Post hoc Analysis: Use of Bisoprolol in NOCAD

Bisoprolol is clinically feasible option in reducing resting heart rate (RHR) and improving left ventricular ejection fraction (LVEF), thereby enhancing cardiac function. A recent post-hoc analysis of the BISOCARD study highlighted these benefits in Indian patients with non-obstructive coronary artery disease (NOCAD) who had undergone percutaneous coronary intervention (PCI).

This analysis provides real-world evidence of bisoprolol’s safety and effectiveness in the management of patients diagnosed with NOCAD who underwent PCI.

Bisoprolol is a selective β1-receptor antagonist, which has shown to offer anti-ischemic and anti-hypertensive benefits by reducing myocardial oxygen demand, lowering RHR, and improving LVEF.

The study has been published in the December 2024 issue of Cureus.

CAD, NOCAD & Implications in India:

Indians have the highest rates of CAD, with 20-50% higher mortality. NOCAD, defined as <50% stenosis in the left main coronary artery, affects ~50% of patients undergoing elective coronary angiography. Despite nonobstructive arteries, these patients face recurrent chest pain, reduced quality of life, and increased risks of mortality and MI, highlighting the need for proactive care.

Study Overview:

The study was a multi-centered, concurrent, observational, single-arm, open-label clinical investigation aimed at evaluating bisoprolol's efficacy and safety in real-world NOCAD scenarios.

It enrolled 800 CAD patients as the intent-to-treat (ITT) population across 80 outpatient centers in India, ensuring broad representation. Among ITT patients, 611 (76.37%) were male and 189 (23.63%) were female, with hypertension present in 100% of cases. The NOCAD group, representing 47.25% of the ITT population (per-protocol set), consisted of 378 patients, with 286 (75.66%) males and 92 (24.34%) females. The mean age of NOCAD patients was 58.63 years, with hypertension, dyslipidemia, and type 2 diabetes as common risk factors and comorbidities.

The study spanned 24 weeks, evaluating parameters such as resting heart rate (RHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and left ventricular ejection fraction (LVEF).

Patients received bisoprolol in doses of 2.5mg, 5mg, and 10mg per day as per the direction of the physician, and outcomes were assessed at baseline and after 24 weeks of treatment.

The primary objectives of the study were to evaluate the change in mean values of RHR and LVEF after 24 weeks of treatment with bisoprolol. The secondary objectives included assessing changes in SBP and DBP after 24 weeks and monitoring the occurrence of treatment-emergent adverse events (TEAEs).

Some of the key findings from the study are:

Efficacy of Bisoprolol on Heart Rate, Blood Pressure, and LV Function

Among NOCAD Patients (n=378)

• RHR: Initial RHR in NOCAD patients was 88.3 bpm. After 24 weeks, it was significantly reduced to 76.15 bpm, showing a change of -12.14 bpm (p<0.01).
• After 24 weeks baseline systolic blood pressure (SBP) of 146.06 mmHg decreased to 129.67 mmHg, showing a reduction of -16.30 mmHg (p<0.01). Similarly, the diastolic blood pressure (DBP) dropped from a baseline of 91.96 mmHg to 82.92 mmHg, a reduction of -9.05 mmHg (p<0.01)
• LVEF: The baseline LVEF was 46.85%. It showed significant improvement and reached 51.53% at 24 weeks, a change of 4.68% (p<0.01).

Efficacy in NOCAD Patients in Relation to History of Ischemic Events

• Among the NOCAD group, 236 patients (62.43%) had a prior history of ischemic events at baseline.
• After 24 weeks of treatment, significant improvements were observed, including a mean reduction in RHR by 12.46 bpm, SBP by 19.91 mmHg, DBP by 9.85 mmHg, and a mean increase in LVEF by 5.66%.

• In the 142 patients (37.57%) without a history of ischemic events, notable changes included a mean reduction in RHR by 11.59 bpm, SBP by 10.33 mmHg, DBP by 7.72 mmHg, and a mean improvement in LVEF by 3.04%.

Evaluating the Safety of Bisoprolol

Over the 24-week evaluation period, treatment-emergent adverse events (TEAE) occurred in 60 NOCAD patients (15.87%), including chest congestion (6.61%), asthenia (5.03%), hypotension (4.76%), muscular weakness (3.70%), and bradycardia (1.85%). All events were mild, transient, and did not necessitate treatment withdrawal.

This study found that bisoprolol was effective and well-tolerated in preserving and improving cardiac function and parameters, including RHR, SBP, DBP, and LVEF among NOCAD patients in the Indian population with coexisting hypertension. These findings suggest that adding bisoprolol to standard NOCAD treatment regimens may improve the quality of care.

*CAD: Coronary Artery Disease; DBP: Diastolic Blood Pressure; LVEF: Left Ventricular Ejection Fraction, RHR: Resting Heart Rate; SBP: Systolic Blood Pressure, TEAE: treatment-emergent adverse events

Reference:

1) Pinto B, Kulkarni GR, Kumar S, Deb A, Fischer L, Khandelwal A, Korukonda KR, Nair R. Cross-Sectional Analyses to Assess the Clinical Safety and Effectiveness of Bisoprolol in Patients With Non-obstructive Coronary Artery Disease Who Underwent Percutaneous Coronary Intervention: A Post-hoc Analysis. Cureus. 2024 Dec 3;16(12):e75021. doi: 10.7759/cureus.75021. PMID: 39749095; PMCID: PMC11694328.