Fall risk and cardiovascular outcomes of first-line antihypertensive medications in nursing home residents.

BACKGROUND: Little evidence exists about the comparative effects of first-line antihypertensive medications (i.e., renin-angiotensin-aldosterone converting enzyme inhibitors (RAASi), amlodipine, or thiazide diuretics) in older adults with limited life expectancy. We compared the rates of injurious falls and short-term cardiovascular events between different first-line antihypertensive medication classes in adults receiving care in nursing homes (NH). METHODS: This was a retrospective cohort of Medicare fee-for-service beneficiaries receiving care in NHs. Patients newly dispensed first-line antihypertensive medications were identified using Part D claims (2015-2018) and linked with clinical assessments (i.e., Minimum Data Set). Fall-related injuries (FRI), hip fractures, and major adverse cardiac events (MACE) outcomes were identified using hospitalization claims. Patients were followed from the date of antihypertensive dispensing until the occurrence of outcomes, death, disenrollment, or 6-month follow-up. Inverse-probability-of-treatment-weighted (IPTW) cause-specific hazards regression models were used to compare outcomes between patients who were new users of RAASi, amlodipine, or thiazides. RESULTS: Our cohort included 16,504 antihypertensive users (RAASi, n = 9574; amlodipine, n = 5049; thiazide, n = 1881). Mean age was 83.5 years (± 8.2), 70.6% were female, and 17.2% were non-white race. During a mean follow-up of 5.3 months, 326 patients (2.0%) experienced an injurious fall, 1590 (9.6%) experienced MACE, and 2123 patients (12.9%) died. The intention-to-treat IPTW hazard ratio (HR) for injurious falls for amlodipine (vs RAASi) use was 0.85 (95% confidence interval (CI) 0.66-1.08) and for thiazides (vs RAASi) was 1.22 (95% CI 0.88-1.66). The rates of MACE were similar between those taking anti-hypertensive medications. Thiazides were discontinued more often than other classes; however, inferences were largely unchanged in as-treated analyses. Subgroup analyses were generally consistent. CONCLUSIONS: Older adults with limited life expectancy experience similar rates of injurious falls and short-term cardiovascular events after initiating any of the first-line antihypertensive medications.

Frailty and Time at Home After Post-Acute Care in Skilled Nursing Facilities.

OBJECTIVES: To examine the association of a claims-based frailty index with time at home, defined as the number of days alive and spent out of hospital or skilled nursing facility (SNF). DESIGN: Cohort Study. SETTING AND PARTICIPANTS: A 5% Medicare random sample of fee-for-service beneficiaries, who had continuous part A and B enrollment in the prior 6 months, that were discharged from a short SNF admission in 2014‒2016. METHODS: Frailty was measured with a validated claims-based frailty index (CFI) (range: 0‒1, higher scores indicating worse frailty) and categorized into nonfrail (CFI <0.25), mild frailty (CFI 0.25‒0.34), and moderate-to-severe frailty (CFI ≥0.35). We measured home time in the 6 months following SNF discharge (range: 0‒182 days with higher values representing more days at home and thus a better outcome). We used logistic regression to assess the association between frailty and short home time, defined as <173 days, adjusting for age, sex, race, region, a comorbidity index, clinical SNF admission characteristics in the Minimum Data Set, and SNF characteristics. RESULTS: In our sample of 144,708 beneficiaries (mean age, 80.8 years, 64.9% female, 85.9% white) who were discharged to community after SNF stay, the mean CFI was 0.26 (standard deviation, 0.07). The mean home time was 165.6 (38.1) days in nonfrail, 154.4 (47.4) days in mild frailty, 145.0 (52.0) days in moderate-to-severe frailty group. After full model adjustments, moderate to severe frailty was associated with a 1.71 (95% CI 1.65‒1.78) higher odds of having short time at home in the 6 months following SNF discharge. CONCLUSION AND IMPLICATIONS: Higher CFI is associated with short time at home in Medicare beneficiaries who are discharged to the community after post-acute SNF stay. Our results support the utility of CFI in identifying SNF patients who need additional resources and interventions to prevent health decline and poor quality of life.

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.

Comparing the association between multiple chronic conditions, multimorbidity, frailty, and survival among older patients with cancer.

INTRODUCTION: The high prevalence of multiple chronic conditions (MCC), multimorbidity, and frailty may affect treatment and outcomes for older adults with cancer. The goal of this study was to use three conceptually distinct measures of morbidity to examine the association between these measures and mortality. MATERIALS AND METHODS: Using Medicare claims data linked with the 2012-2016 Ohio Cancer Incidence Surveillance System we identified older adults with incident primary cancer sites of breast, colorectal, lung, or prostate (n = 29,140). We used claims data to identify their Elixhauser comorbidities, Multimorbidity-Weighted Index (MWI), and Claims Frailty Index (CFI) as measures of MCC, multimorbidity, and frailty, respectively. We used Cox proportional hazard models to examine the association between these measures and survival time since diagnosis. RESULTS: Lung cancer patients had the highest levels of MCC, multimorbidity, and frailty. There was a positive association between all three measures and a greater hazard of death after adjusting for age, sex (colorectal and lung only), and stage. Breast cancer patients with 5+ comorbidities had an adjusted hazard ratio (aHR) of 1.63 (95% confidence interval [CI]: 1.38, 1.93), and those with mild frailty had an aHR of 3.38 (95% CI; 2.12, 5.41). The C statistics for breast cancer were 0.79, 0.78, and 0.79 for the MCC, MWI, and CFI respectively. Similarly, lung cancer patients who were moderately or severely frail had an aHR of 1.82 (95% CI: 1.53, 2.18) while prostate cancer patients had an aHR of 3.39 (95% CI: 2.12, 5.41) and colorectal cancer patients had an aHR of 4.51 (95% CI: 3.23, 6.29). Model performance was nearly identical across the MCC, multimorbidity, and frailty models within cancer type. The models performed best for prostate and breast cancer, and notably worse for lung cancer. The frailty models showed the greatest separation in unadjusted survival curves. DISCUSSION: The MCC, multimorbidity, and frailty indices performed similarly well in predicting mortality among a large cohort of older cancer patients. However, there were notable differences by cancer type. This work highlights that although model performance is similar, frailty may serve as a clearer indicator in risk stratification of geriatric oncology patients than simple MCCs or multimorbidity.

Role of Frailty in Identifying Benefit From Transcatheter Versus Surgical Aortic Valve Replacement.

BACKGROUND: Frailty is associated with a higher risk for adverse outcomes after aortic valve replacement (AVR) for severe aortic valve stenosis, but whether or not frail patients derive differential benefit from transcatheter (TAVR) versus surgical (SAVR) AVR is uncertain. METHODS: We linked adults ≥65 years old in the US CoreValve HiR trial (High-Risk) or SURTAVI trial (Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients) to Medicare claims, February 2, 2011, to September 30, 2015. Two frailty measures, a deficit-based and phenotype-based frailty index (FI), were generated. The treatment effect of TAVR versus SAVR was evaluated within FI tertiles for the primary end point of death and nondeath secondary outcomes, using multivariable Cox regression. RESULTS: Of 1442 (linkage rate =60.0%) individuals included, 741 (51.4%) individuals received TAVR and 701 (48.6%) received SAVR (mean age 81.8±6.1 years, 44.0% female). Although 1-year death rates in the highest FI tertiles (deficit-based FI 36.7% and phenotype-based FI 33.8%) were 2- to 3-fold higher than the lowest tertiles (deficit-based FI 13.4%; hazard ratio, 3.02 [95% CI, 2.26-4.02], P<0.001; phenotype-based FI 17.9%; hazard ratio, 2.05 [95% CI, 1.58-2.67], P<0.001), there were no significant differences in the relative or absolute treatment effect of SAVR versus TAVR across FI tertiles for all death, nondeath, and functional outcomes (all interaction P>0.05). Results remained consistent across individual trials, frailty definitions, and when considering the nonlinked trial data. CONCLUSIONS: Two different frailty indices based on Fried and Rockwood definitions identified individuals at higher risk of death and functional impairment but no differential benefit from TAVR versus SAVR.

Relative risks of adverse events among older adults receiving opioids versus NSAIDs after hospital discharge: A nationwide cohort study.

BACKGROUND: Although analgesics are initiated on hospital discharge in millions of adults each year, studies quantifying the risks of opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) among older adults during this transition are limited. We sought to determine the incidence and risk of post-discharge adverse events among older adults with an opioid claim in the week after hospital discharge, compared to those with NSAID claims only. METHODS AND FINDINGS: We performed a retrospective cohort study using a national sample of Medicare beneficiaries age 65 and older, hospitalized in United States hospitals in 2016. We excluded beneficiaries admitted from or discharged to a facility. We derived a propensity score that included over 100 factors potentially related to the choice of analgesic, including demographics, diagnoses, surgeries, and medication coadministrations. Using 3:1 propensity matching, beneficiaries with an opioid claim in the week after hospital discharge (with or without NSAID claims) were matched to beneficiaries with an NSAID claim only. Primary outcomes included death, healthcare utilization (emergency department [ED] visits and rehospitalization), and a composite of known adverse effects of opioids or NSAIDs (fall/fracture, delirium, nausea/vomiting, complications of slowed colonic motility, acute renal failure, and gastritis/duodenitis) within 30 days of discharge. After propensity matching, there were 13,385 beneficiaries in the opioid cohort and 4,677 in the NSAID cohort (mean age: 74 years, 57% female). Beneficiaries receiving opioids had a higher incidence of death (1.8% versus 1.1%; relative risk [RR] 1.7 [1.3 to 2.3], p < 0.001, number needed to harm [NNH] 125), healthcare utilization (19.0% versus 17.4%; RR 1.1 [1.02 to 1.2], p = 0.02, NNH 59), and any potential adverse effect (25.2% versus 21.3%; RR 1.2 [1.1 to 1.3], p < 0.001, NNH 26), compared to those with an NSAID claim only. Specifically, they had higher relative risk of fall/fracture (4.5% versus 3.4%; RR 1.3 [1.1 to 1.6], p = 0.002), nausea/vomiting (9.2% versus 7.3%; RR 1.3 [1.1 to 1.4], p < 0.001), and slowed colonic motility (8.0% versus 6.2%; RR 1.3 [1.1 to 1.4], p < 0.001). Risks of delirium, acute renal failure, and gastritis/duodenitis did not differ between groups. The main limitation of our study is the observational nature of the data and possibility of residual confounding. CONCLUSIONS: Older adults filling an opioid prescription in the week after hospital discharge were at higher risk for mortality and other post-discharge adverse outcomes compared to those filling an NSAID prescription only.

Identification of Frailty Using a Claims-Based Frailty Index in the CoreValve Studies: Findings from the EXTEND-FRAILTY Study.

Background In aortic valve disease, the relationship between claims-based frailty indices (CFIs) and validated measures of frailty constructed from in-person assessments is unclear but may be relevant for retrospective ascertainment of frailty status when otherwise unmeasured. Methods and Results We linked adults aged ≥65 years in the US CoreValve Studies (linkage rate, 67%; mean age, 82.7±6.2 years, 43.1% women), to Medicare inpatient claims, 2011 to 2015. The Johns Hopkins CFI, validated on the basis of the Fried index, was generated for each study participant, and the association between CFI tertile and trial outcomes was evaluated as part of the EXTEND-FRAILTY substudy. Among 2357 participants (64.9% frail), higher CFI tertile was associated with greater impairments in nutrition, disability, cognition, and self-rated health. The primary outcome of all-cause mortality at 1 year occurred in 19.3%, 23.1%, and 31.3% of those in tertiles 1 to 3, respectively (tertile 2 versus 1: hazard ratio, 1.22; 95% CI, 0.98-1.51; P=0.07; tertile 3 versus 1: hazard ratio, 1.73; 95% CI, 1.41-2.12; P<0.001). Secondary outcomes (bleeding, major adverse cardiovascular and cerebrovascular events, and hospitalization) were more frequent with increasing CFI tertile and persisted despite adjustment for age, sex, New York Heart Association class, and Society of Thoracic Surgeons risk score. Conclusions In linked Medicare and CoreValve study data, a CFI based on the Fried index consistently identified individuals with worse impairments in frailty, disability, cognitive dysfunction, and nutrition and a higher risk of death, hospitalization, bleeding, and major adverse cardiovascular and cerebrovascular events, independent of age and risk category. While not a surrogate for validated metrics of frailty using in-person assessments, use of this CFI to ascertain frailty status among patients with aortic valve disease may be valid and prognostically relevant information when otherwise not measured.

Frailty and Post-hospitalization Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

Given the role of comorbid conditions in the pathophysiology of HFpEF, we aimed to identify and rank the importance of comorbid conditions associated with post-hospitalization outcomes of older adults hospitalized for HFpEF. We examined data from 4,605 Medicare beneficiaries hospitalized in 2007-2014 for HFpEF based on ICD-9-CM codes for acute diastolic heart failure (428.31 or 428.33). To identify characteristics with high importance for prediction of mortality, all-cause rehospitalization, rehospitalization for heart failure, and composite outcome of mortality or all-cause rehospitalization up to 1 year, we developed boosted decision tree ensembles for each outcome, separately. For interpretability, we estimated hazard ratios (HRs) and 95% confidence intervals (CI) using Cox proportional hazards models. Age and frailty were the most important characteristics for prediction of mortality. Frailty was the most important characteristic for prediction of rehospitalization, rehospitalization for heart failure, and the composite outcome of mortality or all-cause rehospitalization. In Cox proportional hazards models, a 1-SD higher frailty score (0.1 on theoretical range of 0 to 1) was associated with a HR of 1.27 (1.06 to 1.52) for mortality, 1.16 (1.07 to 1.25) for all-cause rehospitalization, 1.24 (1.14 to 1.35) for HF rehospitalization, and 1.15 (1.07 to 1.25) for the composite outcome of mortality or all-cause rehospitalization. In conclusion, frailty is an important predictor of mortality and rehospitalization in adults aged ≥66 years with HFpEF.

Comparative Effectiveness and Safety of Sodium-Glucose Cotransporter 2 Inhibitors Versus Glucagon-Like Peptide 1 Receptor Agonists in Older Adults.

OBJECTIVE: Both sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in randomized controlled trials of patients with type 2 diabetes (T2D) generally <65 years old and mostly with cardiovascular disease. We aimed to evaluate the comparative effectiveness and safety of SGLT2i and GLP-1RA among real-world older adults. RESEARCH DESIGN AND METHODS: Using Medicare data (April 2013-December 2016), we identified 90,094 propensity score-matched (1:1) T2D patients ≥66 years old initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE) (i.e., myocardial infarction, stroke, or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections, fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections, and overall mortality. We estimated hazard ratios (HRs) and rate differences (RDs) per 1,000 person-years, controlling for 140 baseline covariates. RESULTS: Compared with GLP-1RA, SGLT2i initiators had similar MACE risk (HR 0.98 [95% CI 0.87, 1.10]; RD -0.38 [95% CI -2.48, 1.72]) and reduced HHF risk (HR 0.68 [95% CI 0.57, 0.80]; RD -3.23 [95% CI -4.68, -1.77]), over a median follow-up of ∼6 months. They also had 0.7 more DKA events (RD 0.72 [95% CI 0.02, 1.41]), 0.9 more LLA (RD 0.90 [95% CI 0.10, 1.70]), 57.1 more genital infections (RD 57.08 [95% CI 53.45, 60.70]), and 7.1 fewer AKI events (RD -7.05 [95% CI -10.27, -3.83]) per 1,000 person-years. CONCLUSIONS: Among older adults, those taking SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and genital infections versus those taking GLP-1RA.

Preoperative Frailty Status and Intensity of End-of-Life Care Among Older Adults After Emergency Surgery.

CONTEXT: Emergency general surgery (EGS) is common and highly morbid for older adults, particularly for those who are frail. However, there are little data on the quality of end-of-life care (EOLC) for this population. OBJECTIVES: We sought to examine the association of frailty with intensity of EOLC for older adults with and without frailty who undergo EGS but die within one year. METHODS: This retrospective cohort study included 100% Medicare fee-for-service beneficiaries, ≥66 years, who underwent one of five EGS procedures with the highest mortality (partial colectomy, small bowel resection, peptic ulcer disease repair, adhesiolysis, or laparotomy) between 2008 and 2014 and died within one year. A validated claims-based frailty index (CFI) identified patients who were not frail (CFI < 0.15), prefrail (0.15 ≤ CFI < 0.25), mildly frail (0.25 ≤ CFI < 0.35), and moderately to severe frail (CFI ≥ 0.35). Multivariable adjusted logistic or Poisson regression compared post-discharge and EOL healthcare utilization. RESULTS: Among 138,916 older EGS adults who died within one year, 32.2% were not frail, 31.7% were prefrail, 29.8% had mild frailty and 6.3% had moderate-to-severe frailty. Decedents with any degree of frailty experienced high-intensity EOLC (P < 0.01), low rates of hospice use (P < 0.01), and fewer days at home. Of those who survived the index hospitalization but died within one year, moderate-to-severely frail decedents had the highest odds of visiting an emergency department (odds ratio [OR] = 1.19, CI = 1.13-1.27), rehospitalization (OR = 1.23, CI = 1.16-1.31), or an intensive care unit admission (OR = 1.22, CI = 1.13-1.30) in the last 30 days of life compared to nonfrail decedents. CONCLUSION: While all older patients undergoing EGS have poor end-of-life outcomes, frail EGS patients receive the highest intensity EOLC and represent a vulnerable population for whom targeted interventions could limit burdensome treatment.

The Impact of Frailty on Long-Term Patient-Oriented Outcomes after Emergency General Surgery: A Retrospective Cohort Study.

OBJECTIVES: Few studies examine the impact of frailty on long-term patient-oriented outcomes after emergency general surgery (EGS). We measured the prevalence of frailty among older EGS patients and examined the impact of frailty on 1-year outcomes. DESIGN: Retrospective cohort study using 2008 to 2014 Medicare claims. SETTING: Acute care hospitals. PARTICIPANTS: Patients 65 years or older who received one of the five EGS procedures with the highest mortality burden (partial colectomy, small bowel resection, peptic ulcer disease repair, adhesiolysis, or laparotomy). MEASUREMENTS: A validated claims-based frailty index (CFI) identified patients who were not frail (CFI < .15), pre-frail (.15 ≤ CFI < .25), mildly frail (.25 ≤ CFI < .35), and moderately to severely frail (CFI ≥ .35). Multivariable Cox regression compared 1-year mortality. Multivariable Poisson regression compared rates of post-discharge hospital encounters (hospitalizations, intensive care unit stay, emergency department visit) and home time over 1 year after discharge. All regression models adjusted for age, sex, race, admission from facility, procedure, sepsis, inpatient palliative care delivery, trauma center designation, hospital bed size, and teaching status, and they were clustered by patient and hospital referral region. RESULTS: Among 468 459 older EGS adults, 37.4% were pre-frail, 12.4% were mildly frail, and 3.6% were moderately to severely frail. Patients with mild frailty experienced a higher risk of 1-year mortality compared with non-frail patients (hazard ratio = 1.97; confidence interval [CI] = 1.94-2.01). In the year after discharge, patients with mild and moderate to severe frailty had more hospital encounters compared with non-frail patients (7.8 and 11.5 vs 2.0 per person-year; incidence rate ratio [IRR] = 4.01; CI = 3.93-4.08 vs IRR = 5.89; CI = 5.70-6.09, respectively). Patients with mild and moderate to severe frailty also had fewer days at home in the year after discharge compared with non-frail patients (256 and 203 vs 302 mean days; IRR = .97; CI = .96-.97 vs IRR = .95; CI = .94-.95, respectively). CONCLUSION: Older EGS patients with frailty are at increased risk for poor 1-year outcomes and decreased home time. Targeted interventions for older EGS patients with frailty during the index EGS hospitalization are urgently needed to improve long-term outcomes. J Am Geriatr Soc 68:1037-1043, 2020.

Sex-Specific Determinants of Outcomes After Transcatheter Aortic Valve Replacement.

Background Women account for a large proportion of patients treated with transcatheter aortic valve replacement, yet there remain conflicting reports about the effect of sex on outcomes. Moreover, the sex-specific prevalence and prognostic impact of frailty has not been systematically studied in the context of transcatheter aortic valve replacement. Methods and Results A preplanned analysis of the FRAILTY-AVR study (Frailty Aortic Valve Replacement) was performed to analyze the determinants of outcomes in older women and men undergoing transcatheter aortic valve replacement. FRAILTY-AVR was a multinational, prospective, observational cohort assembled at 14 institutions in North America and Europe from 2012 to 2017. Multivariable logistic regression models were stratified by sex and adjusted for covariates. Interaction between sex and each of these covariates was assessed. The primary outcome was 12-month mortality, and the secondary outcome was 1-month composite mortality or major morbidity. The cohort consisted of 340 women and 419 men. Women were older and had higher predicted risk of mortality. Women were more likely to have physical frailty traits, but not cognitive or psychosocial frailty traits, and global indices of frailty were similarly associated with adverse events regardless of sex. Women were more likely to require discharge to a rehabilitation facility, particularly those with physical frailty at baseline, although their functional status was similar to men at 12 months. The risk of 1-month mortality or major morbidity was greater in women, particularly those treated with larger prostheses. The risk of 12-month mortality was not greater in women, with the exception of those with pulmonary hypertension, in whom, there was a significant interaction for increased mortality. Conclusions The present study highlights sex-specific differences in older adults undergoing transcatheter aortic valve replacement and draws attention to the impact of physical frailty in women and their potential risk associated with oversized prostheses and pulmonary hypertension.