Cost-effectiveness of bivalirudin in pediatric ventricular assist devices.

BACKGROUND: Despite recent data suggesting improved outcomes with bivalirudin vs heparin in pediatric Ventricular assist devices (VAD), higher costs remain a barrier. This study quantified trends in bivalirudin use and compared outcomes, resource utilization, and cost-effectiveness associated with bivalirudin vs heparin. METHODS: Children age 0 to 6 year who received VAD from 2009 to 2021 were identified in Pediatric Health Information System. Bivalirudin use was evaluated using trend analysis and outcomes were compared using Fine-Gray subdistrubtion hazard ratios (SHR). Daily-level hospital costs were compared due to differences in length of stay. Cost-effectiveness was evaluated using incremental cost-effectiveness ratio (ICER). RESULTS: Of 691 pediatric VAD recipients (median age 1 year, IQR 0-2), 304 (44%) received bivalirudin with 90% receiving bivalirudin in 2021 (trend p-value <0.01). Bivalirudin had lower hospital mortality (26% vs 32%; adjusted SHR 0.57, 95% CI 0.40-0.83) driven by lower VAD mortality (20% vs 27%; adjusted SHR 0.46, 95% CI 0.32-0.77) after adjusting for year, age, diagnosis, and center VAD volume. Post-VAD length of stay was longer for bivalirudin than heparin (median 91 vs 64 days, respectively, p < 0.001). Median daily-level costs were lower among bivalirudin (cost ratio 0.87, 95% CI 0.79-0.96) with higher pharmacy costs offset by lower imaging, laboratory, supply, and room/board costs. Estimated ICER for bivalirudin vs heparin was $61,192 per quality-adjusted life year gained with a range of $27,673 to $131,243. CONCLUSIONS: Bivalirudin use significantly increased over the past decade and is now used in 90% young pediatric VAD recipients. Bivalirudin was associated with significantly lower hospital mortality and an ICER <$65,000, making it a cost-effective therapy for pediatric VAD recipients.

A meta-analysis and cost-minimization analysis of bivalirudin versus heparin in high-risk patients for percutaneous coronary intervention.

This meta-analysis was performed to compare the safety, efficacy, and pharmacoeconomic of bivalirudin versus heparin in high-risk patients for percutaneous coronary interventions (PCI). Earlier meta-analysis comparing bivalirudin and heparin during PCI demonstrated that bivalirudin caused less bleeding with more stent thrombosis. However, little data were available on the safety of bivalirudin versus heparin in high-risk patients for PCI. Thus, we performed a meta-analysis to evaluate the efficacy and safety in the "high-risk" patients. A systematic search of electronic databases was conducted up to July 30, 2020. The Cochrane Risk of Bias assessment tool was used to assess the quality of included studies. The primary outcomes were all-cause death and major adverse cardiac events (MACE); secondary outcomes were major and minor bleeding, followed by a cost-minimization analysis comparing bivalirudin and heparin using a local drug and medical costs reported in China. Subgroup analysis was based on the type of disease of the high-risk population. Finally, a total of 10 randomized controlled trials involved 42,699 patients were collected. The Cochrane Risk of Bias Tool was employed to appraise the research quality. No significant difference was noted between bivalirudin and heparin regarding all-cause death and MACE. However, subgroup analysis showed that bivalirudin caused less major bleeding in female (OR:0.65, 95% CI:0.53-0.79), diabetes (OR:0.55, 95%CI:0.42-0.73), and CKD (OR:0.59, 95%CI:0.63-1.65). The scatterers of the included literature were approximately symmetrical, and no research was outside the funnel plot. Additionally, cost-minimization analysis showed that heparin was likely to represent a cost-effective option compared with bivalirudin in China, with potential savings of 2129.53 Chinese Yuan (CNY) per patient for one PCI. Overall, the meta-analysis showed that although bivalirudin appeared to have a lower risk of major bleeding rate, the overall effectiveness and safety between the two groups showed no significant difference in high-risk patients for PCI. But the results of the cost-minimization analysis showed that heparin could be a potential cost-saving drug than bivalirudin in patients for PCI in China.

Description of Bivalirudin Use for Anticoagulation in Pediatric Patients on Mechanical Circulatory Support.

BACKGROUND: Although heparin has previously been the anticoagulant of choice during mechanical circulatory support (MCS), there is a lack of consistency in dose-response in pediatric patients. Bivalirudin offers more consistent dose-response in adults; however, there are limited data for pediatrics use. OBJECTIVE: The purpose was to characterize the usage, dosage, and safety profile of bivalirudin when used for pediatric MCS in a tertiary care pediatric hospital. METHODS: A retrospective review of pediatric patients receiving bivalirudin for extracorporeal membrane oxygenation/ventricular assist device (ECMO/VAD) anticoagulation was conducted. The primary outcome was the average dose of bivalirudin. Additional outcomes included initial and maximum bivalirudin dose, time to first therapeutic activated partial thromboplastin time (aPTT), time within goal aPTT range, bleeding and clotting complications, and cost. Data were compared between ECMO and VAD patients. RESULTS: Thirty-four patients were included. The median dose of bivalirudin was 0.37 mg/kg/h (interquartile range [IQR] = 0.21-0.56), with a maximum dose of 0.62 mg/kg/h (IQR = 0.33-0.91). VAD patients had a higher median and maximum dose as compared with ECMO patients. Patients achieved their therapeutic goal in a median of 6.1 hours and averaged 61.9% time within therapeutic aPTT. One patient had significant hemorrhage, whereas 3 patients had clotting requiring a circuit change. Bivalirudin acquisition cost was higher than heparin. CONCLUSION AND RELEVANCE: Bivalirudin dosing in ECMO and VAD patients is consistent with dosing seen in previous reports but may be higher in VAD patients. Comparative studies between heparin and bivalirudin are necessary to compare cost-effective outcomes for pediatric patients.

EGLP-1 lowers body weight better than exendin-4 by reducing food intake and increasing basal energy expenditure in diet-induced obese mice.

It is well known that GLP-1 activates GLP-1R to reduce body weight by inhibiting eating. GLP-1 is cleaved by the neutral endopeptidase (NEP) 24.11 into a pentapeptide GLP-1 (32-36) amide, which increases basal energy expenditure and inhibits weight gain in obese mice. It is well known that GLP-1 analogs can reduce weight by suppressing eating. However, there are few reports of reducing weight through the dual effects of inhibiting eating and increasing basic energy. Here, we report the peptide EGLP-1, a GLP-1 analogue, which can reduce food intake and increase basal energy expenditure. In C2C12 myotubes, EGLP-1 can increase both phosphorylation of acetyl CoA carboxylase (ACC) and the ratio between phosphorylation of ACC and the total expression of ACC (pACC/ACC). In diet-induced obese mice, EGLP-1 is more effective than exendin-4 in reducing body weight, reducing fat mass and improving hepatic steatosis. At the same time, EGLP-1 can improve hyperglycemia, reduce food intake, and improve insulin resistance, just like exendin-4. In addition, EGLP-1, not exendin-4, can improve physiological parameters associated with lipid metabolism and increase oxygen consumption by increasing uncoupling proteins 3 (UCP3) expression and pACC/ACC ratio in skeletal muscle. Taken together, this data showed that EGLP-1 is able to reduce body weight by reducing food intake and increasing basal energy expenditure, suggesting it may be more effective in treating diabetic and non-diabetic overweight or obese people than pure GLP-1R agonist exendin-4.

Development of peptide therapeutics: A nonclinical safety assessment perspective.

Novel peptide drugs continue to gain interest as effective modalities against previously undruggable targets. As with any other technology, development and safety assessment of peptides presents with various complex challenges. Additionally, there is a lack of specific regulatory guidance for peptide development, with the industry relying mainly on associating existing small molecule [ICH M3(R2)] and biologic [ICH S6(R1)] guidance. To gain insights into regulatory requirements for therapeutic peptides, we developed a dataset of peptides approved in the United States from 1998 through 2019 for which the summary basis of approval (SBA) packages are publicly available. The dataset comprises a total of 47 peptides (22 chemically synthesized, 6 semi-synthetic, 18 recombinant, and 1 natural). This article summarizes our learnings from the dataset in regards to the development paradigm, guidances followed, strategies for selection of toxicology species; requirements and/or value of genotoxicity and immunogenicity assessment; impurity, metabolite, and safety pharmacology assessment; and safety assessment of peptides containing non-proteogenic amino acids. In the context of the learnings from the dataset, the authors provide their recommendations for improvement of strategies to develop peptide drugs.

Assessment method for deamidation in proteins using carboxylic acid derivatization-liquid chromatography-tandem mass spectrometry.

An analytical method for the degree of protein deamidation has been developed by using carboxy group derivatization and liquid chromatography-tandem mass spectrometry (LCMS/MS). The fragment peptides (LGEYGFQNALIVR and YNGVFQECCQAEDK) obtained by digesting bovine serum albumin (BSA) with trypsin and their asparagine deamidated peptides (LGEYGFQDALIVR and YDGVFQECCQAEDK) were selected as model peptides, and their carboxy groups were derivatized with ethylamine. This derivatization enabled a clear distinction between natural peptides and deamidated peptides by mass, allowing for facile distinction by LCMS/MS before and after deamidation. Good linearity was confirmed for four peptides used in this study via isotope dilution mass spectrometry, showing that protein deamidation can be evaluated by the present method. To confirm the validity of this method for the evaluation of deamidation, natural peptides and deamidated peptides were mixed in arbitrary ratios, and degree of deamidation in these solution was analyzed. This confirmed that accurate evaluation was possible at deamidation degree values of ca. 10 %, 5 %, 2.5 %, and 1 %. Additionally, an accelerated storage test of BSA demonstrated that the deamidation of asparagine at position 404 of BSA progressed by 4 % in 9 weeks at 40 °C and pH 8 in the dark, and that the deamidation process can be traced over time.

Cost-effectiveness analysis of ocriplasmin versus watchful waiting for treatment of symptomatic vitreomacular adhesion in the US.

Aim: Evaluate the cost-effectiveness of ocriplasmin in symptomatic vitreomacular adhesion (VMA) with or without full-thickness macular hole ≤400 µm versus standard of care. Methods: A state-transition model simulated a cohort through disease health states; assignment of utilities to health states reflected the distribution of visual acuity. Efficacy of ocriplasmin was derived from logistic regression models using Ocriplasmin for Treatment for Symptomatic Vitreomacular Adhesion Including Macular Hole trial data. Model inputs were extracted from Phase III trials and published literature. The analysis was conducted from a US Medicare perspective. Results: Lifetime incremental cost-effectiveness ratio was US$4887 per quality-adjusted life year gained in the total population, US$4255 and US$10,167 in VMA subgroups without and with full-thickness macular hole, respectively. Conclusion: Ocriplasmin was cost effective compared with standard of care in symptomatic VMA.

Prospective, double blinded, comparative assessment of the pharmacological activity of Cerebrolysin and distinct peptide preparations for the treatment of embolic stroke.

BACKGROUND: Our previous work in acute ischemic stroke and TBI models focused on efficacy and pharmacological parameters of Cerebrolysin®. In this prospective, randomized, blinded, placebo-controlled study we compared efficacy of neuropeptide preparations with putative neurotrophic potential to the reference product Cerebrolysin® by assessing functional outcome and lesion volumes after embolic stroke in a rodent model. METHODS: Male Wistar rats were subjected to embolic right middle cerebral artery occlusion and were treated with: 1) Cognistar® (Cerebroprotein Hydrolysate) 2.5 ml/kg, 2) Cerebrolysat® 2.5 ml/kg, 3) Cortexin® 1.7 mg/kg, 4) Cerebrolysin® 2.5 ml/kg, or 5) 1 ml of saline according to a pre-generated randomization plan. Dosages were defined according to the packet leaflet of the corresponding preparation and were adapted to the animal model as previously described. All enrolled rats received intraperitoneal injections once daily for 10 consecutive days, starting 4 h after occlusion. Functional outcome was assessed once weekly over four weeks by using a battery of behavioral tests. Infarct volume was measured four weeks after occlusion. Generalized Estimation Equations (GEE) was performed to study the treatment effect on overall functional recovery at day 28 (primary outcome), compared to saline controls. RESULTS: Similar functional outcome was observed for saline control, Cognistar®, Cerebrolysat® and Cortexin®; in contrast, a significantly improved neurological outcome was observed with Cerebrolysin® treatment in comparison to saline as well as to the comparator drug treatment (p < .002). However, there was no significant difference in lesion volumes between rats treated with either Cortexin® (33.5 ±â€¯1.9%), Cerebrolysat® (28.5 ±â€¯2.4%), Cognistar® (34.7 ±â€¯2.0%), or Cerebrolysin® (26.5 ±â€¯2.3%) compared to saline-treated rats (30.8 ±â€¯2.1%). CONCLUSION: Among all tested neuropeptide preparations, Cerebrolysin® was the only agent that was associated with a significant improvement of neurological outcome after stroke.

Enzyme-Linked Immunosorbent Assay for T-Cell Dependent Immunogenicity Assessment of Therapeutic Peptides.

Immunogenicity assessment of therapeutic peptides, proteins, oligonucleotides, and hybrid molecules, such as nucleopeptides, is a major aspect in understanding their safety and efficacy. Both T-cell independent and dependent immune reactions contribute to an immunogenic response against antigen, including secretion of cytokines and production of an antigen-specific antibody. Various assays exist for detecting and quantifying such immunogenic responses by human T-cells ex vivo or in mouse serum, which primarily include enzyme-linked immunosorbent assay (ELISA, direct and indirect), flow-cytometry and surface plasmon resonance (SPR). ELISA is a popular choice due to its robustness, reliability, sensitivity, ease of automation, and the requirement of simple equipment commonly available in most molecular biology and biochemistry laboratories. The chapter describes the detailed protocol of cytokine analysis by an ELISA method and highlights few crucial steps to be considered while performing the assay for successful immunogenicity studies.

ASSESSMENT OF ANATOMICAL AND FUNCTIONAL OUTCOMES WITH OCRIPLASMIN TREATMENT IN PATIENTS WITH VITREOMACULAR TRACTION WITH OR WITHOUT MACULAR HOLES: Results of OVIID-1 Trial.

PURPOSE: To evaluate the anatomical and functional outcomes with ocriplasmin in patients with vitreomacular traction (VMT) with or without macular hole (MH). METHODS: In a Phase 4, multicenter, single-arm, open-label study, eligible patients (VMT with focal adhesion, without epiretinal membrane, and with MH ≤400 µm [if present]) received a single intravitreal injection of ocriplasmin. Nonsurgical resolution of VMT (Day 28 [primary endpoint]), best-corrected visual acuity, MH closure, vitrectomy rate, and safety were assessed through Day 180. RESULTS: Overall, 466 patients were included in the full analysis set, of whom 47.4% had VMT resolution by Day 28; resolution rates in patients with VMT without MH, VMT with MH ≤250 µm, and VMT with MH >250 to ≤400 µm were 43.4%, 68.6%, and 62.7%, respectively. Macular hole closure was higher in eyes with VMT and MH ≤250 µm (57.1%) than in eyes with VMT and MH >250 to ≤400 µm (27.5%) at Day 28. Overall, 30.8% of patients with VMT resolution gained ≥10 letters in best-corrected visual acuity at Day 180. Adverse events were consistent with the known safety profile of ocriplasmin. CONCLUSION: Ocriplasmin is effective for resolution of VMT without or with MH (≤400 µm); treatment outcomes can be optimized with patient selection.

Economic and Quality-of-Life Outcomes of Natriuretic Peptide-Guided Therapy for Heart Failure.

BACKGROUND: The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial prospectively compared the efficacy of an N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided heart failure treatment strategy (target NT-proBNP level <1,000 pg/ml) with optimal medical therapy alone in high-risk patients with heart failure and reduced ejection fraction. When the study was stopped for futility, 894 patients had been enrolled. OBJECTIVES: The purpose of this study was to assess treatment-related quality-of-life (QOL) and economic outcomes in the GUIDE-IT trial. METHODS: The authors prospectively collected a battery of QOL instruments at baseline and 3, 6, 12, and 24 months post-randomization (collection rates 90% to 99% of those eligible). The principal pre-specified QOL measures were the Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and the Duke Activity Status Index (DASI). Cost data were collected for 735 (97%) U.S. RESULTS: Baseline variables were well balanced in the 446 patients randomized to the NT-proBNP-guided therapy and 448 to usual care. Both the KCCQ and the DASI improved over the first 6 months, but no evidence was found for a strategy-related difference (mean difference [biomarker-guided - usual care] at 24 months of follow-up 2.0 for DASI [95% confidence interval (CI): -1.3 to 5.3] and 1.1 for KCCQ [95% CI: -3.7 to 5.9]). Total winsorized costs averaged $5,919 higher in the biomarker-guided strategy (95% CI: -$1,795, +$13,602) over 15-month median follow-up. CONCLUSIONS: A strategy of NT-proBNP-guided HF therapy had higher total costs and was not more effective than usual care in improving QOL outcomes in patients with heart failure and a reduced ejection fraction. (Guiding Evidence Based Therapy Using Biomarker Intensified Treatment [GUIDE-IT]; NCT01685840).

Budget impact analysis of ocriplasmin for the treatment of symptomatic vitreomacular adhesion in the USA.

BACKGROUND: Vitreomacular traction (VMT) treatment options include watchful waiting, vitrectomy and intravitreal ocriplasmin injection (Jetrea®). This analysis used results from the recently completed OASIS randomized clinical trial to evaluate the 2-year budget impact of ocriplasmin injection availability for treatment of Stage I or II VMT without epiretinal membrane formation in a modeled US health plan. MATERIALS & METHODS: VMT prevalence, treatment patterns and disease resolution rates were from literature, a US retinal-specialist survey and the OASIS trial. Medicare payment rates were applied and a national scenario analysis was conducted. RESULTS: With ocriplasmin available, vitrectomy use and complications-related costs decreased. Budget impact of ocriplasmin to the health plan was US$143,599 over 2 years or US$0.0060 per-member per-month. CONCLUSION: Ocriplasmin was projected to be minimally cost-additive at US$0.0060 per-member per-month over 2 years.

The comparative safety and effectiveness of bivalirudin versus heparin monotherapy in patients on dialysis undergoing percutaneous coronary intervention: Insights from the Blue Cross Blue Shield of Michigan cardiovascular consortium.

BACKGROUND: Dialysis patients are at a higher risk of bleeding after percutaneous coronary intervention (PCI); however, due to their exclusion from randomized clinical trials, the optimal antithrombotic regimen for this population remains unknown. We sought to evaluate the comparative safety and effectiveness of bivalirudin monotherapy versus unfractionated heparin (UFH) monotherapy in dialysis patients undergoing PCI. METHODS: We included dialysis patients who underwent PCI in a multicenter registry between January 2010 and September 2015 at 47 Michigan hospitals. We compared in-hospital outcomes between bivalirudin versus UFH; excluding those treated with glycoprotein IIb/IIIa inhibitors. Optimal full matching was used to account for the nonrandom use of these drugs. RESULTS: Of 177,963 patients who underwent PCI, 4,303 (2.4%) were on dialysis. Among those, 1,257 (29.2%) received bivalirudin monotherapy and 2,112 (49.1%) received UFH monotherapy. Patients treated with bivalirudin had fewer comorbidities. After matching, there were no significant differences in outcomes between those who received bivalirudin versus UFH: bleeding (adjusted odds ratio: 0.67; 95% confidence interval: 0.41-1.07; P = 0.093); major bleeding (0.81; 0.19-3.50; P = 0.77); transfusion (1.01; 0.77-1.33; P = 0.96); repeat PCI (0.57; 0.14-2.24; P = 0.42); stent thrombosis (0.56; 0.05-5.83; P = 0.63); and death (0.84; 0.46-1.51; P = 0.55). CONCLUSIONS: We found no significant differences in in-hospital outcomes between bivalirudin and UFH monotherapy among dialysis patients undergoing PCI. Randomized clinical trials are needed to determine the optimal anticoagulant regimen for this population. © 2017 Wiley Periodicals, Inc.

Optimal P2Y12 Inhibitor in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Network Meta-Analysis.

OBJECTIVES: The study sought to compare the clinical efficacy and safety of P2Y12 inhibitors in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous intervention (PPCI). BACKGROUND: Limited data exist regarding the comparative efficacy and safety of P2Y12 inhibitors in STEMI patients undergoing PPCI. METHODS: Clinical trials enrolling STEMI patients were identified and relevant data was extracted. Major adverse cardiovascular events (MACE) were defined as the composite of all cause mortality, MI, and target vessel revascularization. Network meta-analysis was performed using Bayesian methods. RESULTS: A total of 37 studies with 88,402 STEMI patients and 5,077 MACE were analyzed. Outcomes at 1 month (22 studies and 60,783 patients) suggest that prasugrel was associated with: lower MACE than clopidogrel (standard dose odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.50 to 0.69; high-dose OR: 0.60, 95% CI: 0.51 to 0.71; upstream OR: 0.79, 95% CI: 0.66 to 0.94), and ticagrelor (standard dose OR: 0.69, 95% CI: 0.56 to 0.84; upstream OR: 0.72, 95% CI: 0.50 to 1.05); lower mortality and MI than clopidogrel and standard ticagrelor; lower stroke risk than standard clopidogrel and standard or upstream ticagrelor; and lower stent thrombosis than standard or upstream clopidogrel. At 1-year (10 studies, n = 40,333) prasugrel was associated with lower mortality and MACE than other P2Y12 inhibitors. MACE was particularly lower with prasugrel in studies where patients received bivalirudin, drug-eluting stents, and but not glycoprotein IIb/IIIa inhibitor. CONCLUSIONS: In STEMI patients undergoing PPCI, prasugrel and ticagrelor are more efficacious than clopidogrel; in addition, prasugrel was superior to ticagrelor particularly in conjunction with bivalirudin and drug-eluting stents.

Association Of Bleeding Avoidance Strategies with age-related bleeding and In-hospital mortality in patients undergoing percutaneous coronary Interventions.

BACKGROUND: The association of bleeding avoidance strategy (BAS) (consisting of a combination of radial access, bivalirudin [rather than heparin +/- glycoprotein GPIIb/IIIa antagonists], and/or vascular closure devices after femoral access) with bleeding and in-hospital outcomes has not been evaluated among elderly patients undergoing percutaneous coronary interventions (PCI). METHODS: We studied BAS use, bleeding and in-hospital mortality among 121,635 patients categorized by age (<50, 50-59, 60-69, 70-79, and ≥80years) undergoing PCI from the BMC2 registry (1/2010-12/2013). RESULTS: The use of BAS decreased marginally with age and despite improved utilization over time, remained lower among the elderly. BAS was used in a much lower risk cohort among all age groups. Nonetheless, compared with no BAS, the use of this strategy was associated with lower bleeding (adjusted OR 0.984, 95% CI 0.980-0.985) and in-hospital mortality (adjusted OR 0.996, 95% CI 0.994-0.997) among all age-groups. Similar relative reduction in the risk of bleeding was observed among all age groups with BAS use with lowest risk (thus greatest absolute risk reduction given their highest risk for bleeding) for the oldest cohort. CONCLUSIONS: BAS use decreased with age among patients undergoing PCI despite its association with lower in-hospital mortality. Although overall utilization improved over time, it still remained lower in the elderly cohort, a group likely to benefit most from it. These data identified an opportunity to design strategies to improve BAS use particularly among high-risk elderly patients undergoing PCI so as to decrease bleeding and reduce related adverse events and costs.

Review of economic studies and budget impact analysis of ocriplasmin as a treatment of vitreomacular traction. / Revisión de estudios económicos y análisis de impacto presupuestario de la ocriplasmina como tratamiento de la tracción vitreomacular.

OBJECTIVE: To review the evidence on the cost-effectiveness of ocriplasmin as a treatment for vitreomacular traction (VMT), and to estimate the impact on the Spanish National Health System (NHS). MATERIAL AND METHODS: 1) Systematic review. The following databases were searched in January 2015: MEDLINE, PREMEDLINE, EMBASE, CRD, the Cochrane Library, and key websites. Selection criteria were: full economic evaluations that compared ocriplasmin with usual care ('watch and wait' and/or vitrectomy) in patients with VMT. The outcomes to extract were costs of the alternatives and the incremental cost-effectiveness ratio. Studies of budget impact analysis were also included. The methodological quality was assessed, and a narrative synthesis of the included studies was carried out. 2) Estimation of budget impact. The impact on the budget as a result of the introduction of ocriplasmin in the NHS was estimated, including data from different sources. RESULTS: Six studies were identified, none of them performed in Spain. The two best studies concluded that ocriplasmin is cost-effective in their respective countries (Canada and United Kingdom), but only in patients with certain conditions (without epiretinal membrane, for example). The results of the budget impact analysis are different between countries. The analysis for Spain showed that the introduction of ocriplasmin would mean a saving over 1 million Euros for the NHS in 5 years. CONCLUSIONS: The cost-effectiveness of ocriplasmin has not been demonstrated in Spain. However, good studies performed in other countries found that ocriplasmin is cost-effective in selected patients. Given the current prices in Spain, ocriplasmin could involve a saving for the Spanish NHS.

Bivalirudin is associated with improved clinical and economic outcomes in heart failure patients undergoing percutaneous coronary intervention: Results from an observational database.

BACKGROUND: Outcomes with bivalirudin compare favorably with heparin ± GPIIb/IIIa receptor inhibition (heparin ± GPI) during percutaneous coronary intervention (PCI). Patients with congestive heart failure (CHF) have increased risk for complications. The objective was to investigate clinical and economic outcomes for bivalirudin ± GPI vs. heparin ± GPI among PCI patients with CHF. METHODS: Using the Premier Hospital Database, PCI patients with CHF were stratified by anticoagulant: bivalirudin, bivalirudin ± GPI, heparin and heparin ± GPI. The probability of receiving bivalirudin ± GPI was estimated using individual and hospital variables. Using propensity scores, each bivalirudin ± GPI patient was matched to a heparin ± GPI patient. The primary outcome was in-hospital death. Bleeding rates, transfusion, length of stay and in-hospital cost were ascertained. RESULTS: Overall, 116,313 patients at 315 hospitals received bivalirudin (n = 45,559) bivalirudin + GPI (n = 8,115), heparin (n = 27,972) or heparin + GPI (n = 34,667). Patients had STEMI (21.2%), NSTEMI (29.1%), unstable angina (16.6%), stable angina (5.7%) or other ischemic heart disease (24.2%). Of these, 79.1% of bivalirudin patients matched, resulting in 84,948 analyzed patients. Compared with heparin ± GPI patients, bivalirudin ± GPI patients had fewer deaths (3.3% vs. 3.9%; p < 0.0001), less clinically apparent bleeding (10.2% vs. 11.4%; p < 0.0001), clinically apparent bleeding with transfusion (2.7% vs. 3.2%, p <0.0001), and transfusion (8.5% vs. 9.8%, p < 0.0001). Patients receiving bivalirudin had shorter length of stay (6.3 vs. 6.8 days; p < 0.0001) and lower in-hospital cost (mean $26,706 vs. $27,166 [median $19,414 vs. $19,798]; p < 0.0001). In conclusion, this is the largest retrospective analysis of PCI patients with CHF and demonstrates bivalirudin ± GPI compared with heparin ± GPI is associated with lower inpatient rates of death, bleeding, and cost.

The comparative efficacy of bivalirudin is markedly attenuated by use of radial access: insights from Blue Cross Blue Shield of Michigan Cardiovascular Consortium.

AIM: The purpose of our study was to evaluate the relative impact of bivalirudin on bleeding outcomes associated with trans-radial interventions (TRI) in real world practice. METHODS AND RESULTS: Data for patients undergoing percutaneous coronary intervention (PCI) between January 2010 and March 2014 at the 47 hospitals participating in the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) were utilized. Propensity matching was used within cohorts defined by access site. The impact of bivalirudin use on in-hospital outcomes was evaluated with Fisher's exact tests. Among patients undergoing trans-femoral interventions (TFI), use of bivalirudin was associated with a reduction in bleeding compared with both glycoprotein IIb/IIIa inhibitors (GPI; 1.67 vs. 3.46%, absolute risk reduction (ARR) 1.79%, odds ratio, OR, 0.47, confidence interval, CI, 0.41-0.54, number needed to treat, NNT 56, P < 0.001) and heparin (1.26 vs. 1.76%, ARR 0.5%, OR 0.71, CI 0.61-0.82, NNT 197, P < 0.001). Among patients undergoing TRI, there was a more modest absolute reduction in bleeding with bivalirudin compared with GPI (0.79 vs. 1.41%, ARR 0.62%, OR 0.56, CI 0.34-0.90, NNT 161, P = 0.016) and no difference in bleeding compared with heparin (0.46 vs. 0.46%, OR 1, CI 0.54-1.84, P = 1). CONCLUSION: Bivalirudin is markedly efficacious in reducing bleeding in patients undergoing TFI. The reduction in bleeding associated with bivalirudin use is minimal to absent in patients undergoing TRI. Given its lower cost and comparable outcomes, heparin should be the preferred anticoagulation strategy in those undergoing radial PCI.