Economic analysis of endovascular repair versus surveillance for patients with small abdominal aortic aneurysms

BackgroundThe Positive Impact of EndoVascular Options for Treating Aneurysms Early (PIVOTAL) trial enrolled individuals with small (4.0- to 5.0-cm diameter) abdominal aortic aneurysms (AAA) and reported no difference in rupture or aneurysm-related death for patients who received early endovascular repair (EVAR) vs surveillance with serial imaging studies. We evaluated resource use, medical cost, and quality of life outcomes associated with the PIVOTAL treatment strategies.MethodsThis prospective economic and quality of life study was conducted within a randomized trial, with PIVOTAL sites participating in the quality of life (n = 67) and economic (n = 63) studies. The PIVOTAL trial randomized 728 patients (366 early EVAR and 362 surveillance). We used information from 701 quality of life (351 early EVAR and 350 surveillance) and 614 economic (314 early EVAR and 300 surveillance) study participants enrolled in the PIVOTAL trial. The main outcome measures were total medical costs and the aneurysm repair rate at 48 months.ResultsAfter 6 months, the rate of aneurysm repair was 96 vs 10 per 100 patients in the early EVAR and surveillance groups, respectively (difference, 86; 95% confidence interval [CI], 82-90; P < .0001), and total medical costs were greater in the early EVAR group ($33,471 vs$5520; difference, $27,951; 95$25,156-$30,746; P < .0001). In months 7 through 48, however, the rate of aneurysm repair was 54 per 100 patients in the surveillance group, and total medical costs were higher for patients in the surveillance vs the early EVAR group ($40,592 vs $15,197; difference,$25,394; 95% CI, $15,184-$35,605; P < .0001). At 48 months' follow-up, early EVAR patients had greater cumulative use of AAA repair (97 vs 64 per 100 patients; difference, 34; 95% CI, 21-46; P < .0001), but there was no difference in total medical costs ($48,669 vs$46,112; difference, $2557; 95$8043 to $13,156; P = .64). After discounting at 3$47,765 vs $43,532; difference, 4232; 95$5561 to $14,025; P = .40). There were no treatment-related differences in quality of life at 24 months.ConclusionsA treatment strategy involving early repair of smaller AAA with EVAR is associated with no difference in total medical costs at 48 months vs surveillance with serial imaging studies. Longer follow-up is required to determine whether the late medical cost increases observed for surveillance will persist beyond 48 months

The UCSD shortness of breath questionnaire has longitudinal construct validity in idiopathic pulmonary fibrosis

SummaryBackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that often causes disabling dyspnea. In IPF and other lung diseases, patient-reported outcomes (PROs)—questionnaires designed to gather information from the patient's perspective—can determine whether therapies affect dyspnea or other outcomes meaningful to patients. Before a PRO can be used confidently as an outcome measure in a longitudinal trial, studies must demonstrate the PRO's ability to capture change over time in the target population. Our goal in this study was to examine whether the UCSD Shortness of Breath Questionnaire does so in patients with IPF.MethodsWe used data from the Sildenafil Trial of Exercise Performance in Idiopathic Pulmonary Fibrosis (STEP-IPF) to perform analyses that examined associations between UCSD scores and five external measures (anchors) at baseline and over time. Anchors included the Activity domain from St. George's Respiratory Questionnaire (SGRQ-A), the Physical Functioning domain from the SF-36 (SF36-PF), forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLCO), and distance walked during a timed walk test (6MWD). Linear regression models were used to examine relationships between UCSD scores and anchors over time.ResultsAt baseline, UCSD scores were weakly correlated with percent predicted FVC (−0.21, p = 0.005) and percent predicted DLCO (−0.20, p = 0.008), moderately correlated with 6MWD (−0.39, p < 0.0001) and strongly correlated with SGRQ-A (0.79, p < 0.0001) and SF36-PF (−0.72, p < 0.0001). Change over time in UCSD scores was associated with change in FVC (estimate = 2.54, standard error [SE] = 1.23, p = 0.04), SGRQ-A (estimate = 7.94, SE = 1.11, p < 0.0001), SF36-PF (estimate = 6.00, SE = 1.13, p < 0.0001), and 6MWD (estimate = 4.23, SE = 1.18, p = 0.0004) but not DLCO (estimate = 0.33, SE = 1.33, p = 0.80).ConclusionsThese results support the validity of the UCSD to assess change in dyspnea over time in patients with IPF

Outcomes of cardiac surgery in patients age ≥80 years: results from the National Cardiovascular Network

AbstractOBJECTIVESThe purpose of this study was to evaluate characteristics and outcomes of patients age ≥80 undergoing cardiac surgery.BACKGROUNDPrior single-institution series have found high mortality rates in octogenarians after cardiac surgery. However, the major preoperative risk factors in this age group have not been identified. In addition, the additive risks in the elderly of valve replacement surgery at the time of bypass are unknown.METHODSWe report in-hospital morbidity and mortality in 67,764 patients (4,743 octogenarians) undergoing cardiac surgery at 22 centers in the National Cardiovascular Network. We examine the predictors of in-hospital mortality in octogenarians compared with those predictors in younger patients.RESULTSOctogenarians undergoing cardiac surgery had fewer comorbid illnesses but higher disease severity and surgical urgency than younger patients. Octogenarians had significantly higher in-hospital mortality after cardiac surgery than younger patients: coronary artery bypass grafting (CABG) only (8.1% vs. 3.0%), CABG/aortic valve (10.1% vs. 7.9%), CABG/mitral valve (19.6% vs. 12.2%). In addition, they had twice the incidence of postoperative stroke and renal failure. The preoperative clinical factors predicting CABG mortality in the very elderly were quite similar to those for younger patients with age, emergency surgery and prior CABG being the powerful predictors of outcome in both age categories. Of note, elderly patients without significant comorbidity had in-hospital mortality rates of 4.2% after CABG, 7% after CABG with aortic valve replacement (CABG/AVR), and 18.2% after CABG with mitral valve replacement (CABG/MVR).CONCLUSIONSRisks for octogenarians undergoing cardiac surgery are less than previously reported, especially for CABG only or CABG/AVR. In selected octogenarians without significant comorbidity, mortality approaches that seen in younger patients

Effect of Natriuretic Peptide-Guided Therapy on Hospitalization or Cardiovascular Mortality in High-Risk Patients With Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

Importance: The natriuretic peptides are biochemical markers of heart failure (HF) severity and predictors of adverse outcomes. Smaller studies have evaluated adjusting HF therapy based on natriuretic peptide levels ( guided therapy ) with inconsistent results. Objective: To determine whether an amino-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided treatment strategy improves clinical outcomes vs usual care in high-risk patients with HF and reduced ejection fraction (HFrEF). Design, Settings, and Participants: The Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure (GUIDE-IT) study was a randomized multicenter clinical trial conducted between January 16, 2013, and September 20, 2016, at 45 clinical sites in the United States and Canada. This study planned to randomize 1100 patients with HFrEF (ejection fraction ≤40%), elevated natriuretic peptide levels within the prior 30 days, and a history of a prior HF event (HF hospitalization or equivalent) to either an NT-proBNP-guided strategy or usual care. Interventions: Patients were randomized to either an NT-proBNP-guided strategy or usual care. Patients randomized to the guided strategy (n = 446) had HF therapy titrated with the goal of achieving a target NT-proBNP of less than 1000 pg/mL. Patients randomized to usual care (n = 448) had HF care in accordance with published guidelines, with emphasis on titration of proven neurohormonal therapies for HF. Serial measurement of NT-proBNP testing was discouraged in the usual care group. Main Outcomes and Measures: The primary end point was the composite of time-to-first HF hospitalization or cardiovascular mortality. Prespecified secondary end points included all-cause mortality, total hospitalizations for HF, days alive and not hospitalized for cardiovascular reasons, the individual components on the primary end point, and adverse events. Results: The data and safety monitoring board recommended stopping the study for futility when 894 (median age, 63 years; 286 [32%] women) of the planned 1100 patients had been enrolled with follow-up for a median of 15 months. The primary end point occurred in 164 patients (37%) in the biomarker-guided group and 164 patients (37%) in the usual care group (adjusted hazard ratio [HR], 0.98; 95% CI, 0.79-1.22; P = .88). Cardiovascular mortality was 12% (n = 53) in the biomarker-guided group and 13% (n = 57) in the usual care group (HR, 0.94; 95% CI; 0.65-1.37; P = .75). None of the secondary end points nor the decreases in the NT-proBNP levels achieved differed significantly between groups. Conclusions and Relevance: In high-risk patients with HFrEF, a strategy of NT-proBNP-guided therapy was not more effective than a usual care strategy in improving outcomes. Trial Registration: clinicaltrials.gov Identifier: NCT01685840

Rationale and design of the GUIDE-IT study: Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure.

OBJECTIVES: The GUIDE-IT (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) study is designed to determine the safety, efficacy, and cost-effectiveness of a strategy of adjusting therapy with the goal of achieving and maintaining a target N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of BACKGROUND: Elevations in natriuretic peptide (NP) levels provide key prognostic information in patients with HF. Therapies proven to improve outcomes in patients with HF are generally associated with decreasing levels of NPs, and observational data show that decreases in NP levels over time are associated with favorable outcomes. Results from smaller prospective, randomized studies of this strategy thus far have been mixed, and current guidelines do not recommend serial measurement of NP levels to guide therapy in patients with HF. METHODS: GUIDE-IT is a prospective, randomized, controlled, unblinded, multicenter clinical trial designed to randomize approximately 1,100 high-risk subjects with systolic HF (left ventricular ejection fraction ≤40%) to either usual care (optimized guideline-recommended therapy) or a strategy of adjusting therapy with the goal of achieving and maintaining a target NT-proBNP level of CONCLUSIONS: The GUIDE-IT study is designed to definitively assess the effects of an NP-guided strategy in high-risk patients with systolic HF on clinically relevant endpoints of mortality, hospitalization, quality of life, and medical resource use. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure [GUIDE-IT]; NCT01685840)

Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: The IRONOUT HF Randomized Clinical Trial.

Importance: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. Objective: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. Design, Setting, and Participants: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF ( Interventions: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. Main Outcomes and Measures: The primary end point was a change in peak oxygen uptake (V̇o2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). Results: Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak V̇o2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak V̇o2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P \u3e .05. Conclusions and Relevance: Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. Trial Registration: clinicaltrials.gov Identifier: NCT02188784

Comparative Effectiveness of Drug-Eluting Versus Bare-Metal Stents in Elderly Patients Undergoing Revascularization of Chronic Total Coronary Occlusions Results From the National Cardiovascular Data Registry, 2005–2008

ObjectivesThis study sought to investigate the long-term effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS).BackgroundImproved recanalization techniques have increased interest in percutaneous coronary intervention (PCI) for chronic total coronary occlusion (CTO). The long-term effectiveness of DES and BMS is not known.MethodsWe used data from 10,261 stable patients age ≥65 years at 889 U.S. hospitals who underwent CTO PCI from January 1, 2005, to December 31, 2008, in the NCDR (National Cardiovascular Data Registry) CathPCI Registry with linked Medicare inpatient claims for follow-up. Patient and procedural characteristics, and 30-month death, myocardial infarction, revascularization, and hospitalization for bleeding were evaluated by stent type. Outcomes following stenting were adjusted and compared using propensity score matching.ResultsDES were used for CTO PCI in 8,218 (80%) and BMS in 2,043 (20%). DES patients were younger (74.0 vs. 75.5 years, p < 0.001), had longer lesions (18.8 vs. 16.5 mm, p < 0.001), received more stents (≥2 stents in 45.7% vs. 37.9%, p < 0.001), and underwent multivessel PCI (18.9% vs. 15.1%, p < 0.001). DES implantation was associated with a lower hazard of mortality (hazard ratio [HR]: = 0.72, 95% confidence interval [CI]: 0.60 to 0.86, p < 0.001), a similar hazard for myocardial infarction (HR: 0.85, 95% CI: 0.61 to 1.19, p = 0.35), and subsequent revascularization (HR: 0.94, 95% CI: 0.79 to 1.12, p = 0.48), including PCI (HR: 0.98, 95% CI: 0.83 to 1.19, p = 0.87) and coronary artery bypass grafting (HR: 0.71, 95% CI: 0.46 to 1.10, p = 0.12). Hospitalization for bleeding was also similar for DES versus BMS (HR: 0.92; 95% CI: 0.61 to 1.39, p = 0.70).ConclusionsCompared with BMS, DES use in stable patients undergoing CTO PCI was associated with lower mortality, as well as similar myocardial infarction and repeat revascularization rates without an increase in subsequent bleeding requiring hospitalization

Percutaneous Coronary Intervention and Drug-Eluting Stent Use Among Patients ≥85 Years of Age in the United States

ObjectivesThis study assessed the comparative effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) among patients ≥85 years of age.BackgroundDespite an aging population, little is known about the comparative effectiveness of DES versus BMS among patients age ≥85 years undergoing percutaneous coronary intervention (PCI).MethodsWe examined 471,006 PCI patients age ≥65 years at 947 hospitals in the National Cardiovascular Data Registry between 2004 and 2008 and linked to Medicare claims data. Long-term outcomes (median follow-up 640.8 ± 423.5 days) were compared between users of DES and BMS.ResultsPatients age ≥85 years comprise an increasing proportion of PCIs performed among elderly subjects, yet rates of DES use declined the most in this age group. Compared with BMS, use of DES was associated with lower mortality: age ≥85 years, 29% versus 38% (adjusted hazard ratio [HR]: 0.80 [95% confidence interval (CI): 0.77 to 0.83]); age 75 to 84 years, 17% versus 25% (HR: 0.77 [95% CI: 0.75 to 0.79]); and age 65 to 74 years, 10% versus 16% (HR: 0.73 [95% CI: 0.71 to 0.75]). However, the adjusted mortality difference narrowed with increasing age (pinteraction <0.001). In contrast, the adjusted HR for myocardial infarction rehospitalization associated with DES use was significantly lower with increasing age: age ≥85 years, 9% versus 12% (HR: 0.77 [95% CI: 0.71 to 0.83]); age 75 to 84 years, 7% versus 9% (HR: 0.81 [95% CI: 0.77 to 0.84]); and age 65 to 74 years, 7% versus 8% (HR: 0.84 [95% CI: 0.80 to 0.88]) (pinteraction <0.001).ConclusionsIn this national study of older patients undergoing PCI, declines in DES use were most pronounced among those aged ≥85 years, yet lower adverse-event rates associated with DES versus BMS use were observed

Baseline features of the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial

Aim Describe the distinguishing features of heart failure (HF) patients with reduced ejection fraction (HFrEF) in the VICTORIA (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction) trial. Methods and results Key background characteristics were evaluated in 5050 patients randomized in VICTORIA and categorized into three cohorts reflecting their index worsening HF event. Differences within the VICTORIA population were assessed and compared with PARADIGM-HF (Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and COMMANDER HF (A Study to Assess the Effectiveness and Safety of Rivaroxaban in Reducing the Risk of Death, Myocardial Infarction, or Stroke in Participants with Heart Failure and Coronary Artery Disease Following an Episode of Decompensated Heart Failure). VICTORIA patients had increased risk of mortality and rehospitalization: New York Heart Association class (40% class III), atrial fibrillation (45%), diabetes (47%), hypertension (79%) and mean estimated glomerular filtration rate of 61.5 mL/min/1.73m2. Baseline standard of HF care was very good: 60% received triple therapy. Their N-terminal pro-B-type natriuretic peptide was 3377 pg/mL [interquartile range (IQR) 1992-6380]. Natriuretic peptides were 30% higher level in the 67% patients with HF hospitalization Conclusions VICTORIA comprises a broadly generalizable high-risk population of three unique clinical strata of worsening chronic HFrEF despite very good HF therapy. VICTORIA will establish the role of vericiguat, a soluble guanylate cyclase stimulator, in HFrEF