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Increasing the Precision of Hypertension Treatment Through Personalized Trials: a Pilot Study

  • Ian M. KronishEmail author
  • Ying Kuen Cheung
  • Daichi Shimbo
  • Jacob Julian
  • Benjamin Gallagher
  • Faith Parsons
  • Karina W. Davidson
Article

Abstract

Background

There are substantial differences in the effects of blood pressure (BP) medications in individual patients. Yet, the current standard approach to prescribing BP medications is not personalized.

Objective

To determine the feasibility of individualizing the selection of BP medications through pragmatic personalized (i.e., N-of-1) trials.

Design

Series of N-of-1 trials.

Setting

Outpatient.

Patients

Hypertensive adults prescribed none or one BP medication.

Intervention

Participation in a flexible, open-label personalized trial of two to three BP medications (NCT02744456).

Measurements

BP was measured twice per day with a validated home BP device. Frequency and severity of side effects were assessed at the end of the day via an electronic questionnaire. Patients’ BP medication preference was assessed after reviewing BP lowering and side effect results with a study clinician. Feasibility was assessed by determining the proportion of patients who adhered to self-assessments. Benefit was assessed by asking patients to rate the helpfulness of participation and whether they would recommend personalized trials to other hypertensive patients.

Key Results

Of ten patients enrolled, two dropped out prior to initiation, one discovered white coat hypertension through ambulatory BP monitoring, and seven (mean age 58 years, 71% of women) completed personalized trials. All seven were compliant with home BP monitoring and side effect tracking. All seven recommended personalized trials of BP medications to others. Thiazides were preferred by three patients, renin-angiotensin system–blocking agents by two patients, a combination of thiazide and beta-blocker by one patient, and any of three classes by one patient.

Conclusions

Personalized trials of BP medications were feasible and led to improved treatment precision. Heterogeneity of patient preferences and of therapeutic BP response for first-line BP medications can be determined through a personalized trial approach.

KEY WORDS

hypertension primary care clinical trials disease management health care delivery 

Notes

Funding

The study was funded by the National Center for Advancing Translational Sciences (U01 TR001873). Dr. Kronish and Dr. Davidson received additional support from the National Library of Medicine (R01 LM012836).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they do not have a conflict of interest.

Supplementary material

11606_2019_4831_MOESM1_ESM.docx (13.7 mb)
ESM 1 (DOCX 14078 kb)

References

  1. 1.
    Tarn DM, Heritage J, Paterniti DA, Hays RD, Kravitz RL, Wenger NS. Physician communication when prescribing new medications. Arch Intern Med. 2006;166(17):1855–62.Google Scholar
  2. 2.
    Gu Q, Burt VL, Dillon CF, Yoon S. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension: the National Health And Nutrition Examination Survey, 2001 to 2010. Circulation. 2012;126(17):2105–14.Google Scholar
  3. 3.
    Dickerson JE, Hingorani AD, Ashby MJ, Palmer CR, Brown MJ. Optimisation of antihypertensive treatment by crossover rotation of four major classes. Lancet. 1999;353(9169):2008–13.Google Scholar
  4. 4.
    Deary AJ, Schumann AL, Murfet H, Haydock SF, Foo RS, Brown MJ. Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs. J Hypertens. 2002;20(4):771–7.Google Scholar
  5. 5.
    Edmonds D, Huss R, Jeck T, Mengden T, Schubert M, Vetter W. Individualizing antihypertensive therapy with enalapril versus atenolol: the Zurich experience. J Hypertens Suppl. 1990;8(4):S49–52.Google Scholar
  6. 6.
    Waeber B, Burnier M, Nussberger J, Brunner HR. Trials using a crossover design and ambulatory blood pressure recordings to determine the efficacy of antihypertensive agents in individual patients. J Hypertens Suppl. 1990;8(4):S37–41.Google Scholar
  7. 7.
    Gong Y, McDonough CW, Wang Z, Hou W, Cooper-DeHoff RM, Langaee TY, et al. Hypertension susceptibility loci and blood pressure response to antihypertensives: results from the pharmacogenomic evaluation of antihypertensive responses study. Circ Cardiovasc Genet. 2012;5(6):686–91.Google Scholar
  8. 8.
    Cooper-DeHoff RM, Johnson JA. Hypertension pharmacogenomics: in search of personalized treatment approaches. Nat Rev Nephrol. 2016;12(2):110–22.Google Scholar
  9. 9.
    Duan N, Kravitz RL, Schmid CH. Single-patient (n-of-1) trials: a pragmatic clinical decision methodology for patient-centered comparative effectiveness research. J Clin Epidemiol. 2013;66(8 Suppl):S21–8.Google Scholar
  10. 10.
    Kravitz RL DN, eds, and the DEcIDE Methods Center N-of-1 Guidance Panel (Duan N, Eslick I, Gabler NB, Kaplan HC, Kravitz RL, Larson EB, Pace WD, Schmid CH, Sim I, Vohra S). Design and Implementation of N-of-1 Trials: A User’s Guide. AHRQ Publication No.13(14)-EHC122-EF. Rockville: MD; February 2014.Google Scholar
  11. 11.
    Guyatt GH, Haynes RB, Jaeschke RZ, Cook DJ, Green L, Naylor CD, et al. Users’ Guides to the Medical Literature: XXV. Evidence-based medicine: principles for applying the Users’ Guides to patient care. Evidence-Based Medicine Working Group. JAMA. 2000;284(10):1290–6.Google Scholar
  12. 12.
    Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: the ultimate strategy for individualizing medicine? Per Med. 2011;8(2):161–73.Google Scholar
  13. 13.
    Shimbo D, Abdalla M, Falzon L, Townsend RR, Muntner P. Role of Ambulatory and Home Blood Pressure Monitoring in Clinical Practice: A Narrative Review. Ann Intern Med. 2015;163(9):691–700.Google Scholar
  14. 14.
    Vohra S, Shamseer L, Sampson M, Bukutu C, Schmid CH, Tate R, et al. CONSORT extension for reporting N-of-1 trials (CENT) 2015 Statement. J Clin Epidemiol. 2016;76:9–17.Google Scholar
  15. 15.
    Kravitz RL DN, Vohra S, Li J, the DEcIDE Methods Center N-of-1 Guidance Panel. Introduction to N-of-1 Trials: Indications and Barriers. In: Kravitz RL DN, eds, and the DEcIDE Methods Center N-of-1 Guidance Panel (Duan N, Eslick I, Gabler NB, Kaplan HC, Kravitz RL, Larson EB, Pace WD, Schmid CH, Sim I, Vohra S), ed. Design and Implementation of N-of-1 Trials: A User’s Guide. AHRQ Publication No. 13(14)-EHC122-EF. Rockville, MD: Agency foe Healthcare Research and Quality; 2014:1–11.Google Scholar
  16. 16.
    Degner LF, Sloan JA, Venkatesh P. The Control Preferences Scale. Can J Nurs Res. 1997;29(3):21–43.Google Scholar
  17. 17.
    Siu AL, Force USPST. Screening for high blood pressure in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;163(10):778–86.Google Scholar
  18. 18.
    Pickering TG, Miller NH, Ogedegbe G, Krakoff LR, Artinian NT, Goff D, et al. Call to action on use and reimbursement for home blood pressure monitoring: executive summary: a joint scientific statement from the American Heart Association, American Society Of Hypertension, and Preventive Cardiovascular Nurses Association. Hypertension. 2008;52(1):1–9.Google Scholar
  19. 19.
    Chatellier G, Day M, Bobrie G, Menard J. Feasibility study of N-of-1 trials with blood pressure self-monitoring in hypertension. Hypertension. 1995;25(2):294–301.Google Scholar
  20. 20.
    Estrada CA, Young MJ. Patient preferences for novel therapy: an N-of-1 trial of garlic in the treatment for hypertension. J Gen Intern Med. 1993;8(11):619–21.Google Scholar
  21. 21.
    Materson BJ, Reda DJ, Preston RA, Cushman WC, Massie BM, Freis ED, et al. Response to a second single antihypertensive agent used as monotherapy for hypertension after failure of the initial drug. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents. Arch Intern Med. 1995;155(16):1757–62.Google Scholar
  22. 22.
    Kronish IM, Alcántara C, Duer-Hefele J, St Onge T, Davidson KW, Carter EJ, et al. Patients and primary care providers identify opportunities for personalized (N-of-1) trials in the mobile health era. J Clin Epidemiol. 2017;89:236-237.Google Scholar
  23. 23.
    Kravitz RL, Duan N, Niedzinski EJ, Hay MC, Subramanian SK, Weisner TS. What ever happened to N-of-1 trials? Insiders’ perspectives and a look to the future. Milbank Q. 2008;86(4):533–55.Google Scholar
  24. 24.
    Kravitz RL, Paterniti DA, Hay MC, Subramanian S, Dean DE, Weisner T, et al. Marketing therapeutic precision: Potential facilitators and barriers to adoption of n-of-1 trials. Contemp Clin Trials. 2009;30(5):436–45.Google Scholar
  25. 25.
    Barr C, Marois M, Sim I, Schmid CH, Wilsey B, Ward D, et al. The PREEMPT study - evaluating smartphone-assisted n-of-1 trials in patients with chronic pain: study protocol for a randomized controlled trial. Trials. 2015;16:67.Google Scholar

Copyright information

© Society of General Internal Medicine 2019

Authors and Affiliations

  • Ian M. Kronish
    • 1
    Email author
  • Ying Kuen Cheung
    • 2
  • Daichi Shimbo
    • 1
  • Jacob Julian
    • 1
  • Benjamin Gallagher
    • 3
  • Faith Parsons
    • 1
  • Karina W. Davidson
    • 1
  1. 1.Center for Behavioral Cardiovascular HealthColumbia University Irving Medical CenterNew YorkUSA
  2. 2.Department of Biostatistics, Mailman School of Public HealthColumbia UniversityNew YorkUSA
  3. 3.Section of General Internal Medicine, Department of Internal Medicine, Yale School of MedicineYale UniversityNew HavenUSA

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