Effectiveness of Statins for Primary Prevention of Cardiovascular Disease in Low- and Medium-Risk Males: A Causal Inference Approach with Observational Data

doi:10.3390/jpm12050658

. 2022 Apr 20;12(5):658.

doi: 10.3390/jpm12050658.

Effectiveness of Statins for Primary Prevention of Cardiovascular Disease in Low- and Medium-Risk Males: A Causal Inference Approach with Observational Data

Armando Chaure-Pardos^{1

2

3}, Isabel Aguilar-Palacio^{2

3

4}, Mª José Rabanaque^{2

3

4}, Mª Jesús Lallana^{2

3

5}, Lina Maldonado^{2

3

6}, Sara Castel-Feced^{2

3

4}, Julián Librero⁷, José Antonio Casasnovas^{2

8}, Sara Malo^{2

3

4}

Affiliations

¹ Directorate of Public Health, Government of Aragón, 50017 Zaragoza, Spain.
² Instituto de Investigación Sanitaria de Aragón (IIS Aragón), 50009 Zaragoza, Spain.
³ Grupo de Investigación en Servicios Sanitarios de Aragón (GRISSA), 50009 Zaragoza, Spain.
⁴ Preventive Medicine and Public Health Department, University of Zaragoza, 50009 Zaragoza, Spain.
⁵ Primary Health Care, Servicio Aragonés de Salud, 50017 Zaragoza, Spain.
⁶ Department of Economic Structure, Economic History and Public Economics, University of Zaragoza, 50009 Zaragoza, Spain.
⁷ Unidad de Metodología, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, 31008 Pamplona, Spain.
⁸ Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, 50009 Zaragoza, Spain.

PMID: 35629081
PMCID: PMC9146525
DOI: 10.3390/jpm12050658

Effectiveness of Statins for Primary Prevention of Cardiovascular Disease in Low- and Medium-Risk Males: A Causal Inference Approach with Observational Data

Armando Chaure-Pardos et al. J Pers Med. 2022.

. 2022 Apr 20;12(5):658.

doi: 10.3390/jpm12050658.

Authors

Affiliations

¹ Directorate of Public Health, Government of Aragón, 50017 Zaragoza, Spain.
² Instituto de Investigación Sanitaria de Aragón (IIS Aragón), 50009 Zaragoza, Spain.
³ Grupo de Investigación en Servicios Sanitarios de Aragón (GRISSA), 50009 Zaragoza, Spain.
⁴ Preventive Medicine and Public Health Department, University of Zaragoza, 50009 Zaragoza, Spain.
⁵ Primary Health Care, Servicio Aragonés de Salud, 50017 Zaragoza, Spain.
⁶ Department of Economic Structure, Economic History and Public Economics, University of Zaragoza, 50009 Zaragoza, Spain.
⁷ Unidad de Metodología, Navarrabiomed, Hospital Universitario de Navarra (HUN), Universidad Pública de Navarra (UPNA), IdiSNA, 31008 Pamplona, Spain.
⁸ Department of Medicine, Psychiatry and Dermatology, University of Zaragoza, 50009 Zaragoza, Spain.

PMID: 35629081
PMCID: PMC9146525
DOI: 10.3390/jpm12050658

Abstract

In this study, we analyzed the effectiveness of statin therapy for the primary prevention of cardiovascular disease (CVD) in low- and medium-risk patients. Using observational data, we estimated effectiveness by emulating a hypothetical randomized clinical trial comparing statin initiators with statin non-initiators. Two approaches were used to adjust for potential confounding factors: matching and inverse probability weighting in marginal structural models. The estimates of effectiveness were obtained by intention-to-treat and per-protocol analysis. The intention-to-treat analysis revealed an absolute risk reduction of 7.2 (95% confidence interval (CI95%), -6.6-21.0) events per 1000 subjects treated for 5 years in the matched design, and 2.2 (CI95%, -3.9-8.2) in the marginal structural model. The per-protocol analysis revealed an absolute risk reduction of 16.7 (CI95%, -3.0-36) events per 1000 subjects treated for 5 years in the matched design and 5.8 (CI95%, 0.3-11.4) in the marginal structural model. The indication for statin treatment for primary prevention in individuals with low and medium cardiovascular risk appears to be inefficient, but improves with better adherence and in subjectvs with higher risk.

Keywords: cardiovascular diseases; comparative effectiveness; hydroxymethylglutaryl-CoA reductase inhibitors; prevention and control.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

**Figure 1**
Example of sample restriction for low-density lipoprotein cholesterol.

See this image and copyright information in PMC

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References

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1. Mihaylova B., Emberson J., Blackwell L., Keech A., Simes J., Barnes E.H., Voysey M., Gray A., Collins R., Baigent C., et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–590. doi: 10.1016/S0140-6736(12)60367-5. - DOI - PMC - PubMed
1. Glynn R.J., Koenig W., Nordestgaard B.G., Shepherd J., Ridker P.M. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: Exploratory analysis of a randomized trial. Ann. Intern. Med. 2010;152:488–496. doi: 10.7326/0003-4819-152-8-201004200-00005. - DOI - PMC - PubMed
1. Yusuf S., Bosch J., Dagenais G., Zhu J., Xavier D., Liu L., Pais P., López-Jaramillo P., Leiter L.A., Dans A., et al. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N. Engl. J. Med. 2016;374:2021–2031. doi: 10.1056/NEJMoa1600176. - DOI - PubMed
1. Danaei G., Rodríguez L.A.G., Cantero O.F., Logan R., Hernán M.A. Observational data for comparative effectiveness research: An emulation of randomised trials of statins and primary prevention of coronary heart disease. Stat. Methods Med. Res. 2013;22:70–96. doi: 10.1177/0962280211403603. - DOI - PMC - PubMed

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[1] Taylor F., Huffman M.D., Macedo A.F., Moore T.H.M., Burke M., Davey Smith G., Ward K., Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst. Rev. 2013;1:CD004816. doi: 10.1001/jama.2013.281348. - DOI - PMC - PubMed

[2] Taylor F., Huffman M.D., Macedo A.F., Moore T.H.M., Burke M., Davey Smith G., Ward K., Ebrahim S. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst. Rev. 2013;1:CD004816. doi: 10.1001/jama.2013.281348. - DOI - PMC - PubMed

[3] Mihaylova B., Emberson J., Blackwell L., Keech A., Simes J., Barnes E.H., Voysey M., Gray A., Collins R., Baigent C., et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–590. doi: 10.1016/S0140-6736(12)60367-5. - DOI - PMC - PubMed

[4] Mihaylova B., Emberson J., Blackwell L., Keech A., Simes J., Barnes E.H., Voysey M., Gray A., Collins R., Baigent C., et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–590. doi: 10.1016/S0140-6736(12)60367-5. - DOI - PMC - PubMed

[5] Glynn R.J., Koenig W., Nordestgaard B.G., Shepherd J., Ridker P.M. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: Exploratory analysis of a randomized trial. Ann. Intern. Med. 2010;152:488–496. doi: 10.7326/0003-4819-152-8-201004200-00005. - DOI - PMC - PubMed

[6] Glynn R.J., Koenig W., Nordestgaard B.G., Shepherd J., Ridker P.M. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: Exploratory analysis of a randomized trial. Ann. Intern. Med. 2010;152:488–496. doi: 10.7326/0003-4819-152-8-201004200-00005. - DOI - PMC - PubMed

[7] Yusuf S., Bosch J., Dagenais G., Zhu J., Xavier D., Liu L., Pais P., López-Jaramillo P., Leiter L.A., Dans A., et al. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N. Engl. J. Med. 2016;374:2021–2031. doi: 10.1056/NEJMoa1600176. - DOI - PubMed

[8] Yusuf S., Bosch J., Dagenais G., Zhu J., Xavier D., Liu L., Pais P., López-Jaramillo P., Leiter L.A., Dans A., et al. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N. Engl. J. Med. 2016;374:2021–2031. doi: 10.1056/NEJMoa1600176. - DOI - PubMed

[9] Danaei G., Rodríguez L.A.G., Cantero O.F., Logan R., Hernán M.A. Observational data for comparative effectiveness research: An emulation of randomised trials of statins and primary prevention of coronary heart disease. Stat. Methods Med. Res. 2013;22:70–96. doi: 10.1177/0962280211403603. - DOI - PMC - PubMed

[10] Danaei G., Rodríguez L.A.G., Cantero O.F., Logan R., Hernán M.A. Observational data for comparative effectiveness research: An emulation of randomised trials of statins and primary prevention of coronary heart disease. Stat. Methods Med. Res. 2013;22:70–96. doi: 10.1177/0962280211403603. - DOI - PMC - PubMed

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Effectiveness of Statins for Primary Prevention of Cardiovascular Disease in Low- and Medium-Risk Males: A Causal Inference Approach with Observational Data

Affiliations

Effectiveness of Statins for Primary Prevention of Cardiovascular Disease in Low- and Medium-Risk Males: A Causal Inference Approach with Observational Data

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

Figures

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References

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