What is the clinical evidence from this study?

Study design: Cohort. Population: schizophrenia (n=315). Intervention: Clozapine vs. general population. Primary outcome: age-standardized prevalence of heart failure (OR 3.2 (Japan) / OR 6.9 (China), 95% CI 1.4-6.4 (Japan) / 3.6-12.0 (China)).

What question did this study set out to answer?

This study examines the risk of long-term clozapine-induced cardiotoxicity in schizophrenia patients.

June 12, 2026Medical SciencesOpen Access

Risk of Long-Term Clozapine Medication over Decades for Cardiac Adverse Events Including Heart Failure and Its Pathophysiology: A Japan and China Retrospective Cohort Analysis

View Full Paper

Ask AI

Bookmark

Key result

Long-term clozapine is linked to up to ~590% higher heart failure prevalence versus the general population.

OR 3.2 (Japan) / OR 6.9 (China)
95% CI 1.4-6.4 (Japan) / 3.6-12.0 (China)
n=315

Why the study?

The risk of cardiotoxicity induced by long-term clozapine medication has not yet been fully elucidated.

Does long-term clozapine monotherapy increase the risk of heart failure in patients with schizophrenia compared to the general population?

Population

315 patients with schizophrenia receiving clozapine monotherapy in Japan and China

Comparison

Patients prescribed clozapine vs general population

Design

Multicenter retrospective cohort study

Authors

RORuri Okubo NYNobutomo Yamamoto XSXiaojun Shao

Discussion

Member takes

Overview

Clozapine was associated with higher heart failure prevalence; hypothesis-generating for independent cardiotoxicity and prospective monitoring studies.

Key Points

This study examines the risk of long-term clozapine-induced cardiotoxicity in schizophrenia patients.
Multicenter retrospective cohort study of schizophrenia patients in Japan and China
Included cases from 2025 with NT-proBNP concentration and LVEF data
Statistical analysis involved blood examinations and echocardiography results.
Heart failure prevalence was higher in clozapine patients versus the general population (OR 3.2 in Japan, OR 6.9 in China)
Identified risk factors for stage-B heart failure include prolonged exposure, higher plasma clozapine levels, and increased monocytes
Over 70% of heart failure cases did not present metabolic complications, indicating HFpEF likely.

Study Design

Type

Cohort (n=315)

Multicenter

Yes

Structured PICO

Does long-term clozapine monotherapy increase the risk of heart failure in patients with schizophrenia compared to the general population?

Population

315 patients with schizophrenia in Japan and China receiving long-term clozapine monotherapy, evaluated for heart failure using NT-proBNP and echocardiography.

Exposure

Long-term clozapine monotherapy (mean exposure duration 57.5 ± 4.0 months in Japan, 208.1 ± 11.0 months in China).

Comparator

General population (for age-standardized prevalence comparison).

Outcome

Prevalence of heart failure (including asymptomatic stage-B heart failure).safety

Main Result

Effect estimate: OR 3.2 (Japan) / OR 6.9 (China) (95% CI 1.4-6.4 (Japan) / 3.6-12.0 (China))

Long-term clozapine use is associated with a significantly increased risk of late-onset, asymptomatic heart failure (likely HFpEF), suggesting a need for routine NT-proBNP monitoring in this population.

Cite This Study

Okubo et al. (2026) conducted a cohort in schizophrenia (n=315). Clozapine vs. general population was evaluated on age-standardized prevalence of heart failure (OR 3.2 (Japan) / OR 6.9 (China), 95% CI 1.4-6.4 (Japan) / 3.6-12.0 (China)). Long-term clozapine exposure was associated with a higher prevalence of heart failure compared to the general population in Japan (OR 3.2; 95% CI 1.4-6.4) and China (OR 6.9; 95% CI 3.6-12.0).

synapsesocial.com/papers/6a2bd1386550ea4541ffe986 https://doi.org/10.3390/medsci14020306

View Full Paper

Ask AI

Bookmark

June 12, 2026Medical SciencesOpen Access

Risk of Long-Term Clozapine Medication over Decades for Cardiac Adverse Events Including Heart Failure and Its Pathophysiology: A Japan and China Retrospective Cohort Analysis

View Full Paper

Ask AI

Bookmark

Key result

Long-term clozapine is linked to up to ~590% higher heart failure prevalence versus the general population.

OR 3.2 (Japan) / OR 6.9 (China)
95% CI 1.4-6.4 (Japan) / 3.6-12.0 (China)
n=315

Why the study?

The risk of cardiotoxicity induced by long-term clozapine medication has not yet been fully elucidated.

Does long-term clozapine monotherapy increase the risk of heart failure in patients with schizophrenia compared to the general population?

Population

315 patients with schizophrenia receiving clozapine monotherapy in Japan and China

Comparison

Patients prescribed clozapine vs general population

Design

Multicenter retrospective cohort study

Authors

RORuri Okubo NYNobutomo Yamamoto XSXiaojun Shao

Discussion

Member takes

Overview

Clozapine was associated with higher heart failure prevalence; hypothesis-generating for independent cardiotoxicity and prospective monitoring studies.

Key Points

This study examines the risk of long-term clozapine-induced cardiotoxicity in schizophrenia patients.
Multicenter retrospective cohort study of schizophrenia patients in Japan and China
Included cases from 2025 with NT-proBNP concentration and LVEF data
Statistical analysis involved blood examinations and echocardiography results.
Heart failure prevalence was higher in clozapine patients versus the general population (OR 3.2 in Japan, OR 6.9 in China)
Identified risk factors for stage-B heart failure include prolonged exposure, higher plasma clozapine levels, and increased monocytes
Over 70% of heart failure cases did not present metabolic complications, indicating HFpEF likely.

Study Design

Type

Cohort (n=315)

Multicenter

Yes

Structured PICO

Does long-term clozapine monotherapy increase the risk of heart failure in patients with schizophrenia compared to the general population?

Population

315 patients with schizophrenia in Japan and China receiving long-term clozapine monotherapy, evaluated for heart failure using NT-proBNP and echocardiography.

Exposure

Long-term clozapine monotherapy (mean exposure duration 57.5 ± 4.0 months in Japan, 208.1 ± 11.0 months in China).

Comparator

General population (for age-standardized prevalence comparison).

Outcome

Prevalence of heart failure (including asymptomatic stage-B heart failure).safety

Main Result

Effect estimate: OR 3.2 (Japan) / OR 6.9 (China) (95% CI 1.4-6.4 (Japan) / 3.6-12.0 (China))

Cite This Study

synapsesocial.com/papers/6a2bd1386550ea4541ffe986 https://doi.org/10.3390/medsci14020306

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

View Full Paper

Ask AI

Bookmark