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Single-Pill Combination Product Availability of the Antihypertensive Regimens Used for Intensive Systolic Blood Pressure Treatment in the Systolic Blood Pressure Intervention Trial

Originally publishedhttps://doi.org/10.1161/HYPERTENSIONAHA.123.21132Hypertension. 2023;80:1749–1758

    BACKGROUND:

    Single-pill combination (SPC) antihypertensive products improve blood pressure control and medication adherence among patients with hypertension. It is unknown to what degree commercially available SPC products could be used to target an intensive systolic blood pressure goal of <120 mm Hg.

    METHODS:

    This cross-sectional analysis included participants randomized to the intensive treatment arm (goal systolic blood pressure <120 mm Hg) of the Systolic Blood Pressure Intervention Trial (SPRINT) using ≥2 antihypertensive medication classes at the 12-month postrandomization visit. Antihypertensive medication data were collected using pill bottle review by research coordinators, and regimens were categorized by the unique combinations of antihypertensive classes. We calculated the proportion of regimens used, which are commercially available as one of the 7 SPC class combinations in the United States as of January 2023.

    RESULTS:

    Among the 3833 SPRINT intensive arm participants included (median age, 67.0 years; 35.5% female), participants were using 219 unique antihypertensive regimens. The 7 regimens for which there are class-equivalent SPC products were used by 40.3% of participants. Only 3.2% of all medication class regimens used are available as a class-equivalent SPC product (7/219). There are no SPC products available with 4 or more medication classes, which were used by 1060 participants (27.7%).

    CONCLUSIONS:

    Most SPRINT participants in the intensive arm used an antihypertensive medication regimen, which is not commercially available as a class equivalent SPC product. To achieve the SPRINT results in real-world settings, maximize the potential benefit of SPCs, and reduce pill burden, improvements in the product landscape are needed.

    REGISTRATION:

    URL: https://www.clinicaltrials.gov/ct2/show/NCT01206062; Unique identifier: NCT01206062.

    Footnotes

    *J.B. King and C.G. Derington contributed equally.

    For Sources of Funding and Disclosures, see page 1757.

    Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/HYPERTENSIONAHA.123.21132.

    Correspondence to: Jordan King, PharmD, MS, Department of Population Health Sciences University of Utah, 295 Chipeta Way, Williams Bldg, Salt Lake City, UT 84108. Email

    REFERENCES

    • 1. Wright JT, Williamson J, Whelton P, Snyder J, Sink K, Roccoo M, Reboussin D, Mahboob R, Oparil S, Lewis C, et al. A randomized trial of intensive versus standard blood-pressure control.N Engl J Med. 2015; 373:2103–2116. doi: 10.1056/NEJMoa1511939CrossrefMedlineGoogle Scholar
    • 2. Cushman WC, Ringer RJ, Rodriguez CJ, Evans GW, Bates JT, Cutler JA, Hawfield A, Kitzman DW, Nasrallah IM, Oparil S, et al; SPRINT Research Group. Blood pressure intervention and control in SPRINT.Hypertension. 2022; 79:2071–2080. doi: 10.1161/HYPERTENSIONAHA.121.17233LinkGoogle Scholar
    • 3. Wright JT, Dunn JK, Cutler JA, Davis BR, Cushman WC, Ford CE, Haywood LJ, Leenen FHHH, Margolis KL, Papademetriou V, et al. Outcomes in hypertensive black and nonblack patients treated with chlorthalidone, amlodipine, and lisinopril.J Am Med Assoc. 2005; 293:1595–1608. doi: 10.1001/jama.293.13.1595CrossrefMedlineGoogle Scholar
    • 4. Cushman WC, Ford CE, Einhorn PT, Wright JT, Preston RA, Davis BR, Basile JN, Whelton PK, Weiss RJ, Bastien A, et al; ALLHAT Collaborative Research Group. Blood pressure control by drug group in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).J Clin Hypertens (Greenwich). 2008; 10:751–760. doi: 10.1111/j.1751-7176.2008.00015.xCrossrefMedlineGoogle Scholar
    • 5. Verma AA, Khuu W, Tadrous M, Gomes T, Mamdani MM. Fixed-dose combination antihypertensive medications, adherence, and clinical outcomes: a population-based retrospective cohort study.PLoS Med. 2018; 15:e1002584. doi: 10.1371/journal.pmed.1002584CrossrefMedlineGoogle Scholar
    • 6. Rea F, Corrao G, Merlino L, Mancia G. Initial antihypertensive treatment strategies and therapeutic inertia evidence from a large population-based cohort.Hypertension. 2018; 72:846–853. doi: 10.1161/HYPERTENSIONAHA.118.11308LinkGoogle Scholar
    • 7. Feldman RD, Zou GY, Vandervoort MK, Wong CJ, Nelson SAE, Feagan BG. A simplified approach to the treatment of uncomplicated hypertension.Hypertension. 2009; 53:646–653. doi: 10.1161/HYPERTENSIONAHA.108.123455LinkGoogle Scholar
    • 8. Salam A, Atkins ER, Hsu B, Webster R, Patel A, Rodgers A. 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; 37:1567–1573. doi: 10.1097/HJH.0000000000002089CrossrefMedlineGoogle Scholar
    • 9. Salam A, Kanukula R, Atkins E, Wang X, Islam S, Kishore SP, Jaffe MG, Patel A, Rodgers A. 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; 37:1768–1774. doi: 10.1097/HJH.0000000000002096CrossrefMedlineGoogle Scholar
    • 10. Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials.Am J Med. 2009; 122:290–300. doi: 10.1016/j.amjmed.2008.09.038CrossrefMedlineGoogle Scholar
    • 11. Parati G, Kjeldsen S, Coca A, Cushman WC, Wang J. Adherence to single-pill versus free-equivalent combination therapy in hypertension: a systematic review and meta-analysis.Hypertension. 2021; 77:692–705. doi: 10.1161/HYPERTENSIONAHA.120.15781LinkGoogle Scholar
    • 12. Bryan AS, Moran AE, Mobley CM, Derington CG, Rodgers A, Zhang Y, Fontil V, Shea S, Bellows BK. Cost-effectiveness analysis of initial treatment with single-pill combination antihypertensive medications [published online February 15, 2023].J Hum Hypertens. doi: 10.1038/s41371-023-00811-3. https://www.nature.com/articles/s41371-023-00811-3CrossrefGoogle Scholar
    • 13. SPRINT Research Group. Final report of a trial of intensive versus standard blood-pressure control.N Engl J Med. 2021; 384:1921–1930.CrossrefMedlineGoogle Scholar
    • 14. Derington CG, Bress AP, Moran AE, Weintraub WS, Herrick JS, Cushman WC, Kronish IM, Stults B, Shimbo D, Muntner P, et al. Antihypertensive medication regimens used in the systolic blood pressure intervention trial.Hypertension. 2023; 80:590–597. doi: 10.1161/HYPERTENSIONAHA.122.20373LinkGoogle Scholar
    • 15. Derington CG, Bress AP, Herrick JS, Jacobs JA, Zheutlin AR, Conroy MB, Cushman WC, King JB. Antihypertensive medication regimens used by hypertensive US adults and the potential for fixed-dose combination products: the National Health and Nutrition Examination Surveys 2015-2020.J Am Heart Assoc. 2023; 12:e028573. doi: 10.1161/JAHA.122.028573LinkGoogle Scholar
    • 16. Ambrosius WT, Sink KM, Foy CG, Berlowitz DR, Cheung AK, Cushman WC, Fine LJ, Goff DC, Johnson KC, Killeen AA, et al. The design and rationale of a multicenter clinical trial comparing two strategies for control of systolic blood pressure: the Systolic Blood Pressure Intervention Trial (SPRINT).Clin Trials. 2014; 11:532–546. doi: 10.1177/1740774514537404CrossrefMedlineGoogle Scholar
    • 17. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D; Group M of D in RDS. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation.Ann Intern Med. 1999; 130:461–470. doi: 10.7326/0003-4819-130-6-199903160-00002CrossrefMedlineGoogle Scholar
    • 18. D’Agostino RB, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, Kannel WB. General cardiovascular risk profile for use in primary care: the framingham heart study.Circulation. 2008; 117:743–753. doi: 10.1161/CIRCULATIONAHA.107.699579LinkGoogle Scholar
    • 19. Systolic Blood Pressure Intervention Trial (SPRINT) protocol version 5.0.2015;Google Scholar
    • 20. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, et al; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC7 Report.JAMA. 2003; 289:2560–2572. doi: 10.1001/jama.289.19.2560CrossrefMedlineGoogle Scholar
    • 21. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report from the Panel Members Appointed to the Eighth Joint National Committee (JNC8).JAMA. 2014; 311:507–520. doi: 10.1001/jama.2013.284427CrossrefMedlineGoogle Scholar
    • 22. Choudhry NK, Kronish IM, Vongpatanasin W, Ferdinand KC, Pavlik VN, Egan BM, Schoenthaler A, Miller NH, Hyman DJ. Medication adherence and blood pressure control: a scientific statement from the American Heart Association.Hypertension. 2022; 79:E1–E14. doi: 10.1161/HYP.0000000000000203LinkGoogle Scholar
    • 23. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, 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 P.J Am Coll Cardiol. 2018; 71:e127–e248. doi: 10.1016/j.jacc.2017.11.006CrossrefMedlineGoogle Scholar
    • 24. Lauffenburger JC, Landon JE, Fischer MA. Effect of combination therapy on adherence among US patients initiating therapy for hypertension: a cohort study.J Gen Intern Med. 2017; 32:619–625. doi: 10.1007/s11606-016-3972-zCrossrefMedlineGoogle Scholar
    • 25. Ritchey M, Tsipas S, Loustalot F, Wozniak G. Use of pharmacy sales data to assess changes in prescription-and payment-related factors that promote adherence to medications commonly used to treat hypertension, 2009 and 2014.PLoS One. 2016; 11:e0159366. doi: 10.1371/journal.pone.0159366CrossrefMedlineGoogle Scholar
    • 26. Bress AP, Kramer H, Khatib R, Beddhu S, Cheung AK, Hess R, Bansal VK, Cao G, Yee J, Moran AE, et al. Potential deaths averted and serious adverse events incurred from adoption of the SPRINT intensive blood pressure regimen in the United States: Projections From NHANES.Circulation. 2017; 135:1617–1628. doi: 10.1161/CIRCULATIONAHA.116.025322LinkGoogle Scholar
    • 27. Chalasani R, Krishnamurthy S, Suda KJ, Newman TV, Delaney SW, Essien UR. Pursuing pharmacoequity: determinants, drivers, and pathways to progress.J Health Polit Policy Law. 2022; 47:709–729. doi: 10.1215/03616878-10041135CrossrefMedlineGoogle Scholar
    • 28. Essien UR, Dusetzina SB, Gellad WF. A policy prescription for reducing health disparities—achieving pharmacoequity.JAMA. 2021; 326:1793–1794. doi: 10.1001/jama.2021.17764CrossrefMedlineGoogle Scholar
    • 29. Sheppard JP, Lown M, Burt J, Temple E, Lowe R, Ashby H, Todd O, Allen J, Ford GA, Fraser R, et al. Generalizability of blood pressure lowering trials to older patients: cross-sectional analysis.J Am Geriatr Soc. 2020; 68:2508–2515. doi: 10.1111/jgs.16749CrossrefMedlineGoogle Scholar
    • 30. Anderson TS, Odden MC, Penko J, Kazi DS, Bellows BK, Bibbins-Domingo K. Characteristics of populations excluded from clinical trials supporting intensive blood pressure control guidelines.J Am Heart Assoc. 2021; 10:e019707. doi: 10.1161/JAHA.120.019707LinkGoogle Scholar
    • 31. Anderson TS, Odden M, Penko J, Kazi DS, Bellows BK, Bibbins-Domino K. Generalizability of Clinical Trials Supporting the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline.JAMA Intern Med. 2020; 180:795–797. doi: 10.1001/jamainternmed.2020.0051CrossrefMedlineGoogle Scholar

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