Post-Intervention Acceptability of a Multicomponent Intervention for Hypertension Management in Primary Care Clinics by Health Care Providers and Patients: A Qualitative Study of a Cluster RCT in Singapore.

Background: Hypertension is a major public health challenge, globally. Recently, we reported findings from cluster randomized trial in 8 primary care clinics in Singapore and showed that a multicomponent "SingHypertension" intervention comprising 1) motivational conversation by trained nurses, 2) telephone-based follow-ups, 3) standardized algorithm with single-pill combination (SPC) antihypertensive medications, and 4) subsidy on SPC antihypertensive drugs was effective on improving BP control. This paper presents the acceptability of SingHypertension multicomponent intervention among the key stakeholders. Methods: We conducted post-implementation interviews of 38 stakeholders, including 18 patients and 20 healthcare providers (HCPs) in 4 primary care clinics randomized to the multicomponent "SingHypertension" intervention in Singapore. We used Theoretical Framework for Acceptability (TFA) framework with a focus on affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness and self-efficacy to assess stakeholders' acceptability of the intervention. Results: SingHypertension multicomponent intervention had high perceived effectiveness and a good fit with the value system and ethics of patients and HCPs. Physicians appreciated the guidance from standardized training in hypertension management. Although workload was increased, the nurses felt rewarded for their positive interactions with the patients during motivational conversation sessions and the telephone follow-ups. Most patients reported high self-efficacy levels, improved lifestyles, and adherence to antihypertensive medications. The limited choice of SPC medication, lack of subsidy beyond the trial duration, and shortage of nurses were significant challenges to wide-scale implementation. All HCPs and patients supported scaling up the intervention across primary care clinics. Conclusion: SingHypertension multicomponent intervention is acceptable to the key stakeholders in Singapore. Taken together with the effectiveness of the intervention, our findings make a compelling case for scaling-up SingHypertension in primary care clinics in Singapore and possibly other countries with similar healthcare infrastructure.

Cost-Effectiveness of a Multicomponent Primary Care Intervention for Hypertension.

BACKGROUND: The SingHypertension primary care clinic intervention, which consisted of clinician training in hypertension management, subsidized single-pill combination medications, nurse-delivered motivational conversations and telephone follow-ups, improved blood pressure control and cardiovascular disease (CVD) risk scores relative to usual care among patients with uncontrolled hypertension in Singapore. This study quantified the incremental cost-effectiveness, in terms of incremental cost per unit reduction disability-adjusted life years, of SingHypertension relative to usual care for patients with hypertension from the health system perspective. METHODS AND RESULTS: We developed a Markov model to simulate CVD events and associated outcomes for a hypothetical cohort of patients over a 10-year period. Costs were measured in US dollars, and effectiveness was measured in disability-adjusted life years averted. We present base-case results and conducted deterministic and probabilistic sensitivity analyses. Based on a willingness-to-pay threshold of US $55 500 per DALY averted, SingHypertension was cost-effective for patients with hypertension (incremental cost-effectiveness ratio: US $24 765 per disability-adjusted life year averted) relative to usual care. This result held even if risk reduction was assumed to decline linearly to 0 over 10 years but not sooner than 7 years. Incremental cost-effectiveness ratios were most sensitive to the magnitude of the reduction in CVD risk; at least a 0.13% to 0.16% point reduction in 10-year CVD risk is required for cost-effectiveness. Probabilistic sensitivity analysis indicates that SingHypertension has a 78% chance of being cost-effective at the willingness-to-pay threshold. CONCLUSIONS: SingHypertension represents good value for the money for reducing CVD incidence, morbidity, and mortality and should be considered for wide-scale implementation in Singapore and possibly other countries. REGISTRATION INFORMATION: REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02972619.

Statistical analysis plan for management of hypertension and multiple risk factors to enhance cardiovascular health in Singapore: the SingHypertension pragmatic cluster randomized controlled trial.

INTRODUCTION: Cardiovascular disease (O'Lone E, Viecelli AK, Craig JC, Tong A, Sautenet B, Herrington WG, et al., Am J Kidney Dis 76(1):109-20, 2020) remains the leading cause of death in Singapore. Uncontrolled hypertension confers the highest attributable risk of CVD and remains a significant public health issue with sub-optimal blood pressure (BP) control rates. The aim of the trial is to evaluate the effectiveness and cost-effectiveness of a multicomponent intervention (MCI) versus usual care on lowering BP among adults with uncontrolled hypertension visiting primary care clinics in Singapore. This article describes the statistical analysis plan for the primary and secondary objectives related to intervention effectiveness. METHODS: The study is a cluster randomized trial enrolling 1000 participants with uncontrolled hypertension aged ≥ 40 years from eight primary care clinics in Singapore. The unit of randomization is the clinic, with eight clusters (clinics) randomized in a 1:1 ratio to either MCI or usual care. All participants will be assessed at baseline, 12 months, and 24 months with measurements of systolic and diastolic BP, antihypertensive and statin medication use, medication adherence, physical activity level, anthropometric parameters, smoking status, and dietary habits. The primary objective of this study is to assess the effectiveness of MCI versus usual care on mean SBP at the 2-year follow-up. The primary outcome is SBP at 24 months. SBP at baseline, 12, and 24 months will be modeled at the subject level using a likelihood-based, linear mixed-effects model repeated measures (MMRM) analysis with treatment group and follow-up as fixed effects, random cluster (clinic) effects, Gaussian error distribution, and adjustment to degrees of freedom using the Satterthwaite approximation. Secondary outcomes will be analyzed using a similar modeling approach incorporating generalized techniques appropriate for the type of outcome. DISCUSSION: The trial will allow us to determine whether the MCI has an impact on BP and cardiovascular risk factors over a 2-year follow-up period and inform recommendations for health planners in scaling up these strategies for the benefit of society at large. A pre-specified and pre-published statistical analysis plan mitigates reporting bias and data driven approaches. TRIAL REGISTRATION: ClinicalTrials.gov NCT02972619 . Registered on 23 November 2016.

Adiposity measures and pre-diabetes or diabetes in adults with hypertension in Singapore polyclinics.

Identification of hypertensive patients with pre-diabetes or diabetes is important for timely prevention of complications including vascular disease. We aimed to compare the association and discrimination of central obesity measures (waist circumference [WC] and waist-to-height ratio [WHtR]) with generalized obesity measure (body mass index [BMI]) in relation to pre-diabetes and diabetes among a group of Asian hypertensive patients for the first time. We used the baseline data of 925 subjects aged 40 years or older with uncontrolled hypertension recruited at eight primary care clinics in Singapore. Information on height, weight, WC, fasting blood glucose, and hemoglobin A1c (HbA1c) was collected. Pre-diabetes or diabetes was defined as having reported physician-diagnosed diabetes or taking anti-diabetes medication, fasting blood glucose ≥ 5.6 mmol/dL or HbA1c ≥ 5.7%. Among 925 subjects, 495 (53.5%) had pre-diabetes or diabetes. In logistic regression models, BMI was not associated with pre-diabetes or diabetes after adjusting for WC or WHtR, while a positive association remained with both WC and WHtR after adjustment of BMI. Both WC and WHtR had significantly better discrimination than BMI (respective area under ROC curve: 0.63 for WC, 0.63 for WHtR, and 0.60 for BMI; P = 0.019), and adding WC or WHtR on top of BMI further correctly reclassified 42.7% and 38.7% hypertensive patients to the right risk group of pre-diabetes or diabetes indicated by net reclassification improvement. However, WHtR was not superior to WC. In conclusion, our results suggested that central obesity has stronger association with and better discrimination for pre-diabetes or diabetes than generalized obesity.