Anti-Hypertensive Medication Combinations in the United States ============================================================== * Michael E. Johansen * Jonathan Yun * James M. Griggs * Elizabeth Anne Jackson * Caroline R. Richardson ## Abstract *Background:* Examining the anti-hypertensive regimens of individuals with different comorbidities may offer insights into how we can improve hypertension management. *Methods:* The Medical Expenditure Panel Survey (2013–2015) was used to describe the most common single-, two-, three-, and four-drug hypertension regimens among hypertensive adults in four different comorbidity groups: 1. Hypertension only; 2. Hypertension and diabetes; 3. Hypertension and cardiovascular disease (coronary heart disease or stroke history); and 4. Hypertension, diabetes, and cardiovascular disease. *Results:* 15,901 adults with hypertension taking anti-hypertensive medications were included in the study. 58.6% (95% CI: 57.3–59.8) took multiple anti-hypertensive medications, but the proportion of adults taking multiple anti-hypertensives varied by comorbidity group. Regimens including an ACE-inhibitor/ARB were the most prevalent regimens among individuals taking ≥2 anti-hypertensive medications. The most common two-drug regimen for both the hypertension-only and hypertension-diabetes groups was an ACE-inhibitor/ARB with thiazide. The most prevalent regimen for the two cardiovascular disease groups was an ACE-inhibitor/ARB with beta-blocker. *Conclusions:* Most individuals with hypertension use between 2–5 medications and the medications comprising these regimens vary by comorbidity. The ACCOMPLISH trial suggested that certain combinations may lead to superior cardiovascular outcomes. Research comparing the efficacy of different hypertension medication combinations among individuals with different comorbidities could lead to better patient hypertensionrelated outcomes. * Angiotensin-Converting Enzyme Inhibitors * Antihypertensive Agents * Chronic Disease * Comorbidity * Coronary Artery Disease * Disease Management * Guideline Adherence * Hypertension * Outcomes Assessment * Surveys and Questionnaires * Thiazides Most adults taking antihypertensives in the United States take multiple agents.1 In addition, the Eighth Joint National Committee recommends providers initiate 2-drug regimens for patients newly diagnosed with stage 2 hypertension.2 Studies of hypertension drug regimens in the United States have investigated 2-drug regimens for adults1 and Medicare recipients4 but haven't compared multi-drug regimens for individuals with different comorbidities. Analyzing multi-drug regimens for individuals by comorbidity is worthwhile because certain drugs and drug combinations may offer differential benefits by comorbidity. ## Methods Using data from the 2013 through 2015 Medical Expenditure Panel Survey (MEPS), we describe the most common single-, 2-, 3-, and 4-drug hypertension regimens among hypertensive adults with 1) hypertension only (HTN-only); 2) hypertension and diabetes (HTN-DM); 3) hypertension and cardiovascular disease (ie, coronary heart disease or history of stroke) (HTN-CVD); and 4) hypertension, diabetes, and CVD (HTN-DM-CVD) (Table 1). View this table: [Table 1.](http://www.jabfm.org/content/33/1/143/T1) Table 1. Proportion of Adult 2013 to 2017 Medical Expenditure Panel Survey Respondents Taking Each Medication Regimen by Comorbidity Group MEPS is a nationally representative survey of the noninstitutionalized US civilian population. Every year, MEPS collects sociodemographic, self-reported medical conditions, and medication information from 2 overlapping panels of respondents, following each panel for 2 years. Self-reported chronic prescriptions from MEPS have been validated using claims data.3 Our sample included hypertensive adults without heart failure who took any antihypertensives during the year. We categorized antihypertension medications into 5 classes: 1) angiotensin converting-enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB); 2) thiazide diuretics; 3) calcium-channel blockers (CCB); 4) β-blockers; and 5) other agents (loop diuretics, spironolactone, clonidine, hydralazine). Individuals with ≥3 prescriptions or ≥90 tablets/capsules during each year were considered medication users. We used STATA (version 13, StataCorp LLC, College Station, TX) and applied complex survey weights to all analyses. The OhioHealth Institutional Review Board ruled this study exempt. ## Results Of the 76,792 adults included in the survey, 15,901 adults, or a survey adjusted 22.6% (95% CI, 21.9 to 23.3), had hypertension and took antihypertensive(s). Seventy percent (95% CI, 68.4 to 70.9) took an ACEI/ARB, 39.2% (95% CI, 37.9 to 40.5) took a β-blocker, 36.1% (95% CI, 34.7 to 37.5) took a thiazide, and 28.7% (95% CI, 27.6 to 29.9) took a CCB. Most (58.6% [95% CI, 57.3 to 59.8]) of our sample took multiple antihypertensives, but this varied by comorbidity group. The HTN-only group had the smallest proportion taking multiple antihypertensives; followed by the HTN-DM, HTN-CVD, and HTN-DM-CVD groups. Regimens including an ACEI/ARB were the most prevalent regimens among individuals taking ≥2 antihypertensives. The most common 2-drug regimen for both the HTN-only and HTN-DM groups was an ACEI/ARB with thiazide. The most prevalent regimen for the 2 CVD (HTN-CVD and HTN-DM-CVD) groups was an ACEI/ARB with β-blocker. Among individuals with CVD, 61.2% (95% CI, 58.7 to 63.4) took a β-blocker. ## Discussion Most individuals in our sample took multi-drug regimens, a finding compatible with previous studies.1,4 Notably, the ACEI/ARB-CCB combination was used less often than the ACEI/ARB-thiazide combination. One large randomized control trial applicable to the United States population, ACCOMPLISH, tested these combinations among individuals at high-risk of cardiovascular events and showed an ACEI-CCB may prevent more cardiovascular events than ACE-thiazide. However, ACCOMPLISH was stopped early for benefit and has not been replicated or adopted into guidelines. Our study has several limitations. Self-reported medical conditions may not accurately represent important conditions used to select antihypertensives (eg, chronic renal failure). The lack of exact medication-usage dates may overestimate the number of medications taken at 1 time. Most individuals with hypertension use between 2 and 5 medications, which vary by comorbidity, but nearly all randomized clinical trials examine outcomes for single agents. A better understanding of the outcomes associated with different antihypertensive combinations among individuals with different comorbidities could improve hypertension management. ## Notes * This article was externally peer reviewed. * *Funding:* JY is supported by HRSA Grant T32-HP14001. No other funding was used on this research. * *Conflict of interest:* none declared. * MEJ had full access to all study data and takes responsibility for the integrity of the data and the accuracy of the data analysis. * To see this article online, please go to: [http://jabfm.org/content/33/1/143.full](http://jabfm.org/content/33/1/143.full). * Received for publication April 9, 2019. * Revision received July 12, 2019. * Accepted for publication July 19, 2019. ## References 1. 1.Gu Q, Burt VL, Dillon CF, Yoon S. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension. Circulation 2012;126:2105–14. [Abstract/FREE Full Text](http://www.jabfm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTQ6ImNpcmN1bGF0aW9uYWhhIjtzOjU6InJlc2lkIjtzOjExOiIxMjYvMTcvMjEwNSI7czo0OiJhdG9tIjtzOjIwOiIvamFiZnAvMzMvMS8xNDMuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 2. 2.James PA, Oparil S, Carter BL, 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 (JNC 8). JAMA 2014;311:507–20. [CrossRef](http://www.jabfm.org/lookup/external-ref?access_num=10.1001/jama.2013.284427&link_type=DOI) [PubMed](http://www.jabfm.org/lookup/external-ref?access_num=24352797&link_type=MED&atom=%2Fjabfp%2F33%2F1%2F143.atom) [Web of Science](http://www.jabfm.org/lookup/external-ref?access_num=000330589800024&link_type=ISI) 3. 3.Hill SC, Zuvekas SH, Zodet MW. Implications of the accuracy of MEPS prescription drug data for health services research. Inquiry 2011;48:242–59. [PubMed](http://www.jabfm.org/lookup/external-ref?access_num=22235548&link_type=MED&atom=%2Fjabfp%2F33%2F1%2F143.atom) 4. 4.Kent ST, Shimbo D, Huang L, et al. Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007–2010. PloS One 2014;9:e105888. [CrossRef](http://www.jabfm.org/lookup/external-ref?access_num=10.1371/journal.pone.0105888&link_type=DOI) [PubMed](http://www.jabfm.org/lookup/external-ref?access_num=25153199&link_type=MED&atom=%2Fjabfp%2F33%2F1%2F143.atom) 5. 5.Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008;359:2417–28. [CrossRef](http://www.jabfm.org/lookup/external-ref?access_num=10.1056/NEJMoa0806182&link_type=DOI) [PubMed](http://www.jabfm.org/lookup/external-ref?access_num=19052124&link_type=MED&atom=%2Fjabfp%2F33%2F1%2F143.atom) [Web of Science](http://www.jabfm.org/lookup/external-ref?access_num=000261325900003&link_type=ISI)