. 2022 Mar;10(3):e369-e379.

doi: 10.1016/S2214-109X(21)00551-9.

Use of statins for the prevention of cardiovascular disease in 41 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data

Maja E Marcus¹, Jennifer Manne-Goehler², Michaela Theilmann³, Farshad Farzadfar⁴, Sahar Saeedi Moghaddam⁵, Mohammad Keykhaei⁴, Amirali Hajebi⁴, Scott Tschida⁶, Julia M Lemp³, Krishna K Aryal⁷, Matthew Dunn⁸, Corine Houehanou⁹, Silver Bahendeka¹⁰, Peter Rohloff¹¹, Rifat Atun¹², Till W Bärnighausen¹³, Pascal Geldsetzer¹⁴, Manuel Ramirez-Zea¹⁵, Vineet Chopra¹⁶, Michele Heisler¹⁷, Justine I Davies¹⁸, Mark D Huffman¹⁹, Sebastian Vollmer²⁰, David Flood²¹

Affiliations

¹ Department of Economics and Centre for Modern Indian Studies, University of Goettingen, Göttingen, Germany.
² Division of Infectious Diseases, Harvard Medical School, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
³ Heidelberg Institute of Global Health, Heidelberg University and University Hospital, Heidelberg, Germany.
⁴ Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Center for Indigenous Health Research, Wuqu' Kawoq, Tecpán, Guatemala.
⁷ Public Health Promotion and Development Organization, Kathmandu, Nepal.
⁸ School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁹ Laboratory of Epidemiology of Chronic and Neurological Diseases, Faculty of Health Sciences, University of Abomey-Calavi, Cotonou, Benin.
¹⁰ Department of Internal Medicine, MKPGMS Uganda Martyrs University, Kampala, Uganda; Saint Francis Hospital Nsambya, Kampala, Uganda.
¹¹ Division of Global Health Equity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Indigenous Health Research, Wuqu' Kawoq, Tecpán, Guatemala.
¹² Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA; Department of Global Health and Population, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA.
¹³ Department of Global Health and Population, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA; Heidelberg Institute of Global Health, Heidelberg University and University Hospital, Heidelberg, Germany; Africa Health Research Institute, Somkhele, South Africa.
¹⁴ Heidelberg Institute of Global Health, Heidelberg University and University Hospital, Heidelberg, Germany; Division of Primary Care and Population Health, Stanford University, Stanford, CA, USA.
¹⁵ INCAP Research Center for the Prevention of Chronic Diseases, Institute of Nutrition of Central America and Panama, Guatemala City, Guatemala.
¹⁶ Division of Hospital Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, USA; Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA.
¹⁷ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA; Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA.
¹⁸ Institute for Applied Health Research, University of Birmingham, Birmingham, UK; Centre for Global Surgery, Department of Global Health, Stellenbosch University, Cape Town, South Africa; Medical Research Council/Wits University Rural Public Health and Health Transitions Research Unit, Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
¹⁹ Department of Medicine and Global Health Center, Washington University in St Louis, St Louis, MO, USA; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
²⁰ Department of Economics and Centre for Modern Indian Studies, University of Goettingen, Göttingen, Germany. Electronic address: svollmer@uni-goettingen.de.
²¹ Center for Indigenous Health Research, Wuqu' Kawoq, Tecpán, Guatemala; Division of Hospital Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, USA; INCAP Research Center for the Prevention of Chronic Diseases, Institute of Nutrition of Central America and Panama, Guatemala City, Guatemala. Electronic address: dcflood@umich.edu.

PMID: 35180420
PMCID: PMC8896912
DOI: 10.1016/S2214-109X(21)00551-9

Use of statins for the prevention of cardiovascular disease in 41 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data

Maja E Marcus et al. Lancet Glob Health. 2022 Mar.

. 2022 Mar;10(3):e369-e379.

doi: 10.1016/S2214-109X(21)00551-9.

Authors

Affiliations

¹ Department of Economics and Centre for Modern Indian Studies, University of Goettingen, Göttingen, Germany.
² Division of Infectious Diseases, Harvard Medical School, Boston, MA, USA; Medical Practice Evaluation Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
³ Heidelberg Institute of Global Health, Heidelberg University and University Hospital, Heidelberg, Germany.
⁴ Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁶ Center for Indigenous Health Research, Wuqu' Kawoq, Tecpán, Guatemala.
⁷ Public Health Promotion and Development Organization, Kathmandu, Nepal.
⁸ School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁹ Laboratory of Epidemiology of Chronic and Neurological Diseases, Faculty of Health Sciences, University of Abomey-Calavi, Cotonou, Benin.
¹⁰ Department of Internal Medicine, MKPGMS Uganda Martyrs University, Kampala, Uganda; Saint Francis Hospital Nsambya, Kampala, Uganda.
¹¹ Division of Global Health Equity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Indigenous Health Research, Wuqu' Kawoq, Tecpán, Guatemala.
¹² Department of Global Health and Social Medicine, Harvard Medical School, Boston, MA, USA; Department of Global Health and Population, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA.
¹³ Department of Global Health and Population, Harvard TH Chan School of Public Health, Harvard University, Boston, MA, USA; Heidelberg Institute of Global Health, Heidelberg University and University Hospital, Heidelberg, Germany; Africa Health Research Institute, Somkhele, South Africa.
¹⁴ Heidelberg Institute of Global Health, Heidelberg University and University Hospital, Heidelberg, Germany; Division of Primary Care and Population Health, Stanford University, Stanford, CA, USA.
¹⁵ INCAP Research Center for the Prevention of Chronic Diseases, Institute of Nutrition of Central America and Panama, Guatemala City, Guatemala.
¹⁶ Division of Hospital Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, USA; Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA.
¹⁷ Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA; Center for Clinical Management Research, Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI, USA.
¹⁸ Institute for Applied Health Research, University of Birmingham, Birmingham, UK; Centre for Global Surgery, Department of Global Health, Stellenbosch University, Cape Town, South Africa; Medical Research Council/Wits University Rural Public Health and Health Transitions Research Unit, Faculty of Health Sciences, School of Public Health, University of the Witwatersrand, Johannesburg, South Africa.
¹⁹ Department of Medicine and Global Health Center, Washington University in St Louis, St Louis, MO, USA; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA; The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
²⁰ Department of Economics and Centre for Modern Indian Studies, University of Goettingen, Göttingen, Germany. Electronic address: svollmer@uni-goettingen.de.
²¹ Center for Indigenous Health Research, Wuqu' Kawoq, Tecpán, Guatemala; Division of Hospital Medicine, Department of Medicine, University of Michigan, Ann Arbor, MI, USA; INCAP Research Center for the Prevention of Chronic Diseases, Institute of Nutrition of Central America and Panama, Guatemala City, Guatemala. Electronic address: dcflood@umich.edu.

PMID: 35180420
PMCID: PMC8896912
DOI: 10.1016/S2214-109X(21)00551-9

Abstract

Background: In the prevention of cardiovascular disease, a WHO target is that at least 50% of eligible people use statins. Robust evidence is needed to monitor progress towards this target in low-income and middle-income countries (LMICs), where most cardiovascular disease deaths occur. The objectives of this study were to benchmark statin use in LMICs and to investigate country-level and individual-level characteristics associated with statin use.

Methods: We did a cross-sectional analysis of pooled, individual-level data from nationally representative health surveys done in 41 LMICs between 2013 and 2019. Our sample consisted of non-pregnant adults aged 40-69 years. We prioritised WHO Stepwise Approach to Surveillance (STEPS) surveys because these are WHO's recommended method for population monitoring of non-communicable disease targets. For countries in which no STEPS survey was available, a systematic search was done to identify other surveys. We included surveys that were done in an LMIC as classified by the World Bank in the survey year; were done in 2013 or later; were nationally representative; had individual-level data available; and asked questions on statin use and previous history of cardiovascular disease. Primary outcomes were the proportion of eligible individuals self-reporting use of statins for the primary and secondary prevention of cardiovascular disease. Eligibility for statin therapy for primary prevention was defined among individuals with a history of diagnosed diabetes or a 10-year cardiovascular disease risk of at least 20%. Eligibility for statin therapy for secondary prevention was defined among individuals with a history of self-reported cardiovascular disease. At the country level, we estimated statin use by per-capita health spending, per-capita income, burden of cardiovascular diseases, and commitment to non-communicable disease policy. At the individual level, we used modified Poisson regression models to assess statin use alongside individual-level characteristics of age, sex, education, and rural versus urban residence. Countries were weighted in proportion to their population size in pooled analyses.

Findings: The final pooled sample included 116 449 non-pregnant individuals. 9229 individuals reported a previous history of cardiovascular disease (7·9% [95% CI 7·4-8·3] of the population-weighted sample). Among those without a previous history of cardiovascular disease, 8453 were eligible for a statin for primary prevention of cardiovascular disease (9·7% [95% CI 9·3-10·1] of the population-weighted sample). For primary prevention of cardiovascular disease, statin use was 8·0% (95% CI 6·9-9·3) and for secondary prevention statin use was 21·9% (20·0-24·0). The WHO target that at least 50% of eligible individuals receive statin therapy to prevent cardiovascular disease was achieved by no region or income group. Statin use was less common in countries with lower health spending. At the individual level, there was generally higher statin use among women (primary prevention only, risk ratio [RR] 1·83 [95% CI 1·22-2·76), and individuals who were older (primary prevention, 60-69 years, RR 1·86 [1·04-3·33]; secondary prevention, 50-59 years RR 1·71 [1·35-2·18]; and 60-69 years RR 2·09 [1·65-2·65]), more educated (primary prevention, RR 1·61 [1·09-2·37]; secondary prevention, RR 1·28 [0·97-1·69]), and lived in urban areas (secondary prevention only, RR 0·82 [0·66-1·00]).

Interpretation: In a diverse sample of LMICs, statins are used by about one in ten eligible people for the primary prevention of cardiovascular diseases and one in five eligible people for secondary prevention. There is an urgent need to scale up statin use in LMICs to achieve WHO targets. Policies and programmes that facilitate implementation of statins into primary health systems in these settings should be investigated for the future.

Funding: National Clinician Scholars Program at the University of Michigan Institute for Healthcare Policy and Innovation, and National Institute of Diabetes and Digestive and Kidney Diseases.

Translation: For the Spanish translation of the abstract see Supplementary Materials section.

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Conflict of interest statement

Declaration of interests JML reports graduate research funding from the German Academic Scholarship Foundation. RA reports contracts with Novo Nordisk, Union for International Cancer Control's, National Institute for Health Research, and Sloan Memorial Kettering Hospital, outside of the submitted work. RA also reports payments or honoraria from Merck, Novartis, and F Hoffmann-La Roche, outside of the submitted work. TWB reports support from the Alexander von Humboldt Foundation. MH reports grants from the National Institutes of Health and receives salary support from Physician for Human Rights. MDH received funding in the past 3 years from the World Heart Federation to serve as its senior programme advisor for the Emerging Leaders programme, which has been supported by Boehringer Ingelheim, Novartis, Bupa, and AstraZeneca. MDH also received support from the American Heart Association, Verily, AstraZeneca, and American Medical Association for work unrelated to this research. MDH plans to submit patents for heart failure polypill. MDH has received meeting or travel support from the American Heart Association and World Heart Federation. MDH has an appointment at The George Institute for Global Health, which has a patent, licence, and has received investment funding with intent to commercialise fixed-dose combination therapy through its social enterprise business, George Medicines. DF reports grant funding within the past 3 years from a Pilot and Feasibility Grant funded by the Michigan Center for Diabetes Translational Research (NIH Grant P30-DK092926) and a grant from the Swinmurn Foundation to implement a sustainable diabetes clinic in Guatemala. DF also reports volunteer affiliations with Wuqu’ Kawoq and GlucoSalud, outside of the submitted work. During the course of this study, DF has received research fellowship funding from National Clinician Scholars Program at the University of Michigan Institute for Healthcare Policy & Innovation. All other authors declare no competing interests.

Figures

**Figure 1:. Pooled estimates of self-reported use of statins for the primary and secondary prevention of cardiovascular disease in 41 low-income and middle-income countries**
The sample includes non-pregnant individuals aged 40–69 years (age 40–64 years for Burkina Faso, Kyrgyzstan, Myanmar, and Tokelau). Estimates account for survey design and weighting by each country’s 2019 population of individuals who were aged 40–69 years. The error bars represent 95% CIs. The vertical dashed line represents the WHO target that at least 50% of eligible people use statins.

**Figure 2:. Self-reported statin use for primary prevention (A) and secondary prevention (B) by per-capita health spending**
The sample includes non-pregnant individuals aged 40–69 years (aged 40–64 years for Burkina Faso, Kyrgyzstan, Myanmar, and Tokelau). Per-capita health spending is in current international dollars in the year the survey was done. Estimates account for survey design and weighting. The vertical error bars represent 95% CIs. The horizontal dashed line represents the WHO target that at least 50% of eligible people use statins. The diagonal line depicts an ordinary least-squares regression with each country having the same weight. The Iraq survey is excluded from the primary prevention analysis because use of statins was asked only among people self-reporting previous cardiovascular disease. The standardised regression coefficients were 0.55 (95% CI 0.28–0.82) for primary prevention and 0.51 (0.23–0.79) for secondary prevention. AZE=Azerbaijan. BEN=Benin. BFA=Burkina Faso. BGD=Bangladesh. BLR=Belarus. BTN=Bhutan. BWA=Botswana. DZA=Algeria. ECU=Ecuador. ETH=Ethiopia. GEO=Georgia. GUY=Guyana. IRN=Iran. IRQ=Iraq. JOR=Jordan. KEN=Kenya. KGZ=Kyrgyzstan. KIR=Kiribati. LBN=Lebanon. LKA=Sri Lanka. MAR=Morocco. MDA=Moldova. MEX=Mexico. MMR=Myanmar. MNG=Mongolia. NPL=Nepal. NRU=Nauru. SDN=Sudan. SLB=Solomon Islands. SWZ=Eswatini. TJK=Tajikistan. TK=Tokelau. TKM=Turkmenistan. TLS=Timor-Leste. TUV=Tuvalu. UGA=Uganda. VCT=St Vincent and the Grenadines. VNM=Vietnam. ZMB=Zambia.

Figure 3:. Relative and absolute differences in statin use for secondary prevention of cardiovascular disease by country using modified Poisson regressions for sex (A), age (B), education (C), and residence (D)
All regressions were adjusted for sex and age. Age was included in three categories (40–49 years, 50–59 years, and 60–69 years) for all the regressions except for in (B) age, in which it was dichotomised as age 55 years or older versus younger than age 55 years. The regressions account for sample weights, stratification in survey design, and clustering at the level of the primary sampling unit. Error bars show the 95% CIs. Education was not available in the survey from Tokelau. Rural versus urban residence was unavailable in 14 surveys (Botswana, Ecuador, Eswatini, Kiribati, Lebanon, Myanmar, Nauru, Solomon Islands, Sri Lanka, St Vincent and the Grenadines, Tajikistan, Timor-Leste, Tokelau, and Tuvalu). Differences in the ordering of countries by RRs versus average marginal effects is due to the difference in baseline statin use among countries. RR=risk ratio. AFG=Afghanistan. ARM=Armenia. AZE=Azerbaijan. BEN=Benin. BFA=Burkina Faso. BGD=Bangladesh. BLR=Belarus. BTN=Bhutan. BWA=Botswana. DZA=Algeria. ECU=Ecuador. ETH=Ethiopia. GEO=Georgia. GUY=Guyana. IRN=Iran. IRQ=Iraq. JOR=Jordan. KEN=Kenya. KGZ=Kyrgyzstan. KIR=Kiribati. LBN=Lebanon. LKA=Sri Lanka. MAR=Morocco. MDA=Moldova. MEX=Mexico. MMR=Myanmar. MNG=Mongolia. NPL=Nepal. NRU=Nauru. SDN=Sudan. SLB=Solomon Islands. SWZ=Eswatini. TJK=Tajikistan. TK=Tokelau. TKM=Turkmenistan. TLS=Timor-Leste. TUV=Tuvalu. UGA=Uganda. VCT=St Vincent and the Grenadines. VNM=Vietnam. ZMB=Zambia.

**Figure 4:. Relative and absolute differences in statin use across the pooled sample using modified Poisson regressions for primary prevention (A) and secondary prevention (B)**
Results are presented as RRs (95% CIs) and average marginal effects weighting each country by its 2019 population of individuals aged 40–69 years. The models include each of the covariates listed in the plot, country-level fixed effects, and account for clustering at the level of the primary sampling unit. Due to incomplete data, the surveys from Botswana, Ecuador, Eswatini, Kiribati, Lebanon, Myanmar, Nauru, Solomon Islands, Sri Lanka, St Vincent and the Grenadines, Tajikistan, Timor-Leste, Tokelau, and Tuvalu were excluded from the pooled regression analysis. The Iraq survey only contributes to the analysis of secondary prevention of cardiovascular disease. p values refer to the output from the modified Poisson regression model rather than p value of the average marginal effect. RR=risk ratio.

See this image and copyright information in PMC

Comment in

Statins: are they appropriate for all patients?
Raal FJ, Mohamed F. Raal FJ, et al. Lancet Glob Health. 2022 Mar;10(3):e305-e306. doi: 10.1016/S2214-109X(21)00572-6. Lancet Glob Health. 2022. PMID: 35180403 Free PMC article. No abstract available.
Barriers to statin use in the Philippines.
Feliciano KT, Dychiao RGK, Eala MAB, Paguio JA, Guinto RR. Feliciano KT, et al. Lancet Glob Health. 2022 Jun;10(6):e796. doi: 10.1016/S2214-109X(22)00201-7. Lancet Glob Health. 2022. PMID: 35561717 No abstract available.
Statin use in low-income and middle-income countries.
Neuhann F, Kumwenda T, Mahanani MR, Heller T, Steffen HM. Neuhann F, et al. Lancet Glob Health. 2022 Jul;10(7):e954. doi: 10.1016/S2214-109X(22)00219-4. Lancet Glob Health. 2022. PMID: 35714643 No abstract available.
Statin use in low-income and middle-income countries - Authors' reply.
Flood D, Marcus ME, Bahendeka SK, Moghaddam SS, Houehanou C, Vollmer S, Huffman MD. Flood D, et al. Lancet Glob Health. 2022 Jul;10(7):e955-e956. doi: 10.1016/S2214-109X(22)00217-0. Lancet Glob Health. 2022. PMID: 35714644 Free PMC article. No abstract available.

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Use of statins for the prevention of cardiovascular disease in 41 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data

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Use of statins for the prevention of cardiovascular disease in 41 low-income and middle-income countries: a cross-sectional study of nationally representative, individual-level data

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