The efficacy and safety of co-administration of fimasartan and rosuvastatin to patients with hypertension and dyslipidemia

Moo-Yong Rhee, Taehoon Ahn, Kiyuk Chang, Shung Chull Chae, Tae-Hyun Yang, Wan Joo Shim, Tae Soo Kang, Jae-Kean Ryu, Deuk-Young Nah, Tae-Ho Park, In-Ho Chae, Seung Woo Park, Hae-Young Lee, Seung-Jea Tahk, Young Won Yoon, Chi Young Shim, Dong-Gu Shin, Hong Seog Seo, Sung Yun Lee, Doo Il Kim, Jun Kwan, Seung-Jae Joo, Myung Ho Jeong, Jin-Ok Jeong, Ki Chul Sung, Seok Yeon Kim, Sang-Hyun Kim, Kook-Jin Chun, Dong Joo Oh, Moo-Yong Rhee, Taehoon Ahn, Kiyuk Chang, Shung Chull Chae, Tae-Hyun Yang, Wan Joo Shim, Tae Soo Kang, Jae-Kean Ryu, Deuk-Young Nah, Tae-Ho Park, In-Ho Chae, Seung Woo Park, Hae-Young Lee, Seung-Jea Tahk, Young Won Yoon, Chi Young Shim, Dong-Gu Shin, Hong Seog Seo, Sung Yun Lee, Doo Il Kim, Jun Kwan, Seung-Jae Joo, Myung Ho Jeong, Jin-Ok Jeong, Ki Chul Sung, Seok Yeon Kim, Sang-Hyun Kim, Kook-Jin Chun, Dong Joo Oh

Abstract

Background: Hypertension and dyslipidemia are major risk factors of cardiovascular disease (CVD) events. The objective of this study was to evaluate the efficacy and safety of the co-administration of fimasartan and rosuvastatin in patients with hypertension and hypercholesterolemia.

Methods: We conducted a randomized double-blind and parallel-group trial. Patients who met eligible criteria after 4 weeks of therapeutic life change were randomly assigned to the following groups. 1) co-administration of fimasartan 120 mg/rosuvastatin 20 mg (FMS/RSV), 2) fimasartan 120 mg (FMS) alone 3) rosuvastatin 20 mg (RSV) alone. Drugs were administered once daily for 8 weeks.

Results: Of 140 randomized patients, 135 for whom efficacy data were available were analyzed. After 8 weeks of treatment, the FMS/RSV treatment group showed greater reductions in sitting systolic (siSBP) and diastolic (siDBP) blood pressures than those in the group receiving RSV alone (both p < 0.001). Reductions in siSBP and siDBP were not significantly different between the FMS/RSV and FMS alone groups (p = 0.500 and p = 0.734, respectively). After 8 weeks of treatment, FMS/RSV treatment showed greater efficacy in percentage reduction of low-density lipoprotein cholesterol (LDL-C) level from baseline than that shown by FMS alone treatment (p < 0.001). The response rates of siSBP with FMS/RSV, FMS alone, and RSV alone treatments were 65.22, 55.56, and 34.09%, respectively (FMS/RSV vs. RSV, p = 0.006). The LDL-C goal attainment rates with FMS/RSV, RSV alone, and FMS alone treatments were 80.43%, 81.82%, and 15.56%, respectively (FMS/RSV vs. FMS, p < 0.001). Incidence of adverse drug reactions with FMS/RSV treatment was 8.33%, which was similar to those associated with FMS and RSV alone treatments.

Conclusion: This study demonstrated that the co-administration of fimasartan and rosuvastatin to patients with both hypertension and hypercholesterolemia was efficacious and safe.

Trial registration: ClinicalTrials.gov Identifier: NCT02166814 . 16 June 2014.

Keywords: Fimasartan; Hypercholesterolemia; Hypertension; Rosuvastatin.

Figures

Fig. 1
Fig. 1
Subject disposition and reasons for study discontinuation. Reasons for discontinuation included (1) withdrawal of consent, (2) protocol violations, (3) lack of efficacy, (4) adverse events, and (5) other reasons. FMS: fimasartan; RSV, rosuvastatin. FMS/RSV: fimasartan 120 mg/rosuvastatin 20 mg treatment; FMS: fimasartan 120 mg alone treatment; RSV: rosuvastatin 20 mg alone treatment; FAS: full analysis set; PPS: per-protocol set
Fig. 2
Fig. 2
(a) Response rate and (b) control rate of sitting systolic blood pressure (siSBP), and (c) goal attainment rate of low-density lipoprotein cholesterol (LDL-C) by fimasartan 120 mg/rosuvastatin 20 mg (FMS/RSV) treatment, fimasartan 120 mg alone (FMS) treatment, and rosuvastatin 20 mg alone (RSV) treatment at week 8. (Full analysis set)
Fig. 3
Fig. 3
Percentage of patients who reached sitting systolic blood pressure (siSBP) and low-density lipoprotein cholesterol (LDL-C) goals after fimasartan 120 mg/rosuvastatin 20 mg (FMS/RSV) treatment, fimasartan 120 mg alone (FMS) treatment, or rosuvastatin 20 mg alone (RSV) treatment at week 8

References

    1. Johnson ML, Pietz K, Battleman DS, Beyth RJ. Prevalence of comorbid hypertension and dyslipidemia and associated cardiovascular disease. Am J Manag Care. 2004;10:926–932.
    1. Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med. 1992;152:56–64. doi: 10.1001/archinte.1992.00400130082009.
    1. Kannel WB. Fifty years of Framingham Study contributions to understanding hypertension. J Hum Hypertens. 2000;14:83–90. doi: 10.1038/sj.jhh.1000949.
    1. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) J Hypertens. 2013;31:1281–1357. doi: 10.1097/.
    1. Expert Panel on Detection E, Treatment of High Blood Cholesterol in A Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III) JAMA. 2001;285:2486–2497. doi: 10.1001/jama.285.19.2486.
    1. Emberson J, Whincup P, Morris R, Walker M, Ebrahim S. Evaluating the impact of population and high-risk strategies for the primary prevention of cardiovascular disease. Eur Heart J. 2004;25:484–491. doi: 10.1016/j.ehj.2003.11.012.
    1. Kim S, Shin DW, Yun JM, Hwang Y, Park SK, Ko YJ, et al. Medication Adherence and the Risk of Cardiovascular Mortality and Hospitalization Among Patients With Newly Prescribed Antihypertensive Medications. Hypertension. 2016;67:506–512.
    1. Simpson SH, Eurich DT, Majumdar SR, Padwal RS, Tsuyuki RT, Varney J, et al. A meta-analysis of the association between adherence to drug therapy and mortality. BMJ. 2006;333:15. doi: 10.1136/bmj.38875.675486.55.
    1. Gupta AK, Arshad S, Poulter NR. Compliance, safety, and effectiveness of fixed-dose combinations of antihypertensive agents: a meta-analysis. Hypertension. 2010;55:399–407. doi: 10.1161/HYPERTENSIONAHA.109.139816.
    1. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007;120:713–719. doi: 10.1016/j.amjmed.2006.08.033.
    1. National Cholesterol Education Program Expert Panel on Detection E, Treatment of High Blood Cholesterol in A Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106:3143–3421.
    1. Coleman A, Freeman P, Steel S, Shennan A. Validation of the Omron 705IT (HEM-759-E) oscillometric blood pressure monitoring device according to the British Hypertension Society protocol. Blood Press Monit. 2006;11:27–32. doi: 10.1097/01.mbp.0000189788.05736.5f.
    1. Rhee MY, Baek SH, Kim W, Park CG, Park SW, Oh BH, et al. Efficacy of fimasartan/hydrochlorothiazide combination in hypertensive patients inadequately controlled by fimasartan monotherapy. Drug Des Devel Ther. 2015;9:2847–2854. doi: 10.2147/DDDT.S82098.
    1. Lee HY, Kim YJ, Ahn T, Youn HJ, Chull Chae S, Seog Seo H, et al. A Randomized, Multicenter, Double-blind, Placebo-controlled, 3 x 3 Factorial Design, Phase II Study to Evaluate the Efficacy and Safety of the Combination of Fimasartan/Amlodipine in Patients With Essential Hypertension. Clin Ther. 2015;37:2581–2596. doi: 10.1016/j.clinthera.2015.02.019.
    1. Lee H, Yang HM, Lee HY, Kim JJ, Choi DJ, Seung KB, et al. Efficacy and tolerability of once-daily oral fimasartan 20 to 240 mg/d in Korean Patients with hypertension: findings from Two Phase II, randomized, double-blind, placebo-controlled studies. Clin Ther. 2012;34:1273–1289. doi: 10.1016/j.clinthera.2012.04.021.
    1. Olsson AG, Pears J, McKellar J, Mizan J, Raza A. Effect of rosuvastatin on low-density lipoprotein cholesterol in patients with hypercholesterolemia. Am J Cardiol. 2001;88:504–508. doi: 10.1016/S0002-9149(01)01727-1.
    1. Lee SE, Kim YJ, Lee HY, Yang HM, Park CG, Kim JJ, et al. Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension. Clin Ther. 2012;34:552–568. doi: 10.1016/j.clinthera.2012.01.024.
    1. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial) Am J Cardiol. 2003;92:152–160. doi: 10.1016/S0002-9149(03)00530-7.
    1. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM, Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–2207. doi: 10.1056/NEJMoa0807646.
    1. Mazzaglia G, Ambrosioni E, Alacqua M, Filippi A, Sessa E, Immordino V, et al. Adherence to antihypertensive medications and cardiovascular morbidity among newly diagnosed hypertensive patients. Circulation. 2009;120:1598–1605. doi: 10.1161/CIRCULATIONAHA.108.830299.
    1. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clin Ther. 2001;23:1296–1310. doi: 10.1016/S0149-2918(01)80109-0.
    1. Mateo JF, Gil-Guillen VF, Mateo E, Orozco D, Carbayo JA, Merino J. Multifactorial approach and adherence to prescribed oral medications in patients with type 2 diabetes. Int J Clin Pract. 2006;60:422–428. doi: 10.1111/j.1368-5031.2006.00799.x.
    1. Fung V, Huang J, Brand R, Newhouse JP, Hsu J. Hypertension treatment in a medicare population: adherence and systolic blood pressure control. Clin Ther. 2007;29:972–984. doi: 10.1016/j.clinthera.2007.05.010.
    1. 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;20:771–777. doi: 10.1097/00004872-200204000-00037.
    1. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) JAMA. 2002;288:2981–2997. doi: 10.1001/jama.288.23.2981.
    1. Maranon R, Reckelhoff JF. Sex and gender differences in control of blood pressure. Clin Sci (Lond) 2013;125:311–318. doi: 10.1042/CS20130140.
    1. Martin PD, Dane AL, Nwose OM, Schneck DW, Warwick MJ. No effect of age or gender on the pharmacokinetics of rosuvastatin: a new HMG-CoA reductase inhibitor. J Clin Pharmacol. 2002;42:1116–1121. doi: 10.1177/009127002401382722.
    1. Nazir S, Iqbal Z, Nasir F. Impact of menopause on pharmacokinetics of rosuvastatin compared with premenopausal women. Eur J Drug Metab Pharmacokinet. 2016;41:505–509. doi: 10.1007/s13318-015-0285-2.

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