Impact of Internet-Based Pharmacy Care on Patient-Reported Outcomes in Congenital Heart Disease-Associated Pulmonary Hypertension in Yunnan, China

Summary

This study investigated Internet-based pharmaceutical care (IPC) integrated with patient-reported outcomes (PROs) among 657 postoperative patients with pulmonary arterial hypertension associated with congenital heart disease in Yunnan, China. IPC effectively reduced pulmonary arterial pressure and enhanced health utility. Markov modeling confirmed IPC was highly cost‑effective, supporting its clinical application.

Abstract

This study evaluated the effectiveness and cost-effectiveness of Internet-based pharmaceutical care (IPC) incorporating patient-reported outcomes (PROs) in postoperative patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD). A cohort study was conducted at Fuwai Yunnan Hospital between July 2018 and June 2025. Patients received IPC interventions consisting of WeChat-based health education and PRO assessments using the EuroQol EQ-5D-3L and medication compliance questionnaires. A Markov cohort model with a 26-cycle (52-year) horizon was applied to assess the long-term economic value of IPC-PROs. A total of 657 PAH-CHD patients were enrolled, including 422 patients in the IPC group and 235 in the control group. At 90 days post-surgery, the mean pulmonary arterial pressure in the IPC group was significantly lower than that in the control group (33.07 ± 21.62 mmHg vs. 50.17 ± 26.35 mmHg, p. < 0.05). The postoperative health utility improved from 0.6762 to 0.9770 following IPC intervention, while medication compliance scores remained near-perfect throughout the 24-month follow-up period. The Markov cohort simulation demonstrated that the IPC group achieved a gain of 17.0 quality-adjusted life years (QALYs) at a cost of ¥156.87 per patient, resulting in an incremental cost-effectiveness ratio (ICER) of ¥184.11/QALY, which was substantially below the willingness-to-pay threshold of ¥202,800. These findings indicate that IPC integrated with PROs is an effective and cost-effective strategy for improving postoperative outcomes in PAH-CHD patients in Yunnan Province, China.

Introduction

Pulmonary arterial hypertension (PAH) is a grave cardiovascular condition, characterized by a life-threatening, persistent increase in blood pressure within the pulmonary arteries¹. This can result in heightened right ventricular load, chronic right ventricular dilation, right heart failure, and ultimately death^1,2. PAH is diagnosed when the mean pulmonary arterial pressure exceeds 25 mmHg at rest³. PAH associated with congenital heart disease (PAH-CHD) is prevalent among patients with uncorrected congenital heart conditions. Previous studies have shown that PAH-CHD patients experience rebound elevations in pulmonary pressure for 60 days post-operation. The suboptimal efficacy of postoperative drug therapy may be attributed to poor medication adherence among patients^4,5.

Pharmaceutical care, encompassing medication management, personalized plan formulation, and health status monitoring, significantly improves medication adherence and treatment outcomes^6,7,8. Internet-based pharmaceutical care (IPC) evolves from data collection and analysis to personalized intelligence, tailoring treatments to achieve precision medicine⁹. This model not only boosts patient engagement in medical decision-making and enables real-time medication adjustments⁹, but also allows pharmacists to assess treatment efficacy through patient-reported outcomes (PROs), thereby ensuring the delivery of high-quality healthcare services.

Two previous studies have reported the use of PROs in pulmonary arterial hypertension. However, both studies had limitations, including limited sample sizes (53 and 110 patients) and relatively short follow-up periods (six months and 16 months)^10,11. Furthermore, IPC-PROs foster equitable distribution of medical resources, ensuring that patients in remote areas have access to quality medical care. However, the application of IPC-PROs in the postoperative management of PAH-CHD patients remains uncharted territory, and their economic implications remain unexplored. The objective of this study was to investigate whether IPC can lead to superior therapeutic and cost-effective outcomes post-surgery. This study may provide evidence to support postoperative management strategies for patients with PAH-CHD.

Protocol

This study was approved by the Ethics Committee of Fuwai Yunnan Cardiovascular Hospital (No. 2023-046-01). The requirement for individual informed consent was waived for retrospectively collected data from July 1, 2018, to June 30, 2023 (n = 234) due to the retrospective nature of the study. Informed consent was obtained from all participants in the prospective cohort.

Study Design and Participants
From July 1, 2018, to June 30, 2025, a total of 657 patients with PAH-CHD were admitted and treated at Fuwai Yunnan Hospital, Chinese Academy of Medical Sciences/Affiliated Cardiovascular Hospital of Kunming Medical University, Kunming, China.

Inclusion/Exclusion Criteria
The inclusion criteria were as follows: (1) PAH-CHD based on the 2022 ESC/ERS guidelines¹; (2) patients who had taken medication following surgery or interventional occlusion. The exclusion criteria included: (1) patients with severe lung, liver, or renal diseases; (2) patients with communication problems or other impairments such as visual or hearing impairment. The enrolled patients had not previously participated in any other national or community health support program related to their PAH-CHD health issues.

The retrospective cohort and prospective IPC intervention were conducted in different periods. To minimize potential bias from changes in medical standards and drug policies, all patients were diagnosed and managed according to the 2022 ESC/ERS guidelines, with unified therapeutic protocols and a centralized drug procurement platform.

Internet-based Pharmaceutical Care and PROs
From July 1, 2023, to June 30, 2025, a total of 422 patients with PAH-CHD received an IPC-PRO intervention. The structured, patient-centered IPC program included standardized health education, regular medication follow-up, and PRO assessment. A dedicated pharmacist was responsible for daily online management, including medication counseling, adverse drug reaction monitoring, treatment compliance supervision, and health guidance. Patients were enrolled in a WeChat group managed by the pharmacist, with weekly follow-up messages, monthly medication reminders, and on-demand counseling sessions throughout the 2-year intervention. Electronic health education materials were distributed 22 times on a fixed schedule. PROs questionnaires (EQ-5D-3L and medication compliance) were administered online via WeChat; patients completed assessments independently, with pharmacist assistance available when needed. Missing responses were followed up within 24 h via WeChat or telephone, and valid values were supplemented by mean imputation if necessary.

The PROs were designed based on relevant literature⁹ and patient interviews¹⁰, consisting of two parts: EuroQol Projects EQ-5D-3L (Identifier: 1952-RA) for health utility assessment (Q1–Q5), and a medication compliance questionnaire (Q6–Q7). Patients completed the initial PROs questionnaire upon enrollment to provide baseline data (Table 1).

Markov Cohort Model
PAH was defined by three Markov cohort states: poorly controlled PAH, well-controlled PAH, and death. The Markov cohort cycle period was two years. The average age of enrolled patients was 23.34 ± 21.75 years, and the average life expectancy in Yunnan Province was 75.3 years in 2025. PROs questionnaires were administered online via WeChat as self-reported instruments, with pharmacist assistance provided when necessary. Missing items were followed up within 24 h and handled by mean imputation. The willingness-to-pay (WTP) threshold was calculated based on Yunnan Province's 2024 per capita gross domestic product (¥67,600)¹². Decision-analysis software was used with a legitimate institutional license to simulate health transitions and calculate quality-adjusted life years (QALYs) over 26 cycles (52 years). Costs and health utilities were discounted at 5% annually.

Statistical Analysis
Dichotomous objective outcomes (PAH and 40 indicators) were analyzed for treatment efficacy. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used for multidimensional indicator analysis¹⁰. OPLS-DA analysis was performed using multivariate statistical software. Analyses were performed using spreadsheet and statistical analysis software. Data are presented as mean ± standard deviation. Statistical significance was set at p. < 0.05.

Results

Patient Characteristics
According to the criteria, 657 PAH-CHD patients were enrolled and followed up. The follow-up loss rate was less than 1%, mainly due to loss of contact. High retention was supported by long-term Internet follow-up and pharmacist management. The dropout rate was less than 1% due to loss of contact. There were no significant differences in baseline characteristics, including age pre-intervention and post-intervention pulmonary artery systolic pressure, between male (n = 246) and ...

Discussion

In the Markov Cohort analysis, we determined that IPC-PROs were cost-effective for postoperative PAH-CHD patients. Due to the inclusion of PAH drugs in the centralized procurement catalog and resulting price reductions, direct drug costs were not factored into the Markov cohort analysis. Drug procurement was facilitated through the Yunnan Centralized Drug Purchasing and Trading System, which includes centralized volume-based drug procurement^13,14. Targeted PAH dr...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Desktop / Laptop Computer	Common commercial computers	N/A	General hardware for running all above software, managing research data and daily online IPC service operation.
EQ-5D-3L Questionnaire	EuroQol Group	https://euroqol.org/	Authorized patient-reported outcome (PROs) scale for evaluating health utility. Adapted for children aged 0–3 years based on adolescent and adult versions in this study.
GraphPad Prism 6	GraphPad Software, USA	9.5.1.733	Graphing and statistical software used for general statistical analysis, data visualization, clinical trend graph plotting and inter-group difference tests.
Microsoft Excel	Microsoft Corporation, USA	16.0.20026.20112	Office and data management tool used for raw data sorting, descriptive statistics, cost accounting and patient baseline data collation.
Simca 14.1 software	Sartorius Stedim Data Analytics AB	14.1.0.2047	Multivariate statistical analysis software used for clinical indicator processing, OPLS-DA dimensionality reduction and group discrimination analysis.
TreeAge Pro 2011 software	TreeAge Software, Inc.	1.0.12.1-v20110119	Decision-analysis software used for Markov cohort model simulation, health state transition modeling, QALYs and ICER calculation.
WeChat (Tencent)	Tencent Holdings Limited	https://weixin.qq.com/	Cloud communication platform for implementing Internet-based pharmaceutical care (IPC). Used for regular follow-up, medication reminders, one-on-one counseling, distribution of electronic health education materials, and online administration of EQ-5D-3L and medication compliance questionnaires.