Cost-Utility Analysis of Vericiguat in Heart Failure with Reduced Ejection Fraction After Worsening Heart Failure Events in China.

OBJECTIVE: Vericiguat is a new medication to demonstrate clinical efficacy in heart failure with reduced ejection fraction (HFrEF) after worsening heart failure (WHF) events, but its cost-utility was unknown. We aimed to assess the cost-utility of combining the application of vericiguat with standard treatment in HFrEF patients who had WHF events. METHODS: A multistate Markov model was implemented to mimic the economic results of HFrEF patients who had WHF events in China after receiving vericiguat or placebo. An analysis of cost-utility was conducted; most parameters were set according to the published studies and related databases. All the utilities and costs were decreased at a rate of 5% annually. The incremental cost-effectiveness ratios (ICERs) were the primary outcome measure. We also conducted sensitivity analyses. RESULTS: Over a 20 year lifetime horizon, additional use of vericiguat led to an elevated cost from US$9725.03 to US$20,660.76 at the current vericiguat costs. This was related to increased quality-adjusted life years (QALYs) from 2.50 to 2.66, along with an ICER of US$65,057.24 per QALY, which was over the willingness-to-pay (WTP) threshold of US$36,096.30 per QALY. If the vericiguat costs were discounted at 80%, it contributed to an ICER of US$12,226.77 per QALY. Additional use of vericiguat for patients with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) of ≤ 5314 pg per ml produced an ICER of US$23,688.46 per QALY. The outcomes of the one-way sensitivity analysis showed the risk of death from cardiovascular disease in both groups was variable with the highest sensitivity. The probabilistic sensitivity analysis showed that 41.6% of the mimicked population receiving vericiguat combined with standard therapy was cost-effective at the WTP threshold of US$36,096.30 per QALY. CONCLUSIONS: From the perspective of Chinese public healthcare system, the combined use of vericiguat and standard treatment in patients with HFrEF following WHF events did not generate advantages in cost-utility in China but was a cost-effective therapeutic strategy for those who with plasma NT-proBNP of ≤ 5314 pg per ml.

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.

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.

Updated Cost-Effectiveness of Intravitreal Ocriplasmin for Vitreomacular Adhesion and Macular Hole.

BACKGROUND AND OBJECTIVE: The purpose of this study is to provide an updated assessment of cost-efficacy of intravitreal ocriplasmin (IVO) for vitreomacular adhesion (VMA) and macular holes (MH). PATIENTS AND METHODS: This was a single-center, multiple-physician, institutional review board-approved, retrospective, 15-month cost-effectiveness analysis study (January 2015 to April 2016). Clinical charts and billing records of 247 patients with VMA and MH were reviewed. Patients were divided into group 1 (VMA and MH treated by pars plana vitrectomy [PPV]), group 2 (VMA and MH treated by IVO), and group 3 (VMA treated by IVO). Success rates of interventions in each group were compared, including cost-effectiveness, cost per line-year, and cost per quality-adjusted life-year (QALY). RESULTS: Success rates for initial intervention were 98% in group 1, 55.6% in group 2, and 67.7% in group 3. Cost of PPV at our institution was $6,538.00 and cost of IVO (2016) was $3,480.00. Using a cohort-based computer Markov model, the treatment decision tree demonstrated group 1 was less cost-effective, with cost per line of $2,654.39, cost per line-year saved of $185.62, and cost per QALY of $6,187.00. Group 2 was cost-effective with cost per line of $2,456.25, cost per line-year saved of $171.77, and cost per QALY of $5,726.00. The difference in cost-effectiveness showed IVO was more cost-effective than PPV, with a difference in cost per line of $198.14, cost per line-year saved of $13.85, and cost per QALY of $461.00. CONCLUSIONS: IVO is a more cost-effective intervention than vitrectomy for the treatment of VMA and MH in the setting of judicious use in appropriate patients. The success rate of IVO in our patient population was greater than currently published rates and most certainly impacted probability of cost-efficacy. Further research targeting optimizing IVO success rate is needed. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e240-e248.].

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.

A cost effectiveness study establishing the impact and accuracy of implementing the NICE guidelines lowering plasma NTproBNP threshold in patients with clinically suspected heart failure at our institution.

AIMS: The 2014 National Institute of Clinical Excellence (NICE) guidelines on the management of acute heart failure recommended using a plasma NT-proBNP threshold of 300pg/ml to assist in ruling out the diagnosis of heart failure (HF), updating previous guidelines recommending using a threshold of 400pg/ml. NICE based their recommendations on 6 studies performed in other countries. This study sought to determine the diagnostic and economic implications of using these thresholds in a large unselected UK population. METHODS: Patient and clinical demographics were recorded for all consecutive suspected HF patients over 12months, as well as clinical outcomes including time to HF hospitalisation and time to death (follow up 15.8months). RESULTS: Of 1995 unselected patients admitted with clinically suspected HF, 1683 (84%) had a NTproBNP over the current NICE recommended threshold, of which 35% received a final diagnosis of HF. Lowering the threshold from 400 to 300pg/ml would have involved screening an additional 61 patients and only would have identified one new patient with HF (sensitivity 0.985, NPV 0.976, area under the curve (AUC) at 300pg/ml 0.67; sensitivity 0.983, NPV 0.977, AUC 0.65 at 400pg/ml). The economic implications of lowering the threshold would have involved additional costs of £42,842.04 (£702.33 per patient screened, or £ 42,824.04 per new HF patient). CONCLUSION: Applying the recent updated NICE guidelines to an unselected real world population increases the AUC but would have a significant economic impact and only identified one new patient with heart failure.

Combining Cerebrospinal Fluid Biomarkers and Neuropsychological Assessment: A Simple and Cost-Effective Algorithm to Predict the Progression from Mild Cognitive Impairment to Alzheimer's Disease Dementia.

BACKGROUND: Correctly diagnosing Alzheimer's disease (AD) in prodromal phases would allow the adoption of experimental therapeutic strategies that could selectively interrupt the pathogenetic process before neuronal damage becomes irreversible. Therefore, great efforts have been aimed at finding early reliable disease markers. OBJECTIVE: The aim of this study was to identify a simple, cost effective, and reliable diagnostic algorithm to predict conversion from mild cognitive impairment (MCI) to AD. METHODS: 96 consecutive MCI patients admitted to the Neurology department of San Raffaele Hospital in Milan between January 2009 and January 2015 were included. All patients underwent neuropsychological assessment and lumbar puncture with CSF analysis of amyloid-ß 42 (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) levels. Each patient underwent clinical and neuropsychological follow-up, in order to identify a possible progression from MCI to AD. The mean follow up time was 36.73 months. RESULTS: 37 out of 96 MCI converted to AD during follow up. CSF analysis and neuropsychological assessment reliably detected MCI patients who developed AD. In a subsample of 43 subjects, a Composite Cognitive Score (CCS) was calculated including episodic memory, executive function, and verbal fluency tests. Combining together CSF biomarkers and CCS increased the accuracy of the single predictors, correctly classifying 86% of patients with a specificity of 96% and a Positive Predictive Value of 93%. DISCUSSION: Even if preliminary, our data seem to suggest that CSF analysis and neuropsychological assessment could detect MCI patients who will convert to AD with high confidence. Their relative low cost and availability could make them worldwide essential tools in future clinical trials.

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.

A Review of Potential Marine-derived Hypotensive and Anti-obesity Peptides.

Bioactive peptides are food derived components, usually consisting of 3-20 amino acids, which are inactive when incorporated within their parent protein. Once liberated by enzymatic or chemical hydrolysis, during food processing and gastrointestinal transit, they can potentially provide an array of health benefits to the human body. Owing to an unprecedented increase in the worldwide incidence of obesity and hypertension, medical researchers are focusing on the hypotensive and anti-obesity properties of nutritionally derived bioactive peptides. The role of the renin-angiotensin system has long been established in the aetiology of metabolic diseases and hypertension. Targeting the renin-angiotensin system by inhibiting the activity of angiotensin-converting enzyme (ACE) and preventing the formation of angiotensin II can be a potential therapeutic approach to the treatment of hypertension and obesity. Fish-derived proteins and peptides can potentially be excellent sources of bioactive components, mainly as a source of ACE inhibitors. However, increased use of marine sources, poses an unsustainable burden on particular fish stocks, so, the underutilized fish species and by-products can be exploited for this purpose. This paper provides an overview of the techniques involved in the production, isolation, purification, and characterization of bioactive peptides from marine sources, as well as the evaluation of the ACE inhibitory (ACE-I) activity and bioavailability.

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.

Bivalirudin in percutaneous coronary intervention, is it the anticoagulant of choice?

For decades, unfractionated heparin (UFH) has been widely used in catheterization laboratories for anticoagulation for percutaneous coronary intervention (PCI). The direct thrombin inhibitors, bivalirudin, has emerged as an alternative to UFH for PCI procedures, due to its lower bleeding risk. More recently, randomized trials and meta-analyses questioned the efficacy of bivalirudin, and demonstrated that bivalirudin might be associated with a higher incidence of ischemic events and in particular stent thrombosis. In this review, we discuss the pharmacology of bivalirudin along with the clinical evidence comparing bivalirudin versus UFH in patients undergoing PCI for various indications.

[Alternatives to heparin and protamine anticoagulation for cardiopulmonary bypass in cardiac surgery]. / Les différentes alternatives d'anticoagulation au couple héparine/protamine en chirurgie cardiaque sous circulation extra-corporelle.

PURPOSE: Heparin anticoagulation followed by protamine reversal is commonly used in cardiopulmonary bypass (CPB) cardiac procedures, but this strategy has some limitations. The primary objective of this study was to determine the reliable alternatives for anticoagulation during CPB for cardiac surgery. For each drug proposed, the secondary objectives were to outline the main advantages and disadvantages, to propose a therapeutic protocol, and to provide a cost-benefit analysis. SOURCE: A systematic review of the literature was performed between September 2012 and December 2013. It was based on the protocol established by the "Cochrane collaboration Handbook". Twenty articles were analyzed. The Thériaque database from the University Hospital of Grenoble made the economic analysis possible. PRINCIPAL FINDINGS: Seven alternative anticoagulation strategies were considered: danaparoid sodium, lepirudin, argatroban, bivalirudin, ancrod, idraparinux, and EP217609. Danaparoid sodium has issues with individual variability. Several studies (EVOLUTION-ON, CHOOSE-ON) proposed a reliable therapeutic protocol for bivalirudin. Ancrod resulted in an increase in the transfusion of blood products. Direct thrombin inhibitors offer a promising alternative. EP217609 is a synthetic anticoagulant currently undergoing Phase IIa clinical trials. It is an indirect inhibitor of factor Xa, a direct inhibitor of free and bound thrombin, and can be neutralized by avidin. CONCLUSIONS: The ideal anticoagulation strategy for cardiac surgery with CPB does not exist. Heparin and protamine remain the gold standard for anticoagulation therapy. To date, bivalirudin is the most promising molecule despite its high cost and lack of a readily available antagonist.

Bivalirudin for acute coronary syndromes: premises, promises and doubts.

Bivalirudin is a valuable anticoagulant option in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention. Advantages over heparin as a parenteral anticoagulant include more predictable pharmacokinetics and pharmacodynamics, shorter half-life, no need for cofactors, some degree of antiplatelet effect, and the ability to inhibit clot-bound thrombin. Clinical evidence supporting the use of bivalirudin over heparin in current ACS guidelines, however, derives mostly from early randomised trials that may no longer reflect current management patterns, now including the use of oral antiplatelet agents more potent than clopidogrel (i.e. prasugrel or ticagrelor) and a broader implementation of strategies to reduce bleeding (i.e. radial access for percutaneous coronary intervention, and use of glycoprotein IIb/IIIa inhibitors only in bailout situations). Defining the fine balance between bivalirudin efficacy and safety over heparins in the context of other antithrombotic treatments remains a challenge in clinical practice, particularly in a fast-evolving scenario, such as ACS, where numerous new trials have been presented in very recent times. Here we provide an up-to-date overview of the evidence on the use of bivalirudin in ACS, with focus on new data, open issues, and future directions.

Application of taste sensing system for characterisation of enzymatic hydrolysates from shrimp processing by-products.

The objective of this study was to investigate the potential of an instrumental taste-sensing system to distinguish between shrimp processing by-products hydrolysates produced using different proteases and hydrolysis conditions, and the possible association of taste sensor outputs with human gustatory assessment, salt content, and bioactivity. Principal component analysis of taste sensor output data categorised samples according to the proteases used for hydrolysis. High umami sensor outputs were characteristic of bromelain- and Flavourzyme-produced hydrolysates, compared to low saltiness and high bitterness outputs of Alcalase-produced hydrolysates, and high saltiness and low umami outputs of Protamex-produced hydrolysates. Extensively hydrolysed samples showed higher sourness outputs. Saltiness sensor outputs were correlated with conductivity and sodium content, while umami sensor responses were related to gustatory sweetness, bitterness and umami, as well as angiotensin-I converting enzyme inhibitory activity. Further research should explore the dose dependence and sensitivity of each taste sensor to specific amino acids and peptides.

The clinical and economic impact of bivalirudin for percutaneous coronary intervention.

Bivalirudin (BVR) is a direct thrombin inhibitor used as an adjunctive antithrombotic agent in combination with aspirin and an ADP-receptor blocker in patients with acute coronary syndrome undergoing percutaneous coronary intervention. When compared to a strategy of heparin plus a glycoprotein IIb/IIIa inhibitor, BVR has been shown in a number of randomized clinical trials to be at least as effective at reducing ischemic endpoints and to have a consistently lower rate of bleeding complications. In addition, various economic analyses have shown it to be cost-effective compared to heparin plus a glycoprotein IIb/IIIa inhibitor and this, coupled with its proven clinical efficacy, has led to the incorporation of BVR into both EU and US clinical guidelines. Previous studies with BVR have mostly assessed its use in patients treated with aspirin and clopidogrel and further studies are ongoing to determine its role in combination with newer, more potent oral antiplatelet agents.

Bivalirudin for the treatment of ST-segment elevation myocardial infarction: a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer (The Medicines Company) of bivalirudin to submit evidence for its clinical and cost effectiveness within its licensed indication for the treatment of adults with ST-segment elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention (PPCI), as part of NICE's single technology appraisal (STA) process. The School of Health and Related Research (ScHARR) at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG), which produced a review of the evidence within the manufacturer's submission to NICE. This article describes the manufacturer's submission, the ERG review and NICE's subsequent decisions. The main evidence was derived from one randomized controlled trial (RCT) of STEMI patients intended for PPCI, comparing bivalirudin with unfractionated heparin plus glycoprotein IIb/IIIa inhibitors (GPIs). Bivalirudin was associated with a significant reduction in cardiac mortality at 30 days (p = 0.03) and at 1-year follow-up (p = 0.005), and a significant reduction in major bleeding at 30 days (p < 0.001) and 1 year (p < 0.0001), compared with heparin plus GPI. Stent thrombosis up to 24 hours following PPCI was significantly (p < 0.001) more common with bivalirudin. However, there was no significant treatment effect for stent thrombosis from 1 to 30 days (p = 0.28), or at 1-year follow-up (p = 0.53). There were no significant treatment group differences at 30 days and at 1 year in stroke (p = 0.68 and p = 0.99, respectively), in myocardial infarction [MI] (p = 0.90 and p = 0.22, respectively), or in the need for the revascularization of the target vessel for ischaemia (p = 0.18 and p = 0.12, respectively). There were two decision-analytic models: the base-case scenario used 1-year follow-up data from the RCT; and a sensitivity analysis used 3-year follow-up data. Resource use was primarily drawn from this RCT. Health-related quality-of-life (HR-QOL) estimates were drawn from a UK cohort study. Both models evaluated the incremental costs and outcomes of bivalirudin compared with heparin plus GPI for patients with STEMI intended for PPCI. The analysis adopted a UK NHS perspective over a lifetime horizon. Unit costs were based on year 2009-2010 prices. The model adopted a decision-tree structure to reflect initial events for the initial period (stroke, repeat MI, minor/major bleeding events, repeat revascularization and death) and a two-state Markov component to simulate longer-term survival. The economic analysis suggested that bivalirudin is expected to dominate the heparin plus GPI strategy. This finding was consistent across the probabilistic sensitivity analysis and the vast majority of deterministic sensitivity analyses undertaken. Three exceptions to this finding were observed for the following sensitivity analyses: (1) the exclusive use of eptifibatide as the GPI (incremental cost-effectiveness ratio [ICER] = £1,764); (2) the combination of 100 % eptifibatide use, 100 % radial arterial access and no differential length between strategies for initial hospital stay (ICER = £4,106); and (3) a longer length of ward stay (increase of 0.33 days) for the initial hospitalization (ICER = £415). The Appraisal Committee (AC) gave a positive recommendation for bivalirudin for the treatment of adults with STEMI undergoing PPCI.

Isolation and characterization of pepsin-solubilized collagen from the integument of sea cucumber (Stichopus vastus).

BACKGROUND: Sea cucumber (Stichopus vastus) is considered an underutilized resource, since only its stomach and intestines are eaten raw as salad in a few countries and the remaining parts, especially the integument rich in collagen, is discarded. Hence a valuable by-product having potential nutraceutical and pharmaceutical applications is wasted. In the present investigation, pepsin-solubilized collagen (PSC) from the integument of S. vastus was isolated, purified and characterized. RESULTS: Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis showed that the purified collagen was of type I, consisting of three α1 chains of approximately 122 kDa each. The peptide map of PSC digested by V8 protease was different from that of calf skin type I collagen. Fourier transform infrared spectroscopy revealed that the triple helical structure was well preserved in isolated collagen. The denaturation temperature of PSC was 21.23 °C and showed good gel-forming capability at pH 6.5 and 300 mmol L⁻¹ NaCl. CONCLUSION: It is inferred that the collagen isolated from S. vastus integument has potential for use as an alternative to land-based mammalian collagen in food, nutraceuticals and pharmaceutical industries.

Cost analysis of bivalirudin versus reference anticoagulants without GP IIb/IIIa inhibitors in patients undergoing percutaneous coronary intervention for acute coronary syndrome in routine clinical practice. Pompidou registry.

Randomized controlled trials have shown improved short-term bleeding outcomes for bivalirudin compared to other anticoagulant in patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). This study analyzed the cost/efficacy profile of bivalirudin-based anticoagulation strategy versus non bivalirudin-based anticoagulant strategy without use of GP IIb/IIIa inhibitors in routine clinical practice. From January 2009 to December 2010, 216 patients who underwent PCI for ACS at hospital Georges-Pompidou without GP IIb/IIIa inhibitors were studied. Of these patients, 24 (11%) received bivalirudin and 192 (88%) received others anticoagulants (mainly unfractionated heparin or low molecular weight heparin). Ischemic events and bleeding or transfusion were slightly lower in bivalirudin group (0 vs. 4.2%, P=0.60 and 4.2 vs. 8.9%, P=0.70, respectively). In spite of a higher cost of the medication, the overall cost of the bivalirudin strategy was slightly lower (9167±3688 € vs. 14,016±14,749 €, P=0.23), in relation with a shorter average duration of the hospital stay. In conclusion, in this limited, single-center, population of patients with ACS, the clinical efficacy and safety of bivalirudin appeared at least as good as that of reference anticoagulants in real world clinical practice, with no increase in overall costs.