Cost analysis of chronic heart failure management in Malaysia: A multi-centred retrospective study.

Background: Estimation of the economic burden of heart failure (HF) through a complete evaluation is essential for improved treatment planning in the future. This estimation also helps in reimbursement decisions for newer HF treatments. This study aims to estimate the cost of HF treatment in Malaysia from the Ministry of Health's perspective. Materials and methods: A prevalence-based, bottom-up cost analysis study was conducted in three tertiary hospitals in Malaysia. Chronic HF patients who received treatment between 1 January 2016 and 31 December 2018 were included in the study. The direct cost of HF was estimated from the patients' healthcare resource utilisation throughout a one-year follow-up period extracted from patients' medical records. The total costs consisted of outpatient, hospitalisation, medications, laboratory tests and procedure costs, categorised according to ejection fraction (EF) and the New York Heart Association (NYHA) functional classification. Results: A total of 329 patients were included in the study. The mean ± standard deviation of total cost per HF patient per-year (PPPY) was USD 1,971 ± USD 1,255, of which inpatient cost accounted for 74.7% of the total cost. Medication costs (42.0%) and procedure cost (40.8%) contributed to the largest proportion of outpatient and inpatient costs. HF patients with preserved EF had the highest mean total cost of PPPY, at USD 2,410 ± USD 1,226. The mean cost PPPY of NYHA class II was USD 2,044 ± USD 1,528, the highest among all the functional classes. Patients with underlying coronary artery disease had the highest mean total cost, at USD 2,438 ± USD 1,456, compared to other comorbidities. HF patients receiving angiotensin-receptor neprilysin-inhibitor (ARNi) had significantly higher total cost of HF PPPY in comparison to patients without ARNi consumption (USD 2,439 vs. USD 1,933, p < 0.001). Hospitalisation, percutaneous coronary intervention, coronary angiogram, and comorbidities were the cost predictors of HF. Conclusion: Inpatient cost was the main driver of healthcare cost for HF. Efficient strategies for preventing HF-related hospitalisation and improving HF management may potentially reduce the healthcare cost for HF treatment in Malaysia.

Combined Analysis of Two Parallel Randomized Trials of Sirolimus-Coated and Paclitaxel-Coated Balloons in Coronary In-Stent Restenosis Lesions.

BACKGROUND: Paclitaxel-coated balloons (PCBs) are a preferred treatment option for coronary in-stent restenosis. To date, data from randomized trials of alternative drug coatings are lacking. The aim of the randomized Malaysian and German-Swiss randomized trials was to investigate a novel sirolimus-coated balloon (SCB) compared with a PCB in in-stent restenosis. METHODS: One hundred one patients with drug-eluting stent in-stent restenosis were enrolled in 2 identical randomized trials comparing the novel SCB (SeQuent SCB, 4 µg/mm²) with the clinically proven PCB (SeQuent Please, 3 µg/mm²). Primary end point was angiographic late lumen loss at 6 months. Secondary end points included procedural success, major adverse cardiac events, and individual clinical end points such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.25±0.57 mm in the PCB group versus 0.26±0.60 mm in the SCB group. Mean difference between SCB and PCB was 0.01 (95% CI, -0.23 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. Clinical events up to 12 months did not differ between the groups. CONCLUSIONS: This first-in man comparison of a novel SCB with a crystalline coating showed similar angiographic and clinical outcomes in the treatment of coronary drug-eluting stent in-stent restenosis compared with PCB. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02996318, NCT03242096.

Treatment of Coronary De Novo Lesions by a Sirolimus- or Paclitaxel-Coated Balloon.

OBJECTIVES: The aim of this randomized controlled trial was to investigate a novel sirolimus-coated balloon (SCB) compared with the best investigated paclitaxel-coated balloon (PCB). BACKGROUND: There is increasing clinical evidence for the treatment of coronary de novo disease using drug-coated balloons. However, it is unclear whether paclitaxel remains the drug of choice or if sirolimus is an alternative, in analogy to drug-eluting stents. METHODS: Seventy patients with coronary de novo lesions were enrolled in a randomized, multicenter trial to compare a novel SCB (SeQuent SCB, B. Braun Melsungen; 4 µg/mm2) with a PCB (SeQuent Please, B. Braun Melsungen; 3 µg/mm2). The primary endpoint was angiographic late lumen loss (LLL) at 6 months. Secondary endpoints included major adverse cardiovascular events and individual clinical endpoints such as cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment LLL was 0.01 ± 0.33 mm in the PCB group versus 0.10 ± 0.32 mm in the SCB group. The mean difference between SCB and PCB was 0.08 (95% CI: -0.07 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. However, negative LLL was more frequent in the PCB group (60% of lesions vs 32% in the SCB group; P = 0.019). Major adverse cardiovascular events up to 12 months also did not differ between the groups. CONCLUSIONS: This first-in-human comparison of a novel SCB with a crystalline coating showed similar angiographic outcomes in the treatment of coronary de novo disease compared with a clinically proven PCB. However, late luminal enlargement was more frequently observed after PCB treatment. (Treatment of Coronary De-Novo Stenosis by a Sirolimus Coated Balloon or a Paclitaxel Coated Balloon Catheter Malaysia [SCBDNMAL]; NCT04017364).

Treatment of Coronary Drug-Eluting Stent Restenosis by a Sirolimus- or Paclitaxel-Coated Balloon.

OBJECTIVES: The aim of this randomized controlled trial was to investigate a novel sirolimus-coated balloon (SCB) compared with the best investigated paclitaxel-coated balloon (PCB). BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging. PCBs are an established treatment option outside the United States with a Class I, Level of Evidence: A recommendation in the European guidelines. However, their efficacy is better in bare-metal stent (BMS) ISR compared with drug-eluting stent (DES) ISR. METHODS: Fifty patients with DES ISR were enrolled in a randomized, multicenter trial to compare a novel SCB (SeQuent SCB, 4 µg/mm2) with a clinically proven PCB (SeQuent Please Neo, 3 µg/mm2) in coronary DES ISR. The primary endpoint was angiographic late lumen loss at 6 months. Secondary endpoints included procedural success, major adverse cardiovascular events, and individual clinical endpoints such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.21 ± 0.54 mm in the PCB group versus 0.17 ± 0.55 mm in the SCB group (p = NS; per-protocol analysis). Clinical events up to 12 months also did not differ between the groups. CONCLUSIONS: This first-in-man comparison of a novel SCB with a crystalline coating shows similar angiographic outcomes in the treatment of coronary DES ISR compared with a clinically proven PCB. (Treatment of Coronary In-Stent Restenosis by a Sirolimus [Rapamycin] Coated Balloon or a Paclitaxel Coated Balloon [FIM LIMUS DCB]; NCT02996318).

Pharmacometabolomics analysis of plasma to phenotype clopidogrel high on treatment platelets reactivity in coronary artery disease patients.

Dual antiplatelet therapy (DAPT) of clopidogrel and aspirin is crucial for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, some patients may endure clopidogrel high on treatment platelets reactivity (HTPR) which may cause thromboembolic events. Clopidogrel HTPR is multifactorial with some genetic and non-genetic factors contributing to it. We aimed to use nuclear magnetic resonance (1H NMR) pharmacometabolomics analysis of plasma to investigate this multifactorial and identify metabolic phenotypes and pathways associated with clopidogrel HTPR. Blood samples were collected from 71 CAD patients planned for interventional angiographic procedure (IAP) before the administration of clopidogrel 600 mg loading dose (LD) and 6 h after the LD. Platelets function testing was done 6 h post-LD using VerifyNow® P2Y12 assay. Pre-dose and post-dose plasma samples were analysed using 1H NMR. Multivariate statistical analysis was used to indicate the discriminating metabolites. Two metabotypes, each with 34 metabolites (pre-dose and post-dose) were associated with clopidogrel HTPR. Pathway analysis of these metabotypes revealed that aminoacyl-tRNA biosynthesis, nitrogen metabolism and glycine-serine-threonine metabolism are the most perturbed metabolic pathways associated with clopidogrel HTPR. Furthermore, the identified biomarkers indicated that clopidogrel HTPR is multifactorial where the metabolic phenotypes of insulin resistance, type two diabetes mellitus, obesity, gut-microbiota and heart failure are associated with it. Pharmacometabolomics analysis of plasma revealed new insights on the implicated metabolic pathways and the predisposing factors of clopidogrel HTPR.