This Indian phase IV study of vericiguat offers valuable insights into the demographic and clinical profile of patients with HFrEF. The study population, with a mean age of 58 years and male predominance (73.7%), reflected the typical demographics of patient with HFrEF. The mean body mass index (BMI) of 24.63 kg/m2 and a significant proportion of patients with comorbidities such as diabetes (45.9%), hypertension (42.4%), and CAD (63.9%) emphasized the multifactorial nature of the disease. Most patients were classified as NYHA class II (73.2%) or III (24.9%), highlighting a population with moderate symptomatic burden. The male predominance observed in our study is in line with the existing Indian HF registries (as per the Trivandrum Heart Failure Registry and National Heart Failure Registry of India), which similarly report a higher proportion of men in both chronic and worsening HF populations [9, 10]. This suggests that our cohort reflects real-world clinical practice and the broader epidemiologic pattern seen across India.

The presence of AF at baseline was lower in VERINA patients (4.9%) compared to VICTORIA (45%), PARADIGM-HF (37%), and DAPA-HF (38.2%) [6, 8, 11]. Firstly, according to the Trivandrum Heart Failure Registry (THFR), Indian patients with HF present at a younger age (mean ~ 60 years), about a decade younger than Western HF cohorts (mean ~ 70 years). Since AF prevalence increases sharply with age, this age gap contributes significantly to lower AF rates [12]. Secondly, VERINA patients had lower baseline NT-proBNP levels which indicates less advanced HF and lower atrial strain [13]. Thirdly, South Asian and, in particular, Indian populations are known to document lower AF prevalence compared to the Western population which may be due to genetic, lifestyle, or environmental factors [14, 15]. Finally, lack of diagnosis of paroxysmal or asymptomatic AF cannot be eliminated, especially in the context of a post-marketing surveillance study where intensive electrocardiogram (ECG) monitoring is not conducted at baseline as is done in RCTs.

Renal impairment was prevalent, with 42% of patients having an eGFR < 60 mL/min/1.73 m2. About 4% of the patients had eGFR ≥ 15 to ≤ 30 mL/min/1.73 m2. In the VICTORIA trial, vericiguat showed beneficial effects in patients with declining renal function (eGFR < 30 mL/min/1.73 m2) [6]. All pivotal HF trials with renin–angiotensin–aldosterone system (RAAS) inhibitors only included patients with an eGFR > 30 mL/min/1.73 m2. A recent study on empagliflozin in patients with chronic HF enrolled those with an eGFR > 20 mL/min/1.73 m2. In the VICTORIA trial, patients with an eGFR < 30 mL/min/1.73 m2 were more unwell, having additional comorbidities, elevated NYHA class, and higher NT-proBNP levels [16]. This phase IV study also observed a higher baseline mean NT-proBNP (6623 pg/mL) in patients with eGFR ≥ 15 to ≤ 30 mL/min/1.73 m2.

Frequent hospitalizations due to HF, with a median time of 3 months since the last hospitalization, emphasize the progressive and recurrent nature of the disease.

Patients were younger (mean age 58 years) than those in VICTORIA (mean age 67.3 years) and DAPA-HF (mean age 63.8 years), indicating that in the VERINA cohort, worsening occurred in the younger population [6, 8]. The gender distribution was consistent across studies, with male individuals comprising about 73–78% of patients. The VERINA cohort demonstrated a lower mean BMI (24.63 kg/m2) compared to VICTORIA (27.8 kg/m2) and DAPA-HF (28.2 kg/m2). Additionally, the blood pressure profile of VERINA patients (mean SBP 116.3 mmHg) was slightly lower than in other trials, indicating potential differences in baseline hemodynamics or management practices. LVEF was comparable across studies, with median values around 30%, aligning with the definition of HFrEF.

Medical history data highlight a lower prevalence of AF and DM in the VERINA cohort (4.9% and 45.9%, respectively) compared to VICTORIA and DAPA-HF, where AF and DM were present in 40–47% of patients [6, 8]. Interestingly, the VERINA cohort reported higher rates of CAD (63.9%), reflecting a population with ischemic etiology as a predominant underlying factor. Despite high use of beta-blockers (84.9%), MRAs (80.5%), and SGLT2 inhibitors (75.6%), only 52.7% of patients received ARNI, suggesting gaps in the GDMT implementation, potentially because of tolerability issues or contraindications. Furthermore, a significantly higher proportion of patients were on ARNI in VERINA study compared to VICTORIA (14.5%) and DAPA-HF (not reported), likely as a result of differences in guideline uptake or availability of ARNI.

Despite compelling scientific evidence of the benefits of maximum targeted dosing of GDMT, target doses are usually not achieved in clinical practice. Up to 80% of patients with HFrEF received less than recommended doses of ARNI/ARB/ACEI, beta-blockers (BB), SGLT2i, and MRA [17]. In this study, 91.1% patients reached target dose of 10 mg of vericiguat consistent with VICTORIA [6]. NT-proBNP were substantially lower in VERINA (median 1262 pg/mL) compared to VICTORIA (3377 pg/mL) and DAPA-HF (1608 pg/mL). This could reflect differences in enrollment criteria or disease severity. The relatively lower rates of advanced device use, such as ICDs and biventricular pacemakers, in VERINA further underscore the need for region-specific evaluations of HF care practices.

In a real-world study by Okami et al., the mean age was 75.5 years, with 69% of patients being male [18]. When compared with the VERINA study, both studies reported a male predominance, with 73.7% in the VERINA cohort and 69% in Okami et al.’s study, reflecting a greater prevalence of HFrEF in men [19]. A high prevalence of comorbidities was also noted in both studies, particularly hypertension (42.4% in VERINA vs. 91.7% in Okami et al.) and CAD (63.9% in VERINA vs. 71.3% in Okami et al.), while CKD prevalence was comparable, with 42% of patients in VERINA having an eGFR < 60 mL/min/1.73 m2 and 32.3% in Okami et al.’s study, with 32.5% of those starting on 2.5 mg of vericiguat. Despite these similarities, the studies differ in the mean age of the populations; the VERINA cohort had a younger demographic (mean age 58 years) compared to the older population in Okami et al.’s study (mean age 75.5 years), clearly indicating rising rates of HF in the younger population. This alarming burden of HF in India despite a younger population than in developed nations, highlights the importance of early detection and patient-specific interventions to reduce the burden of HF and improve long-term outcomes among younger populations [12, 20].

Our study is subject to limitations. Firstly, conditions such as AF might have been underdiagnosed as a result of the absence of intensive ECG monitoring at baseline. Secondly, the evaluation of GDMT criteria did not account for individual drug dosages or adherence, because of the unavailability of these data. The baseline comparability may be affected by the potential heterogeneity in background GDMT use and variations in local prescribing patterns across centers, especially with respect to ARNI and SGLT2i. Although the sample size was relatively small, it reflects the early adoption of vericiguat in real-world settings and offers valuable preliminary evidence from clinical practice. Confounder adjustment was not performed, but the study presents detailed demographic and clinical profiles that support appropriate interpretation of the findings. The data for real-world safety, tolerability, and effectiveness of vericiguat has been collected and will be published on the basis of the final clinical study report (CSR).