Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda

Abstract

Background: Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda.

Methods and findings: This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure <140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation. Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p < 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care.

Conclusions: In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA.

Trial registration: ClinicalTrials.gov NCT01864603.

Conflict of interest statement

EDC and his institution have received grants from the NIH and the European & Developing Countries Clinical Trials Partnership (EDCTP). All other authors have declared that no competing interests exist.

Figures

Fig 1. Study flow diagram.

Baseline and year 3 BP was measured at CHCs. Vital status was measured in all study participants regardless of CHC participation. BP, blood pressure; CHC, community health campaign; HTN, hypertension; yr3, year 3.

Fig 2. Cumulative incidence of mortality by year 3.

Estimates obtained using 2-stage TMLE to estimate and compare community-level mortality by 3 years. Vertical error bars depict arm-specific 95% CIs. Baseline hypertension severity defined by lowest of 3 BP measurements and classified as Grade 1 (BP 140–159/90–99 mm Hg), Grade 2 (BP 160–179/100–109 mm Hg), Grade 3 (BP ≥180/110 mm Hg). BP, blood pressure; CI, confidence interval; RR, relative risk; TMLE, targeted maximum likelihood estimation.

Fig 3. Kaplan–Meier curve depicting cumulative incidence of mortality by trial arm.

Participants with unknown year 3 vital status were censored at the time they were last known to be alive.

Fig 4. Hypertension control at year 3.

Estimates obtained using 2-stage TMLE to estimate and compare community-level hypertension control at year 3 population-level BP measurement. Vertical error bars depict arm-specific 95% CIs. Hypertension control defined as lowest of 3 BPs

Fig 5. Cascade of hypertension care in 20 communities in Uganda.

Figure represents the proportion attaining each cascade step, among those attaining the prior step. Estimates obtained using 2-stage TMLE to estimate and compare the community-level proportion attaining each cascade step. Vertical error bars depict arm-specific 95% CIs. Linkage to care defined as ≥1 visit for hypertension care in the first year after baseline hypertension screening. Engagement in care defined as ≥1 clinic visit for hypertension care in each of 3 years of study follow-up. Hypertension control defined as the lowest of 3 BP measurements

Fig 6. Predictors of 3-year mortality.

Predictors of mortality by study year 3 using multivariable TMLE, with relative risks for each variable compared to reference value. Horizontal error bars depict predictor-specific 95% CIs. Reference values for relevant categorical variables include female, grade 1 hypertension, age 18–29 years, normal BMI, baseline HIV uninfected, and baseline absence of diabetes. Baseline hypertension severity defined by lowest of 3 BP measurements and classified as Grade 1 (BP 140–159/90–99 mm Hg), Grade 2 (BP 160–179/100–109 mm Hg), Grade 3 (BP ≥180/110 mm Hg). BMI categories include underweight (BMI 2), normal (BMI 18.5–24.9 kg/m2), overweight (BMI 25–29.9 kg/m2), or obese (BMI ≥30 kg/m2). BL, baseline; BMI, body mass index; BP, blood pressure; CI, confidence interval; DM, diabetes mellitus; HTN, hypertension; TMLE, targeted maximum likelihood estimation.