Pharmacogenetic Risk Scores for Perindopril Clinical and Cost Effectiveness in Stable Coronary Artery Disease: When Are We Ready to Implement?
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ABSTRACT:
SUBMITTER: Luzum JA
PROVIDER: S-EPMC4943290 | biostudies-literature | 2016 Mar
REPOSITORIES: biostudies-literature
Publications
Pharmacogenetic Risk Scores for Perindopril Clinical and Cost Effectiveness in Stable Coronary Artery Disease: When Are We Ready to Implement?
Luzum Jasmine A JA Lanfear David E DE
Journal of the American Heart Association 20160328 3
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Project description:BackgroundPatients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model.Methods and resultsClinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 to 2. As a consequence, estimated annual numbers needed to treat ranged from as low as 29 (clinical risk score ≥10 and PGXscore of 0) to 521 (clinical risk score ≤6 and PGXscore of 2). Furthermore, our data suggest that long-term perindopril prescription in patients with a PGXscore of 0 to 2 is cost-effective.ConclusionsBoth baseline clinical phenotype, as well as genotype determine the efficacy of widely prescribed ACE inhibition in stable CAD. Integration of clinical and pharmacogenetic determinants in a combined risk prediction model demonstrated a very wide range of gradients of absolute treatment benefit.
| S-EPMC4943245 | biostudies-literature
Project description:Introduction and objectivesNumerous studies have assessed cost-effectiveness of different treatment modalities for stable angina. Direct comparisons, however, are uncommon. We therefore set out to compare the efficacy and mean cost per patient after 1 and 3 years of follow-up, of the following treatments as assessed in randomized controlled trials (RCT): medical therapy (MT), percutaneous coronary intervention (PCI) without stent (PTCA), with bare-metal stent (BMS), with drug-eluting stent (DES), and elective coronary artery bypass graft (CABG).MethodsRCT comparing at least two of the five treatments and reporting clinical and cost data were identified by a systematic search. Clinical end-points were mortality and myocardial infarction (MI). The costs described in the different trials were standardized and expressed in US $ 2008, based on purchasing power parity. A network meta-analysis was used to compare costs.ResultsFifteen RCT were selected. Mortality and MI rates were similar in the five treatment groups both for 1-year and 3-year follow-up. Weighted cost per patient however differed markedly for the five treatment modalities, at both one year and three years (P<0.0001). MT was the least expensive treatment modality: US $3069 and 13 864 after one and three years of follow-up, while CABG was the most costly: US $27 003 and 28 670 after one and three years. PCI, whether with plain balloon, BMS or DES came in between, but was closer to the costs of CABG.ConclusionsAppreciable savings in health expenditures can be achieved by using MT in the management of patients with stable angina.
| S-EPMC4045726 | biostudies-literature
Project description:PurposeTo determine lifetime cost-effectiveness of diagnostic evaluation strategies for individuals with stable chest pain and suspected coronary artery disease (CAD).MethodsExercise treadmill testing (ETT), stress echocardiography (SE), myocardial perfusion scintigraphy (MPS), coronary computed tomographic angiography (CCTA), and invasive coronary angiography (ICA) were assessed alone, or in succession to each other.ResultsInitial ETT followed by imaging wherein ETT was equivocal or unable to be performed appeared more cost-effective than any strategy employing initial testing by imaging.ConclusionAs pre-test likelihood of CAD varies, different modalities including SE, CCTA, and MPS result in improved costs and enhanced effectiveness.
| S-EPMC5410386 | biostudies-literature
Project description:BackgroundHIV-infected patients are at increased risk of coronary artery disease (CAD). We evaluated the cost-effectiveness of cardiac screening for HIV-positive men at intermediate or greater CAD risk.DesignWe developed a lifetime microsimulation model of CAD incidence and progression in HIV-infected men.MethodsInput parameters were derived from two HIV cohort studies and the literature. We compared no CAD screening with stress testing and coronary computed tomography angiography (CCTA)-based strategies. Patients with test results indicating 3-vessel/left main CAD underwent invasive coronary angiography (ICA) and received coronary artery bypass graft surgery. In the stress testing + medication and CCTA + medication strategies, patients with 1-2-vessel CAD results received lifetime medical treatment without further diagnostics whereas in the stress testing + intervention and CCTA + intervention strategies, patients with these results underwent ICA and received percutaneous coronary intervention.ResultsCompared to no screening, the stress testing + medication, stress testing + intervention, CCTA + medication, and CCTA + intervention strategies resulted in 14, 11, 19, and 14 quality-adjusted life days per patient and incremental cost-effectiveness ratios of 49,261, 57,817, 34,887 and 56,518 Euros per quality-adjusted life year (QALY), respectively. Screening only at higher CAD risk thresholds was more cost-effective. Repeated screening was clinically beneficial compared to one-time screening, but only stress testing + medication every 5 years remained cost-effective. At a willingness-to-pay threshold of 83,000 €/QALY (∼ 100,000 US$/QALY), implementing any CAD screening was cost-effective with a probability of 75-95%.ConclusionsScreening HIV-positive men for CAD would be clinically beneficial and comes at a cost-effectiveness ratio comparable to other accepted interventions in HIV care.
| S-EPMC3841232 | biostudies-literature
Project description:IntroductionCurrently, 15-20% of individuals with coronary artery disease (chronic coronary syndrome [CCS]) or peripheral artery disease (PAD) receiving routine treatment experience cardiovascular events (CVEs) within 3-4 years. Using PICOSTEPS (Patients-Intervention-Comparators-Outcomes-Setting-Time-Effects-Perspective-Sensitivity analysis) reporting, we evaluated the cost-effectiveness of recently approved rivaroxaban 2.5 mg twice daily in combination with acetylsalicylic acid 100 mg daily (RIV + ASA) for the prevention of CVEs among Finns with CCS or symptomatic PAD.MethodsMyocardial infarction, ischemic stroke, intracranial hemorrhage, acute limb ischemia, amputations, major extracranial bleeding, venous thromboembolism, and cardiovascular deaths were modeled in a Markov model examining a cohort of patients with CCS or symptomatic PAD. Relative effects of the intervention (RIV + ASA) and comparator (ASA) were based on the COMPASS trial. The primary outcome was 3%/year discounted incremental cost-effectiveness ratio (ICER), defined as cost (2019 euros) per quality-adjusted life year (QALY) gained in the Finnish setting over a lifetime horizon. In addition to nonfatal and fatal CVEs, the effects factored Finnish non-CVE mortality, quality of life, and direct costs from a public payer perspective. Disaggregated costs and QALYs, costs per life year gained (LYG), and ischemic strokes avoided, net monetary benefit (NMB), expected value of perfect information (EVPI), economic value-added (EVA), cost-effectiveness table, and acceptability frontier were examined. Probabilistic and deterministic sensitivity analyses were conducted.ResultsIn the deterministic comparison with ASA over a lifetime horizon, RIV + ASA resulted in a benefit of 0.404 QALYs and 0.474 LYGs for an additional cost of €3241, resulting in an ICER of €8031/QALY. The probabilistic ICER was €4313/QALY (EVPI €1829/patient). RIV + ASA had positive NMB (€8791/patient), low EVPI (€88/patient), high EVA (€8703/patient), and 91% probability of cost-effectiveness using the willingness-to-pay of €25,254/QALY. The primary result was conservative and robust for RIV + ASA.ConclusionRIV + ASA was a cost-effective treatment alternative compared with ASA in patients with CCS or symptomatic PAD in Finland.
| S-EPMC7467417 | biostudies-literature
Project description:PurposeOne of the major challenges in the management of familial hypercholesterolemia (FH) is the stratification of cardiovascular risk in asymptomatic subjects. Our purpose is to investigate the performance of clinical scoring systems, Montreal-FH-score (MFHS), SAFEHEART risk (SAFEHEART-RE) and FH risk score (FHRS) equations and Dutch Lipid Clinic Network (DLCN) diagnostic score, in predicting extent and severity of CAD at coronary computed tomography angiography (CCTA) in asymptomatic FH.Material and methodsOne-hundred and thirty-nine asymptomatic FH subjects were prospectively enrolled to perform CCTA. MFHS, FHRS, SAFEHEART-RE and DLCN were assessed for each patient. Atherosclerotic burden scores at CCTA (Agatston score [AS], segment stenosis score [SSS]) and CAD-RADS score were calculated and compared to clinical indices.ResultsNon-obstructive CAD was found in 109 patients, while 30 patients had a CAD-RADS ≥ 3. Classifying the two groups according to AS, values varied significantly for MFHS (p < 0.001), FHRS (p < 0.001) and SAFEHEART-RE (p = 0.047), while according to SSS only MFHS and FHRS showed significant differences (p < 0.001). MFHS, FHRS and SAFEHEART-RE, but not DLCN, showed significant differences between the two CAD-RADS groups (p < .001). MFHS proved to have the best discriminatory power (AUC = 0.819; 0.703-0.937, p < 0.001) at ROC analysis, followed by FHRS (AUC = 0.795; 0.715-0.875, p < .0001) and SAFEHEART-RE (AUC = .725; .61-.843, p < .001).ConclusionsGreater values of MFHS, FHRS and SAFEHEART-RE are associated to higher risk of obstructive CAD and might help to select asymptomatic patients that should be referred to CCTA for secondary prevention.
| S-EPMC10119045 | biostudies-literature
Project description:BackgroundTraditional cardiac rehabilitation programs are centre-based and clinically supervised, with their safety and effectiveness well established. Notwithstanding the established benefits, cardiac rehabilitation remains underutilised. A possible alternative would be a hybrid approach where both centre-based and tele-based methods are combined to deliver cardiac rehabilitation to eligible patients. The objective of this study was to determine the long-term cost-effectiveness of a hybrid cardiac telerehabilitation and if it should be recommended to be implemented in the Australian context.MethodsFollowing a comprehensive literature search, we chose the Telerehab III trial intervention that investigated the effectiveness of a long-term hybrid cardiac telerehabilitation program. We developed a decision analytic model to estimate the cost-effectiveness of the Telerehab III trial using a Markov process. The model included stable cardiac disease and hospitalisation health states and simulations were run using one-month cycles over a five-year time horizon. The threshold for cost-effectiveness was set at $AU 28,000 per quality-adjusted life-year (QALY). For the base analysis, we assumed that 80% completed the programme. We tested the robustness of the results using probabilistic sensitivity and scenario analyses.ResultsTelerehab III intervention was more effective but more costly and was not cost-effective, at a threshold of $28,000 per QALY. For every 1,000 patients who undergo cardiac rehabilitation, employing the telerehabilitation intervention would cost $650,000 more, and 5.7 QALYs would be gained, over five years, compared to current practice. Under probabilistic sensitivity analysis, the intervention was cost-effective in only 18% of simulations. Similarly, if the intervention compliance was increased to 90%, it was still unlikely to be cost-effective.ConclusionHybrid cardiac telerehabilitation is highly unlikely to be cost-effective compared to the current practice in Australia. Exploration of alternative models of delivering cardiac telerehabilitation is still required. The results presented in this study are useful for policymakers wanting to make informed decisions about investment in hybrid cardiac telerehabilitation programs.
| S-EPMC10198753 | biostudies-literature
Project description:BackgroundRecent evidence indicates that Shexiang Baoxin Pill (MUSKARDIA), as an add-on treatment to standard therapy for stable coronary artery disease (CAD), is effective. Nevertheless, the cost-effectiveness of introducing the Shexiang Baoxin Pill (Abbreviation SBP) to the current standard treatment for patients with CAD in China remains unknown.ObjectiveThe objective of this study was to assess the cost-effectiveness of introducing SBP into the current standard treatment in China for patients with CAD.MethodThe effects of two treatment strategies-the SBP group (SBP combined with standard therapy) and the standard therapy group (placebo combined with standard therapy)-were simulated using a long-term Markov model. The simulation subjects might experience non-fatal MI and/or stroke or vascular or non-vascular death events. The study parameters were primarily derived from the MUSKARDIA trial, which was a multicenter, double-blind, placebo-controlled phase IV randomized clinical trial. Furthermore, age-related change, event costs, and event utilities were drawn from publicly available sources. Both costs and health outcomes were discounted at 5.0% per annum. One-way and probabilistic sensitivity analyses were conducted to verify the robustness of the model. Based on the MUSKARDIA trial results, the risk with the events of major adverse cardiovascular events (MACE) was decreased (P < 0.05) in the female subgroup treated with SBP therapy compared with standard therapy. Consequently, a scenario analysis based on subgroups of Chinese females was conducted for this study. Incremental cost-effectiveness ratios (ICERs) were assessed for each strategy for costs per quality-adjusted life-year (QALY) saved.ResultsAfter 30 years of simulation, the SBP group has added 0.32 QALYs, and the cost has been saved 841.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -2628.13 CNY per QALY. Scenario analyses of Chinese females showed that, after 30 years of simulation, the SBP therapy has been increased by 0.82 QALYs, and the cost has been reduced by 19474.00 CNY. Compared with the standard therapy, the ICER for the SBP therapy was -26569.51 CNY per QALY. Similar results were obtained in various extensive sensitivity analyses.ConclusionsThis is the first study to evaluate the cost-effectiveness of SBP in the treatment of CAD. In conclusion, SBP as an add-on treatment to standard therapy appears to be a cost-effective strategy for CAD in Chinese patients.
| S-EPMC10906875 | biostudies-literature
Project description:The potential of personalized medicine to transform the treatment of mood disorders has been widely touted in psychiatry, but has not been quantified. We estimated the costs and benefits of a putative pharmacogenetic test for antidepressant response in the treatment of major depressive disorder (MDD) from the societal perspective. Specifically, we performed cost-effectiveness analyses using state-transition probability models incorporating probabilities from the multicenter STAR*D effectiveness study of MDD. Costs and quality-adjusted life years (QALYs) were compared for sequential antidepressant trials, with or without guidance from a pharmacogenetic test for differential response to selective serotonin reuptake inhibitors (SSRIs). Likely SSRI responders received an SSRI, whereas likely nonresponders received the norepinephrine/dopamine reuptake inhibitor bupropion. For a 40-year old with MDD, applying the pharmacogenetic test and using the non-SSRI bupropion for those at higher risk for nonresponse cost $93,520 per additional QALY compared with treating all patients with an SSRI first and switching sequentially in the case of nonremission. Cost per QALY dropped below $50,000 for tests with remission rate ratios as low as 1.5, corresponding to odds ratios approximately 1.8-2.0. Tests for differential antidepressant response could thus become cost effective under certain circumstances. These circumstances, particularly availability of alternative treatment strategies and test effect sizes, can be estimated and should be considered before these tests are broadly applied in clinical settings.
| S-EPMC3312011 | biostudies-literature
Project description:Upon activation, platelets release a host of soluble and vesicular signals, collectively termed the ‘platelet releasate’ (PR). The contents of this PR play a significant role in haemostasis, inflammation, and pathologic sequelae. Despite this, proteomic studies investigating the PR in coronary artery disease have not been performed. We undertook a comparative label-free quantitative (LFQ) proteomic profiling of the 1U/ml thrombin-induced PR from 13 acute coronary syndrome (ACS-STEMI) versus 14 stable angina pectoris patients using a tandem mass spectrometry approach. We identified differentially released platet proteins including tetranectin (CLEC3B), protein disulfide-isomerase-A3 (PDIA3), coagulation factor V (F5) and fibronectin (FN1). Strikingly, all 9 differential proteins were associated with the GO cellular component term ‘extracellular vesicle’ and reduced levels of EVs were detected in plasma of ACS-STEMI patients. Network analysis revealed 3 PR proteins either reduced (F5; FN1) or absent (CLEC3B) in ACS-STEMI patients, which are strongly connected to both the clotting cascade and major druggable targets on platelets. This moderated signature highlights the possible basis of platelet dysfunction in ACS-STEMI and may prove useful for non-invasive risk assessment of the progression of coronary artery disease.
2020-06-05 | PXD009356 | Pride