2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year's worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Comparative safety and cardiovascular effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in nursing homes.

AIM: Studies examining the safety and effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs) among community-dwelling adults may not generalize to nursing home (NH) residents, who are typically older and more multimorbid. We compared the safety and cardiovascular effectiveness of SGLT2is and GLP-1RAs among US NH residents. MATERIALS AND METHODS: Eligible individuals were aged ≥66 years with type 2 diabetes mellitus and initiated an SGLT2i or GLP-1RA in an NH between 2013 and 2018. Safety outcomes included fall-related injuries, hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infection or genital infection, and acute kidney injury in the year following treatment initiation. Cardiovascular effectiveness outcomes included death, major adverse cardiovascular events and hospitalization for heart failure. Per-protocol adjusted hazard ratios (HR) were calculated using stabilized inverse probability of treatment and censoring weighted cause-specific hazard regression models accounting for 127 covariates. RESULTS: The study population included 7710 residents (31.08% SGLT2i, 68.92% GLP-1RA). Compared with GLP-1RA initiators, SGLT2i initiators had higher rates of DKA (HR 1.95, 95% confidence limits 1.27, 2.99) and death (HR 1.18, 95% confidence limits 1.02, 1.36). Rates of urinary tract infection or genital infection, acute kidney injury, major adverse cardiovascular events, and heart failure were also elevated, while rates of fall-related injuries and hypoglycaemia were reduced, but all estimates were imprecise and highly compatible with no difference. CONCLUSIONS: SGLT2is do not have superior, and may have inferior, effectiveness compared with GLP-1RAs for cardiovascular and mortality outcomes in NH residents. Residents initiating SGLT2is should be monitored closely for DKA.

Cross-Ancestry Investigation of Venous Thromboembolism Genomic Predictors.

BACKGROUND: Venous thromboembolism (VTE) is a life-threatening vascular event with environmental and genetic determinants. Recent VTE genome-wide association studies (GWAS) meta-analyses involved nearly 30 000 VTE cases and identified up to 40 genetic loci associated with VTE risk, including loci not previously suspected to play a role in hemostasis. The aim of our research was to expand discovery of new genetic loci associated with VTE by using cross-ancestry genomic resources. METHODS: We present new cross-ancestry meta-analyzed GWAS results involving up to 81 669 VTE cases from 30 studies, with replication of novel loci in independent populations and loci characterization through in silico genomic interrogations. RESULTS: In our genetic discovery effort that included 55 330 participants with VTE (47 822 European, 6320 African, and 1188 Hispanic ancestry), we identified 48 novel associations, of which 34 were replicated after correction for multiple testing. In our combined discovery-replication analysis (81 669 VTE participants) and ancestry-stratified meta-analyses (European, African, and Hispanic), we identified another 44 novel associations, which are new candidate VTE-associated loci requiring replication. In total, across all GWAS meta-analyses, we identified 135 independent genomic loci significantly associated with VTE risk. A genetic risk score of the significantly associated loci in Europeans identified a 6-fold increase in risk for those in the top 1% of scores compared with those with average scores. We also identified 31 novel transcript associations in transcriptome-wide association studies and 8 novel candidate genes with protein quantitative-trait locus Mendelian randomization analyses. In silico interrogations of hemostasis and hematology traits and a large phenome-wide association analysis of the 135 GWAS loci provided insights to biological pathways contributing to VTE, with some loci contributing to VTE through well-characterized coagulation pathways and others providing new data on the role of hematology traits, particularly platelet function. Many of the replicated loci are outside of known or currently hypothesized pathways to thrombosis. CONCLUSIONS: Our cross-ancestry GWAS meta-analyses identified new loci associated with VTE. These findings highlight new pathways to thrombosis and provide novel molecules that may be useful in the development of improved antithrombosis treatments.

Comparative performance of distinct frailty measures among patients undergoing percutaneous left atrial appendage closure.

AIMS: Frailty is associated with increased morbidity and mortality in patients undergoing left atrial appendage closure (LAAC). This study aimed to compare the performance of two claims-based frailty measures in predicting adverse outcomes following LAAC. METHODS: We identified patients 66 years and older who underwent LAAC between October 1, 2016, and December 31, 2019, in Medicare fee-for-service claims. Frailty was assessed using the previously validated Hospital Frailty Risk Score (HFRS) and Kim Claims-based Frailty Index (CFI). Patients were identified as frail based on HFRS ≥5 and CFI ≥0.25. RESULTS: Of the 21,787 patients who underwent LAAC, frailty was identified in 45.6% by HFRS and 15.4% by CFI. There was modest agreement between the two frailty measures (kappa 0.25, Pearson's correlation 0.62). After adjusting for age, sex, and comorbidities, frailty was associated with higher risk of 30-day mortality, 1-year mortality, 30-day readmission, long hospital stay, and reduced days at home (p < .01 for all) regardless of the frailty measure used. The addition of frailty to standard comorbidities significantly improved model performance to predict 1-year mortality, long hospital stay, and reduced days at home (Delong p-value < .001). CONCLUSION: Despite significant variation in frailty detection and modest agreement between the two frailty measures, frailty status remained highly predictive of mortality, readmissions, long hospital stay, and reduced days at home among patients undergoing LAAC. Measuring frailty in clinical practice, regardless of the method used, may provide prognostic information useful for patients being considered for LAAC, and may inform shared decision-making in this population.

Prognostic Importance of Atrial Fibrillation and Anticoagulation in Alcoholic Versus Dilated Cardiomyopathy.

AIMS: Limited data exist to describe the prognostic impact of atrial fibrillation (AF) and oral anticoagulation on patients with alcoholic cardiomyopathy (ACM) compared with dilated cardiomyopathy (DCM) and were investigated in this study. METHODS: Using Danish nationwide registries, a cohort analysis was conducted to assess the prognostic differences for patients with a first diagnosis of ACM versus DCM with and without AF 1994-2018 (followed until end 2019). Our study also assessed differences in mortality following initiation of anticoagulation in both populations. RESULTS: Totally, 1237 patients with ACM (33% with AF) and 17,211 individuals with DCM (33% with AF) were included. Those with ACM were more often men (89 versus 71%) and younger than patients with DCM (mean age 56 versus 64 years). Cumulative 5-year mortality was greater among patients with ACM, compared with DCM, regardless of AF (ACM with AF 49% [95% CI: 44-54%], ACM without AF 48% [45-53%], DCM with AF 41% [39-42%], DCM without AF 30% [29-31%], P < 0.0001). The prognosis associated with AF was statistically significantly different in people with ACM and DCM (adjusted hazards ratio 0.85 [95% CI: 0.74-0.98] versus 1.04 [1.00-1.09] in ACM and DCM, P < 0.0001). The mortality associated with oral anticoagulation was similar in ACM and DCM (hazards ratio 0.81 [0.61-1.07] versus 0.87 [0.80-0.94], P = 0.49). CONCLUSIONS: Patients with ACM had a worse prognosis when compared with patients with DCM, but this did not appear to be driven by AF. Patients with ACM were observed to have similar associated risk benefits of oral anticoagulation as DCM.

Frailty and Cardiovascular Mortality: A Narrative Review.

PURPOSE OF REVIEW: The goal of the narrative review is to provide an overview of the epidemiology of frailty in cardiovascular disease and cardiovascular mortality and discuss applications of frailty in cardiovascular care of older adults. RECENT FINDINGS: Frailty is highly prevalent in older adults with cardiovascular disease and is a robust, independent predictor of cardiovascular death. There is a growing interest in using frailty to inform management of cardiovascular disease either through pre- or post-treatment prognostication or by delineating treatment heterogeneity in which frailty serves to distinguish patients with differential harms or benefits from a given therapy. Frailty can enable more individualized treatment in older adults with cardiovascular disease. Future studies are needed to standardize frailty assessment across cardiovascular trials and enable implementation of frailty assessment in cardiovascular clinical practice.

Automated Electronic Phenotyping of Cardioembolic Stroke.

BACKGROUND AND PURPOSE: Oral anticoagulation is generally indicated for cardioembolic strokes, but not for other stroke causes. Consequently, subtype classification of ischemic stroke is important for risk stratification and secondary prevention. Because manual classification of ischemic stroke is time-intensive, we assessed the accuracy of automated algorithms for performing cardioembolic stroke subtyping using an electronic health record (EHR) database. METHODS: We adapted TOAST (Trial of ORG 10172 in Acute Stroke Treatment) features associated with cardioembolic stroke for derivation in the EHR. Using administrative codes and echocardiographic reports within Mass General Brigham Biobank (N=13 079), we iteratively developed EHR-based algorithms to define the TOAST cardioembolic stroke features, revising regular expression algorithms until achieving positive predictive value ≥80%. We compared several machine learning-based statistical algorithms for discriminating cardioembolic stroke using the feature algorithms applied to EHR data from 1598 patients with acute ischemic strokes from the Massachusetts General Hospital Ischemic Stroke Registry (2002-2010) with previously adjudicated TOAST and Causative Classification of Stroke subtypes. RESULTS: Regular expression-based feature extraction algorithms achieved a mean positive predictive value of 95% (range, 88%-100%) across 11 echocardiographic features. Among 1598 patients from the Massachusetts General Hospital Ischemic Stroke Registry, 1068 had any cardioembolic stroke feature within predefined time windows in proximity to the stroke event. Cardioembolic stroke tended to occur at an older age, with more TOAST-based comorbidities, and with atrial fibrillation (82.3%). The best model was a random forest with 92.2% accuracy and area under the receiver operating characteristic curve of 91.1% (95% CI, 87.5%-93.9%). Atrial fibrillation, age, dilated cardiomyopathy, congestive heart failure, patent foramen ovale, mitral annulus calcification, and recent myocardial infarction were the most discriminatory features. CONCLUSIONS: Machine learning-based identification of cardioembolic stroke using EHR data is feasible. Future work is needed to improve the accuracy of automated cardioembolic stroke identification and assess generalizability of electronic phenotyping algorithms across clinical settings.

Temporal trends in cause-specific mortality among individuals with newly diagnosed atrial fibrillation in the Framingham Heart Study.

BACKGROUND: All-cause mortality following atrial fibrillation (AF) has decreased over time. Data regarding temporal trends in causes of death among individuals with AF are scarce. The aim of our study was to analyze temporal trends in cause-specific mortality and predictors for cardiovascular (CVD) and non-CVD deaths among participants with incident AF in the Framingham Heart Study. METHODS: We categorized all newly diagnosed AF cases according to age at AF diagnosis (< 70, 70 to < 80, and ≥ 80 years) and epoch of AF diagnosis (< 1990, 1990-2002, and ≥ 2003). We followed participants until death or the last follow-up. We categorized death causes into CVD, non-CVD, and unknown causes. For each age group, we tested for trends in the cumulative incidence of cause-specific death across epochs. We fit multivariable Fine-Gray models to assess subdistribution hazard ratios (HR) between clinical risk factors at AF diagnosis and cause-specific mortality. RESULTS: We included 2125 newly diagnosed AF cases (mean age 75.5 years, 47.8% women). During a median follow-up of 4.8 years, 1657 individuals with AF died. There was evidence of decreasing CVD mortality among AF cases diagnosed < 70 years and 70 to < 80 years (ptrend < 0.001) but not ≥ 80 years (p = 0.76). Among the cases diagnosed < 70 years, the cumulative incidence of CVD death at 75 years was 67.7% in epoch 1 and 13.9% in epoch 3; among those 70 to < 80 years, the incidence at 85 years was 58.9% in epoch 1 and 18.9% in epoch 3. Advancing age (HR per 1 SD increase 6.33, 95% CI 5.44 to 7.37), prior heart failure (HR 1.49, 95% CI 1.14-1.94), and prior myocardial infarction (HR 1.44, 95% CI 1.15-1.80) were associated with increased rate of CVD death. CONCLUSIONS: In this community-based cohort, CVD mortality among AF cases decreased over time. Most deaths in individuals with AF are no longer CVD-related, regardless of age at AF diagnosis.

Atrial Fibrillation Risk and Discrimination of Cardioembolic From Noncardioembolic Stroke.

Background and Purpose- Classification of stroke as cardioembolic in etiology can be challenging, particularly since the predominant cause, atrial fibrillation (AF), may not be present at the time of stroke. Efficient tools that discriminate cardioembolic from noncardioembolic strokes may improve care as anticoagulation is frequently indicated after cardioembolism. We sought to assess and quantify the discriminative power of AF risk as a classifier for cardioembolism in a real-world population of patients with acute ischemic stroke. Methods- We performed a cross-sectional analysis of a multi-institutional sample of patients with acute ischemic stroke. We systematically adjudicated stroke subtype and examined associations between AF risk using CHA2DS2-VASc, Cohorts for Heart and Aging Research in Genomic Epidemiology-AF score, and the recently developed Electronic Health Record-Based AF score, and cardioembolic stroke using logistic regression. We compared the ability of AF risk to discriminate cardioembolism by calculating C statistics and sensitivity/specificity cutoffs for cardioembolic stroke. Results- Of 1431 individuals with ischemic stroke (age, 65±15; 40% women), 323 (22.6%) had cardioembolism. AF risk was significantly associated with cardioembolism (CHA2DS2-VASc: odds ratio [OR] per SD, 1.69 [95% CI, 1.49-1.93]; Cohorts for Heart and Aging Research in Genomic Epidemiology-AF score: OR, 2.22 [95% CI, 1.90-2.60]; electronic Health Record-Based AF: OR, 2.55 [95% CI, 2.16-3.04]). Discrimination was greater for Cohorts for Heart and Aging Research in Genomic Epidemiology-AF score (C index, 0.695 [95% CI, 0.663-0.726]) and Electronic Health Record-Based AF score (0.713 [95% CI, 0.681-0.744]) versus CHA2DS2-VASc (C index, 0.651 [95% CI, 0.619-0.683]). Examination of AF scores across a range of thresholds indicated that AF risk may facilitate identification of individuals at low likelihood of cardioembolism (eg, negative likelihood ratios for Electronic Health Record-Based AF score ranged 0.31-0.10 at sensitivity thresholds 0.90-0.99). Conclusions- AF risk scores associate with cardioembolic stroke and exhibit moderate discrimination. Utilization of AF risk scores at the time of stroke may be most useful for identifying individuals at low probability of cardioembolism. Future analyses are warranted to assess whether stroke subtype classification can be enhanced to improve outcomes in undifferentiated stroke.

Temporal trends in pharmacologic prophylaxis for venous thromboembolism after hip and knee replacement in older adults.

Trends in prescription for venous thromboembolism (VTE) prophylaxis following total hip (THR) and knee replacement (TKR) since the approval of direct oral anticoagulants (DOACs) and the 2012 guideline endorsement of aspirin are unknown, as are the risks of adverse events. We examined practice patterns in the prescription of prophylaxis agents and the risk of adverse events during the in-hospital period (the 'in-hospital sample') and 90 days following discharge (the 'discharge sample') among adults aged ⩾ 65 undergoing THR and TKR in community hospitals in the Institute for Health Metrics database over a 30-month period during 2011 to 2013. Eligible medications included fondaparinux, DOACs, low molecular weight heparin (LMWH), other heparin products, warfarin, and aspirin. Outcomes were validated by physician review of source documents: VTE, major hemorrhage, cardiovascular events, and death. The in-hospital and the discharge samples included 10,503 and 5722 adults from 65 hospitals nationwide, respectively (mean age 73, 74 years; 61%, 63% women). Pharmacologic prophylaxis was near universal during the in-hospital period (93%) and at discharge (99%). DOAC use increased substantially and was the prophylaxis of choice for nearly a quarter (in-hospital) and a third (discharge) of the patients. Aspirin was the sole discharge prophylactic agent for 17% and 19% of patients undergoing THR and TKR, respectively. Warfarin remained the prophylaxis agent of choice for patients aged 80 years and older. The overall risk of adverse events was low, at less than 1% for both the in-hospital and discharge outcomes. The low number of adverse events precluded statistical comparison of prophylaxis regimens.

Atrial Fibrillation: Epidemiology, Pathophysiology, and Clinical Outcomes.

The past 3 decades have been characterized by an exponential growth in knowledge and advances in the clinical treatment of atrial fibrillation (AF). It is now known that AF genesis requires a vulnerable atrial substrate and that the formation and composition of this substrate may vary depending on comorbid conditions, genetics, sex, and other factors. Population-based studies have identified numerous factors that modify the atrial substrate and increase AF susceptibility. To date, genetic studies have reported 17 independent signals for AF at 14 genomic regions. Studies have established that advanced age, male sex, and European ancestry are prominent AF risk factors. Other modifiable risk factors include sedentary lifestyle, smoking, obesity, diabetes mellitus, obstructive sleep apnea, and elevated blood pressure predispose to AF, and each factor has been shown to induce structural and electric remodeling of the atria. Both heart failure and myocardial infarction increase risk of AF and vice versa creating a feed-forward loop that increases mortality. Other cardiovascular outcomes attributed to AF, including stroke and thromboembolism, are well established, and epidemiology studies have championed therapeutics that mitigate these adverse outcomes. However, the role of anticoagulation for preventing dementia attributed to AF is less established. Our review is a comprehensive examination of the epidemiological data associating unmodifiable and modifiable risk factors for AF and of the pathophysiological evidence supporting the mechanistic link between each risk factor and AF genesis. Our review also critically examines the epidemiological data on clinical outcomes attributed to AF and summarizes current evidence linking each outcome with AF.

Use of Lecanemab for Patients With Cardiovascular Disease: The Challenge of Uncertainty.

This Viewpoint discusses lecanemab use and the risk of cerebral macrohemorrhage for patients with mild cognitive impairment or early dementia.

Anticoagulation reversal in vitamin K antagonist-associated intracerebral hemorrhage: a systematic review.

The effect of rapid anticoagulation reversal on mortality and functional outcome in vitamin K antagonist-associated intracerebral hemorrhage (VKA-ICH) is uncertain. Given the approval of idarucizumab for dabigatran reversal and pending approval for andexanet alfa for reversal of factor Xa inhibitors, a systematic appraisal of the effectiveness of reversal for VKA-ICH would provide a bench mark for current practice. We performed PubMed searches and reviewed current guidelines. Using pre-specified inclusion and exclusion criteria, studies were reviewed by two physicians independently. Data elements abstracted included study design, sample size, inclusion and exclusion criteria; patient characteristics at presentation; time to presentation and therapy; dose and timing of warfarin reversal agents; functional outcome and mortality. Studies were assessed for risk of bias. Twenty-one studies met the selection criteria. The overall quality of the studies was poor with small sample size for the majority and all studies being either case series or retrospective observational in design. Inclusion criteria were not uniform. Interpretation of the effectiveness of vitamin K antagonist reversal on functional outcome was not feasible due to lack of standard protocols in the management of VKA-ICH including choice, dose, and timing of reversal agent, timing of subsequent INR monitoring, and decision for repeat imaging. Confounding by indication, lack of universal reporting of functional outcome, and use of varied scales for the endpoint further limited a summary interpretation. Despite availability of reversal agents, mortality and morbidity remain high following VKA-ICH. Evidence for improvement in neurological outcome is limited.

Incidence of severe renal dysfunction among individuals taking warfarin and implications for non-vitamin K oral anticoagulants.

BACKGROUND: The purpose of this study is to assess incidence and risk factors for severe renal dysfunction in patients requiring oral anticoagulation to help guide initial drug choice and provide a rational basis for interval monitoring of renal function for patients prescribed non-vitamin K oral anticoagulants. METHODS: Patients on warfarin for atrial fibrillation or venous thromboembolism were consecutively enrolled from January 2007 to December 2010. Baseline kidney function was assessed, and patients were followed to their first decline of kidney function to creatinine clearance<30 mL/min. Multivariate regression assessed independent risk factors for the primary outcome. Severe renal impairment based on baseline kidney function was assessed by Kaplan-Meier analyses. RESULTS: Of 787 patients identified, 34 were excluded for baseline CrCl <30 mL/min. The mean age was 71 years, and 74% and 31% had hypertension and diabetes mellitus, respectively. At baseline, 23% (n=174) had moderate chronic kidney disease (CKD) (CrCl 30-59mL/min), whereas 31% had mild CKD (CrCl 60-89mL/min). Severe renal impairment occurred in 92 patients (12%), 25% of which was seen within 5.3 months. Of those with baseline stage 3 CKD, 37% developed severe renal impairment. Stage 3 CKD conferred a 14-fold increased risk in the development of severe renal dysfunction (odds ratio 14.5, 95% CI 6.7-31.3, P<.001). Coronary artery disease was also associated with severe renal impairment (odds ratio 2.2, 95% CI 1.3-3.8, P=.004). CONCLUSIONS: Acute and chronic renal dysfunction is common among individuals requiring long-term anticoagulant therapy. Patients with moderate chronic kidney disease and coronary artery disease are at the highest short-term risk of developing severe renal impairment. More frequent monitoring of these patients is warranted.

Anticoagulation in the older adult: optimizing benefit and reducing risk.

The risk for both arterial and venous thrombosis increases with age. Despite the increasing burden of strokes related to atrial fibrillation (AF) and venous thromboembolism (VTE) among older adults, the use of anticoagulant therapy is limited in this population due to the parallel increase in risk of serious hemorrhage. Understanding the risks and their underlying mechanisms would help to mitigate adverse events and improve persistence with these life-saving therapies. The objectives of this review are to: (1) elucidate the age-related physiologic changes that render this high risk subgroup susceptible to hemorrhage, (2) identify mutable risk factors and hazards contributing to an increased bleeding risk in older individuals, and (3) discuss interventions to optimize anticoagulation therapy in this population.

Assessing the Benefits and Harms of Pharmacotherapy in Older Adults with Frailty: Insights from Pharmacoepidemiologic Studies of Routine Health Care Data.

The objective of this review is to summarize and appraise the research methodology, emerging findings, and future directions in pharmacoepidemiologic studies assessing the benefits and harms of pharmacotherapies in older adults with different levels of frailty. Older adults living with frailty are at elevated risk for poor health outcomes and adverse effects from pharmacotherapy. However, current evidence is limited due to the under-enrollment of frail older adults and the lack of validated frailty assessments in clinical trials. Recent advancements in measuring frailty in administrative claims and electronic health records (database-derived frailty scores) have enabled researchers to identify patients with frailty and to evaluate the heterogeneity of treatment effects by patients' frailty levels using routine health care data. When selecting a database-derived frailty score, researchers must consider the type of data (e.g., different coding systems), the length of the predictor assessment period, the extent of validation against clinically validated frailty measures, and the possibility of surveillance bias arising from unequal access to care. We reviewed 13 pharmacoepidemiologic studies published on PubMed from 2013 to 2023 that evaluated the benefits and harms of cardiovascular medications, diabetes medications, anti-neoplastic agents, antipsychotic medications, and vaccines by frailty levels. These studies suggest that, while greater frailty is positively associated with adverse treatment outcomes, older adults with frailty can still benefit from pharmacotherapy. Therefore, we recommend routine frailty subgroup analyses in pharmacoepidemiologic studies. Despite data and design limitations, the findings from such studies may be informative to tailor pharmacotherapy for older adults across the frailty spectrum.