Overuse of short-acting ß2-agonists in asthma is associated with increased risk of exacerbation and mortality: a nationwide cohort study of the global SABINA programme.

BACKGROUND: Overuse of short-acting ß2-agonists (SABA) may indicate poor asthma control and adverse health outcomes. Contemporary population-based data on use, risk factors and impact of SABA (over)use on asthma exacerbations and mortality are scarce, prompting initiation of the global SABINA (SABA use IN Asthma) programme. METHODS: By linking data from Swedish national registries, asthma patients aged 12-45 years with two or more collections of drugs for obstructive lung disease during 2006-2014 were included. SABA overuse was defined as collection of more than two SABA canisters in a 1-year baseline period following inclusion. SABA use was grouped into 3-5, 6-10 and ≥11 canisters per baseline-year. Cox regression was used to examine associations between SABA use and exacerbation (hospitalisations and/or oral corticosteroid claims) and mortality. RESULTS: The analysis included 365 324 asthma patients (mean age 27.6 years; 55% female); average follow-up was 85.4 months. 30% overused SABA, with 21% collecting 3-5 canisters per year, 7% collecting 6-10 canisters per year and 2% collecting ≥11 canisters per year. Increasing number of collected SABA canisters was associated with increased risk of exacerbation, as follows. 3-5 canisters: hazard ratio (HR) 1.26 (95% CI 1.24-1.28); 6-10 canisters: 1.44 (1.41-1.46); and ≥11 canisters: 1.77 (1.72-1.83), compared to two or fewer canisters per year. Higher SABA use was associated with incrementally increased mortality risk (2564 deaths observed), as follows. 3-5 canisters: HR 1.26 (95% CI 1.14-1.39); 6-10 canisters 1.67 (1.49-1.87); and ≥11 canisters: 2.35 (2.02-2.72) compared to two or fewer canisters per year. CONCLUSION: One-third of asthma patients in Sweden collected three or more SABA canisters annually. SABA overuse was associated with increased risks of exacerbation and mortality. These findings emphasise that monitoring of SABA usage should be key in improving asthma management.

Concomitant use of drugs known to cause interactions with oral antiplatelets-polypharmacy in acute coronary syndrome outpatients in Finland.

PURPOSE: Use of oral antiplatelets (OAPs) is essential for preventing thrombotic events in patients with acute coronary syndrome (ACS). Effects of clopidogrel, prasugrel, and ticagrelor may be enhanced due to pharmacodynamic interactions, but as CYP substrates, they are prone to pharmacokinetic interactions too. The aim was to study polypharmacy in ACS patients following hospital discharge. METHODS: This observational drug utilization study linked patient-level data from nationwide registers. The study population consisted of adult ACS patients discharged from Finnish hospitals in 2009-2013. Logistic regression was used to model the probability of drug-drug interactions with odd ratios for predefined predictors such as age, gender, and ACS type. RESULTS: In the cohort of 54,416 ACS patients, 91% of those treated with OAP received clopidogrel. Of clopidogrel-treated patients, 12% purchased warfarin at least once while on clopidogrel treatment. Old age, male sex, ST-elevation myocardial infarction as index event, and a history of previous ACS events were associated with an increased risk of warfarin-OAP interaction (p < 0.001 for all). Ibuprofen, and serotonergic drugs tramadol, citalopram, and escitalopram were the next most common drugs causing pharmacodynamic interactions. In general, concomitant use of drugs known to cause pharmacokinetic interactions was rare, but both esomeprazole and omeprazole were prescribed in more than 6% of clopidogrel-treated patients. CONCLUSIONS: Warfarin and ibuprofen were the most commonly used concomitant medications causing pharmacodynamic interactions and potentially increasing the risk of bleeding in OAP-treated patients. Esomeprazole and omeprazole were used in clopidogrel-treated patients although there are alternatives available for gastric protection.

Predictors for repeated hyperkalemia and potassium trajectories in high-risk patients - A population-based cohort study.

Understanding predictors and trajectories of increased potassium may inform testing and treatment of hyperkalemia. We examined predictors for repeated hyperkalemia among patients after first-time renin angiotensin system inhibitor (RASi) prescription, chronic kidney disease (CKD), or chronic heart failure (CHF); and we also examined potassium trajectories in these patients after their first hyperkalemia event. We used Danish population-based registries to identify all patients with first-time RASi prescription, incident CKD, or incident CHF (2000-2012). For patients with a first hyperkalemia event, potassium trajectories over the following 6 months were examined. The predictors associated with repeated hyperkalemia were assessed, with repeated hyperkalemia defined as a potassium test >5.0 mmol/L after the first event within 6 months. Overall 262,375 first-time RASi users, 157,283 incident CKD patients, and 14,600 incident CHF patients were included. Of patients with a first hyperkalemia event, repeated hyperkalemia within 6 months occurred in 37% of RASi users, 40% with CKD, and 49% of patients with CHF. Predictors included severe hyperkalemia, low eGFR, diabetes, and spironolactone use. In all cohorts, the median potassium levels declined over 2-4 weeks after a hyperkalemia event for the first time, but reverted to levels higher than before the initial hyperkalemia event in those who had repeated hyperkalemia. Following hyperkalemia, discontinuation of RASi and spironolactone was common in the RASi and CHF cohorts. Repeated hyperkalemia was common among the explored cohorts. The first hyperkalemia event was an indicator of increased median potassium levels. Predictors may identify patients likely to benefit from intensified monitoring and intervention.

Oral corticosteroid use, morbidity and mortality in asthma: A nationwide prospective cohort study in Sweden.

BACKGROUND: Patterns and determinants of long-term oral corticosteroid (OCS) use in asthma and related morbidity and mortality are not well-described. In a nationwide asthma cohort in Sweden, we evaluated the patterns and determinants of OCS use and risks of OCS-related morbidities and mortality. METHODS: Data for 217 993 asthma patients (aged ≥ 6 years) in secondary care were identified between 2007 and 2014 using Swedish national health registries. OCS use at baseline was categorized: regular users (≥5 mg/d/y; n = 3299; 1.5%); periodic users (>0 but <5 mg/d/y; n = 49 930; 22.9%); and nonusers (0 mg/d/y; n = 164 765; 75.6%). Relative risks of becoming a regular OCS user and for morbidity and mortality were analysed using multivariable Cox regression. RESULTS: At baseline, 24% of asthma patients had used OCS during the last year and 1.5% were regular users. Of those not using OCS at baseline, 26% collected at least one OCS prescription and 1.3% became regular OCS users for at least 1 year during the median follow-up of 5.3 years. Age at asthma diagnosis, increasing GINA severity and Charlson Comorbidity Index were associated with regular OCS use. Compared to periodic and non-OCS use, regular use was associated with increased incidence of OCS-related morbidities and greater all-cause mortality, adjusted HR 1.34 (95% CI 1.24-1.45). CONCLUSIONS: Oral corticosteroids use is frequent for asthma patients, and many are regular users. Regular OCS use is associated with increased risk of morbidity and mortality. These findings indicate that there is a need of other treatment options for patients with severe asthma who are using regular OCS.

Usage of PCI and long-term cardiovascular risk in post-myocardial infarction patients: a nationwide registry cohort study from Finland.

BACKGROUND: Despite currently available treatments, the burden of myocardial infarction (MI) morbidity and mortality remains prominent. The aim of this was to investigate the risk of developing subsequent cardiovascular events in MI patients. METHODS: This was an observational, retrospective cohort database linkage study using patient level data from Finland. Cox proportional hazards models were used to assess the association of risk between the preselected covariates and incidence of specific outcomes. The primary endpoints were new MI, stroke, cardiovascular mortality and overall mortality. RESULTS: Finnish adult MI patients alive 7 days after discharge in 2009-2012 were included. The study cohort consisted of 32,909 MI patients, of whom 25,875 (79%) survived 12 months without subsequent MI or stroke. ST-elevation MI (STEMI) was associated with lower risk of subsequent MI and overall mortality compared to non-STEMI patients. Percutaneous coronary intervention (PCI) was used two times more often in STEMI patients, but patients with prior stroke were more than two times less likely to have PCI. Dementia/Alzheimer's disease decreased the use of PCI as much as age over 85 years. Female sex was an independent factor for not undergoing PCI (OR 0.75, P < 0.001 compared to men) but was nevertheless associated with lower risk of new MI and mortality (HR 0.8-0.9, P < 0.001 for all). Increased age was associated with increased event risk and PCI with decreased event risk. CONCLUSIONS: Risk of cardiovascular events and mortality after MI increases steeply with age. Although at higher risk, aging patients and those with cardiovascular comorbidities are less likely to receive PCI after MI. Female sex is associated with better survival after MI regardless of less intensive treatment in women.

Editor's Choice - Impact of Comorbidity, Medication, and Gender on Amputation Rate Following Revascularisation for Chronic Limb Threatening Ischaemia.

OBJECTIVE/BACKGROUND: Chronic limb threatening ischaemia (CLTI) has a high risk of amputation and mortality. Increased knowledge on how sex, comorbidities, and medication influence these outcomes after revascularisation may help optimise results and patient selection. METHODS: This population based observational cohort study included all individuals revascularised for CLTI in Sweden during a five year period (10,617 patients in total). Data were retrieved and merged from mandatory national healthcare registries, and specifics on amputations were validated with individual medical records. RESULTS: Mean age at revascularisation was 76.8 years. Median follow up was 2.7 years (range 0-6.6 years). Male sex (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.33), renal insufficiency (HR 1.57, 95% CI 1.32-1.87), diabetes (HR 1.45, 95% CI 1.32-1.60), and heart failure (HR 1.17, 95% CI 1.05-1.31) were independently associated with an increased amputation rate, whereas the use of statins (HR 0.71, 95% CI 0.64-0.78) and low dose acetylsalicylic acid (HR 0.77, 95% CI 0.70-0.86) were associated with a reduced amputation rate. For the combined end point of amputation or death, an association with increased rates was found for male sex (HR 1.25, 95% CI 1.18-1.32), renal insufficiency (HR 1.94, 95% CI 1.75-2.14), heart failure (HR 1.50, 95% CI 1.40-1.60), and diabetes (HR 1.31, 95% CI 1.23-1.38). The use of statins (HR 0.74, 95% CI 0.67-0.82) and low dose acetylsalicylic acid (HR 0.82, 95% CI 0.77-0.88]) were related to a reduced risk of amputation or death. CONCLUSIONS: Renal insufficiency is the strongest independent risk factor for both amputation and amputation/death in revascularised CLTI patients, followed by diabetes and heart failure. Men with CLTI have worse outcomes than women. These results may help govern patient selection for revascularisation procedures. Statin and low dose acetylsalicylic acid are associated with an improved limb outcome. This underlines the importance of preventive medication to reduce general cardiovascular risk and increase limb salvage.

Elevated Potassium Levels in Patients With Congestive Heart Failure: Occurrence, Risk Factors, and Clinical Outcomes: A Danish Population-Based Cohort Study.

BACKGROUND: Data on the true burden of hyperkalemia in patients with heart failure (HF) in a real-world setting are limited. METHODS AND RESULTS: Incidence rates of hyperkalemia (first blood test with a potassium level >5.0 mmol/L) in primary or hospital care were assessed in a population-based cohort of patients with incident HF diagnoses in northern Denmark from 2000 to 2012. Risk factors and clinical outcomes were compared in patients with HF with versus without hyperkalemia. Of 31 649 patients with HF, 39% experienced hyperkalemia (mean follow-up, 2.2 years). Risks of experiencing a second, third, or fourth event were 43%, 54%, and 60%, respectively. Among patients with HF with stage 3A, 3B, 4, or 5 kidney dysfunction, 26%, 35%, 44%, and 48% experienced hyperkalemia within the first year. Important hyperkalemia risk factors included chronic kidney disease (prevalence ratio, 1.46; 95% confidence interval [CI], 1.43-1.49), diabetes mellitus (prevalence ratio, 1.38; 95% CI, 1.32-1.45), and spironolactone use (prevalence ratio, 1.48; 95% CI, 1.42-1.54). In patients with HF who developed hyperkalemia, 53% had any acute-care hospitalization 6 months before the hyperkalemia event, increasing to 74% 6 months after hyperkalemia (before-after risk ratio, 1.41; 95% CI, 1.38-1.44). Compared with matched patients with HF without hyperkalemia, adjusted 6-month hazard ratios in patients with hyperkalemia were 2.75-fold (95% CI, 2.65-2.85) higher for acute-care hospitalization and 3.39-fold (95% CI, 3.19-3.61) higher for death. CONCLUSIONS: Almost 4 in 10 patients with HF develop hyperkalemia, and many patients have recurrent hyperkalemia episodes. Hyperkalemia risk is strongly associated with degree of reduced kidney function and use of spironolactone. Hyperkalemia is associated with severe clinical outcomes and death in HF.

Long-term cardiovascular outcome, use of resources, and healthcare costs in patients with peripheral artery disease: results from a nationwide Swedish study.

Aims: Data on long-term healthcare costs of patients with peripheral artery disease (PAD) is limited, and the aim of this study was to investigate healthcare costs for PAD patients at a nationwide level. Methods and results: A cohort study including all incident patients diagnosed with PAD in the Swedish National Patient Register between 2006-2014, and linked to cause of death- and prescribed drug registers. Mean per-patient annual healthcare costs (2015 Euros [€]) (hospitalisations and out-patient visits) were divided into cardiovascular (CV), lower limb and non-CV related cost. Results were stratified by high and low CV risk. The study included 66,189 patients, with 221,953 observation-years. Mean total healthcare costs were €6,577, of which 26% was CV-related (€1,710), during the year prior to the PAD diagnosis. First year after PAD diagnosis, healthcare costs were €12,549, of which €3,824 (30%) was CV-related and €3,201 (26%) lower limb related. High-risk CV patients had a higher annual total healthcare and CV related costs compared to low risk CV patients during follow-up (€7,439 and €1,442 versus €4,063 and €838). Annual lower limb procedure costs were €728 in the PAD population, with lower limb revascularisations as key cost driver (€474). Conclusion: Non-CV related hospitalizations and outpatient visits were the largest cost contributors for PAD patients. There is a substantial increase in healthcare costs in the first year after being diagnosed with PAD, driven by PAD follow-up and lower limb related procedures. Among the CV-related costs, hospitalisations and outpatient visits related to PAD represented the largest costs.

Culprit and Nonculprit Recurrent Ischemic Events in Patients With Myocardial Infarction: Data From SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies).

BackgroundLong-term disease progression after myocardial infarction (MI) is inadequately understood. We evaluated the pattern and angiographic properties (culprit lesion [CL]/non-CL [NCL]) of recurrent MI (re-MI) in a large real-world patient population. Methods and ResultsOur observational study used prospectively collected data in 108 615 patients with first-occurrence MI enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) between July 1, 2006 and November 29, 2014. During follow-up (median, 3.2 years), recurrent hospitalization for MI occurred in 11 117 patients (10.2%). Of the patients who underwent coronary angiography for the index MI, a CL was identified in 44 332 patients. Of those patients, 3464 experienced an re-MI; the infarct originated from the NCL in 1243 patients and from the CL in 655 patients. In total, 1566 re-MIs were indeterminate events and could not be classified as NCL or CL re-MIs. The risk of re-MI within 8 years related to the NCL was 0.06 (95% confidence interval [CI], 0.05-0.06), compared with 0.03 (95% CI, 0.02-0.03) for the CL. There were no large differences in baseline characteristics of patients with subsequent NCL versus CL re-MIs. Independent predictors of NCL versus CL re- MI were multivessel disease (odds ratio, 2.29; 95% CI, 1.87-2.82), male sex (odds ratio, 1.36; 95% CI, 1.09-1.71), and a prolonged time between the index and re-MI (odds ratio, 1.16; 95% CI, 1.10-1.22). ConclusionsIn a large cohort of patients with first-occurrence MI undergoing percutaneous coronary intervention, the risk of re-MI originating from a previously untreated lesion was twice higher than the risk of lesions originating from a previously stented lesion. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT03099395.

Elevated potassium levels in patients with chronic kidney disease: occurrence, risk factors and clinical outcomes-a Danish population-based cohort study.

Background: Data on the true burden of hyperkalemia (HK) in patients with chronic kidney disease (CKD) in a real-world setting are scarce. Methods: The incidence rate of HK [first blood test with an elevated blood potassium level level >5.0 mmol/L] in primary or hospital care was assessed in a population-based cohort of all newly diagnosed CKD patients [second estimated glomerular filtration rate (eGFR) measurement <60 mL/min/1.73 m2 or hospital diagnosis] in northern Denmark. Risk factors and clinical outcomes were compared for CKD patients with HK and matched CKD patients without HK. Results: Of 157 766 patients with CKD, 28% experienced HK, for an overall HK incidence rate of 70/1000 person-years. Among patients with Stage 3A, 3B, 4 or 5 CKD, 9, 18, 31 and 42%, respectively, experienced HK within the first year. Important HK risk factors included diabetes {prevalence ratio [PR] 1.74 [95% confidence interval (CI) 1.69-1.79]}, heart failure [PR 2.31 (95% CI 2.23-2.40)] and use of angiotensin-converting enzyme inhibitors [PR 1.45 (95% CI 1.42-1.48)], potassium supplements [PR 1.59 (95% CI 1.55-1.62)] or spironolactone [PR 2.53 (95% CI 2.44-2.63)]. In CKD patients who developed HK, 34% had any acute hospitalization 6 months before the HK event, increasing to 57% 6 months after HK [before-after risk ratio 1.72 (95% CI 1.69-1.74)]. The 6-month mortality following HK was 26%, versus 6% in matched non-HK patients. Compared with non-HK patients, 6-month hazard ratios for any acute hospitalization in HK patients were 2.11-fold higher, including hazard ratios of 2.07 for cardiac diagnoses, 2.29 for ventricular arrhythmias, 3.26 for cardiac arrest, 4.77 for intensive care and 4.85 for death. Conclusions: More than one in four CKD patients develops HK. Patients with severe CKD, diabetes, heart failure or use of spironolactone are at high risk. HK is associated with severe clinical outcomes.

Cardiovascular outcomes in patients with peripheral arterial disease as an initial or subsequent manifestation of atherosclerotic disease: Results from a Swedish nationwide study.

OBJECTIVE: Long-term progression of peripheral arterial disease (PAD) as initial manifestation of atherosclerotic arterial disease is not well described. Cardiovascular (CV) risk was examined in different PAD populations diagnosed in a hospital setting in Sweden. METHODS: Data for this retrospective cohort study were retrieved by linking data on morbidity, medication use, and mortality from Swedish national registries. Primary CV outcome was a composite of myocardial infarction, ischemic stroke (IS), and CV death. Kaplan-Meier analysis and Cox proportional hazards modeling was used for describing risk and relative risk. RESULTS: Of 66,189 patients with an incident PAD diagnosis (2006-2013), 40,136 had primary PAD, 16,786 had PAD + coronary heart disease (CHD), 5803 had PAD + IS, and 3464 had PAD + IS + CHD. One-year cumulative incidence rates of major CV events for the groups were 12%, 21%, 29%, and 34%, respectively. Corresponding numbers for 1-year all-cause death were 16%, 22%, 33%, and 35%. Compared with the primary PAD population, the relative risk increase for CV events was highest in patients with PAD + IS + CHD (hazard ratio [HR], 2.01), followed by PAD + IS (HR, 1.87) and PAD + CHD (HR, 1.42). Despite being younger, the primary PAD population was less intensively treated with secondary preventive drug therapy. CONCLUSIONS: PAD as initial manifestation of atherosclerotic disease diagnosed in a hospital-based setting conferred a high risk: one in eight patients experienced a major CV event and one in six patients died within 1 year. Despite younger age and substantial risk of future major CV events, patients with primary PAD received less intensive secondary preventive drug therapy.

Clinical factors associated with initiation of and persistence with ADP receptor-inhibiting oral antiplatelet treatment after acute coronary syndrome: a nationwide cohort study from Finland.

OBJECTIVES: To study patient selection for and persistence with ADP receptor-inhibiting oral antiplatelet (OAP) treatment after acute coronary syndrome (ACS). DESIGN: Observational, retrospective, cohort study linking real-life patient-level register data. SETTING: Nationwide drug usage study using data of patients with ACS discharged from hospitals in Finland. PARTICIPANTS: The study population consisted of 54 416 patients (aged ≥18 years) following hospital admission for unstable angina pectoris or myocardial infarction during 2009-2013. Patients were classified as either OAP or non-OAP users based on drug purchases within 7 days of discharge. OUTCOME MEASURES: Initiation of and a 12-month persistence with OAP medication. RESULTS: In total, 49% of patients with ACS received OAP treatment after hospital discharge. Women represented 40% of the population, but only 32% of them became OAP users (adjusted OR for initiation compared with men 0.8; p<0.001). Patients not treated with percutaneous coronary intervention (PCI), elderly and patients with dementia/Alzheimer's disease, atrial fibrillation or warfarin treatment were less likely to be treated with OAP. If initiated, they were less likely to complete the recommended 12 months' medication (adjusted risk increment >38% and p<0.001 for all). The OAP users showed good compliance with immediate initiation (92% within 1 day of discharge) and high mean medication possession rate (99%). Among OAP users, the usage of other secondary prevention drugs after ACS was more common than in non-OAP-treated patients (difference >20 percentage points for each). CONCLUSIONS: Only half of the patients with ACS received guideline-recommended ADP receptor-inhibiting OAP treatment after hospital discharge, suggesting suboptimal treatment practices. Non-PCI-treated patients and patients with increased age, unstable angina, dementia or atrial fibrillation appear to have the highest risk of deficient treatment with OAPs. OAP users, however, showed good compliance during drug usage.

Initiation of and long-term adherence to secondary preventive drugs after acute myocardial infarction.

BACKGROUND: Secondary preventive drug therapy following acute myocardial infarction (AMI) is recommended to reduce the risk of new cardiovascular events. The aim of this nationwide cohort study was to examine the initiation and long-term use of secondary preventive drugs after AMI. METHODS: The prescription of drugs in 42,707 patients < 85 years discharged alive from hospital after AMI in 2009-2013 was retrieved by linkage of the Norwegian Patient Register, the Norwegian Prescription Database, and the Norwegian Cause of Death Registry. Patients were followed for up to 24 months. RESULTS: The majority of patients were discharged on single or dual antiplatelet therapy (91 %), statins (90 %), beta-blockers (82 %), and angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor II blockers (ARB) (60 %). Patients not undergoing percutaneous coronary intervention (PCI) (42 %) were less likely to be prescribed secondary preventive drugs compared with patients undergoing PCI. This was particular the case for dual antiplatelet therapy (43 % vs. 87 %). The adherence to prescribed drugs was high: 12 months after index AMI, 84 % of patients were still on aspirin, 84 % on statins, 77 % on beta-blockers and 57 % on ACEI/ARB. Few drug and dose adjustments were made during follow-up. CONCLUSION: Guideline-recommended secondary preventive drugs were prescribed to most patients discharged from hospital after AMI, but the percentage receiving such therapy was significantly lower in non-PCI patients. The long-time adherence was high, but few drug adjustments were performed during follow-up. More attention is needed to secondary preventive drug therapy in AMI patients not undergoing PCI.

Initiation and persistence with dual antiplatelet therapy after acute myocardial infarction: a Danish nationwide population-based cohort study.

OBJECTIVES: The study investigated dual antiplatelet therapy (DAPT) patterns over time and patient characteristics associated with the various treatments in a myocardial infarction (MI) population. DESIGN: A registry-based observational cohort study was performed using antecedent data. SETTING: This study linked morbidity, mortality and medication data from Danish national registries. PARTICIPANTS: All 28 449 patients admitted to a Danish hospital with a first-time MI and alive at discharge from 2009 through 2012 were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was initiation of DAPT and secondary outcomes comprised persistence in DAPT treatment and switches between DAPT treatments. RESULTS: The overall proportion of patients prescribed DAPT increased from 68% (CL 95% 67-69%) to 73% (CL 95% 72-74%) from 2009 to 2012. For treatment of patients with and without percutaneous coronary intervention (PCI), the corresponding numbers were from 87% (CL 95% 86-88%) to 91% (CL 95% 90-92%) and from 49% (CL 95% 47-50%) to 52% (CL 95% 51-54%), respectively. Non-PCI patients had a higher cardiovascular risk compared with PCI patients. Among PCI patients, age>75 years, atrial fibrillation, diabetes and peripheral arterial disease were associated with a higher risk of treatment breaks for DAPT. Among patients without PCI, ticagrelor treatment was associated with an increased risk of treatment breaks during the first 12 months compared with clopidogrel treatment. CONCLUSIONS: From 2009 to 2012, there was an increase in the proportion of patients with MI receiving DAPT, and a longer duration of DAPT. Still, a large proportion of patients without PCI are discharged either without DAPT or with a short DAPT duration. These findings may indicate the need for more careful attention to DAPT for patients with MI not undergoing PCI in Denmark.

Contemporary cardiovascular risk and secondary preventive drug treatment patterns in peripheral artery disease patients undergoing revascularization.

OBJECTIVE: Peripheral artery disease (PAD) is common worldwide, and PAD patients are increasingly offered lower limb revascularization procedures. The aim of this population-based study was to describe the current risk for cardiovascular (CV) events and mortality and also to elucidate the current pharmacologic treatment patterns in revascularized lower limb PAD patients. METHODS: This observational, retrospective cohort study analyzed prospectively collected linked data retrieved from mandatory Swedish national health care registries. The Swedish National Registry for Vascular Surgery database was used to identify revascularized PAD patients. Current risk for CV events and death was analyzed, as were prescribed drugs aimed for secondary prevention. A Cox proportional hazard regression model was used to explore risk factors for suffering a CV event. RESULTS: Between May 2008 and December 2013, there were 18,742 revascularized PAD patients identified. Mean age was 70.0 years among patients with intermittent claudication (IC; n = 6959) and 76.8 years among patients with critical limb ischemia (CLI; n = 11,783). Antiplatelet therapy, statins, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and beta-blockers were used by 73%, 60%, 57%, and 49% at admission for revascularization. CV event rate (a composite of myocardial infarction, ischemic stroke, or CV death) at 12, 24, and 36 months was 5.1% (95% confidence interval [CI], 4.5-5.6), 9.5% (95% CI, 8.7-10.3), and 13.8% (95% CI, 12.8-14.8) in patients with IC and 16.8% (95% CI, 16.1-17.6), 25.9% (95% CI, 25.0-26.8), and 34.3% (95% CI, 33.2-35.4) in patients with CLI. Best medical treatment, defined as any antiplatelet or anticoagulant therapy along with statin treatment, was offered to 65% of IC patients and 45% of CLI patients with little change during the study period. Statin therapy was associated with reduced CV events (hazard ratio, 0.76; 95% CI, 0.71-0.81; P < .001), whereas treatment with low-dose aspirin was not. CONCLUSIONS: Revascularized PAD patients are still at a high risk for CV events without a declining time trend. A large proportion of both IC and CLI patients were not offered best medical treatment. The most commonly used agent was aspirin, which was not associated with CV event reduction. This study calls for improved medical management and highlights an important and partly unmet medical need among revascularized PAD patients.

Association Between Paradoxical HDL Cholesterol Decrease and Risk of Major Adverse Cardiovascular Events in Patients Initiated on Statin Treatment in a Primary Care Setting.

BACKGROUND AND OBJECTIVES: Statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are unrelated. Many patients initiated on statins experience a paradoxical decrease in HDL-C. The aim of this study was to evaluate the association between a decrease in HDL-C and risk of major adverse cardiovascular events (MACE). METHODS: Data from 15,357 primary care patients initiated on statins during 2004-2009 were linked with data from mandatory national hospital, drug-dispensing, and cause-of-death registers, and were grouped according to HDL-C change: decreased ≥0.1 mmol/L, unchanged ±0.1 or ≥0.1 mmol/L increased. To evaluate the association between decrease in HDL-C and risk of MACE, a sample of propensity score-matched patients from the decreased and unchanged groups was created, using the latter group as reference. MACE was defined as myocardial infarction, unstable angina pectoris, ischaemic stroke, or cardiovascular mortality. Cox proportional hazards models were used to estimate relative risks. RESULTS: HDL-C decreased in 20%, was unchanged in 58%, and increased in 22% of patients initiated on statin treatment (96% treated with simvastatin). The propensity score-matched sample comprised 5950 patients with mean baseline HDL-C and LDL-C of 1.69 and 4.53 mmol/L, respectively. HDL-C decrease was associated with 56% higher MACE risk (hazard ratio 1.56; 95% confidence interval 1.12-2.16; p < 0.01) compared with the unchanged HDL-C group. CONCLUSIONS: Paradoxical statin-induced reduction in HDL-C was relatively common and was associated with increased risk of MACE.

Treatment pattern of contemporary dual antiplatelet therapies after acute coronary syndrome: a Swedish nationwide population-based cohort study.

OBJECTIVES: New dual antiplatelet therapies (DAPTs) have been introduced in clinical practice for patients with acute coronary syndrome (ACS). This nationwide study investigated DAPT patterns over time and patient characteristics associated with the various treatments in a population with ACS. DESIGN: This observational cohort study linked morbidity, mortality and medication data from Swedish national registries. RESULTS: Overall, 91% (104 012 patients) of all patients admitted to the hospital with an ACS (2009-2013) were alive after discharge and included in this study. Compared with 2009, in 2013 patients investigated with angiography increased by 10%, patients revascularized with percutaneous coronary intervention (PCI) increased by 11% and patients prescribed DAPT increased by 8%. Mean DAPT duration increased from 225 to 298 days in patients investigated with angiography, and from 155 to 208 days in patients who were not investigated with angiography. Furthermore, in patients undergoing angiography a treatment switch from clopidogrel to ticagrelor was observed. DAPT with prasugrel was used to a low extent. Approximately 10% of patients initiated on prasugrel or ticagrelor switched to clopidogrel during the first year of treatment. CONCLUSION: During the study more patients underwent angiography and PCI. There was an increase in the proportion of ACS patients receiving DAPT, as well as longer duration of DAPT in line with ESC guidelines. Among DAPT-treated patients, ticagrelor has emerged as the preferred P2Y12 antagonist in patients undergoing angiography, whereas clopidogrel tended to be prescribed to patients treated non-invasively.

Using big data from health records from four countries to evaluate chronic disease outcomes: a study in 114 364 survivors of myocardial infarction.

AIMS: To assess the international validity of using hospital record data to compare long-term outcomes in heart attack survivors. METHODS AND RESULTS: We used samples of national, ongoing, unselected record sources to assess three outcomes: cause death; a composite of myocardial infarction (MI), stroke, and all-cause death; and hospitalized bleeding. Patients aged 65 years and older entered the study 1 year following the most recent discharge for acute MI in 2002-11 [n = 54 841 (Sweden), 53 909 (USA), 4653 (England), and 961 (France)]. Across each of the four countries, we found consistent associations with 12 baseline prognostic factors and each of the three outcomes. In each country, we observed high 3-year crude cumulative risks of all-cause death (from 19.6% [England] to 30.2% [USA]); the composite of MI, stroke, or death [from 26.0% (France) to 36.2% (USA)]; and hospitalized bleeding [from 3.1% (France) to 5.3% (USA)]. After adjustments for baseline risk factors, risks were similar across all countries [relative risks (RRs) compared with Sweden not statistically significant], but higher in the USA for all-cause death [RR USA vs. Sweden, 1.14 (95% confidence interval 1.04-1.26)] and hospitalized bleeding [RR USA vs. Sweden, 1.54 (1.21-1.96)]. CONCLUSION: The validity of using hospital record data is supported by the consistency of estimates across four countries of a high adjusted risk of death, further MI, and stroke in the chronic phase after MI. The possibility that adjusted risks of mortality and bleeding are higher in the USA warrants further study.

Long-term resource use patterns and healthcare costs after myocardial infarction in a clinical practice setting: results from a contemporary nationwide registry study.

Aims: Long-term contemporary nationwide data on resource use and healthcare costs after myocardial infarction (MI) in a clinical practice setting are not widely studied, and the aim of this study was to investigate resource use patterns and healthcare costs in patients with MI in a nationwide clinical practice setting. Methods and results: This retrospective cohort study included all patients identified in the compulsory Swedish nationwide patient register with a diagnosis of MI between 1 July 2006 and 30 June 2011. Cardiovascular hospitalization and outpatient visits data from the patient register were combined with data from the cause of death register and the drug utilization register. For a subset of patients, data were also available from a primary care register. Healthcare resource use patterns and annual costs [reported in 2014 euros (€) converted from Swedish kronor (SEK) using the exchange rate €1 = SEK 9.33)] were estimated for the year prior to the occurrence of MI as well as for a maximum follow-up period of 6 years post-MI. The study included 97 252 patients with a diagnosis of MI with a total number of 285 351 observation years. The majority of healthcare consumption occurred within the first year of MI where patients were on average hospitalized 1.55 times, made 1.08 outpatient care visits, and 3.80 primary care visits. In the long term, for the majority of resource use categories, average consumption was higher in the years after MI compared with the year prior to MI. Healthcare costs at 6 years of follow-up were approximately €20 000 of which €12 460 occurred in the first year, and the major part was attributed to hospitalizations. Conclusion: For patients with 6 years of follow-up after MI, healthcare costs were approximately €20 000. The major part of costs occurred in the first year after MI and was driven by hospitalizations. ClinicalTrials.gov identifier: NCT01984307.

Statin prescription patterns, adherence, and attainment of cholesterol treatment goals in routine clinical care: a Danish population-based study.

PURPOSE: To examine the annual rate and cumulative prevalence of statin use in Denmark 2004-10, including adherence of use and attainment of cholesterol targets. METHODS: We included all individuals aged 18-86 years with a first statin prescription in Northern Denmark in 2004-10. We calculated the annual rate and cumulative prevalence of statin use. We examined cholesterol values before and after start of statins and the proportion reaching targets according to European guidelines and cardiovascular risk group. RESULTS: The study population consisted of 161,646 new statin users (51% men; median age 62 years). The peak rate of new statin initiators occurred in 2008, and a cumulative prevalence of 94 users per 1,000 population was reached in 2010. In total, 98% of new users started with simvastatin. Eighty-eight percent (142,897) did not switch statin type during follow-up. Overall persistence was 84%. The reduction in median total cholesterol in new statin users was 28% (from 6.3 mmol/L to 4.5 mmol/L), while it was 43% (from 4.0 mmol/L to 2.3 mmol/L) for low-density lipoprotein cholesterol. Among patients with very high cardiovascular risk, 66% attained the recommended total cholesterol target; corresponding figures were 74% among high-risk patients and 80% among low- to moderate-risk patients. Corresponding figures for low-density lipoprotein cholesterol were 54%, 82%, and 88%, respectively. CONCLUSIONS: Statin use has become very prevalent in Danish adults, with high adherence. Cholesterol reduction after statin initiation is similar to that found in clinical trials, yet a substantial proportion of patients does not reach target cholesterol levels.