Impact of non-adherence to direct oral anticoagulants amongst Swedish patients with non-valvular atrial fibrillation: results from a real-world cost-utility analysis.

AIMS: A third of non-valvular atrial fibrillation (NVAF) patients are non-adherent to direct oral anticoagulants (DOACs). Estimates of the economic value of full adherence and the cost of two types of adherence improving interventions are important to healthcare planners and decision-makers. METHODS: A cost-utility analysis estimated the impact of non-adherence over a 20-year horizon, for a patient cohort with a mean age of 77 years, based on data from the Stockholm Healthcare database of NVAF patients with incident stroke between 2011 and 2018. Adherence was defined using a medication possession ratio (MPR) cut-off of 90%; primary outcomes were the number of ischemic strokes and associated incremental cost-utility ratio. RESULTS: Hypothetical comparisons between cohorts of 1,000 patients with varying non-adherence levels and full adherence (MPR >90%) predicted an additional number of strokes ranging from 117 (MPR = 81-90%) to 866 (MPR <60%), and years of life lost ranging from 177 (MPR = 81- 90%) to 1,318 (MPR < 60%; discounted at 3%). Chronic disease co-management intervention occurring during each DOAC prescription renewal and patient education intervention at DOAC initiation will be cost-saving to the health system if its cost is below SEK 143 and SEK 4,655, and cost-effective if below SEK 858 and SEK 28,665, respectively. CONCLUSION: Adherence improving interventions for NVAF patients on DOACs such as chronic disease co-management and patient education can be cost-saving and cost-effective, within a range of costs that appear reasonable to the Swedish healthcare system.

Atrial fibrillation (AF) is the most common type of chronic cardiac arrhythmia and a major risk factor for ischemic stroke (IS). The objective of this study was to compare the costs and health outcomes associated with adherence to direct oral anticoagulant (DOAC) therapy in Sweden. The study also aimed to demonstrate the potential benefits of developing interventions to improve DOAC adherence. DOAC therapy (DOACs; apixaban, dabigatran, edoxaban, and rivaroxaban) has been approved in Europe for the prevention of stroke in adult patients with AF. It has been demonstrated to provide warfarin-similar reductions in stroke risk in NVAF patients, with reductions in mortality and intracranial hemorrhage. However, non-adherence to DOAC medication prevents patients and healthcare systems from fully benefiting from DOAC therapy, resulting in a lower benefit than those seen in randomized controlled trials. DOAC non-adherence is where AF patients deviate from the DOAC treatment regimen as prescribed by health providers. This study suggested that non-adherence to DOAC therapy has a substantial impact on ischemic stroke risk and significant additional healthcare system costs. Patient education and chronic disease co-management (two types of DOAC adherence improving intervention) can be cost-saving and cost-effective within a range of costs that appear reasonable to the Swedish healthcare system. Healthcare policy-makers should prioritize initiatives aimed at improving DOAC adherence in order to improve outcomes in AF.

Low-dose aspirin and risk of gastric and oesophageal cancer: A population-based study in the United Kingdom using The Health Improvement Network.

There is increasing interest regarding potential protective effects of low-dose aspirin against various gastrointestinal cancers. We aimed to quantify the association between use of low-dose aspirin and risk of gastric/oesophageal cancer using a population-based primary care database in the UK. Between January 2005 and December 2015, we identified a cohort of 223 640 new users of low-dose aspirin (75-300 mg/day) and a matched cohort of nonusers at the start of follow-up from The Health Improvement Network. Cohorts were followed to identify incident cases of gastric/oesophageal cancer. Nested case-control analyses were conducted and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for current vs nonuse of low-dose aspirin using logistic regression. Current use was defined as when low-dose aspirin lasted 0 to 90 days before the index date (event date for cases, random date for controls) and previous duration was ≥1 year. We identified 727 incident cases of gastric cancer and 1394 incident cases of oesophageal cancer. ORs (95% CIs) were 0.46 (0.38-0.57) for gastric cancer and 0.59 (0.51-0.69) for oesophageal cancer. The effect remained consistent with no clear change seen between previous duration of low-dose aspirin use of 1-3, 3-5 or >5 years. The reduced risks was seen with 75 mg/day, and effects were consistent in lag-time analyses. In conclusion, our results indicate that use of low-dose aspirin is associated with a 54% reduced risk of gastric cancer and a 41% reduced risk of oesophageal cancer as supported by mechanistic data.

Impact of chronic kidney disease definition on assessment of its incidence and risk factors in patients with newly diagnosed type 1 and type 2 diabetes in the UK: A cohort study using primary care data from the United Kingdom.

AIM: To estimate the incidence and risk factors of chronic kidney disease (CKD) in patients with newly-diagnosed diabetes using different CKD definitions. METHODS: Using UK primary care data, patients with diabetes (type 1, 4691; type 2, 109,365) and no CKD were followed to identify newly-diagnosed CKD, classified by a broad and narrow CKD definition (to capture diabetes-induced CKD, termed diabetic kidney disease, DKD). Adjusted incidence rates of CKD/DKD were calculated, and risk factors identified using Cox regression. RESULTS: There were 404 CKD cases and 147 DKD cases among patients with type 1 diabetes (T1D), and 29,104 CKD cases, 9284 DKD cases among patients with type 2 diabetes (T2D). Adjusted incidence rates of CKD per 100 years were 5.4 (T1D) and 5.5 (T2D); for DKD they were 1.9 and 1.5, respectively. Risk factors for CKD/DKD were older age, high social deprivation, obesity, cardiovascular disease, hypertension and smoking. Poor glycaemic control in the year after diabetes diagnosis was a strong predictor of CKD/DKD occurrence beyond this first year, and a risk factor for CKD/DKD in T2D. CONCLUSIONS: CKD and DKD remain common in diabetics in the decade after diagnosis. Early prevention of T2D and aggressive treatment of risk factors is urgent.

Predictors of Over-Anticoagulation in Warfarin Users in the UK General Population: A Nested Case-Control Study in a Primary Health Care Database.

BACKGROUND: Many patients on warfarin therapy often present with supratherapeutic international normalized ratio (INR) levels, resulting from the influence of several patient-specific factors, which have been associated with adverse outcomes. OBJECTIVE: This article aims to identify risk factors for over-anticoagulation (INR levels ≥4) in a cohort of patients taking warfarin. METHODS: A cohort of warfarin users aged 18 to 85 years from January 2005 to April 2013 was identified in The Health Improvement Network U.K. primary care database (N = 12,506). A random date was assigned to all patients within their eligible person-time (index date), and a nested case-control analysis was performed with individuals presenting a first episode of INR level ≥4 after the index date used as cases (N = 699) and patients with non-supratherapeutic INR values (≤3) as controls (N = 9,798). Using unconditional logistic regression models, odds ratios with 95% confidence intervals were calculated adjusted for potential confounders. Two sensitivity analyses were performed with alternative definitions of over-anticoagulation (INR levels ≥5 or > 3). RESULTS: Among the factors examined, the strongest predictors of over-anticoagulation were warfarin indication (in particular, valvular atrial fibrillation and valve replacement), renal failure (with the risk increasing steeply with decreasing estimated glomerular filtration rate), cancer, anaemia, respiratory infections treated with antibiotics, chronic obstructive pulmonary disease treated with ß2-agonists, polypharmacy (≥10 medications), low socio-economic status and residency in rural areas. Similar results were obtained when supratherapeutic levels were defined as INR ≥5 or, alternatively, as INR > 3. CONCLUSION: Predictors of supratherapeutic INR levels found in this study might help physicians identify patients where closer INR monitoring is warranted.

Incidence and risk factors for atrial fibrillation in patients with newly diagnosed heart failure.

AIMS: We aimed to identify the incidence and risk factors for first ever atrial fibrillation among patients with newly diagnosed heart failure following initial heart failure diagnosis. METHODS: A heart failure inception cohort of patients aged 20-89 years without atrial fibrillation or cancer (N = 14 457) from 2000 to 2005 was identified from The Health Improvement Network primary care database in the United Kingdom and followed for a mean of 2.67 years. First ever cases of atrial fibrillation were identified and controls (N = 3000) were frequency matched to cases by age and sex. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using unconditional logistic regression. RESULTS: One thousand four hundred and eighty-nine patients (10.3%) developed a first episode of atrial fibrillation: incidence rate 27.3/1000 person-years. A three-fold increased risk of atrial fibrillation was seen in the first 6 months after heart failure diagnosis, OR 3.62 (95% CI: 2.97-4.42) with the risk decreasing thereafter. Other risk factors were excessive alcohol consumption (OR 2.91, 1.60-5.30) and valvular heart disease (OR 1.98, 1.63-2.40) and use of oral steroids (OR 1.76, 95% CI: 1.40-2.22). Reduced risks of atrial fibrillation were found with use of statins (OR 0.65, 95% CI: 0.56-0.76) and ß-blockers (OR 0.78, 95% CI: 0.67-0.91). CONCLUSIONS: The incidence of first ever atrial fibrillation among newly diagnosed heart failure patients is high, especially in the first 6 months after diagnosis. This time relationship, together with the identified risk factors for atrial fibrillation, warrants consideration in the medical care of patients with heart failure.

Impact of hyperkalaemia definition on incidence assessment: implications for epidemiological research based on a large cohort study in newly diagnosed heart failure patients in primary care.

BACKGROUND: Various definitions of hyperkalaemia have been used in clinical research, and data from routine clinical practice on its incidence are sparse. We aimed to establish the incidence of hyperkalaemia in patients with newly diagnosed heart failure in the UK general population using different definitions for the condition. METHODS: We conducted a large retrospective cohort study using data from The Health Improvement Network primary care database. Patients with newly diagnosed heart failure (N = 19,194) were identified and followed until the first occurrence of hyperkalaemia. Different serum potassium (K(+)) thresholds were evaluated as possible definitions for hyperkalaemia, and incidence rates (IRs) calculated using a final operational definition both overall and among patient sub-groups. RESULTS: IRs of hyperkalaemia ranged from 0.92-7.93 per 100 person-years according to the definition. Based on considerable differences in the serum K(+) normal range used between practices, 2176 (11.3 %) individuals were identified with a record of hyperkalaemia using our operational definition of a proportional increase of ≥10 % above the upper bound of the normal range: IR 2.90 per 100 person-years (95 % CI 2.78-3.02) over a mean follow-up of 3.91 years. Incidence rates were higher in older patients, and in those with diabetes or renal impairment. CONCLUSIONS: Hyperkalaemia is a common finding in heart failure patients in primary care, but its incidence can vary nearly ten-fold depending on its definition. Since assessment of hyperkalaemia risk is essential for therapeutic decision making in heart failure patients, this finding warrants consideration in future epidemiological studies.

Cardiovascular and upper gastrointestinal bleeding consequences of low-dose acetylsalicylic acid discontinuation.

It was the aim of this study to investigate whether low-dose acetylsalicylic acid (ASA) therapy for secondary cardiovascular prevention should continue, despite the risk of gastrointestinal bleeding. We aimed to make a clinically meaningful benefit-risk assessment regarding the cardiovascular and gastrointestinal consequences of ASA discontinuation.This case-control study usedThe Health Improvement Network UK primary care database to identify patients aged 50-84 years during 2000-2007 with a first ASA prescription for secondary cardiovascular prevention (N = 39,513). New cases of non-fatal myocardial infarction (MI)/coronary death (n = 1,222), ischaemic stroke (IS)/transient ischaemic attack (TIA) (n = 673) and upper gastrointestinal bleeding (UGIB) (n = 169) were identified after a mean follow-up of 3.2, 3.4 and 4.0 years, respectively. ASA discontinuers before the index date were identified. Attributable risks associated with ASA discontinuation were calculated and National Institute for Health and Clinical Excellence annual economic data were used to estimate healthcare costs. The cumulative incidences of non-fatal MI/coronary death, IS/TIA and UGIB among ASA discontinuers within the first year of follow-up were 17, 11 and 1.6 per 1,000 persons, respectively. This corresponds to eight extra cardiovascular events, and a reduction of 0.4 UGIB events per year compared with current ASA users. Extrapolating to the UK population aged over 50 years, avoiding discontinuation of ASA could prevent 12,786 coronary and 7,672 cerebrovascular events/year, at the expense of 1023 extra UGIB events, saving approximately £100 million/year. In conclusion, preventing patients with cardiovascular disease from discontinuing ASA could result in substantial clinical and economic gains.

Gastroesophageal reflux disease in primary care: using changes in proton pump inhibitor therapy as an indicator of partial response.

OBJECTIVE: Up to one-third of patients with gastroesophageal reflux disease (GERD) in primary care have residual symptoms despite proton pump inhibitor (PPI) therapy. We aimed to characterize partial response to PPIs among adult patients in UK primary care. MATERIAL AND METHODS: Newly diagnosed GERD patients aged 20-79 years who were prescribed PPI for treatment of GERD were identified in The Health Improvement Network. Those with a treatment change suggesting partial response to PPIs (new treatment added to PPI, increased PPI dose, or switching PPI) during the subsequent 6 months were identified as potential cases and confirmed after manual review of each patient's complete computer medical record including free-text comments. Patients without these treatment changes were study controls. A nested case-control analysis was conducted using logistic regression. RESULTS: The proportion of newly diagnosed GERD patients with partial response to PPI therapy was 18.6% (1201/6453). Partial response was associated with female gender (odds ratio [OR]: 1.20; 95% confidence interval [CI]: 1.05-1.37), anxiety or depression (OR: 1.15; 95% CI: 1.00-1.31), and prescription of ≥ 6 drugs in the month before GERD diagnosis (OR: 1.42; 95% CI: 1.14-1.78). Among new PPI users (n = 2907), partial response was associated with esophageal ulcer or Barrett's esophagus at initial diagnosis (OR: 3.14; 95% CI: 1.60-6.17). CONCLUSIONS: Approximately one in five newly diagnosed patients with GERD appear to have a partial response to PPI therapy. Female gender, polymedication, and a severe initial diagnosis may be associated with partial response.