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Background Medical Therapy and Clinical Outcomes From the VICTORIA Trial
Justin A Ezekowitz1, Ciaran J McMullan2, Cynthia M Westerhout1
1Canadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada (J.A.E., C.M.W., P.W.A.).
Insights
Vericiguat demonstrated consistent efficacy in reducing cardiovascular death or heart failure hospitalizations for patients with heart failure with reduced ejection fraction, regardless of background medication adherence. This finding supports its use across diverse patient treatment scenarios.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Heart failure with reduced ejection fraction (HFrEF) management involves guideline-directed medical therapy (GDMT).
- Patient adherence to GDMT can vary, potentially influencing treatment outcomes.
- The VICTORIA trial evaluated vericiguat in HFrEF patients.
Purpose of the Study:
- To assess the relationship between background GDMT use and dosing and the primary composite outcome in the VICTORIA trial.
- To evaluate adherence to key HFrEF medications, including ACE inhibitors, ARBs, ARNIs, beta-blockers, and MRAs.
- To determine if vericiguat's treatment effect varied based on adherence to GDMT.
Main Methods:
- Adherence to GDMT was assessed using basic, indication-corrected, and dose-corrected metrics.
- Multivariable adjustment was used to analyze associations between vericiguat treatment and the primary outcome across adherence groups.
- Hazard ratios (HRs) with 95% confidence intervals (CIs) and P-interaction values were reported.
Main Results:
- High rates of basic and indication-corrected adherence were observed for most GDMT classes.
- Dose-corrected adherence varied, with lower rates for ACE inhibitors/ARBs/ARNIs and beta-blockers.
- The treatment effect of vericiguat on the primary composite outcome was consistent across all adherence levels, showing no significant treatment heterogeneity.
Conclusions:
- Patients in the VICTORIA trial generally received well-managed HFrEF medications.
- Vericiguat's efficacy was consistent regardless of background therapy adherence, even when accounting for indications, contraindications, and tolerance.
- These findings support the reliable efficacy of vericiguat in a broad HFrEF population.
Background:
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.
Methods:
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 Pinteraction are reported.
Results:
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.
Conclusions:
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.
Registration:
URL: https://www.
Clinicaltrials:
gov; Unique identifier: NCT02861534.
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