Polypills in the fight against cardiovascular diseases: a modern review of effectiveness

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Abstract

Cardiovascular diseases (CVD) are the leading cause of global mortality and the leading cause of disability in the world. The leading modifiable risk factors for CVD - the level of systolic blood pressure (SBP) and low-density lipoprotein (LDL) - are responsible for the development of atherosclerosis and atherosclerotic cardiovascular diseases (ACVD). An important area of the evidence-based movement is a multifactorial approach to managing cardiovascular risk, in particular using fixed-dose combination tablets (polypills) containing antihypertensive drugs and statins, which improve blood pressure control and lipid profiles, and also antiplatelet drugs to prevent further ACVD events. The results of studies and meta-analyses assessing the effect of polypills on CVD risk factors and the main outcomes of cardiovascular morbidity and mortality are presented.

A Cochrane meta-analysis of 13 RCTs that examined the effect of polypills on factors in the primary and secondary prevention patient population, as well as subsequent meta-analyses, confirmed significant reductions in the key modifiable risk factors of SBP and LDL. Subsequently, a comprehensive assessment of the effect of polypills was carried out not only on risk factors, but also on outcomes - cardiovascular morbidity and mortality, including in large RCTs (HOPE-3, PolyIran, TIPS-3) and a number of meta-analyses, including up to 25 RCTs. The results showed a significant reduction in the risk of serious adverse cardiovascular events and mortality in primary or secondary prevention against the background of polypills containing antihypertensive drugs and statins, and more pronounced in primary prevention. There was an increase in adherence to polypill therapy, with no significant difference in the frequency of adverse reactions compared to conventional therapy. Fixed combination therapy is especially important for the treatment of hypertension. Moreover, modern trends are the use of combinations of 3 and 4 antihypertensive drugs in half and quarter dosages (quadropills), which, due to the additive effect, increases blood pressure control.

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About the authors

Marina V. Leonova

Interregional public organization Association of Clinical Pharmacologists (Moscow branch)

Author for correspondence.
Email: anti23@mail.ru
ORCID iD: 0000-0001-8228-1114
SPIN-code: 3281-7884

Dr. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Natural Sciences, Member of the Organization

Russian Federation, Moscow

References

  1. Lindstrom M., DeCleene N., Dorsey H., et al. Global Burden of Cardiovascular Diseases and Risks Collaboration, 1990-2021. J Am Coll Cardiol. 2022;80(25):2372–425. doi: 10.1016/j.jacc.2022.11.001.
  2. Wong N.D., Budoff M.J., Ferdinand K., et al. Atherosclerotic cardiovascular disease risk assessment: An American Society for Preventive Cardiology clinical practice statement. Am J Prev Cardiol. 2022;10:100335. doi: 10.1016/j.ajpc.2022.100335.
  3. Bahiru E., de Cates A.N., Farr M.R., et al. Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases. Cochrane Database Syst Rev. 2017;3(3):CD009868. doi: 10.1002/14651858.CD009868.pub3.
  4. Perk J., De Backer G., Gohlke H., et al; European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33(13):1635–701. doi: 10.1093/eurheartj/ehs092.
  5. NICE. Cardiovascular disease prevention. Public health guideline. Published: 22 June 2010. URL: https://www.nice.org.uk/guidance/ PH25.
  6. Stone N.J., Robinson J.G., Lichtenstein A.H., et al; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 Suppl. 2):S1–45. doi: 10.1161/01.cir.0000437738.63853.7a
  7. Secondary prevention of noncommunicable diseases in low- and middle-income countries through community-based and health service interventions: World Health Organization-Wellcome Trust meeting report, 1–3 August 2001. World Health Organization. URL: https://iris.who.int/handle/10665/42567.
  8. Hearts: technical package for cardiovascular disease management in primary health care. World Health Organizat. 2016;1:1–76. URL: https://iris.who.int/bitstream/handle/10665/252661/9789241511377-eng.pdf?sequence=1
  9. Wald N.J., Law M.R. A strategy to reduce cardiovascular disease by more than 80%. BMJ. 2003;326(7404):1419. doi: 10.1136/bmj.326.7404.1419.
  10. Viera A.J., Sheridan S.L., Edwards T., et al. Acceptance of a Polypill approach to prevent cardiovascular disease among a sample of U.S. physicians. Prev Med. 2011;52(1):10–5. doi: 10.1016/j.ypmed.2010.09.016.
  11. Piepoli M.F., Hoes A.W., Agewall S., et al; ESC Scientific Document Group. 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37(29):2315–81. doi: 10.1093/eurheartj/ehw106.
  12. Rodgers A., Patel A., Berwanger O., et al.; PILL Collaborative Group. An international randomised placebo-controlled trial of a four-component combination pill («polypill») in people with raised cardiovascular risk. PLoS One. 2011;6(5):e19857. doi: 10.1371/journal.pone.0019857.
  13. Webster R., Patel A., Selak V., et al; SPACE Collaboration. Effectiveness of fixed dose combination medication (‘polypills’) compared with usual care in patients with cardiovascular disease or at high risk: A prospective, individual patient data meta-analysis of 3140 patients in six countries. Int J Cardiol. 2016;205:147–56. doi: 10.1016/j.ijcard.2015.12.015.
  14. Selak V., Webster R., Stepien S., et al. Reaching cardiovascular prevention guideline targets with a polypill-based approach: a meta-analysis of randomised clinical trials. Heart. 2019;105(1):42–8. doi: 10.1136/heartjnl-2018-313108.
  15. Bahiru E., de Cates A.N., Farr M.R., et al. Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular diseases. Cochrane Database Syst Rev. 2017;3(3):CD009868. doi: 10.1002/14651858.CD009868.pub3.
  16. Joseph P., Roshandel G., Gao P., et al.; Polypill Trialists’ Collaboration. Fixed-dose combination therapies with and without aspirin for primary prevention of cardiovascular disease: an individual participant data meta-analysis. Lancet. 2021;398(10306):1133–46. doi: 10.1016/S0140-6736(21)01827-4.
  17. Rao S., Jamal Siddiqi T., Khan M.S., et al. Association of polypill therapy with cardiovascular outcomes, mortality, and adherence: A systematic review and meta-analysis of randomized controlled trials. Prog Cardiovasc Dis. 2022;73:48–55. doi: 10.1016/j.pcad.2022.01.005.
  18. Mohamed M.G., Osman M., Kheiri B., et al. Polypill for cardiovascular disease prevention: Systematic review and meta-analysis of randomized controlled trials. Int J Cardiol. 2022;360:91–8. doi: 10.1016/j.ijcard.2022.04.085.
  19. Yusuf S., Lonn E., Pais P., et al; HOPE-3 Investigators. Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease. N Engl J Med. 2016;374(21):2032–43. doi: 10.1056/NEJMoa1600177.
  20. Roshandel G., Khoshnia M., Poustchi H., et al. Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran): a pragmatic, cluster-randomised trial. Lancet. 2019;394(10199):672–83. doi: 10.1016/S0140-6736(19)31791-X.
  21. Yusuf S., Joseph P., Dans A., et al; International Polycap Study 3 Investigators. Polypill with or without Aspirin in Persons without Cardiovascular Disease. N Engl J Med. 2021;384(3):216–28. doi: 10.1056/NEJMoa2028220.
  22. Abushouk A.I., Sayed A., Munir M., et al. Fixed-Dose Combination (Polypill) for Cardiovascular Disease Prevention: A Meta-Analysis. Am J Prev Med. 2022;63(3):440–49. doi: 10.1016/j.amepre.2022.03.027.
  23. Sedhom R., Hamed M., Tan W., et al. Meta-Analysis on the Clinical Outcomes With Polypills for Cardiovascular Disease Prevention. Am J Cardiol. 2023;201:211–18. doi: 10.1016/j.amjcard.2023.06.001.
  24. Williams B., Mancia G., Spiering W., et al.; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–104. doi: 10.1093/eurheartj/ehy339.
  25. Whelton P.K., Carey R.M., Aronow W.S., et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018;71(19):e127–248. doi: 10.1016/j.jacc.2017.11.006.
  26. Unger T., Borghi C., Charchar F., et al. 2020 International Society of Hypertension global hypertension practice guidelines. J Hypertens. 2020;38(6):982–1004. doi: 10.1097/HJH.0000000000002453.
  27. World Health Organization. Model list of essential medications. 2017.
  28. Law M.R., Wald N.J., Morris J.K., Jordan R.E. Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ. 2003;326(7404):1427. doi: 10.1136/bmj.326.7404.1427.
  29. Gnanenthiran S.R., Agarwal A., Patel A. Frontiers of cardiovascular polypills: From atherosclerosis and beyond. Trend Cardiovasc Med. 2023;33(3):182–89. doi: 10.1016/j.tcm.2021.12.013.
  30. Salam A., Kanukula R., Atkins E., et al. Efficacy and safety of dual combination therapy of blood pressure-lowering drugs as initial treatment for hypertension: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019;37(9):1768–74. doi: 10.1097/HJH.0000000000002096.
  31. Webster R., Salam A., de Silva H.A., et al; TRIUMPH Study Group. Fixed Low-Dose Triple Combination Antihypertensive Medication vs Usual Care for Blood Pressure Control in Patients With Mild to Moderate Hypertension in Sri Lanka: A Randomized Clinical Trial. JAMA. 2018;320(6):566–79. doi: 10.1001/jama.2018.10359.
  32. Salam A., Atkins E.R., Hsu B., et al. Efficacy and safety of triple versus dual combination blood pressure-lowering drug therapy: a systematic review and meta-analysis of randomized controlled trials. J Hypertens. 2019;37(8):1567–73. doi: 10.1097/HJH.0000000000002089.
  33. Mahmud A. Feely J. Low-dose quadruple antihypertensive combination: more efficacious than individual agents – a preliminary report. Hypertension. 2007;49(2):272–75. doi: 10.1161/01.HYP.0000254479.66645.a3.
  34. Chow C.K., Thakkar J., Bennett A., et al. Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review. Lancet. 2017;389(10073):1035–42. doi: 10.1016/S0140-6736(17)30260-X.
  35. Chow C.K., Atkins E.R., Hillis G.S., et al; QUARTET Investigators. Initial treatment with a single pill containing quadruple combination of quarter doses of blood pressure medicines versus standard dose monotherapy in patients with hypertension (QUARTET): a phase 3, randomised, double-blind, active-controlled trial. Lancet. 2021;398(10305):1043–52. doi: 10.1016/S0140-6736(21)01922-X.

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