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
Matthew D Hickey, James Ayieko, Asiphas Owaraganise, Nicholas Sim, Laura B Balzer, Jane Kabami, Mucunguzi Atukunda, Fredrick J Opel, Erick Wafula, Marilyn Nyabuti, Lillian Brown, Gabriel Chamie, Vivek Jain, James Peng, Dalsone Kwarisiima, Carol S Camlin, Edwin D Charlebois, Craig R Cohen, Elizabeth A Bukusi, Moses R Kamya, Maya L Petersen, Diane V Havlir, Matthew D Hickey, James Ayieko, Asiphas Owaraganise, Nicholas Sim, Laura B Balzer, Jane Kabami, Mucunguzi Atukunda, Fredrick J Opel, Erick Wafula, Marilyn Nyabuti, Lillian Brown, Gabriel Chamie, Vivek Jain, James Peng, Dalsone Kwarisiima, Carol S Camlin, Edwin D Charlebois, Craig R Cohen, Elizabeth A Bukusi, Moses R Kamya, Maya L Petersen, Diane V Havlir
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
References
- Forouzanfar MH, Liu P, Roth GA, Ng M, Biryukov S, Marczak L, et al.. Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990–2015. JAMA. 2017;10(317(2)):165–82. doi: 10.1001/jama.2016.19043
- NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in blood pressure from 1975 to 2015: a pooled analysis of 1479 population-based measurement studies with 19·1 million participants. Lancet. 2017;07 (389(10064)):37–55. doi: 10.1016/S0140-6736(16)31919-5
- Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, et al.. Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population-Based Studies From 90 Countries. Circulation. 2016Aug9;134(6):441–50. doi: 10.1161/CIRCULATIONAHA.115.018912
- Gouda HN, Charlson F, Sorsdahl K, Ahmadzada S, Ferrari AJ, Erskine H, et al.. Burden of non-communicable diseases in sub-Saharan Africa, 1990–2017: results from the Global Burden of Disease Study 2017. Lancet Glob Health. 2019Oct;7(10):e1375–87. doi: 10.1016/S2214-109X(19)30374-2
- Geldsetzer P, Manne-Goehler J, Marcus M-E, Ebert C, Zhumadilov Z, Wesseh CS, et al.. The state of hypertension care in 44 low-income and middle-income countries: a cross-sectional study of nationally representative individual-level data from 1·1 million adults. Lancet. 2019;24(394(10199)):652–62. doi: 10.1016/S0140-6736(19)30955-9
- Ataklte F, Erqou S, Kaptoge S, Taye B, Echouffo-Tcheugui JB, Kengne AP. Burden of undiagnosed hypertension in sub-Saharan Africa: a systematic review and meta-analysis. Hypertension. 2015Feb;65(2):291–8. doi: 10.1161/HYPERTENSIONAHA.114.04394
- Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, et al.. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016Mar5;387(10022):957–67. doi: 10.1016/S0140-6736(15)01225-8
- Bundy JD, Li C, Stuchlik P, Bu X, Kelly TN, Mills KT, et al.. Systolic Blood Pressure Reduction and Risk of Cardiovascular Disease and Mortality: A Systematic Review and Network Meta-analysis. JAMA Cardiol. 2017;01(2(7)):775–81. doi: 10.1001/jamacardio.2017.1421
- El-Sadr WM, Goosby E. Building on the HIV platform: tackling the challenge of noncommunicable diseases among persons living with HIV. AIDS. 2018;01(32Suppl 1):S1–3. doi: 10.1097/QAD.0000000000001886
- Bekker L-G, Alleyne G, Baral S, Cepeda J, Daskalakis D, Dowdy D, et al.. Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society-Lancet Commission. Lancet. 2018;28(392(10144)):312–58. doi: 10.1016/S0140-6736(18)31070-5
- Chamie G, Hickey MD, Kwarisiima D, Ayieko J, Kamya MR, Havlir DV. Universal HIV Testing and Treatment (UTT) Integrated with Chronic Disease Screening and Treatment: the SEARCH study. Curr HIV/AIDS Rep. 2020Aug;17(4):315–23. doi: 10.1007/s11904-020-00500-7
- Kemp CG, Weiner BJ, Sherr KH, Kupfer LE, Cherutich PK, Wilson D, et al.. Implementation science for integration of HIV and non-communicable disease services in sub-Saharan Africa: a systematic review. AIDS. 2018Jul;32:S93–105. doi: 10.1097/QAD.0000000000001897
- Patel P, Speight C, Maida A, Loustalot F, Giles D, Phiri S, et al.. Integrating HIV and hypertension management in low-resource settings: Lessons from Malawi. PLoS Med. 2018;15(3):e1002523. doi: 10.1371/journal.pmed.1002523
- Ameh S, Klipstein-Grobusch K, Musenge E, Kahn K, Tollman S, Gómez-Olivé FX. Effectiveness of an Integrated Approach to HIV and Hypertension Care in Rural South Africa: Controlled Interrupted Time-Series Analysis. J Acquir Immune Defic Syndr. 2017;01(75(4)):472–9. doi: 10.1097/QAI.0000000000001437
- Fairall LR, Folb N, Timmerman V, Lombard C, Steyn K, Bachmann MO, et al.. Educational Outreach with an Integrated Clinical Tool for Nurse-Led Non-communicable Chronic Disease Management in Primary Care in South Africa: A Pragmatic Cluster Randomised Controlled Trial. PLoS Med. 2016Nov;13(11):e1002178. doi: 10.1371/journal.pmed.1002178
- Goudge J, Chirwa T, Eldridge S, Gomez-Olive FXF, Kabudula C, Limbani F, et al.. Can lay health workers support the management of hypertension? Findings of a cluster randomised trial in South Africa. BMJ Glob Health. 2018;3(1):e000577. doi: 10.1136/bmjgh-2017-000577
- Havlir DV, Balzer LB, Charlebois ED, Clark TD, Kwarisiima D, Ayieko J, et al.. HIV Testing and Treatment with the Use of a Community Health Approach in Rural Africa. N Engl J Med. 2019Jul18;381(3):219–29. doi: 10.1056/NEJMoa1809866
- Kwarisiima D, Balzer L, Heller D, Kotwani P, Chamie G, Clark T, et al.. Population-Based Assessment of Hypertension Epidemiology and Risk Factors among. PLoS ONE. 2016;11(5):e0156309. doi: 10.1371/journal.pone.0156309
- Kwarisiima D, Atukunda M, Owaraganise A, Chamie G, Clark T, Kabami J, et al.. Hypertension control in integrated HIV and chronic disease clinics in Uganda in the SEARCH study. BMC Public Health. 2019May6;19(1):511. doi: 10.1186/s12889-019-6838-6
- Kwarisiima D, Kamya MR, Owaraganise A, Mwangwa F, Byonanebye DM, Ayieko J, et al.. High rates of viral suppression in adults and children with high CD4+ counts using a streamlined ART delivery model in the SEARCH trial in rural Uganda and Kenya. J Int AIDS Soc. 2017Jul21;20(Suppl 4):21673. doi: 10.7448/IAS.20.5.21673
- Chamie G, Kwarisiima D, Clark TD, Kabami J, Jain V, Geng E, et al.. Leveraging rapid community-based HIV testing campaigns for non-communicable diseases in rural Uganda. PLoS ONE. 2012;7(8):e43400. doi: 10.1371/journal.pone.0043400
- Whitworth JA. World Health Organization, International Society of Hypertension Writing Group. 2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens. 2003Nov;21(11):1983–92. doi: 10.1097/00004872-200311000-00002
- Ayieko J, Petersen ML, Charlebois ED, Brown LB, Clark TD, Kwarisiima D, et al.. A Patient-Centered Multicomponent Strategy for Accelerated Linkage to Care Following Community-Wide HIV Testing in Rural Uganda and Kenya. J Acquir Immune Defic Syndr. 2019Apr1;80(4):414–22. doi: 10.1097/QAI.0000000000001939
- Balzer LB, Havlir DV, Schwab J, Van Der Laan MJ, Petersen ML. Statistical Analysis Plan for SEARCH Phase I: Health Outcomes among Adults. ArXiv180803231 Stat. 2018Jul25;[preprint].
- Balzer LB, van der MJ, Petersen ML. SEARCH Collaboration. Adaptive pre-specification in randomized trials with and without pair-matching. Stat Med. 2016;10(35(25)):4528–45. doi: 10.1002/sim.7023
- Balzer LB, Ayieko J, Kwarisiima D, Chamie G, Charlebois ED, Schwab J, et al.. Far from MCAR: Obtaining Population-level Estimates of HIV Viral Suppression. Epidemiology. 2020Sep;31(5):620–7. doi: 10.1097/EDE.0000000000001215
- Chang W, Chamie G, Mwai D, Clark TD, Thirumurthy H, Charlebois ED, et al.. Implementation and Operational Research: Cost and Efficiency of a Hybrid Mobile Multidisease Testing Approach With High HIV Testing Coverage in East Africa. J Acquir Immune Defic Syndr. 2016Nov1;73(3):e39–45. doi: 10.1097/QAI.0000000000001141
- van A, Barnabas RV, Norris SA, Micklesfield LK, van H, Celum C. High prevalence of HIV and non-communicable disease (NCD) risk factors in rural KwaZulu-Natal, South Africa. J Int AIDS Soc. 2017;20(2):e25012.
- Govindasamy D, Kranzer K, Schaik N, Noubary F, Wood R, Walensky RP, et al.. Linkage to HIV, TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town, South Africa. PLoS ONE. 2013Nov13;8(11):e80017. doi: 10.1371/journal.pone.0080017
- Kamya MR, Petersen ML, Kwariisima D, Ayieko J, Sang N, Kabami J, et al.. SEARCH Intervention Reduces Mortality at a Population Level in Men with Low CD4 Count. CROI. Seattle, WA; 2019. p. Abstract 138.
- Hickey MD, Ayieko J, Kwarisiima D, Opel FJ, Owaraganise A, Balzer LB, et al.. Improved Viral Suppression With Streamlined Care in the SEARCH Study. J Acquir Immune Defic Syndr. 2020Dec15;85(5):571–8. doi: 10.1097/QAI.0000000000002508
- Gupta S, Kabami J, Chamie G, Sang N, Kwarisiima D, Black D, et al.. Population-Level HIV-Free Infant Survival in the SEARCH Trial. CROI. Boston, MA; 2020. p. Abstract 134LB.
- Mwangwa F, Getahun M, Itiakorit H, Jain V, Koss CA, Owino L, et al.. Streamlined Care: Qualitative Insights into Provider and Patient Experiences with a Differentiated HIV Care Model in rural Kenya and Uganda. ICASA. Kigali, Rwanda; 2019.
- Rathert C, Wyrwich MD, Boren SA. Patient-centered care and outcomes: a systematic review of the literature. Med Care Res Rev. 2013Aug;70(4):351–79. doi: 10.1177/1077558712465774
- Ogedegbe G, Plange-Rhule J, Gyamfi J, Chaplin W, Ntim M, Apusiga K, et al.. Health insurance coverage with or without a nurse-led task shifting strategy for hypertension control: A pragmatic cluster randomized trial in Ghana. PLoS Med. 2018;15(5):e1002561. doi: 10.1371/journal.pmed.1002561
- Frieden M, Zamba B, Mukumbi N, Mafaune PT, Makumbe B, Irungu E, et al.. Setting up a nurse-led model of care for management of hypertension and diabetes mellitus in a high HIV prevalence context in rural Zimbabwe: a descriptive study. BMC Health Serv Res. 2020Jun1;20(1):486. doi: 10.1186/s12913-020-05351-x
- Schwalm J-D, McCready T, Lopez-Jaramillo P, Yusoff K, Attaran A, Lamelas P, et al.. A community-based comprehensive intervention to reduce cardiovascular risk in hypertension (HOPE 4): a cluster-randomised controlled trial. Lancet. 2019Oct5;394(10205):1231–42. doi: 10.1016/S0140-6736(19)31949-X
- Vedanthan R, Kamano JH, DeLong AK, Naanyu V, Binanay CA, Bloomfield GS, et al.. Community Health Workers Improve Linkage to Hypertension Care in Western Kenya. J Am Coll Cardiol. 2019Oct15;74(15):1897–906. doi: 10.1016/j.jacc.2019.08.003
- Pastakia SD, Tran DN, Manji I, Wells C, Kinderknecht K, Ferris R. Building reliable supply chains for noncommunicable disease commodities: lessons learned from HIV and evidence needs. AIDS. 2018Jul;32:S55–61. doi: 10.1097/QAD.0000000000001878
- DiPette DJ, Skeete J, Ridley E, Campbell NRC, Lopez-Jaramillo P, Kishore SP, et al.. Fixed-dose combination pharmacologic therapy to improve hypertension control worldwide: Clinical perspective and policy implications. J Clin Hypertens (Greenwich). 2019;21(1):4–15. doi: 10.1111/jch.13426
- Kasaie P, Weir B, Schnure M, Dun C, Pennington J, Teng Y, et al.. Integrated screening and treatment services for HIV, hypertension and diabetes in Kenya: assessing the epidemiological impact and cost-effectiveness from a national and regional perspective. J Int AIDS Soc. 2020Jun;23(Suppl 1):e25499.
- Shade SB, Osmand T, Kwarisiima D, Brown LB, Luo A, Mwebaza B, et al.. Costs of integrating hypertension care into HIV care in rural East African clinics. AIDS. 2021May1;35(6):911–9. doi: 10.1097/QAD.0000000000002834
- Geng EH, Odeny TA, Lyamuya RE, Nakiwogga-Muwanga A, Diero L, Bwana M, et al.. Estimation of Mortality among HIV-infected people on antiretroviral therapy treatment in east Africa: a sampling based approach in an observational, multisite, cohort study. Lancet HIV. 2015Mar;2(3):e107–16. doi: 10.1016/S2352-3018(15)00002-8
Source: PubMed