Stroke risk in women with atrial fibrillation.

BACKGROUND AND AIMS: Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF. METHODS: Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66-74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age-sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care. RESULTS: The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21-1.32). Model 2 revealed a significant age-sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years. CONCLUSION: Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF.

Non-Inferiority Trials: A Systematic Review on Methodological Quality and Reporting Standards.

BACKGROUND: Non-inferiority (NI) trials require unique trial design and methods, which pose challenges in their interpretation and applicability, risking introduction of inferior therapies in clinical practice. With the abundance of novel therapies, NI trials are increasing in publication. Prior studies found inadequate quality of reporting of NI studies, but were limited to certain specialties/journals, lacked NI margin evaluation, and did not examine temporal changes in quality. We conducted a systematic review without restriction to journal type, journal impact factor, disease state or intervention to evaluate the quality of NI trials, including a comprehensive risk of bias assessment and comparison of quality over time. METHODOLOGY: We searched PubMed and Cochrane Library databases for NI trials published in English in 2014 and 2019. They were assessed for: study design and NI margin characteristics, primary results, and risk of bias for blinding, concealment, analysis method and missing outcome data. RESULTS: We included 823 studies. Between 2014 and 2019, a shift from publication in specialty to general journals (15% vs 28%, p < 0.001) and from pharmacological to non-pharmacological interventions (25% vs 38%, p = 0.025) was observed. The NI margin was specified in most trials for both years (94% vs 95%). Rationale for the NI margin increased (36% vs 57%, p < 0.001), but remained low, with clinical judgement the most common rationale (30% vs 23%), but more 2019 articles incorporating patient values (0.3% vs 21%, p < 0.001). Over 50% of studies were open-label for both years. Gold standard method of analyses (both per protocol + (modified) intention to treat) declined over time (43% vs 36%, p < 0.001). DISCUSSION: The methodological quality and reporting of NI trials remains inadequate although improving in some areas. Improved methods for NI margin justification, blinding, and analysis method are warranted to facilitate clinical decision-making.

Trajectories of P2Y12 inhibitor adherence in patients with acute coronary syndromes.

PURPOSE: P2Y12 inhibitors (P2Y12i) reduce cardiac events after acute coronary syndromes (ACS). However, suboptimal P2Y12i adherence persists. We aimed to examine P2Y12i non-adherence using group-based trajectory methods and to identify adherence predictors. METHODS: We conducted a population-based, retrospective cohort study using administrative data in Ontario, Canada of patients ≥65 years admitted for ACS between April 2014 and March 2018 with a P2Y12i dispensed within 7 days of discharge. We used group-based trajectory models to characterize longitudinal 1-year adherence patterns. Predictors associated with each adherence trajectory were identified by multinomial logistic regression. RESULTS: We included 11 917 patients using clopidogrel and 9763 using ticagrelor, aged [mean ± SD]: 77.33 ± 8.31/73.59 ± 6.79 years; men: 56.2%/65.4%, respectively. We identified 3 longitudinal adherence trajectories, that differed by agent: 75% of clopidogrel and 68% of ticagrelor patients showed a consistently adherent trajectory, while 13%/17% were gradually, and 12%/15% were rapidly non-adherent, respectively (p < 0.001). Differing baseline characteristics in each cohort were associated with observed adherence trajectories. Concomitant atrial fibrillation and prior bleeding history were associated with non-adherence among clopidogrel users. Among ticagrelor users, women and older persons were more likely to be rapidly non-adherent, adherence declining steeply starting 1 month post-ACS. CONCLUSIONS: We identified distinct adherence trajectories for clopidogrel and ticagrelor post-ACS, with 3 out of 4 clopidogrel patients but only 2 out of 3 ticagrelor patients in the consistently adherent trajectory. Intensive interventions targeted to the period of steep adherence decline post-ACS, particularly for women and older persons initiating ticagrelor, and patients with atrial fibrillation on clopidogrel should be considered and investigated further.

Evidence-Based Cardiovascular Disease Medicines' Availability in Low-Cost Generic Drug Programs in the United States : A Cross-Sectional Study.

BACKGROUND: Low-cost generic programs (LCGPs) that expand access to affordable cardiovascular disease (CVD) medicines can assist patients in achieving desired cardiovascular outcomes. It is important that LCGPs offer CVD medicines that promote evidence-based prescribing. OBJECTIVE: To evaluate LCGPs' coverage of evidence-based CVD medications using a clinical framework that examines coverage of core treatments, coverage of options with the highest-quality evidence, and the variety of medication options and strengths that create choices and allow dosing titration. DESIGN: Cross-sectional study. SETTING: Publicly available LCGPs in March and April 2023 in the United States. PARTICIPANTS: 19 LCGPs. MEASUREMENTS: Proportion of LCGPs that offered evidence-based CVD medicines within a clinical framework for 6 CVDs (atrial fibrillation, heart failure, hyperlipidemia, hypertension, post-acute coronary syndrome secondary prevention, and stable angina) according to 4 availability metrics (breadth, choice, high-quality evidence, and titratability). RESULTS: The availability of CVD medication varied by program, drug, and CVD condition. Some programs had more breadth and choice of coverage for most CVDs (H-E-B, Kroger, Mark Cuban Cost Plus Drug Company, and Walmart), whereas many had more focused coverage and others markedly limited offerings. Nearly all LCGPs offered angiotensin-converting enzyme inhibitors, ß-blockers, thiazides, and moderate-intensity statins, but availability was low for higher-cost or lower-use generics (antiplatelets and antiarrhythmics). Core pharmacotherapy coverage and choices were limited for atrial fibrillation and heart failure but widely available for hypertension and hyperlipidemia. LIMITATION: In-depth cost analysis was not investigated. CONCLUSION: Coverage of evidence-based medications for the 6 CVDs investigated varied by LCGP and condition. Because high availability of core CVD pharmacotherapy can enhance optimal disease state management, LCGPs should identify existing limitations in their coverage and continuously revise their formularies to improve the comprehensiveness of CVD medication coverage. PRIMARY FUNDING SOURCE: None.

Association of Neighborhood-Level Material Deprivation With Atrial Fibrillation Care in a Single-Payer Health Care System: A Population-Based Cohort Study.

BACKGROUND: There are limited data on the association of material deprivation with clinical care and outcomes after atrial fibrillation (AF) diagnosis in jurisdictions with universal health care. METHODS: This was a population-based cohort study of individuals ≥66 years of age with first diagnosis of AF between April 1, 2007, and March 31, 2019, in the Canadian province of Ontario, which provides public funding and prohibits private payment for medically necessary physician and hospital services. Prescription medications are subsidized for residents >65 years of age. The primary exposure was neighborhood material deprivation, a metric derived from Canadian census data to estimate inability to attain basic material needs. Neighborhoods were categorized by quintile from Q1 (least deprived) to Q5 (most deprived). Cause-specific hazards regression was used to study the association of material deprivation quintile with time to AF-related adverse events (death or hospitalization for stroke, heart failure, or bleeding), clinical services (physician visits, cardiac diagnostics), and interventions (anticoagulation, cardioversion, ablation) while adjusting for individual characteristics and regional cardiologist supply. RESULTS: Among 347 632 individuals with AF (median age 79 years, 48.9% female), individuals in the most deprived neighborhoods (Q5) had higher prevalence of cardiovascular disease, risk factors, and noncardiovascular comorbidity relative to residents of the least deprived neighborhoods (Q1). After adjustment, Q5 residents had higher hazards of death (hazard ratio [HR], 1.16 [95% CI, 1.13-1.20]) and hospitalization for stroke (HR, 1.16 [95% CI, 1.07-1.27]), heart failure (HR, 1.14 [95% CI, 1.11-1.18]), or bleeding (HR, 1.16 [95% CI, 1.07-1.25]) relative to Q1. There were small differences across quintiles in primary care physician visits (HR, Q5 versus Q1, 0.91 [95% CI, 0.89-0.92]), echocardiography (HR, Q5 versus Q1, 0.97 [95% CI, 0.96-0.99]), and dispensation of anticoagulation (HR, Q5 versus Q1, 0.97 [95% CI, 0.95-0.98]). There were more prominent disparities for Q5 versus Q1 in cardiologist visits (HR, 0.84 [95% CI, 0.82-0.86]), cardioversion (HR, 0.80 [95% CI, 0.76-0.84]), and ablation (HR, 0.45 [95% CI, 0.30-0.67]). CONCLUSIONS: Despite universal health care and prescription medication coverage, residents of more deprived neighborhoods were less likely to visit cardiologists or receive rhythm control interventions after AF diagnosis, even though they exhibited higher cardiovascular disease burden and higher risk of adverse outcomes.

Disagreement between pharmacy claims and direct interview to identify patients with non-adherence to chronic cardiometabolic medications.

BACKGROUND: Accurate methods of identifying patients with suboptimal adherence to cardiometabolic medications are needed, and each approach has benefits and tradeoffs. METHODS: We used data from a large trial of patients with poorly controlled cardiometabolic disease and evidence of medication non-adherence measured using pharmacy claims data whose adherence was subsequently assessed during a telephone consultation with a clinical pharmacist. We then evaluated if the pharmacist assessment agreed with the non-adherence measured using claims. When pharmacist and claims assessments disagreed, we identified reasons why claims were insufficient and used multivariable modified Poisson regression to identify patient characteristics associated with disagreement. RESULTS: Of 1,069 patients identified as non-adherent using claims (proportion of days covered [PDC] <80%), 646 (60.4%) were confirmed as non-adherent on pharmacist interview. For the 423 patients (39.6%) where the interview disagreed with the claims, the most common reasons were paying cash or using an alternate insurance (36.6%), medication discontinuation or regimen change (32.8%), and recently becoming adherent (26.7%). Compared to patients whose claims and interview both showed non-adherence, patients whose interview disagreed with claims were less likely to miss outpatient office visits (RR:0.91, 95%CI:0.85-0.97) and more likely to have a baseline PDC above the median (RR:1.35, 95%CI:1.10-1.64). CONCLUSIONS: Among patients identified as non-adherent by claims, 39.6% were observed to be adherent when assessed during pharmacist consultation. This discrepancy was largely driven by paying out-of-pocket, using alternative insurance, or medication discontinuation or change. These findings have important implications for using pharmacy claims to identify and intervene upon medication non-adherence.

A review of the use of propensity score methods with multiple treatment groups in the general internal medicine literature.

BACKGROUND: Propensity score (PS) methods with two treatment groups (e.g., treated vs. control) is a well-established technique for reducing the effects of confounding in nonrandomized studies. However, researchers are often interested in comparing multiple interventions. PS methods have been modified to incorporate multiple exposures. We described available techniques for PS methods in multicategory exposures (≥3 groups) and examined their use in the medical literature. METHODS: A comprehensive search was conducted for studies published in PubMed, Embase, Google Scholar, and Web of Science until February 27, 2023. We included studies using PS methods for multiple groups in general internal medicine research. RESULTS: The literature search yielded 4088 studies (2616 from PubMed, 86 from Embase, 85 from Google Scholar, 1671 from Web of Science, five from other sources). In total, 264 studies using PS method for multiple groups were identified; 61 studies were on general internal medicine topics and included. The most commonly used method was that of McCaffrey et al., which was used in 26 studies (43%), where the Toolkit for Weighting and Analysis of Nonequivalent Groups (TWANG) method and corresponding inverse probabilities of treatment weights were estimated via generalized boosted models. The next most commonly used method was pairwise propensity-matched comparisons, which was used in 20 studies (33%). The method by Imbens et al. using a generalized propensity score was implemented in six studies (10%). Four studies (7%) used a conditional probability of being in a particular group given a set of observed baseline covariates where a multiple propensity score was estimated using a non-parsimonious multinomial logistic regression model. Four studies (7%) used a technique that estimates generalized propensity scores and then creates 1:1:1 matched sets, and one study (2%) used the matching weight method. CONCLUSIONS: Many propensity score methods for multiple groups have been adopted in the literature. The TWANG method is the most commonly used method in the general medical literature.

National Trends in the Use of Sacubitril/Valsartan.

BACKGROUND: Better understanding of recent sacubitril/valsartan prescription patterns may help identify factors that influence its use. The aim of the study was to characterize sacubitril/valsartan use and dosage patterns nationally. METHODS AND RESULTS: We conducted a population-level cohort study using IQVIA Inc. National Prescription Audit™ data in the United States from August 2016 to July 2019. Over 3 years, there was a 5.6-fold increase in the number of sacubitril/valsartan prescriptions dispensed per month, totaling 3.3 million prescriptions. For the most recent year, this extrapolates to a best-case scenario of 13.8% of patients with heart failure with reduced ejection fraction using sacubitril/valsartan, representing at most one-half of those eligible for sacubitril/valsartan use. During the most recent year, 48.7% of dispensed prescriptions were for the lowest strength (24/26 mg) and only 20.6% for the target strength (97/103 mg). A greater proportion of the target strength was used in younger patients (< 65years: 24.6%; ≥ 85: 11.1%; P<0.0001). Cardiologists prescribed 59.0% of all dispensed prescriptions, and noncardiologists showed a greater increase (7.5-fold vs 4.9-fold; P<0.0001) over time. CONCLUSIONS: Recent use of sacubitril/valsartan has increased greatly in the United States; however, a substantial proportion of eligible patients with heart failure with reduced ejection fraction did not receive treatment, and only 1 in 5 prescriptions dispensed were for the target strength. Further exploration of barriers to the use of sacubitril/valsartan and dosing uptitration and their clinical implications warrant further evaluation.

Comparison of a new 3-item self-reported measure of adherence to medication with pharmacy claims data in patients with cardiometabolic disease.

BACKGROUND: Less than half of patients with cardiometabolic disease consistently take prescribed medications. While health insurers and some delivery organizations use claims to measure adherence, most clinicians do not have access during routine interactions. Self-reported scales exist, but their practical utility is often limited by length or cost. By contrast, the accuracy of a new 3-item self-reported measure has been demonstrated in individuals with HIV. We evaluated its concordance with claims-based adherence measures in cardiometabolic disease. METHODS: We used data from a recently-completed pragmatic trial of patients with cardiometabolic conditions. After 12 months of follow-up, intervention subjects were mailed a survey with the 3-item measure that queries about medication use in the prior 30 days. Responses were linearly transformed and averaged. Adherence was also measured in claims in month 12 and months 1-12 of the trial using proportion of days covered (PDC) metrics. We compared validation metrics for non-adherence for self-report (average <0.80) compared with claims (PDC <0.80). RESULTS: Of 459 patients returning the survey (response rate: 43.5%), 50.1% were non-adherent in claims in month 12 while 20.9% were non-adherent based on the survey. Specificity of the 3-item metric for non-adherence was high (month 12: 0.83). Sensitivity was relatively poor (month 12: 0.25). Month 12 positive and negative predictive values were 0.59 and 0.52, respectively. CONCLUSIONS: A 3-item self-reported measure has high specificity but poor sensitivity for non-adherence versus claims in cardiometabolic disease. Despite this, the tool could help target those needing adherence support, particularly in the absence of claims data.

Fixed-Dose Combination Medications for Treating Hypertension: A Review of Effectiveness, Safety, and Challenges.

PURPOSE OF REVIEW: To summarize the recent evidence on the effectiveness and safety of antihypertensive fixed-dose combination (FDC) medications, and to describe the facilitators and barriers to implementing FDCs in US clinical practice. RECENT FINDINGS: Recent clinical practice guidelines include FDC use for treating high BP. Clinical trials in recent years support the use of antihypertensive FDCs including low-dose triple- and quadruple-therapy FDCs. Initiating a low-to-standard dose dual-therapy FDCs showed better BP control than initiating treatment with a standard-dose monotherapy, and triple-therapy FDCs produced better BP control rates than dual-therapy FDCs. Retrospective cohort studies showed that FDCs are associated with increased medication adherence, reduced clinical inertia, decreased time to BP control, and improved cardiovascular outcomes. We further discussed barriers and facilitators of wider implementation of antihypertensive FDCs in clinical practice. FDC treatment for hypertension is not commonly used despite historical and recent data which support the effectiveness, safety, and benefits of FDCs. Simplified and protocolized treatment algorithms, team-based care, shared decision-making principles are crucial to successful utilization and implementation of FDC in clinical practice.

Prescribing of oral anticoagulants in the emergency department and subsequent long-term use by older adults with atrial fibrillation.

BACKGROUND: Patients with atrial fibrillation frequently seek emergency care. Rates of guideline-concordant oral anticoagulant therapy for stroke prevention are suboptimal in the community. We assessed the association between prescribing of oral anticoagulants in the emergency department (relative to referral to a longitudinal care provider for treatment initiation) and long-term use of oral anticoagulants. METHODS: This retrospective cohort study performed at 15 hospitals in Ontario, Canada, involved patients aged 65 years or older who visited the emergency department between 2009 and 2014, who had a primary diagnosis of atrial fibrillation, were discharged home, and were eligible for and willing to take stroke-prevention therapy. We used inverse probability-of-treatment weighting based on the propensity score to compare patients who were and were not given a prescription for an oral anticoagulant. The primary outcome was a prescription fill for an oral anticoagulant 6 months later. Secondary outcomes included a prescription fill at 1 year, all-cause mortality, and strokes or bleeding events leading to hospital admission. RESULTS: Of 2132 eligible patients, 402 (18.9%) were given a prescription for an oral anticoagulant in the emergency department. After weighting, 67.8% of these patients had filled a prescription for an oral anticoagulant at 6 months versus 37.2% of those who did not receive a prescription in the emergency department (absolute risk increase [ARI] 30.6%, number needed to treat [NNT] 3). At 1 year, the ARI was 23.2% and the NNT was 4. Rates of death, stroke and bleeding events did not differ significantly. INTERPRETATION: In patients with atrial fibrillation who were eligible for stroke prevention, prescribing an oral anticoagulant in the emergency department was associated with substantially higher long-term use of oral anticoagulants compared with deferring to the longitudinal care provider to initiate this therapy. Physicians working in the emergency department should consider initiating oral anticoagulation in eligible patients who are being discharged to home.

Long-term risk of stroke and bleeding post-atrial fibrillation ablation.

BACKGROUND: Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). Studies regarding long-term real-world outcomes post-CA have inconsistently accounted for oral anticoagulation (OAC). OBJECTIVES: To describe patterns of OAC use post-CA and to compare the OAC-adjusted long-term risk of stroke and major bleeding in AF patients with and without CA. METHODS: A population-based cohort of AF patients was constructed in Quebec and Ontario, Canada (1999-2014). Propensity score matching was performed to determine the incidence rates of stroke and major bleeding among those undergoing CA, adjusted for time-dependent OAC use. RESULTS: From the entire cohort, 6391 patients were identified as having undergone CA as compared to 482 977 patients who did not. Of these, 1240 patients with government medical insurance undergoing CA were matched with 2427 patients without CA. Post-CA, 78%, 65%, and 61% remained on an OAC at 1, 2, and 5 years, while 75%, 71%, and 68% of patients not undergoing CA were on OACs at 1, 2, and 5 years. At follow-up, there was no statistically significant difference for stroke (adjusted hazard ratio [HR], 0.88; 95% CI, 0.63 to 1.21) or major bleeding (adjusted HR, 0.88; 95% CI, 0.73 to 1.06). CONCLUSION: No evidence was found that CA significantly decreases the risk of stroke or major bleeding when adjusting for OAC use over time. It may be prudent to continue anticoagulation post-CA based on patient-risk profile until randomized trials demonstrate both reduced stroke rates with CA, and improved safety (balancing stroke and bleeding risk) with OAC discontinuation post-CA.

Effect of early physician follow-up on mortality and subsequent hospital admissions after emergency care for heart failure: a retrospective cohort study.

BACKGROUND: The 1-year mortality rate in patients with heart failure who are discharged from an emergency department is 20%. We sought to determine whether early follow-up after discharge from the emergency department was associated with decreased mortality or subsequent admission to hospital. METHODS: This retrospective cohort study conducted in Ontario, Canada, included adult patients who were discharged from 1 of 163 emergency departments between April 2007 and March 2014 with a primary diagnosis of heart failure. Using a propensity score-matched landmark analysis, we assessed follow-up in relation to mortality and admissions to hospital for cardiovascular conditions. RESULTS: Of 34 519 patients, 16 274 (47.1%) obtained follow-up care within 7 days and 28 846 (83.6%) within 30 days. Compared with follow-up between day 8 and 30, patients with follow-up care within 7 days had a lower rate of mortality over 1 year (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.87-0.97), and a reduced rate of admission to hospital over 90 days (HR 0.87, 95% CI 0.80-0.94) and 1 year (HR 0.92; 95% CI 0.87-0.97); the mortality rate over 90 days in this group trended to a lower rate (HR 0.90, 95% CI 0.10-1.00). Follow-up care within 30 days, compared with patients without 30-day follow-up, was associated with a reduction in 1-year mortality (HR 0.89, 95% CI 0.82-0.97) but not admission to hospital (HR 1.02, 95% CI 0.94-1.10). In this group, there was a trend toward an increase in 90-day admission to hospital (HR 1.14, 95% CI 1.00-1.29). INTERPRETATION: Follow-up care within 7 days of discharge from the emergency department was associated with lower rates of long-term mortality, as well as subsequent hospital admissions, and a trend to lower short-term mortality rates. Timely access to longitudinal care for patients with heart failure who are discharged from the emergency setting should be prioritized.

Factors associated with door-in to door-out delays among ST-segment elevation myocardial infarction (STEMI) patients transferred for primary percutaneous coronary intervention: a population-based cohort study in Ontario, Canada.

BACKGROUND: Compared to ST-segment elevation myocardial infarction (STEMI) patients who present at centres with catheterization facilities, those transferred for primary percutaneous coronary intervention (PCI) have substantially longer door-in to door-out (DIDO) times, where DIDO is defined as the time interval from arrival at a non-PCI hospital, to transfer to a PCI hospital. We aimed to identify potentially modifiable factors to improve DIDO times in Ontario, Canada and to assess the impact of DIDO times on 30-day mortality. METHODS: A population-based, retrospective cohort study of 966 STEMI patients transferred for primary PCI in Ontario in 2012 was conducted. Baseline factors were examined across timely DIDO status. Multivariate logistic regression was used to examine independent predictors of timely DIDO as well as the association between DIDO times and 30-day mortality. RESULTS: The median DIDO time was 55 min, with 20.1% of patients achieving the recommended DIDO benchmark of ≤30 min. Age (OR> 75 vs 18-55 0.30, 95% CI: 0.16-0.56), symptom-to-first medical contact (FMC) time (OR61-120mins vs < 60mins 0.60, 95% CI: 0.39-0.90; OR>120mins vs < 60mins 0.53, 95% CI:0.35-0.81) and emergency medical services transport with a pre-hospital electrocardiogram (ECG) (OREMS transport + ECG vs self-transport 2.63, 95% CI:1.59-4.35) were the strongest predictors of timely DIDO. Patients with timely ECG were more likely to have recommended DIDO times (33.0% vs 12.3%; P < 0.001). A significantly higher proportion of those who met the DIDO benchmark had timely FMC-to-balloon times (78.7% vs 27.4%; P < 0.001). Compared to patients with DIDO time ≤ 30 min, those with DIDO times > 90 min had significantly higher adjusted 30-day mortality rates (OR 2.82, 95% CI:1.10-7.19). CONCLUSIONS: While benchmark DIDO times were still rarely achieved in the province, we identified several potentially modifiable factors in the STEMI system that might be targeted to improve DIDO times. Our findings that patients who received a pre-hospital ECG were still being transferred to non-PCI capable centres suggest strategies addressing this gap may improve patient outcomes.

Regional variations in ambulatory care and incidence of cardiovascular events.

BACKGROUND: Variations in the prevalence of traditional cardiac risk factors only partially account for geographic variations in the incidence of cardiovascular disease. We examined the extent to which preventive ambulatory health care services contribute to geographic variations in cardiovascular event rates. METHODS: We conducted a cohort study involving 5.5 million patients aged 40 to 79 years in Ontario, Canada, with no hospital stays for cardiovascular disease as of January 2008, through linkage of multiple population-based health databases. The primary outcome was the occurrence of a major cardiovascular event (myocardial infarction, stroke or cardiovascular-related death) over the following 5 years. We compared patient demographics, cardiac risk factors and ambulatory health care services across the province's 14 health service regions, known as Local Health Integration Networks (LHINs), and evaluated the contribution of these variables to regional variations in cardiovascular event rates. RESULTS: Cardiovascular event rates across LHINs varied from 3.2 to 5.7 events per 1000 person-years. Compared with residents of high-rate LHINs, those of low-rate health regions received physician services more often (e.g., 4.2 v. 3.5 mean annual family physician visits, p value for LHIN-level trend = 0.01) and were screened for risk factors more often. Low-rate LHINs were also more likely to achieve treatment targets for hypercholes-terolemia (51.8% v. 49.6% of patients, p = 0.03) and controlled hypertension (67.4% v. 53.3%, p = 0.04). Differences in patient and health system factors accounted for 74.5% of the variation in events between LHINs, of which 15.5% was attributable to health system factors alone. INTERPRETATION: Preventive ambulatory health care services were provided more frequently in health regions with lower cardiovascular event rates. Health system interventions to improve equitable access to preventive care might improve cardiovascular outcomes.

Adherence and outcomes to direct oral anticoagulants among patients with atrial fibrillation: findings from the veterans health administration.

BACKGROUND: The direct oral anticoagulants (DOACs) reduce the risk of stroke in moderate to high-risk patients with non-valvular atrial fibrillation (AF). Yet, concerns remain regarding its routine use in real world practice. We sought to describe adherence patterns and the association between adherence and outcomes to the DOACs among outpatients with AF. METHODS: We performed a retrospective cohort study of patients in the VA Healthcare System who initiated pharmacotherapy with dabigatran, rivaroxaban, or apixaban between November 2010 and January 2015 for non-valvular AF with CHA2DS2-VASc score ≥ 2. Adherence was determined using pharmacy refill data and estimated by the proportion of days covered (PDC) over the first year of therapy. Clinical outcomes, including all-cause mortality and stroke, were measured at 6 months and used to assess measures of adherence for each DOAC. RESULTS: A total of 2882 patients were included. Most were prescribed dabigatran (72.7%), compared with rivaroxaban (19.8%) or apixaban (7.5%). The mean PDC was 0.84 ± 0.20 for dabigatran, 0.86 ± 0.18 for rivaroxaban, and 0.89 ± 0.14 for apixaban (p < 0.01). The proportion of non-adherent patients, PDC <0.80, was 27.6% for all and varied according DOAC. Lower adherence to dabigatran was associated with higher risk of mortality and stroke (HR 1.07; 1.03-1.12 per 0.10 decline in PDC). CONCLUSIONS: In a real-world VA population being prescribed anticoagulation for AF, more than one quarter had sub-optimal adherence. Lower adherence was associated with a higher risk of mortality and stroke. Efforts identifying non-adherent patients, and targeted adherence interventions are needed to improve outcomes.

The impact of drug shortages on patients with cardiovascular disease: causes, consequences, and a call to action.

Shortages of cardiovascular drugs have become increasingly common, representing an ongoing public health crisis. Given few therapeutic alternatives to many of the drugs in short supply, these shortages also pose a major challenge for cardiovascular care professionals. Although changes in the regulatory environment have led to some improvements in recent years, problems involving manufacturing processes remain the most common underlying cause. Because of the complex nature of drug shortages, sustainable solutions to prevent and mitigate them will require collaboration between regulatory agencies, drug manufacturers, and other key stakeholder groups. In this report, we describe the scope of the cardiovascular drug shortage crisis in the United States, including its underlying causes and the efforts currently being made to address it. Furthermore, we provide specific recommendations for how cardiovascular care professionals can be involved in efforts to limit the impact of drug shortages on patient care as well as policy changes aimed at preventing and mitigating them.

Rationale and design of the Study of a Tele-pharmacy Intervention for Chronic diseases to Improve Treatment adherence (STIC2IT): A cluster-randomized pragmatic trial.

BACKGROUND: Approximately half of patients with chronic cardiometabolic conditions are nonadherent with their prescribed medications. Interventions to improve adherence have been only modestly effective because they often address single barriers to adherence, intervene at single points in time, or are imprecisely targeted to patients who may not need adherence assistance. OBJECTIVE: To evaluate the effect of a multicomponent, behaviorally tailored pharmacist-based intervention to improve adherence to medications for diabetes, hypertension, and hyperlipidemia. TRIAL DESIGN: The STIC2IT trial is a cluster-randomized pragmatic trial testing the impact of a pharmacist-led multicomponent intervention that uses behavioral interviewing, text messaging, mailed progress reports, and video visits. Targeted patients are those who are nonadherent to glucose-lowering, antihypertensive, or statin medications and who also have evidence of poor disease control. The intervention is tailored to patients' individual health barriers and their level of health activation. We cluster-randomized 14 practice sites of a large multispecialty group practice to receive either the pharmacist-based intervention or usual care. STIC2IT has enrolled 4,076 patients who will be followed up for 12months after randomization. The trial's primary outcome is medication adherence, assessed using pharmacy claims data. Secondary outcomes are disease control and health care resource utilization. CONCLUSION: This trial will determine whether a technologically enabled, behaviorally targeted pharmacist-based intervention results in improved adherence and disease control. If effective, this strategy could be a scalable method of offering tailored adherence support to those with the greatest clinical need.