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Many elderly persons who have a heart attack do not receive beta blockers. These drugs have been shown to reduce the risk of a second heart attack. Researchers analyzed beta blocker use in 115,015 elderly patients who had a heart attack in 1994 or 1995. Of the 45,308 who had no contraindication to beta blocker use, only half received a prescription for a beta blocker when they were discharged from the hospital. The rate of beta blocker use varied from 30.3% to 77.1% depending on the state. Rates were highest in New England. One year after discharge, those taking beta blockers had a 14% lower risk of mortality.

The article discusses a study on the use of hierarchical regression models in assessing the rates of risk-standardized mortality and readmission of patients with heart failure in hospitals identified in the "America's Best Hospitals" ranking by the periodical "U.S. News & World Report" and in those non-ranked facilities. The study noted there was a reduced mean rate of in-hospital mortality in ranked hospitals, compared to non-ranked ones. It is said that ranked hospitals have not shown enough evidence of superiority for readmission.

Objective: To determine the incremental cost-effectiveness of clopidogrel plus aspirin (C + A) compared with aspirin (A) alone during the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management and Avoidance (CHARISMA) trial from a US payer perspective. Background: Although the CHARISMA trial did not find a benefit of adding clopidogrel to aspirin in its overall study cohort, a benefit was suggested in a prespecified subgroup of patients with established cardiovascular (CV) disease. The cost-effectiveness of dual antiplatelet therapy in this population is unknown. Methods: Medical resource utilization was assessed prospectively, and costs for hospitalizations, physician services, outpatient care, and medications were assigned using 2007 US dollars. Life expectancy was estimated contingent on fatal and nonfatal CV events using statistical models of long-term survival from the Saskatchewan Health database. Results: C + A was associated with a 12.5% relative reduction in CV death, myocardial infarction, or stroke compared with A alone (6.9% vs. 7.9%, P = 0.048) over a median 28 months of follow-up. Severe or moderate bleeding events were higher in patients receiving C + A versus A alone (3.6% vs. 2.5%, P < 0.001). Mean cost/patient was $2607 higher for C + A, while projected life expectancy increased by an average of 0.072 years due to fewer in-trial events. The resulting incremental cost-effectiveness ratio (ICER) for C + A was $36,343/year of life gained. Findings were insensitive to discount rate, life expectancy projections, post-event costs, and indirect costs from lost productivity; the ICER was most sensitive to the cost of clopidogrel. Bootstrap analysis demonstrated that the ICER for C + A remained <$50,000/life-year gained in 70.6% of bootstrap replicates and <$100,000/life-year gained in 87.4%. Conclusions: Among patients with established CV disease, adding clopidogrel to aspirin appears to increase life expectancy modestly at a cost generally considered acceptable within the US health-care system. [ABSTRACT FROM AUTHOR]

Background: The phase 3 NEURO-TTRansform trial showed eplontersen treatment for 65 weeks reduced transthyretin (TTR), halted progression of neuropathy impairment, and improved quality of life (QoL) in adult patients with hereditary TTR-mediated amyloidosis with polyneuropathy (ATTRv-PN), vs. historical placebo. Methods: NEURO-TTRansform enrolled patients with ATTRv-PN. A subset of patients were randomized to receive subcutaneous inotersen 300 mg weekly (Weeks 1–34) and subsequently switched to subcutaneous eplontersen 45 mg every 4 weeks (Weeks 37–81). Change in serum TTR and treatment-emergent adverse events (TEAEs) were evaluated through Week 85. Effects on neuropathy impairment, QoL, and nutritional status were also evaluated. Results: Of 24 patients randomized to inotersen, 20 (83%) switched to eplontersen at Week 37 and four discontinued due to AEs/investigator decision. Absolute change in serum TTR was greater after switching from inotersen (−74.3%; Week 35) to eplontersen (−80.6%; Week 85). From the end of inotersen treatment, neuropathy impairment and QoL were stable (i.e., did not progress) while on eplontersen, and there was no deterioration in nutritional status. TEAEs were fewer with eplontersen (Weeks 37–85; 19/20 [95%] patients) compared with inotersen (up to Week 35; 24/24 [100%] patients). Mean platelet counts decreased during inotersen treatment (mean nadir reduction ‒40.7%) and returned to baseline during eplontersen treatment (mean nadir reduction, ‒3.2%). Conclusions: Switching from inotersen to eplontersen further reduced serum TTR, halted disease progression, stabilized QoL, restored platelet count, and improved tolerability, without deterioration in nutritional status. This supports a positive benefit-risk profile for patients with ATTRv-PN who switch from inotersen to eplontersen. [ABSTRACT FROM AUTHOR]

Examines whether Medicare patients with acute myocardial infarction admitted to one of HCI-Mercer's `100 top hospitals' in the United States had better outcomes than patients treated in other hospitals. Suitability of the top 100 list for identifying hospitals with higher financial measures; Lack of evidence that the quality of care was sacrificed for the sake of efficiency.

Ticagrelor reduced major adverse cardiovascular events (MACE) and increased bleeding in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. Limb events including revascularization, acute limb ischemia (ALI), and amputation are major morbidities in patients with T2DM and atherosclerosis. This study sought to determine the effect of ticagrelor on limb events. Patients were randomized to ticagrelor or placebo on top of aspirin and followed for a median of 3 years. MACE (cardiovascular death, myocardial infarction, or stroke), limb events (ALI, amputation, revascularization), and bleeding were adjudicated by an independent and blinded clinical events committee. The presence of peripheral artery disease (PAD) was reported at baseline. Of 19,220 patients randomized, 1,687 (8.8%) had PAD at baseline. In patients receiving placebo, PAD was associated with higher MACE (10.7% vs 7.3%; HR: 1.48; P < 0.001) and limb (9.5% vs 0.8%; HR: 10.67; P < 0.001) risk. Ticagrelor reduced limb events (1.6% vs 1.3%; HR: 0.77; 95% CI: 0.61-0.96; P = 0.022) with significant reductions for revascularization (HR: 0.79; 95% CI: 0.62-0.99; P = 0.044) and ALI (HR: 0.24; 95% CI: 0.08-0.70; P = 0.009). The benefit was consistent with or without PAD (HR: 0.80; 95% CI: 0.58-1.11; and HR: 0.76; 95% CI: 0.55-1.05, respectively; P interaction = 0.81). There was no effect modification of ticagrelor vs placebo based on PAD for MACE (P interaction = 0.40) or TIMI major bleeding (P interaction = 0.3239). Patients with T2DM and atherosclerosis are at high risk of limb events. Ticagrelor decreased this risk, but increased bleeding. Future trials evaluating the combination of ticagrelor and aspirin would further elucidate the benefit/risk of such therapy in patients with PAD, including those without coronary artery disease. (A Study Comparing Cardiovascular Effects of Ticagrelor Versus Placebo in Patients With Type 2 Diabetes Mellitus [THEMIS]: NCT01991795) [Display omitted] [ABSTRACT FROM AUTHOR]

Key Points: Question: Is the antisense oligonucleotide eplontersen associated with changes in serum transthyretin concentration and improvement in neuropathy symptoms among adults with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy? Findings: In this open-label study that enrolled 168 patients (144 assigned to subcutaneous eplontersen) and included 60 historical placebo patients, the eplontersen treatment group demonstrated changes from baseline to week 65/66 consistent with significantly lower serum transthyretin concentration (−81.7% vs −11.2%), less neuropathy impairment, and better quality of life compared with the historical placebo group. Meaning: Among adults with ATTRv polyneuropathy, the eplontersen treatment group had lower serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Importance: Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective: To evaluate eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants: NEURO-TTRansform was an open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) in 168 adults with Coutinho stage 1 or 2 ATTRv polyneuropathy, Neuropathy Impairment Score 10-130, and a documented TTR variant. Patients treated with placebo from NEURO-TTR (NCT01737398; March 2013–November 2017), an inotersen trial with similar eligibility criteria and end points, served as a historical placebo ("placebo") group. Interventions: Subcutaneous eplontersen (45 mg every 4 weeks; n = 144); a small reference group received subcutaneous inotersen (300 mg weekly; n = 24); subcutaneous placebo weekly (in NEURO-TTR; n = 60). Main Outcomes and Measures: Primary efficacy end points at week 65/66 were changes from baseline in serum transthyretin concentration, modified Neuropathy Impairment Score +7 (mNIS+7) composite score (scoring range, –22.3 to 346.3; higher scores indicate poorer function), and Norfolk Quality of Life Questionnaire–Diabetic Neuropathy (Norfolk QoL-DN) total score (scoring range, –4 to 136; higher scores indicate poorer quality of life). Analyses of efficacy end points were based on a mixed-effects model with repeated measures adjusted by propensity score weights. Results: Among 144 eplontersen-treated patients (mean age, 53.0 years; 69% male), 136 (94.4%) completed week-66 follow-up; among 60 placebo patients (mean age, 59.5 years; 68% male), 52 (86.7%) completed week-66 follow-up. At week 65, adjusted mean percentage reduction in serum transthyretin was −81.7% with eplontersen and −11.2% with placebo (difference, −70.4% [95% CI, −75.2% to −65.7%]; P <.001). Adjusted mean change from baseline to week 66 was lower (better) with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, −24.8 [95% CI, −31.0 to −18.6; P <.001) and for Norfolk QoL-DN (−5.5 vs 14.2; difference, −19.7 [95% CI, −25.6 to −13.8]; P <.001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group. Conclusions and Relevance: In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT04136184; EU Clinical Trials Register: EudraCT 2019-001698-10 This open-label, single-group, phase 3 trial evaluates eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in adults with hereditary amyloid transthyretin (ATTRv) polyneuropathy at 40 sites in 15 countries, compared with historical controls. [ABSTRACT FROM AUTHOR]

Rates of acute myocardial infarction (AMI) hospitalizations for elderly Medicare patients decreased during the previous decade. However, trends in population rates of AMI hospitalizations for all adults by subgroups have not been described. Using data from a large all-payer administrative database of hospitalizations, we calculated annual AMI hospitalization rates from 2001 through 2007. Trend analysis was performed across age, gender, and ethnicity categories using survey regression. Overall rate decreased from 314 to 222 AMI hospitalizations per 100,000 patients from 2001 through 2007, representing a 29.2% decrease. Significant decreases were observed in AMI hospitalization rate for each group by age categories (p <0.001) and by gender (p <0.001). When stratified by ethnicity and gender, age-adjusted AMI hospitalization rates in white men and women decreased by 30.8% and 31.4%, whereas black men and women had significantly slower rates of decrease of 13.6% and 12.6%, respectively. In conclusion, although the overall rate of AMI hospitalizations decreased from 2001 through 2007, the observed decrease was smaller for black patients compared to white patients across all age groups studied. [Copyright &y& Elsevier]

The article discusses a study which described the temporal changes in length of stay, discharge disposition, and short-term outcomes among older U.S. patients hospitalized for heart failure. The observational study examined 6,955,461 Medicare fee-for-service hospitalizations for heart failure between 1993 and 2006. The researchers found that the mean length of stay decreased from 8.81 days to 6.33 days between 1993 and 2006. The importance of examining an episode of acute care during a standardized period of assessment is also highlighted by the study.

Background: The association between hospital volume and the death rate for patients who are hospitalized for acute myocardial infarction, heart failure, or pneumonia remains unclear. It is also not known whether a volume threshold for such an association exists. Methods: We conducted cross-sectional analyses of data from Medicare administrative claims for all fee-for-service beneficiaries who were hospitalized between 2004 and 2006 in acute care hospitals in the United States for acute myocardial infarction, heart failure, or pneumonia. Using hierarchical logistic-regression models for each condition, we estimated the change in the odds of death within 30 days associated with an increase of 100 patients in the annual hospital volume. Analyses were adjusted for patients' risk factors and hospital characteristics. Bootstrapping procedures were used to estimate 95% confidence intervals to identify the condition-specific volume thresholds above which an increased volume was not associated with reduced mortality. Results: There were 734,972 hospitalizations for acute myocardial infarction in 4128 hospitals, 1,324,287 for heart failure in 4679 hospitals, and 1,418,252 for pneumonia in 4673 hospitals. An increased hospital volume was associated with reduced 30-day mortality for all conditions (P<0.001 for all comparisons). For each condition, the association between volume and outcome was attenuated as the hospital's volume increased. For acute myocardial infarction, once the annual volume reached 610 patients (95% confidence interval [CI], 539 to 679), an increase in the hospital volume by 100 patients was no longer significantly associated with reduced odds of death. The volume threshold was 500 patients (95% CI, 433 to 566) for heart failure and 210 patients (95% CI, 142 to 284) for pneumonia. Conclusions: Admission to higher-volume hospitals was associated with a reduction in mortality for acute myocardial infarction, heart failure, and pneumonia, although there was a volume threshold above which an increased condition-specific hospital volume was no longer significantly associated with reduced mortality. N Engl J Med 2010;362:1110-8. [ABSTRACT FROM AUTHOR]

Background: Hereditary transthyretin amyloidosis (ATTRv) is associated with polyneuropathy, cardiomyopathy, or both. The effects of eplontersen on cardiac structure and function were assessed., Methods and Results: NEURO-TTRansform was an open-label trial involving 144 adults with ATTRv polyneuropathy (49 patients [34%] with cardiomyopathy) receiving eplontersen throughout and compared with a historical placebo group (n = 60; 30 patients [50%] with cardiomyopathy) from the NEURO-TTR trial at week 65. Treatment effect (eplontersen vs placebo), presented as mean difference (95% confidence interval) was analyzed after adjusting for age, sex, region, baseline value, ATTRv disease stage, previous ATTRv treatment, and V30M transthyretin variant. There were notable differences at baseline between the eplontersen group and historical placebo. In the cardiomyopathy subgroup, 65 weeks of eplontersen treatment was associated with improvement from baseline relative to placebo in left ventricular ejection fraction of 4.3% (95% confidence interval 1.40-21.01; P = .049) and stroke volume 10.64 mL (95% confidence interval 3.99-17.29; P = .002) while the remainder of echocardiographic parameters remained stable., Conclusions: Eplontersen was associated with stable or improved measures of cardiac structure and function vs historical placebo in patients with ATTRv polyneuropathy and cardiomyopathy. Further investigation into eplontersen's effect on transthyretin amyloid cardiomyopathy is being conducted in the CARDIO-TTRansform trial., (Copyright © 2023. Published by Elsevier Inc.)

Aims: Heart failure (HF) substantially limits the ability of patients to engage in physical activities. A detailed understanding of how patients experience these limitations is required to develop valid and sensitive measures for use in clinical research. This qualitative study was designed to provide a thorough description of how HF patients experience physical activity limitations in their daily lives., Methods and Results: Semi-structured interviews were conducted with 40 HF patients. Interview transcripts were coded with the aim of identifying key aspects of physical activity. Patients were divided between HF with preserved ejection fraction (n = 21, 52.5%) and HF with reduced ejection fraction (n = 19, 47.5%); the majority of patients were New York Heart Association Class II (n = 22, 52.5%) or Class III (n = 16, 40.0%). Relevant physical activity themes, including mobility and broader daily function areas, were identified. The most frequently reported mobility limitations involved difficulty walking (up a steep incline, up steps, and long distances), limited walking speed, difficulty standing for long periods of time, and difficulty carrying and lifting objects. These limitations were principally related to three HF symptoms: dyspnoea, tiredness/fatigue, and peripheral oedema. Patients adapted to their symptoms and related mobility limitations in several ways, including taking rests during an activity, doing an activity more slowly, and avoiding/refraining from an activity altogether. The broader daily function areas most commonly impacted by the mobility limitations were housework, exercising or playing sports, and going shopping., Conclusions: Heart failure patients report numerous physical activity limitations. These specific mobility and daily function areas can be measured using clinical outcome assessments (e.g. patient-reported outcomes and performance outcomes) in clinical trials and observational research. Accelerometry can be used to contribute to a holistic picture of patient functioning by passively collecting this type of data., (© 2022 AstraZeneca. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: To examine the effect of the Affordable Care Act (ACA) on changes in premiums for subscribers of nongrandfathered, nongroup insurance plans that were "cancelled.", Study Design: Retrospective multivariate analyses., Methods: Changes in annual premiums post ACA were evaluated across subgroups of subscriber and health plan characteristics. Data was derived from databases containing information on premiums, plan benefit, and demographics for subscribers aged 18 to 64 years within Kaiser Permanente of the Mid-Atlantic States. A linear regression model was used to examine the independent association between subscriber and health plan characteristics on the relative change in premiums., Results: In 2013, 4169 nongroup subscribers were enrolled in plans that were cancelled as a result of the ACA. The median pre-ACA premium was $3240 (range = $780-$39,492), which increased by a median of 21.3% (range = -77.4% to 193.6%), or $685 (range = -$27,464 to $8676), post ACA in 2014. Premiums increased more for high-deductible plans (median = 63.7%) than standard-deductible plans (median = 8.4%). Due to shifts in the age curve, premiums decreased for more than half of women aged 18 to 44 years, but increased by 35.2% for women aged 55 to 64 years. Premiums fell by 15.5% for subscribers who did not pass standard medical underwriting due to preexisting conditions., Conclusions: Changes in premiums in the nongroup market post ACA, varied substantially across subgroups, primarily due to differences in the amount of coverage, changes in rating criteria, shifts in the age curve, and anticipated differences in risk selection and composition of the risk pool. Given the extent of this variation, it would be incorrect to conclude the ACA as being uniformly beneficial or detrimental to subscribers of these cancelled plans.

Purpose: Platinum based chemotherapy is widely used for bladder cancer but is associated with vascular toxicity, especially thromboembolism. We evaluated the short-term (less than 1 year) and intermediate-term (2 to 5 years) vascular toxicity of platinum agents in older patients with bladder cancer., Materials and Methods: We identified Medicare beneficiaries 66 to 94 years old diagnosed with stage II-III bladder cancer from 1998 to 2007 in the SEER-Medicare database. We measured the association between platinum based chemotherapy and vascular events (thromboembolic and nonthromboembolic) using Cox proportional hazard regression models., Results: The sample included 5,057 patients, of whom 21.3% received platinum based chemotherapy. Patients receiving platinum based chemotherapy were more likely to be younger and male with less comorbidity than those not receiving any chemotherapy. During the first year after diagnosis the patients who received platinum based chemotherapy had a higher risk of a thromboembolic event (19.8% vs 11.6%, AHR 1.43, 95% CI 1.17-1.75) compared to those who did not receive chemotherapy. The likelihood of having a thromboembolic outcome was similar whether platinum chemotherapy was cisplatin based (21.1%, AHR 1.56, 95% CI 1.22-2.00) or carboplatin based (18.9%, AHR 1.35, 95% CI 1.07-1.71). During years 2 to 5 after diagnosis there was no significant association between platinum chemotherapy and the risk of thromboembolic events. The risk of nonthromboembolic vascular events was not increased with platinum chemotherapy in either period., Conclusions: Patients receiving platinum based chemotherapy were at higher risk for thromboembolism but not other vascular events, particularly in the first year after diagnosis. This risk of thromboembolism is similar for cisplatin and carboplatin., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: CHARISMA was a landmark randomized clinical trial that failed to demonstrate a benefit of dual antiplatelet therapy (DAPT) over aspirin alone for preventing cardiovascular events. However, subgroup analyses of the trial found fewer major adverse cardiovascular events (MACEs) for patients with established cardiovascular disease but more MACEs for patients with multiple risk factors without established cardiovascular disease. Our objective was to examine DAPT use in contemporary clinical practice after publication of CHARISMA results., Study Design: Retrospective analysis of a large clinical registry of outpatient cardiovascular visits to over 1000 physicians that collected data on patient clinical history, symptoms, vital signs, and medications., Methods: Clinical characteristics and prescription rates of aspirin and clopidogrel were compared for patients with established cardiovascular disease and for patients with only multiple cardiovascular risk factors. Prescription of DAPT by calendar quarter was evaluated from 2008 to 2011 using multivariable Poisson regression models., Results: Of 167,839 patients with established cardiovascular disease, 20.5% were prescribed both aspirin and clopidogrel. Of 20,478 patients with multiple risk factors but no known cardiovascular disease, 3.5% were prescribed both aspirin and clopidogrel. Across 14 calendar quarters, prescription rates of DAPT did not change significantly for patients with established CVD but decreased for patients with multiple risk factors with an incidence rate ratio of 0.77., Conclusions: Use of DAPT is modest in patients with established cardiovascular disease, for whom the CHARISMA trial suggested decreased MACEs, and prescription rates have remained stable over time. Use of DAPT in patients with multiple risk factors only, for whom CHARISMA suggested that DAPT may lead to increased MACE, was low and decreased over time.