Cost-Effectiveness of Dapagliflozin for Chronic Kidney Disease in Japan.

BACKGROUND: The cost-effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors for chronic kidney disease (CKD) has not been evaluated in Japan, so we analyzed the cost-effectiveness of dapagliflozin, an SGLT2 inhibitor, for CKD stages 3a and 3b.Methods and Results: We used the Markov model for CKD to assess the costs and benefits associated with and without dapagliflozin from a health system perspective. We estimated the incremental cost-effectiveness ratio (ICER), expressed as per quality-adjusted life-years (QALYs). An ICER <5 million Japanese yen (JPY)/QALY was judged to be cost-effective. The effect of dapagliflozin on renal and cardiovascular events was based on published clinical trials. In patients with CKD stage 3a, the ICER of dapagliflozin over standard treatment was 4.03 million JPY/QALY gained. With a cost-effectiveness threshold of 5 million JPY/QALY gained, the cost-effectiveness probability of dapagliflozin over standard treatment was 52.6%. In patients with CKD stage 3b, the ICER of dapagliflozin over standard treatment was 0.12 million JPY/QALY gained. The cost-effectiveness probability of dapagliflozin over standard treatment was 75.2%. CONCLUSIONS: The results seemed to show acceptable cost-effectiveness when dapagliflozin was used for CKD stage 3b. On the other hand, cost-effectiveness of dapagliflozin for CKD stage 3a was ambiguous, and further validation is needed.

Cost-Effectiveness of Percutaneous Coronary Intervention Compared With Medical Therapy for Ischemic Heart Disease in Japan.

BACKGROUND: The cost-effectiveness of percutaneous coronary intervention (PCI) for ischemic heart disease is undetermined in Japan. The aim of this study was to analyze the cost-effectiveness of PCI compared with medical therapy for ST-elevation myocardial infarction (STEMI) and angina pectoris (AP) in Japan.Methods and Results:We used Markov models for STEMI and AP to assess the costs and benefits associated with PCI or medical therapy from a health system perspective. We estimated the incremental cost-effectiveness ratio (ICER), expressed as quality-adjusted life-years (QALY), and ICER <¥5 m per QALY gained was judged to be cost-effective. The impact of PCI on cardiovascular events was based on previous publications. In STEMI patients, the ICER of PCI over medical treatment was ¥0.97 m per QALY gained. The cost-effectiveness probability of PCI was 99.9%. In AP patients, the ICER of fractional flow reserve (FFR)-guided PCI over medical treatment was ¥4.63 m per QALY gained. The cost-effectiveness probability of PCI was 50.4%. The ICER of FFR-guided PCI for asymptomatic patients was ¥23 m per QALY gained. CONCLUSIONS: In STEMI patients, PCI was cost-effective compared with medical therapy. In AP patients, FFR-guided PCI for symptomatic patients could be cost-effective compared with medical therapy. FFR-guided PCI for asymptomatic patients with myocardial ischemia was not cost-effective.

Cost-Effectiveness of PCSK9 Inhibitor Plus Statin in Patients With Triple-Vessel Coronary Artery Disease in Japan.

BACKGROUND: The addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy reduces the rate of cardiovascular events. This study examined the cost-effectiveness of PCSK9 inhibitor+statin compared with standard therapy (statin monotherapy) in the treatment of triple-vessel coronary artery disease (CAD) in Japan. Methods and Results: A Markov model was applied to assess the costs and benefits associated with PCSK9 inhibitor+statin over a projected 30-year period from the perspective of a public healthcare payer in Japan. The incremental cost-effectiveness ratio (ICER), expressed as the quality-adjusted life-years (QALYs), was estimated. The effects on survival and numbers of events were based on the FOURIER trial and the CREDO Kyoto registry. The ICER of PCSK9 inhibitor+statin over standard therapy was 13.5 million (95% confidence interval 7.6-23.5 million) Japanese Yen (JPY) per QALY gained for triple-vessel CAD. The probability of the cost-effectiveness of PCSK9 inhibitor+statin vs. standard therapy was 0.0008% at a cost-effectiveness threshold of 5 million JPY. In patients with poorly controlled familial hypercholesterolemia (FH) with triple-vessel CAD, the ICER was 3.4 million JPY per QALY gained. CONCLUSIONS: PCSK9 inhibitor plus statin did not show good cost-effectiveness for triple-vessel CAD; however, it showed good cost-effectiveness for patients with triple-vessel CAD and poorly controlled FH in Japan.

Cost-Effectiveness of Statin Plus Eicosapentaenoic Acid Combination Therapy for Cardiovascular Disease Prevention in Japanese Patients With Hypercholesterolemia　- An Analysis Based on the Japan Eicosapentaenoic Acid Lipid Intervention Study (JELIS).

BACKGROUND: The addition of eicosapentaenoic acid (EPA) to statin therapy has been shown to reduce cardiovascular events. This study examined the cost-effectiveness of EPA plus statin (EPA+statin) combination therapy compared with statin monotherapy for primary and secondary prevention of cardiovascular disease (CVD) in Japan.Methods and Results:A Markov model was applied to assess the costs and benefits associated with EPA+statin combination therapy over a projected 30-year period from the perspective of a public healthcare funder in Japan. The incremental cost-effectiveness ratio (ICER), expressed as quality-adjusted life-years (QALY), was estimated for primary prevention and secondary prevention of CVD in patients with hypercholesterolemia. Impact on survival and number of events were based on the Japan EPA Lipid Intervention Study. Sensitivity analyses examined the influence of various input parameters on costs and outcomes of treatment. ICER was ¥29.6 million per QALY gained in primary prevention and ¥5.5 million per QALY gained in secondary prevention. The probabilities that EPA+statin combination therapy would be cost-effective compared with statin monotherapy were 39% in primary prevention and 49% in secondary prevention at a cost-effectiveness threshold of ¥5 million per QALY gained. Sensitivity analyses showed that EPA was cost-effective in secondary prevention. CONCLUSIONS: EPA+statin combination therapy showed acceptable cost-effectiveness for secondary prevention, but not primary prevention, of CVD in patients with hypercholesterolemia in Japan.

Cost effectiveness of transcatheter aortic valve implantation in patients with aortic stenosis in Japan.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a less invasive treatment for elderly patients with aortic stenosis. However, the cost of TAVI is a major issue. This study analyzed the cost effectiveness of TAVI in Japan. METHODS: We developed an economic model to evaluate the quality-adjusted life years (QALYs) and costs of TAVI, surgical aortic valve replacement (SAVR), and medical therapy over a 10-year time horizon from the perspective of Japanese public healthcare payers. The first model compared transapical or transfemoral TAVI with Sapien valve implantation and medical therapy in inoperable patients. The second model compared transfemoral TAVI with Sapien XT valve implantation and SAVR in operable patients with intermediate surgical risk. We assumed a cost-effectiveness threshold of 5,000,000yen per QALY, and assessed the cost-effectiveness probability with 100,000 simulations. We performed a broad sensitivity analysis to assess the effect of uncertainty on our results. RESULTS: Among inoperable patients, the incremental cost-effectiveness ratio for TAVI compared with medical therapy was 3,918,808yen per QALY. In operable patients, the incremental cost-effectiveness ratio for TAVI compared with SAVR was 7,523,821yen per QALY. The cost-effectiveness probability of TAVI was 60% for inoperable patients and 46% for operable patients. Among inoperable patients, the cost-effective threshold of TAVI was <7,759,085yen. Among operable patients, the cost-effective threshold of TAVI was <5,427,439yen. CONCLUSIONS: This study suggests that TAVI has good cost effectiveness for inoperable patients, but not for operable patients.

Cost-Effectiveness Analysis of Cardiovascular Disease Treatment in Japan.

The quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER) are important concepts in cost-effectiveness analysis, which is becoming increasingly important in Japan. QALY is used to estimate quality of life (QOL) and life years, and can be used to compare the efficacies of cancer and cardiovascular treatments. ICER is defined as the difference in cost between treatments divided by the difference in their effects, with a smaller ICER indicating better cost-effectiveness. Here, we present a review of cost-effectiveness analyses in Japan as well other countries. A number of treatments were shown to be cost-effective, e.g., statin for secondary prevention of cardiovascular disease, aspirin for primary prevention of cardiovascular disease, DOAC for high-risk atrial fibrillation, beta blockers, ACE inhibitors, and ARB for heart failure, sildenafil and bosentan for pulmonary hypertension, CABG for multi-vessel coronary disease, ICD for ventricular tachycardia, and CRT for heart failure with low ejection fraction, while others were not cost-effective, e.g., epoprostenol for pulmonary hypertension and LVAD for end-stage heart failure. Further investigations are required regarding some treatments, e.g., PCSK-9 inhibitors for familial hypercholesterolemia, PCI for multi-vessel coronary disease, catheter ablation for atrial fibrillation, and TAVI for severe aortic stenosis. Ethical aspects should be taken into consideration when utilizing the results of cost-effectiveness analysis in medical policy.

Identification of the State of Maximal Hyperemia in the Assessment of Coronary Fractional Flow Reserve Using Non-Invasive Electrical Velocimetry.

Previous research revealed that, in patients with coronary pressure-derived fractional flow reserve (FFR) in the 'grey zone' (0.75-0.85), repeated FFR assessments sometimes yield conflicting results. One of the causes of the fluctuations in FFR values around the grey zone may be imprecise identification of the point where maximal hyperemia is achieved. Identification of the state of maximal hyperemia during assessment of FFR can be challenging. This study aimed to determine whether non-invasive electrical velocimetry (EV) can be used to identify the state of maximal hyperemia.Stroke volume (SV), SV variation (SVV), and systemic vascular resistance index (SVRI) were determined by EV in 15 patients who underwent FFR assessment. Time intervals from initiation of adenosine infusion to achieving maximal hyperemia (timemFRR), as well as to achieving maximal cardiac output (CO), SV, SVV, and SVRI (timemCO, timemSV, timemSVV, and timemSVRI, respectively), were determined. TimemCO and timemSVV were closer to timemFRR than other values (timemSVV/timemFRR versus timemSVRI/timemFRR = 1.03 ± 0.2 versus 1.36 ± 0.4, P < 0.05). The maximum of SV was difficult to determine owing to considerable variations, but the maximum of SVV was clearly recognized. TimemCO and timemSVV were significantly correlated with timemFFR, with timemSVV showing a stronger correlation than timemSV (timemSVV: r = 0.92, P < 0.01; timemCO: r = 0.80, P < 0.01).Maximal SVV is reached close to maximal hyperemia. Monitoring of SVV with non-invasive EV during FFR assessment can help identify the state of maximal hyperemia.

Mid-term results and costs of coronary artery bypass vs drug-eluting stents for unprotected left main coronary artery disease.

BACKGROUND: The optimal revascularization strategy for unprotected left main coronary artery (ULMCA) disease in the era of drug-eluting stents (DES) has become more controversial between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). METHODS AND RESULTS: Since April 2004, 89 patients underwent CABG, including 82 (92.1%) off-pump procedures and 63 patients underwent PCI with DES for ULMCA disease. Major adverse cardiac and cerebrovascular events (MACCE: death, acute myocardial infarction, stroke and repeat revascularization) and hospitalization costs were compared. Patients in the CABG group were likely to have multivessel disease and higher euroSCORE. The mean follow-up was 2.2+/-1.1 years in the CABG group and 1.6+/-0.8 years in the DES group (P<0.001). The overall survival rate did not differ (P=0.288) between the groups (CABG: 93.4% and DES: 91.9% at 2 years). The MACCE-free survival rate was better (P=0.033) in the CABG group (CABG: 82.2% and DES: 62.6% at 2 years). Total hospitalization costs were lower (P=0.013) in the CABG group (median: 3,225 thousand yen) than in the DES group (median: 4,192 thousand yen). CONCLUSIONS: CABG might be associated with cost-effectiveness and could be still the first revascularization strategy for ULMCA disease.