional logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: In total, 54,025 initiated warfarin, 16,894 rivaroxaban, and 1569 dabigatran. The odds of NSAID use decreased among warfarin initiators (odds ratio (OR) 0.10; 95% confidence interval (CI) 0.09-0.10); 2.6% used NSAID after initiation. In contrast, the odds of NSAID use increased among rivaroxaban (OR 3.56; 95% CI 3.37-3.75) and dabigatran initiators (OR 1.44; 95% CI 1.16-1.78). The proportions using NSAIDs after the initiation were 69 and 32%, respectively. However, NSAID use decreased among dabigatran initiators with confirmed atrial fibrillation (OR 0.46; 95% CI 0.23-0.92) and among rivaroxaban initiators with a daily dose of ≥ 15 mg (OR 0.28; 95% CI 0.19-0.40). CONCLUSIONS: The use of NSAIDs decreases extensively among warfarin initiators which is encouraging. However, the use of NSAIDs increases among rivaroxaban and dabigatran initiators. This is a concern as the bleeding risk may increase due to potential pharmacodynamic interactions.

Accumulation of cardiovascular and diabetes medication among apparently healthy statin initiators.

PURPOSE: To characterize accumulation of drug-modifiable cardiovascular (CV) risk factors in statin initiators who had no prior medication or hospitalizations for CV disease or diabetes. METHODS: A cohort of 45-75-year-old statin initiators in Finland with no prior CV diseases, diabetes or medication for these conditions was followed up for 24 months after statin initiation for accumulation of CV and diabetes drugs. The number of drugs was measured semi-annually since the first statin purchase and analyzed by growth mixture modeling. RESULTS: Of the 11 948 apparently healthy statin initiators, 34% purchased at least one additional CV or diabetes drug during the subsequent 24 months. Of those, 20% redeemed no other CV or diabetes drugs at statin initiation but started to accumulate them after 18 months of follow-up, receiving on average 1.3 other drugs at 24 months. The majority, 59%, redeemed on average 0.5 drugs at statin initiation and accumulated 1.5 drugs by the end of 24-month follow-up. Seventeen percent received 1 additional drug at statin initiation, accumulating on average 3 drugs. The remaining 4% with an average of 2 CV or diabetes drugs at statin initiation redeemed 3.5 additional drugs during the follow-up. CONCLUSIONS: Two years after statin initiation, 2 in 3 apparently healthy initiators could still be defined as such as reflected by CV and diabetes medication use.

Co-Prescribing of Potentially Interacting Drugs during Warfarin Therapy - A Population-Based Register Study.

We analysed the occurrence of co-prescribing of potentially interacting drugs during warfarin therapy in the community-dwelling population of Finland. We identified drugs having interaction potential with warfarin using the Swedish Finnish INteraction X-referencing drug-drug interaction database (SFINX) and obtained data on drug purchases from the nationwide Prescription Register. We defined warfarin users as persons purchasing warfarin in 2010 (n = 148,536) and followed them from their first prescription in 2010 until the end of the calendar year. Co-prescribing was defined as at least 1-day overlap between warfarin and interacting drug episodes. In addition, we identified persons who initiated warfarin therapy between 1 January 2007 and 30 September 2010 (n = 110,299) and followed these incident users for a 3-month period since warfarin initiation. Overall, 74.4% of warfarin users were co-prescribed interacting drugs. Co-prescribing covered 46.4% of the total person-years of warfarin exposure. Interacting drugs that should be avoided with warfarin were co-prescribed for 13.4% of warfarin users. The majority of the co-prescriptions were for drugs that are not contraindicated during warfarin therapy but require special consideration. Among incident users, 57.1% purchased potentially interacting drugs during the 3-month period after initiation, while 9.0% purchased interacting drugs that should be avoided with warfarin. To conclude, the occurrence of co-prescribing of potentially interacting drugs was high during warfarin therapy. Our findings highlight the importance of close monitoring of warfarin therapy and the need for further studies on the clinical consequences of co-prescribing of interacting drugs with warfarin.

Are statin trials in diabetes representative of real-world diabetes care: a population-based study on statin initiators in Finland.

OBJECTIVE: To assess the representativeness of the Heart Protection Study (HPS) and the Collaborative Atorvastatin Diabetes Study (CARDS) for incident statin users. DESIGN: A population-based analysis with linked register data. SETTING: Finland. POPULATION: 56 963 patients with diabetes initiating statin use from 2005 to 2008. MAIN OUTCOME MEASURES: We determined the proportions of real-world patients who fulfilled the eligibility criteria for HPS and CARDS trials and assessed the cardiovascular disease (CVD) event rates, assumed to reflect the background CVD risk, for those eligible and ineligible. We used descriptive statistics to identify the patient characteristics, lipid-lowering interventions and adherence to statin therapy. RESULTS: Of the real-world patients, 57% (N=32 582) fulfilled the eligibility criteria for HPS (DM) and 49% (N=20 499) of those without CVD for CARDS. The patients ineligible for HPS (DM) had a higher cumulative risk for CVD events than those eligible, whereas regarding CARDS the cumulative risks were of similar magnitude. The overall CVD event rates seemed to be comparable to those in the reviewed trials. Both trials were under-representative of women and users of antihypertensive agents and metformin. 27% and 29% of real-world patients had an initial statin dose corresponding to <20 mg of simvastatin. The proportions of patients who were deemed adherent were 57% in the real world and 85% in both trials. CONCLUSIONS: Only half of the real-world patients would have qualified for the HPS (DM) and CARDS, limiting their representativeness for clinical practice. Women and users of antihypertensive agents and metformin were under-represented in both trials. These deviations reflect the changes in diabetes treatment over the years and are not expected to modify the average treatment effects of statins on CVD. Prescribing of lower statin doses in clinical practice than used in the trials and lower adherence may, however, attenuate the benefits in the real world.

Older statin initiators in Finland - cardiovascular risk profiles and persistence of use.

PURPOSE: The benefits of statin treatment initiated in advanced age are largely unknown; however, good adherence to treatment is essential for beneficial effects to be achieved also when treating older people. This study characterizes older statin initiators, including their cardiovascular risk profiles and morbidity, and investigates patterns of treatment persistence. METHODS: Longitudinal register-based study. All statin initiators in Finland aged ≥70 in 2000-2008 (n = 157,709) were identified from the nationwide Prescription Register. Using information from comprehensive health registers, the initiators were classified as having low, moderate, or high cardiovascular risk. For the initiators in 2000 and 2004, patterns of persistence were evaluated over a 4-year follow-up using the anniversary method. RESULTS: The annual number of statin initiators increased from 15,082 to 19,728; the proportion of those aged ≥80 increased from 12.9 to 25.8 %. The prevalence of coronary heart disease at statin initiation decreased from 45.5 to 28.1 %. Only every tenth initiator (9.2-11.7 %) was estimated to have low cardiovascular risk each year. Four in five initiators (76.9-80.5 %) persisted with statin treatment after 1 year. The probability to survive and remain persistent for 4 years was 51.6 % and the probability to discontinue within the first year without restarting in the subsequent 3 years was 9.1 %. There were no noticeable differences in persistence across the risk groups. CONCLUSIONS: Long-term persistence with statins among older people was good across cardiovascular risk groups. These findings are consistent with the notion that the decision on long-term continuation of statin use is made during the first year of treatment.

Sequential cohort design applying propensity score matching to analyze the comparative effectiveness of atorvastatin and simvastatin in preventing cardiovascular events.

BACKGROUND: Sequential cohort design (SCD) applying matching for propensity scores (PS) in accrual periods has been proposed to mitigate bias caused by channeling when calendar time is a proxy for strong confounders. We studied the channeling of patients according to atorvastatin and simvastatin initiation in Finland, starting from the market introduction of atorvastatin in 1998, and explored the SCD PS approach to analyzing the comparative effectiveness of atorvastatin versus simvastatin in the prevention of cardiovascular events (CVE). METHODS: Initiators of atorvastatin or simvastatin use in the 45-75-year age range in 1998-2006 were characterized by their propensity of receiving atorvastatin over simvastatin, as estimated for 17 six-month periods. Atorvastatin (10 mg) and simvastatin (20 mg) initiators were matched 1∶1 on the PS, as estimated for the whole cohort and within each period. Cox regression models were fitted conventionally, and also for the PS matched cohort and the periodically PS matched cohort, to estimate the hazard ratios (HR) for CVEs. FINDINGS: Atorvastatin (10 mg) was associated with a 11%-12% lower incidence of CVE in comparison with simvastatin (20 mg). The HR estimates were the same for a conventional Cox model (0.88, 95% confidence interval 0.85-0.91), for the analysis in which the PS was used to match across all periods and the Cox model was adjusted for strong confounders (0.89, 0.85-0.92), and for the analysis in which PS matching was applied within sequential periods (0.88, 0.84-0.92). The HR from a traditional PS matched analysis was 0.80 (0.77-0.83). CONCLUSIONS: The SCD PS approach produced effect estimates similar to those obtained in matching for PS within the whole cohort and adjusting the outcome model for strong confounders, but at the cost of efficiency. A traditional PS matched analysis without further adjustment in the outcome model produced estimates further away from unity.

Register-based predictors of adherence among new statin users in Finland.

BACKGROUND: Although register-based studies on statin adherence are increasing, for administrative data, little is known about the explanatory power of the predictors that explain adherence. OBJECTIVE: The aim was to explore the ability of variables in administrative data to predict statin adherence in an unselected, universally insured population and, especially, to explore dispensation delay (time elapsed between prescription and dispensation) and out-of-pocket costs as explanatory factors. METHODS: Statin initiators who were aged 45 to 75 years in 2000-2004 (n = 247, 051) were identified in the Finnish Prescription Register. First-year statin adherence was measured as the proportion of days covered (PDC). The effect of variables related to patient, health care, and payment was assessed with multivariable logistic regression. The C statistic was used to evaluate the explanatory power of different models. RESULTS: Overall, 54.6% of the cohort had good adherence (PDC ≥ 80%). The explanatory power of all the models was low (C = 0.666 for the full model). The multivariable models, including only payment variables, had a greater explanatory power (C = 0.627) than models with only patient (C = 0.602) or health care (C = 0.548) variables. A shorter dispensation delay and lower out-of-pocket costs predicted better adherence. Of other patient-related variables, age, presence of acute coronary syndrome, and use of cardiovascular medications were significant predictors of adherence. Type of statin and the prescriber's workplace were also significantly associated with adherence. CONCLUSIONS: Models based on administrative data do not provide useful prediction of statin adherence. Of the individual predictors, long dispensation delay may serve as a practical tool for identifying patients at risk of poor adherence. Increases in out-of-pocket costs predict nonadherence.

Channelling of statin use towards low-risk population and patients with diabetes.

This study based on nationwide comprehensive health registers analysed trends in characteristics of statin users in the whole community-dwelling population of Finland between 1999 and 2008. The annual number of incident users (defined as those purchasing statins for the first time ever) increased 1.6-fold from 50,125 to 78,058 and that of ongoing users (including continuous users and re-initiators) increased 4.6-fold from 114,091 to 521,211. The proportion of incident users without cardiovascular disease (CVD) or diabetes increased from 23.6% to 27.8%, while the proportion of those with diabetes increased from 15.7% to 19.5%. An increasing proportion of ongoing users had diabetes (from 13.8% to 22.8%). The proportion of ongoing users without CVD or diabetes remained below one-fifth; however, their number increased five-fold. Over the study period, there was an obvious shift towards prescribing of higher statin doses both among incident and ongoing users. In conclusion, statin use is expanding to individuals with low cardiovascular risk despite the fact that clinical guidelines emphasize interventions other than pharmacotherapy for this population. At the same time, statin use is increasingly targeted to patients with diabetes, a high-risk group that is likely to benefit from it.

Statin use among older Finns stratified according to cardiovascular risk.

PURPOSE: Statin use has increased in older age groups, although there is little evidence for the benefits of statin therapy in the elderly, especially in low-risk persons. The aim of this paper is to describe recent trends in the prevalence and incidence of statin use among the Finnish older population, according to the person's estimated cardiovascular (CV) event risk. METHODS: We conducted a register study covering the whole community-dwelling population of Finland, aged >70 years in 2000-2008 (N = 883,051). Data on reimbursed purchases of statins, antidiabetic and CV drugs, and pre-existing CV diseases were retrieved from comprehensive national registers. We stratified each person into low, moderate or high CV risk category, and according to age (70-74, 75-79, and >80 years) and sex. RESULTS: Between 2000 and 2008, the age-sex-standardized prevalence of statin use tripled from 12.2 % to 38.7 % (rate ratio 3.0, 95 % CI 3.0-3.1), and the incidence almost doubled (from 3.7 % to 6.8 %; rate ratio 1.8, 95 % CI 1.8-1.9). The prevalence and incidence of statin use were consistently highest among high-risk persons. The greatest relative increases were observed in persons aged >80 years and in those at low risk; however, the proportion of statin users at low CV risk remained the same (∼7 % of all users). CONCLUSIONS: Statin prescribing is shifting towards older age groups. A substantial increase in prevalence and incidence was seen across all risk categories, but the channeling of statin use towards high-risk persons remained unchanged.

Statins and hip fracture prevention--a population based cohort study in women.

OBJECTIVE: To study the association of long-term statin use and the risk of low-energy hip fractures in middle-aged and elderly women. DESIGN: A register-based cohort study. SETTING: Finland. PARTICIPANTS: Women aged 45-75 years initiating statin therapy between 1996 and 2001 with adherence to statins ≥ 80% during the subsequent five years (n = 40,254), a respective cohort initiating hypertension drugs (n = 41 610), and women randomly selected from the population (n = 62 585). MAIN OUTCOME MEASURES: Incidence rate of and hazard ratio (HR) for low-energy hip fracture during the follow-up extending up to 7 years after the 5-year exposure period. RESULTS: Altogether 199 low-energy hip fractures occurred during the 135 330 person-years (py) of follow-up in the statin cohort, giving an incidence rate of 1.5 hip fractures per 1000 py. In the hypertension and the population cohorts, the rates were 2.0 per 1000 py (312 fractures per 157,090 py) and 1.0 per 1000 py (212 fractures per 216 329 py), respectively. Adjusting for a propensity score and individual variables strongly predicting the outcome, good adherence to statins for five years was associated with a 29% decreased risk (HR 0.71; 95% CI 0.58-0.86) of a low-energy hip fracture in comparison with adherent use of hypertension drugs. The association was of the same magnitude when comparing the statin users with the population cohort, the HR being 0.69 (0.55-0.87). When women with poor (<40%), moderate (40 to 80%), and good adherence (≥ 80%) to statins were compared to those with good adherence to hypertension drugs (≥ 80%) or to the population cohort, the protective effect associated with statin use attenuated with the decreasing level of adherence. CONCLUSIONS: 5-year exposure to statins is associated with a reduced risk of low-energy hip fracture in women aged 50-80 years without prior hospitalizations for fractures.

Change in antihypertensive drug prescribing after guideline implementation: a controlled before and after study.

BACKGROUND: Antihypertensive drug choices and treatment levels are not in accordance with the existing guidelines. We aimed to assess the impact of a guideline implementation intervention on antihypertensive drug prescribing. METHODS: In this controlled before and after study, the effects of a multifaceted (education, audit and feedback, local care pathway) quality programme was evaluated. The intervention was carried out in a health centre between 2002 and 2003. From each health care unit (n = 31), a doctor-nurse pair was trained to act as peer facilitators in the intervention.All antihypertensive drugs prescribed by 25 facilitator general practitioners (intervention GPs) and 53 control GPs were retrieved from the nationwide Prescription Register for three-month periods in 2001 and 2003. The proportions of patients receiving specific antihypertensive drugs and multiple antihypertensive drugs were measured before and after the intervention for three subgroups of hypertension patients: hypertension only, with coronary heart disease, and with diabetes. RESULTS: In all subgroups, the use of multiple concurrent medications increased. For intervention patients with hypertension only, the odds ratio (OR) was 1.12 (95% CI 0.99, 1.25; p = 0.06) and for controls 1.13 (1.05, 1.21; p = 0.002). We observed no statistically significant differences in the change in the prescribing of specific antihypertensive agents between the intervention and control groups. The use of agents acting on the renin-angiotensin-aldosterone system increased in all subgroups (hypertension only intervention patients OR 1.19 (1.06, 1.34; p = 0.004) and controls OR 1.24 (1.15, 1.34; p < 0.0001). CONCLUSIONS: A multifaceted guideline implementation intervention does not necessarily lead to significant changes in prescribing performance. Rigorous planning of the interventions and quality projects and their evaluation are essential.

Dynamics of long-term statin therapy.

PURPOSE: Knowledge of the different usage patterns that emerge during a long-term statin therapy is limited. The aim of this study was to characterize statin use, including the rates of reinitiation after extended periods of non-use, transitions between good and poor adherence, and the effect of the length of a drug-free period on the identification of new users. METHODS: The study cohort comprised individuals aged 45-84 years who were identified in the Finnish prescription register as having purchased statins between 1997 and 2007. New users in 1997, including those with no statin purchases during the preceding 3 years, were followed-up until institutionalization, death, or 31 December 2007. Reinitiation rates after ≥180 days with no refill for statins were analyzed using survival analysis. Annual adherence levels and the prevalences of good (proportion of days covered ≥0.80) and poor (<0.80) adherence were calculated for ten 1-year periods following initiation. For statin users in 2007, purchases were captured over the previous 10 years. RESULTS: Based on the data extracted from the Finnish prescription register, 32,760 persons initiated statin treatment in 1997, of whom 48.1% had discontinued it for at least 180 days by the end of the follow-up period. Of the discontinuers, 46.7% restarted the treatment within 1 year and 88.7% by the end of the follow-up. Of those followed up for ≥10 years, 51.8% had ≥6 years of treatment with good adherence. In 2007, 27.7% of the initiators having no statin purchases within the previous year had refills during the preceding 10 years. CONCLUSION: Statin use is dynamic. This should be taken into consideration in clinical practice and when studying the incidence, patterns, and health outcomes of statin use.

Statin adherence and the risk of major coronary events in patients with diabetes: a nested case-control study.

AIMS: To evaluate whether good statin adherence is associated with a reduced incidence of major coronary events (MCEs) among diabetic patients with and without coronary heart disease (CHD). METHODS: Using data derived by linkage of nationwide health databases in Finland, we conducted a nested case-control analysis of 3513 cases with an MCE, a composite of acute myocardial infarction and/or coronary revascularization, and 20,090 matched controls identified from a cohort of 60,677 statin initiators with diabetes. Cases and controls were matched according to gender, time of cohort entry and duration of follow-up and further classified to two risk groups according to the presence of CHD at statin initiation. The incidence of MCEs was compared between patients with good statin adherence (the proportion of days covered ≥80%) and patients with poor statin adherence (<80%). Odds ratios (OR) for MCEs were estimated by conditional logistic regression adjusting for several covariables. RESULTS: Good statin adherence was associated with a reduced incidence of MCEs in those with prior CHD [OR 0.84 (95% CI 0.74-0.95)] and in those without it [OR 0.86 (95% CI 0.78-0.95)]. The association persisted among those followed up for 5 years or longer [OR 0.77 (95% CI 0.58-1.02) and OR 0.79 (95% CI 0.66-0.94) respectively]. In sensitivity analyses, a reduced MCE incidence was observed also in those without any documented cardiovascular disease (CVD) at statin initiation [OR 0.87 (95% CI 0.78-0.96) overall and OR 0.80 (95% CI 0.66-0.97) for those followed up 5 years or longer]. CONCLUSIONS: In patients with diabetes, good adherence to statins predicts reduced incidence of MCEs irrespective of the presence of CHD at statin initiation.