Cost-utility analysis of sacituzumab govitecan versus chemotherapy for the treatment of metastatic triple-negative breast cancer in Singapore.

OBJECTIVE: To assess the cost-effectiveness of sacituzumab govitecan for treating relapsed or refractory metastatic triple-negative breast cancer (TNBC) in Singapore. METHODS: A three-state partitioned survival model was developed to evaluate the cost-effectiveness of sacituzumab govitecan from a healthcare system perspective over 5 years. Clinical inputs were obtained from the ASCENT trial. Health state utilities were retrieved from the literature and direct costs were sourced from public healthcare institutions in Singapore. Sensitivity and scenario analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. RESULTS: Compared with single-agent chemotherapy, sacituzumab govitecan was associated with a base-case incremental cost-effectiveness ratio (ICER) of S$328,000 (US$237,816) per quality-adjusted life year (QALY) gained. One-way sensitivity analyses showed that the ICER was most sensitive to the cost of sacituzumab govitecan and progression-free utility values. Regardless of variation in these parameters, the ICER remained high, and a substantial price reduction was required to reduce the ICER. CONCLUSION: At its current price, sacituzumab govitecan does not represent a cost-effective treatment for relapsed or refractory metastatic TNBC in Singapore. Our findings will be useful to inform funding decisions alongside other factors including clinical effectiveness, safety, and budget impact considerations.

Assessing the cost-effectiveness of mepolizumab as add-on therapy to standard of care for severe eosinophilic asthma in Singapore.

OBJECTIVE: To evaluate the cost-effectiveness of mepolizumab added to standard of care (SOC) compared with SOC alone among patients with severe uncontrolled eosinophilic asthma in the Singapore setting. METHODS: A Markov model with three health states (asthma on mepolizumab and SOC, asthma on SOC alone, and death) was developed from a healthcare system perspective over a lifetime horizon. During each 4-week cycle, patients in the non-death health states could experience asthma exacerbations requiring oral corticosteroid burst, emergency department visit, or hospitalization. Asthma-related mortality following an exacerbation or all-cause mortality could also occur at each cycle. The model was populated using local costs while utilities were derived from international literature. Transition probabilities were obtained from a mixture of Singapore-specific and internationally published data. RESULTS: The base-case analysis comparing mepolizumab plus SOC with SOC alone resulted in an incremental cost-effectiveness ratio (ICER) of SGD335 486 (USD238 195) per quality-adjusted life-year (QALY) gained. Sensitivity analysis demonstrated that the ICER was most sensitive to the price of mepolizumab, followed by the proportion of exacerbations which required hospital intensive care. Despite restricting mepolizumab use to patients with a higher baseline exacerbation rate (3 in the past year) in a scenario analysis, the ICER remained high at SGD238 876 (USD 169 602) per QALY gained. CONCLUSION: At its current price, mepolizumab is not considered a cost-effective use of healthcare resources in Singapore. Substantial price reductions for mepolizumab are required to improve its cost-effectiveness to an acceptable range. These results will be useful to inform national funding decisions.

Cost-effectiveness of daratumumab in combination with lenalidomide and dexamethasone for relapsed and/or refractory multiple myeloma.

OBJECTIVE: This study evaluates the cost-effectiveness of daratumumab (D) in combination with lenalidomide and dexamethasone (Rd) for treatment of relapsed and/or refractory multiple myeloma in patients who have received at least one prior therapy in Singapore. METHODS: A 3-state partitioned survival model was developed to evaluate the cost-effectiveness of lenalidomide and dexamethasone with or without daratumumab from a healthcare system perspective over 10 years. Clinical inputs were obtained from the POLLUX trial. Health state utilities were derived from the literature and direct medical costs obtained from public healthcare institutions. Sensitivity and scenario analyses were conducted to explore uncertainties. RESULTS: DRd was associated with a high base-case incremental cost-effectiveness ratio (ICER) of US$576,247 per quality-adjusted life year (QALY) gained, compared with Rd. According to one-way sensitivity analysis, ICER was most heavily influenced by time horizon, discount rate for outcomes, progression-free utility and cost of daratumumab. Regardless of the variation, DRd remained not cost-effective. Even when the cost of both daratumumab and lenalidomide dropped by 20% and 80%, the ICERs remained high at US$470,400 and US$152,860 per QALY gained. CONCLUSIONS: At current prices, the addition of daratumumab to lenalidomide and dexamethasone does not represent cost-effective use of healthcare resources in Singapore.

Cost-effectiveness of pertuzumab and trastuzumab biosimilar combination therapy as initial treatment for HER2-positive metastatic breast cancer in Singapore.

BACKGROUND: This study evaluates the cost-effectiveness of pertuzumab with trastuzumab biosimilar and docetaxel as initial treatment for HER2-positive metastatic breast cancer (MBC) in Singapore. METHODS: A partitioned survival model with three health states was developed to evaluate the cost-effectiveness of trastuzumab biosimilar and docetaxel with or without pertuzumab from a healthcare system perspective over a 15-year time horizon for patients with HER2-positive MBC. Key clinical inputs were derived from the CLEOPATRA trial. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. RESULTS: The base-case resulted in an incremental cost-effectiveness ratio (ICER) of SGD366,658 (USD272,244) per quality-adjusted life-year (QALY) gained. One-way sensitivity analyses showed that the ICER was sensitive to utilities in the progression-free state, price of pertuzumab and time horizon. When the price for trastuzumab reference biologic (branded) was applied, the ICER was even higher (SGD426,996 [USD317,045]/QALY). CONCLUSION: Although trastuzumab biosimilar reduced the cost of the pertuzumab combination regimen, the ICER remained high and was not cost effective in Singapore's context. As pertuzumab contributed 80% of the overall combination treatment cost, price reductions for pertuzumab will be required to improve the cost-effectiveness of combination treatment to an acceptable level.

Cost-effectiveness of olaparib maintenance therapy when used with and without restriction by BRCA1/2 mutation status for platinum-sensitive relapsed ovarian cancer.

Objectives: To determine whether olaparib maintenance therapy, used with and without restriction by BRCA1/2 mutation status, is cost-effective at the population level for platinum-sensitive relapsed ovarian cancer in Singapore.Methods: A partitioned survival model compared three management strategies: 1) treat all patients with olaparib; 2) test for germline BRCA1/2 mutation, followed by targeted olaparib use in mutation carriers only; 3) observe all patients. Mature overall survival (OS) data from Study 19 and a 15-year time horizon were used and direct medical costs were applied. Sensitivity analyses were conducted to explore uncertainties.Results: Treating all patients with olaparib was the most costly and effective strategy, followed by targeted olaparib use, and observation of all patients. Base-case incremental cost-effectiveness ratios (ICERs) for all-olaparib and targeted use strategies were SGD133,394 (USD100,926) and SGD115,736 (USD87,566) per quality-adjusted life year (QALY) gained, respectively, compared to observation. ICERs were most sensitive to the cost of olaparib, time horizon and discount rate for outcomes. When these parameters were varied, ICERs remained above SGD92,000 (USD69,607)/QALY.Conclusions: At the current price, olaparib is not cost-effective when used with or without restriction by BRCA1/2 mutation status in Singapore, despite taking into account potential OS improvement over a long time horizon.

Cost-effectiveness of ribociclib as initial treatment for premenopausal women with advanced breast cancer in Singapore.

BACKGROUND: CDK4/6 inhibitors have shown promising results for treating advanced breast cancer (ABC) and are routinely used in Singapore. In view of their high costs, it is important to assess their relative value compared to existing standards of care in the local setting. AIMS: This study evaluates the cost-effectiveness of adding ribociclib to goserelin and a nonsteroidal aromatase inhibitor or tamoxifen as initial therapy for premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) ABC in Singapore. METHODS: A partitioned survival model with four health states (progression-free on first-line treatment, progression-free on second-line treatment, progressed disease, and death) was developed from a healthcare system perspective over a 10-year time horizon. Key clinical inputs were derived from the MONALEESA-7 trial, and survival curves were extrapolated beyond the trial period. Health state utilities were derived from the literature and direct medical costs were obtained from local public healthcare institutions. A discount rate of 3% was applied to both costs and outcomes. One-way deterministic and probabilistic sensitivity analyses were conducted to explore uncertainties. RESULTS: The base-case analysis resulted in an incremental cost-effectiveness ratio (ICER) of SGD197, 667 per quality-adjusted life-year. Sensitivity analyses showed that the ICER was sensitive to the survival parametric distribution, ribociclib price, time horizon, and utility weights used. Even when these were varied, ICERs remained high and not cost-effective in the local context. CONCLUSION: At its current price, adding ribociclib to endocrine therapy is unlikely to be cost-effective in Singapore for HR+, HER2- ABC. Results from this study are useful to inform future funding decisions for CDK4/6 inhibitors alongside other factors including clinical effectiveness, safety, and budget impact considerations.

Cost-effectiveness analysis of osimertinib for first-line treatment of locally advanced or metastatic EGFR mutation positive non-small cell lung cancer in Singapore.

OBJECTIVE: Non-small cell lung cancer (NSCLC) accounts for 80-90% of all lung cancer cases and is usually associated with a poor prognosis. However, targeted therapy with first and second generation tyrosine kinase inhibitors (TKIs) has so far improved progression-free survival of epidermal growth factor receptor (EGFR) mutant NSCLC patients. Osimertinib, a third generation EGFR TKI has recently shown improved overall survival of 6.8 months in previously untreated EGFR mutant NSCLC patients. We assessed the cost-effectiveness of osimertinib versus standard EGFR TKIs (gefitinib or erlotinib) as first-line treatment for advanced or metastatic EGFR mutant NSCLC patients in Singapore. METHODS: A partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from the Singapore healthcare payer perspective. Survival curves based on the overall trial population from the FLAURA trial were extrapolated beyond trial period over a 10-year time horizon to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from public healthcare institutions in Singapore. Deterministic and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. RESULTS: Compared with first or second generation TKI, osimertinib had a base-case incremental cost-effectiveness ratio (ICER) of SG$418,839 (US$304,277) per quality-adjusted life year gained. One-way sensitivity analysis showed the ICER was most sensitive to time horizon and variations in progression-free utility values. Scenario analyses showed that a 50% reduction in the cost of osimertinib was still associated with a high ICER that was unlikely to be deemed cost effective. CONCLUSIONS: Osimertinib is not cost effective as a first-line treatment compared to standard EGFR TKIs in advanced EGFR mutant NSCLC patients in Singapore. The findings from our evaluation, alongside other considerations including the lack of survival benefit in the Asian subgroup of the FLAURA trial, will be useful to inform policy makers on funding decisions for NSCLC treatments in Singapore.

Cost utility analysis of tisagenlecleucel vs salvage chemotherapy in the treatment of relapsed/refractory diffuse large B-cell lymphoma from Singapore's healthcare system perspective.

BACKGROUND: Patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) have limited treatment options and poor prognoses. Tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy has shown early promise in improving survival outcomes, but at a high upfront cost. This study evaluated the cost-effectiveness of tisagenlecleucel versus salvage chemotherapy for treating patients with r/r DLBCL who have failed at least 2 lines of systemic therapies. METHODS: A hybrid decision tree and three-state partitioned survival model (progression-free (PF), progressive disease and death) was developed from the Singapore healthcare payer perspective. Survival curves from JULIET trial and CORAL-1 extension study were extrapolated beyond trial period over a 15-year time horizon to estimate the underlying progression-free survival and overall survival parametric distributions for both arms. Health state utilities were retrieved from the literature, and direct costs were sourced from public healthcare institutions in Singapore. One-way probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. RESULTS: Compared with salvage chemotherapy, tisagenlecleucel was associated with a base-case incremental cost-effectiveness ratio (ICER) US$508,530 (S$686,516) per quality adjusted life year (QALY) gained and US$320,200 (S$432,269) per life year (LY) gained. One-way sensitivity analysis showed the ICER was most sensitive to time horizon, PF utility and cost of tisagenlecleucel. Scenario analyses confirmed that the ICERs remained high under favorable assumptions and substantial price reduction was required to reduce the ICER. CONCLUSIONS: Our analysis showed tisagenlecleucel use in r/r DLBCL patients who failed at least 2 prior lines of systemic therapies was associated with exceedingly high ICER, which is unlikely to represent good use of healthcare resources. Comparative clinical evidence from the ongoing trials might provide more insight into future evaluations.

Cost-effectiveness analysis of pembrolizumab monotherapy versus chemotherapy for previously untreated advanced non-small cell lung cancer.

Objective: To assess the cost-effectiveness of pembrolizumab monotherapy compared with standard chemotherapy for the treatment of advanced non-small cell lung cancer (NSCLC) in previously untreated adults who have a high programmed death ligand 1 (PD-L1) tumor proportion score of 50% or greater in Singapore.Materials and methods: A partitioned-survival analysis model was developed from a healthcare system's perspective that extrapolated clinical and economic outcomes of first-line pembrolizumab (maximum treatment duration of 2 years) versus platinum doublet chemotherapy over a 10-year time horizon for patients with advanced NSCLC. The model consisted of three health states: alive with no progression, alive with progression, and dead. Key clinical inputs were based on Kaplan-Meier survival curves from the interim (median follow-up = 11.2 months) and updated analysis (median follow-up = 25.2 months) of the KEYNOTE-024 randomized controlled trial. Local cost data were applied. Utilities were derived from published international estimates. Both one-way and multivariate probabilistic sensitivity analyses (PSA) were conducted to identify key drivers of the results.Results: Using the results from the updated analysis of KEYNOTE-024, patients treated with pembrolizumab experienced more quality adjusted life-years (QALYs), but incurred higher costs compared to chemotherapy over a 10-year time horizon (pembrolizumab: 1.9983 QALYs, SGD215,761; chemotherapy: 1.1317 QALYs, SGD70,444). The base-case incremental cost-effectiveness ratio (ICER) was SGD167,692 per QALY gained. One-way sensitivity analysis showed the ICER was most sensitive to the cost of pembrolizumab, followed by the time horizon. Multivariate PSA indicated that pembrolizumab had 0% probability of being cost-effective at a hypothetical willingness-to-pay threshold of SGD100,000 per QALY gained.Conclusion: While pembrolizumab is superior to standard chemotherapy in improving overall survival and progression-free survival, results suggest that it is unlikely to be cost-effective at its current price in Singapore. Factors including clinical effectiveness, safety, and budget impact should also be considered when making national funding decisions.

Cost-effectiveness of sequential urate lowering therapies for the management of gout in Singapore.

Aims: Allopurinol is the most common urate lowering therapy (ULT) used to treat gout but may cause life-threatening severe cutaneous adverse reactions (SCAR) in a small number of patients. Risk of SCAR is increased for patients with the HLA-B*58:01 genotype. When alternative ULT is required, febuxostat or probenecid are recommended. The aim of this study was to conduct a cost-utility analysis of sequential ULT treatment strategies for gout, including strategies with and without HLA-B*58:01 genotyping prior to treatment initiation, with a view to inform optimal gout management in Singapore.Materials and methods: A Markov model was developed from the Singapore healthcare payer perspective. Reflecting local practice, 12 different treatment strategies containing at least one ULT (allopurinol, febuxostat, probenecid) were evaluated in adults with gout. Response rates (SUA < 6mg/dL) were derived from an in-house network meta-analysis and from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated over a 30-year time horizon, with costs and benefits discounted at 3% per annum. Sensitivity analyses were conducted to explore uncertainties.Results: Sequential treatment of allopurinol 300 mg/day-allopurinol 600 mg/day-probenecid ("standard of care") was cost-effective compared to no ULT, with an ICER of SGD1,584/QALY. Allopurinol300-allopurinol600-probenecid-febuxostat sequence compared to allopurinol300-allopurinol600-probenecid had an ICER of SGD11,400/QALY. All other treatment strategies were dominated by preceding strategies. Treatment strategies incorporating HLA-B*58:01 genotyping before ULT use were dominated by the corresponding non-genotyping strategy.Conclusions: Current standard of care (allopurinol300-allopurinol 600-probenecid) for gout is cost-effective compared with no ULT in the local context. Febuxostat is unlikely to be cost-effective in Singapore at current prices unless it is used last-line.

Cost-Effectiveness Analysis of Sunitinib versus Interferon-Alfa for First-Line Treatment of Advanced and/or Metastatic Renal Cell Carcinoma in Singapore.

OBJECTIVES: This study was conducted to evaluate the cost-effectiveness of sunitinib versus interferon-alfa for the treatment of advanced and/or metastatic renal cell carcinoma (RCC) in Singapore. METHODS: A partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from a healthcare payer perspective over a 10-year time horizon. Survival curves from the pivotal trial of sunitinib versus interferon-alfa were extrapolated beyond the trial period to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from local public healthcare institutions. The sunitinib dose in the model reflected local prescribing practices whereby a combination of 50 mg (28 percent) and 37.5 mg (72 percent) strengths are used. RESULTS: The base-case analysis comparing sunitinib versus interferon-alfa resulted in an incremental cost effectiveness ratio (ICER) of SGD191,061 (USD139,757) per quality-adjusted life-year gained. Sensitivity analysis demonstrated that the ICER was most sensitive to variations in the utility value assumed for the progression-free health state and the price of sunitinib. CONCLUSIONS: In the absence of any price reduction, sunitinib had an exceedingly high ICER and was not considered a cost-effective use of healthcare resources in Singapore's context for the first-line treatment of advanced RCC. The findings from our evaluation will be useful to inform local healthcare decision making and resource allocations for tyrosine kinase inhibitors when appraised alongside comparative clinical effectiveness data and payer affordability considerations.

Comparative efficacy of inhaled medications (ICS/LABA, LAMA, LAMA/LABA and SAMA) for COPD: a systematic review and network meta-analysis.

PURPOSE: To assess the comparative efficacy of short-acting muscarinic antagonists (SAMAs), long-acting muscarinic antagonists (LAMAs), LAMA in combination with long-acting beta-agonists (LABAs; LAMA/LABAs) and inhaled corticosteroids (ICS) in combination with LABA (ICS/LABAs) for the maintenance treatment of COPD. MATERIALS AND METHODS: We systematically reviewed 74 randomized controlled trials (74,832 participants) published up to 15 November 2017, which compared any of the interventions (SAMA [ipratropium], LAMA [aclidinium, glycopyrronium, tiotropium, umeclidinium], LAMA/LABA [aclidinium/formoterol, indacaterol/glycopyrronium, tiotropium/olodaterol, umeclidinium/vilanterol] and ICS/LABA [fluticasone/vilanterol, budesonide/formoterol, salmeterol/fluticasone]) with each other or with placebo. A random-effects network meta-analysis combining direct and indirect evidence was conducted to examine the change from baseline in trough FEV1, transition dyspnea index, St George's Respiratory Questionnaire and frequency of adverse events at weeks 12 and 24. RESULTS: Inconsistency models were not statistically significant for all outcomes. LAMAs, LAMA/LABAs and ICS/LABAs led to a significantly greater improvement in trough FEV1 compared with placebo and SAMA monotherapy at weeks 12 and 24. All LAMA/LABAs, except aclidinium/formoterol, were statistically significantly better than LAMA monotherapy and ICS/LABAs in improving trough FEV1. Among the LAMAs, umeclidinium showed statistically significant improvement in trough FEV1 at week 12 compared to tiotropium and glycopyrronium, but the results were not clinically significant. LAMA/LABAs had the highest probabilities of being ranked the best agents in FEV1 improvement. Similar trends were observed for the transition dyspnea index and St George's Respiratory Questionnaire outcomes. There were no significant differences in the incidences of adverse events among all treatment options. CONCLUSION: LAMA/LABA showed the greatest improvement in trough FEV1 at weeks 12 and 24 compared with the other inhaled drug classes, while SAMA showed the least improvement. There were no significant differences among the LAMAs and LAMA/LABAs within their respective classes.

Cost effectiveness analysis of afatinib versus pemetrexed-cisplatin for first-line treatment of locally advanced or metastatic EGFR mutation positive non-small-cell lung cancer from the Singapore healthcare payer's perspective.

BACKGROUND: Non-small-cell lung cancer (NSCLC) accounts for 85% of all lung cancers and is associated with a poor prognosis. Afatinib is an irreversible ErbB family blocker recommended in clinical guidelines as a first-line treatment for NSCLC which harbours an epidermal growth factor receptor (EGFR) mutation. The objective of this study was to evaluate the cost-effectiveness of afatinib versus pemetrexed-cisplatin for first-line treatment of locally advanced or metastatic EGFR mutation positive NSCLC in Singapore. METHODS: A partitioned survival model with three health states (progression-free, progressive disease and death) was developed from a healthcare payer perspective. Survival curves from the LUX-Lung 3 trial (afatinib versus pemetrexed-cisplatin chemotherapy) were extrapolated beyond the trial period to estimate the underlying progression-free survival and overall survival parametric distributions. Rates of adverse reactions were also estimated from LUX-Lung 3 while health utilities from overseas were derived from the literature in the absence of local estimates. Direct costs were sourced from public healthcare institutions in Singapore. Incremental cost-effectiveness ratios (ICERs) were calculated over a 5 year time horizon. Deterministic and probabilistic sensitivity analyses and additional scenario analyses were conducted to explore the impact of uncertainties and assumptions on the cost-effectiveness results. RESULTS: In the base-case analysis, the ICER for afatinib versus pemetrexed-cisplatin was SG$137,648 per quality-adjusted life year (QALY) gained and SG$109,172 per life-year gained. One-way sensitivity analysis showed the ICER was most sensitive to variations in the utility values, the cost of afatinib and time horizon. Scenario analyses showed that even reducing the cost of afatinib by 50% led to a high ICER which was unlikely to represent a cost-effective use of healthcare resources. CONCLUSIONS: Compared with pemetrexed-cisplatin, afatinib is not cost-effective as a first-line treatment for advanced EGFR mutation-positive NSCLC in Singapore. The findings from our study will be useful to inform local healthcare decision-making and resource allocations for NSCLC treatments, together with other considerations such as clinical effectiveness, safety and affordability of TKIs.

Cost-effectiveness of sacubitril/valsartan versus enalapril in patients with heart failure and reduced ejection fraction.

BACKGROUND: Sacubitril/valsartan reduces cardiovascular death and hospitalizations for heart failure (HF). However, decision-makers need to determine whether its benefits are worth the additional costs, given the low-cost generic status of traditional standard of care. AIMS: To evaluate the cost-effectiveness of sacubitril/valsartan compared to enalapril in patients with HF and reduced ejection fraction, from the Singapore healthcare payer perspective. METHODS: A Markov model was developed to project clinical and economic outcomes of sacubitril/valsartan vs enalapril for 66-year-old patients with HF over 10 years. Key health states included New York Heart Association classes I-IV and deaths; patients in each state incurred a monthly risk of hospitalization for HF and cardiovascular death. Sacubitril/valsartan benefits were modeled by applying the hazard ratios (HRs) in PARADIGM-HF trial to baseline probabilities. Primary model outcomes were total and incremental costs and quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) for sacubitril/valsartan relative to enalapril Results: Compared to enalapril, sacubitril/valsartan was associated with an ICER of SGD 74,592 (USD 55,198) per QALY gained. A major driver of cost-effectiveness was the cardiovascular mortality benefit of sacubitril/valsartan. The uncertainty of this treatment benefit in the Asian sub-group was tested in sensitivity analyses using a HR of 1 as an upper limit, where the ICERs ranged from SGD 41,019 (USD 30,354) to SGD 1,447,103 (USD 1,070,856) per QALY gained. Probabilistic sensitivity analyses showed the probability of sacubitril/valsartan being cost-effective was below 1%, 12%, and 71% at SGD 20,000, SGD 50,000, and SGD 100,000 per QALY gained, respectively. CONCLUSIONS: At the current daily price sacubitril/valsartan may not represent good value for limited healthcare dollars compared to enalapril in reducing cardiovascular morbidity and mortality in HF in the Singapore healthcare setting. This study highlights the cost-benefit trade-off that healthcare professionals and patients face when considering therapy.