Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada (J.A.E., C.M.W., P.W.A.).
Merck & Co Inc, Kenilworth, NJ (C.J.M., J.K.).
Circ Heart Fail. 2023 Sep;16(9):e010599. doi: 10.1161/CIRCHEARTFAILURE.123.010599. Epub 2023 Jul 7.
We examined whether the primary composite outcome (cardiovascular death or heart failure hospitalization) was related to differences in background use and dosing of guideline-directed medical therapy in patients with heart failure with reduced ejection fraction enrolled in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction), a randomized trial of vericiguat versus placebo.
We evaluated the adherence to guideline use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists. We assessed basic adherence; indication-corrected adherence accounting for guideline indications and contraindications; and dose-corrected adherence (indication-corrected adherence+≥50% of drug dose target). Associations between study treatment and the primary composite outcome according to the adherence to guidelines were assessed using multivariable adjustment; adjusted hazard ratios with 95% CIs and are reported.
Of 5050 patients, 5040 (99.8%) had medication data at baseline. For angiotensin-converting enzyme inhibitor, angiotensin-receptor blockers, and angiotensin receptor-neprilysin inhibitors, basic adherence to guidelines was 87.4%, indication-corrected was 95.7%, and dose-corrected was 50.9%. For beta-blockers, basic adherence was 93.1%, indication-corrected was 96.2%, and dose-corrected was 45.4%. For mineralocorticoid receptor antagonists, basic adherence was 70.3%, indication-corrected was 87.1%, and dose-corrected was 82.2%. For triple therapy (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or angiotensin receptor-neprilysin inhibitors+beta-blocker+mineralocorticoid receptor antagonist), basic adherence was 59.7%, indication-corrected was 83.3%, and dose-corrected was 25.5%. Using basic or dose-corrected adherence, the treatment effect of vericiguat was consistent across adherence to guidelines groups, with or without multivariable adjustment with no treatment heterogeneity.
Patients in VICTORIA were well treated with heart failure with reduced ejection fraction medications. The efficacy of vericiguat was consistent across background therapy with very high adherence to guidelines accounting for patient-level indications, contraindications, and tolerance.
URL: https://www.
gov; Unique identifier: NCT02861534.
我们研究了心力衰竭射血分数降低患者中，主要复合终点（心血管死亡或心力衰竭住院）是否与指南指导的医学治疗的背景使用和剂量差异有关，这些患者是 VICTORIA 试验（心力衰竭射血分数降低患者中维立西呱的全球研究）的入组对象，该试验评估了维立西呱与安慰剂相比的疗效。
我们评估了血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂、血管紧张素受体脑啡肽酶抑制剂、β受体阻滞剂和盐皮质激素受体拮抗剂的指南使用依从性。我们评估了基本依从性、考虑了指南适应证和禁忌证的适应证校正依从性、以及剂量校正依从性（适应证校正依从性+≥药物剂量目标的 50%）。使用多变量调整评估了研究治疗与主要复合终点之间的关联；报告了调整后的危险比（95%CI）和 P 值。
在 5050 例患者中，5040 例（99.8%）在基线时有药物数据。对于血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂和血管紧张素受体脑啡肽酶抑制剂，基本依从性为 87.4%，适应证校正为 95.7%，剂量校正为 50.9%。对于β受体阻滞剂，基本依从性为 93.1%，适应证校正为 96.2%，剂量校正为 45.4%。对于盐皮质激素受体拮抗剂，基本依从性为 70.3%，适应证校正为 87.1%，剂量校正为 82.2%。对于三联疗法（血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂或血管紧张素受体脑啡肽酶抑制剂+β受体阻滞剂+盐皮质激素受体拮抗剂），基本依从性为 59.7%，适应证校正为 83.3%，剂量校正为 25.5%。使用基本或剂量校正的依从性，维立西呱的治疗效果在指南依从性组之间一致，无论是否进行多变量调整，均无治疗异质性。
VICTORIA 中的心力衰竭射血分数降低患者接受了良好的心力衰竭药物治疗。维立西呱的疗效在背景治疗中一致，对患者的个体适应证、禁忌证和耐受性考虑了极高的指南依从性。
