Department of Health Policy and Management (B.W.Y., A.P.), Harvard T. H. Chan School of Public Health, Boston, MA.
School of Medicine, University of California San Francisco (B.W.Y.).
Circ Cardiovasc Qual Outcomes. 2023 Jun;16(6):e009793. doi: 10.1161/CIRCOUTCOMES.122.009793. Epub 2023 Jun 6.
The 2022 clinical guidelines for management of heart failure with reduced ejection fraction call for quadruple therapy. Quadruple therapy consists of an angiotensin receptor-neprilysin inhibitor (ARNi), sodium-glucose cotransporter-2 inhibitor (SGLT2i), mineralocorticoid receptor antagonist, and beta blocker. The ARNi and sodium-glucose cotransporter-2 inhibitor are newer additions to standard of care with the ARNi replacing ACE (angiotensin-converting enzyme) inhibitors and angiotensin II receptor blockers.
We investigate the cost-effectiveness of sequentially adding the SGLT2i and ARNi to form quadruple therapy as compared with the previous standard of care with ACE inhibitor/mineralocorticoid receptor antagonist/beta blocker. Using a 2-stage Markov model, we projected the expected lifetime discounted costs and quality-adjusted life years (QALYs) of a simulated cohort of US patients who underwent each treatment option and calculated incremental cost-effectiveness ratios. We assessed incremental cost-effectiveness ratios using criteria for health care value (<$50 000/quality-adjusted life year [QALY] indicating high-value, $50 000-150 000/QALY indicating intermediate value, and >$150 000/QALY indicating low-value) and a standard $100 000/QALY cost-effectiveness threshold.
Compared with the previous standard of care, the SGLT2i addition had an incremental cost-effectiveness ratio of $73 000/QALY and weakly dominated the ARNi addition. The addition of both the ARNi and SGLT2i for quadruple therapy offered 0.68 additional discounted QALYs over the SGLT2i addition alone at a lifetime discounted cost of $66 700, resulting in an incremental cost-effectiveness ratio of $98 500/QALY. In sensitivity analysis varying drug prices, the incremental cost-effectiveness ratio for quadruple therapy ranged from $73 500/QALY using prices available to the US Department of Veterans Affairs to $110 000/QALY using drug list prices.
While quadruple therapy offers intermediate value, it is borderline cost effective compared with adding the SGLT2i alone to previous standard of care. Thus, its cost-effectiveness is sensitive to a payer's ability to negotiate discounts off the increasing list prices for ARNI and SGLT2is. The demonstrated benefits of ARNi and SGLT2is should be weighed against their high prices in payer and policy considerations.
2022 年心力衰竭伴射血分数降低的临床指南呼吁采用四联疗法。四联疗法包括血管紧张素受体-脑啡肽酶抑制剂（ARNi）、钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2i）、盐皮质激素受体拮抗剂和β受体阻滞剂。ARNi 和 SGLT2i 是标准治疗的新添加物，ARNi 取代了 ACE（血管紧张素转换酶）抑制剂和血管紧张素 II 受体阻滞剂。
我们研究了依次添加 SGLT2i 和 ARNi 以形成四联疗法与之前的 ACE 抑制剂/盐皮质激素受体拮抗剂/β受体阻滞剂标准治疗相比的成本效益。使用两阶段马尔可夫模型，我们预测了接受每种治疗方案的美国患者模拟队列的预期终生贴现成本和质量调整生命年（QALY），并计算了增量成本效益比。我们使用卫生保健价值标准（<$50000/QALY 表示高价值，$50000-150000/QALY 表示中等价值，>$150000/QALY 表示低价值）和标准的$100000/QALY 成本效益阈值来评估增量成本效益比。
与之前的标准治疗相比，SGLT2i 的添加具有$73000/QALY 的增量成本效益比，并且略微优于 ARNi 的添加。ARNi 和 SGLT2i 的联合添加用于四联疗法，在终生贴现成本为$66700 时，比单独添加 SGLT2i 可额外获得 0.68 个贴现 QALY，增量成本效益比为$98500/QALY。在药物价格变化的敏感性分析中，四联疗法的增量成本效益比范围从使用美国退伍军人事务部可获得的价格为$73500/QALY 到使用药物清单价格为$110000/QALY。
虽然四联疗法提供了中等价值，但与将 SGLT2i 添加到之前的标准治疗相比，它的成本效益具有边缘性。因此，其成本效益对支付方协商降低 ARNi 和 SGLT2i 不断上涨的目录价格的能力敏感。在支付方和政策考虑因素中，应权衡 ARNi 和 SGLT2i 的高价格与它们的获益。
