title: Safety of the Up-titration of Nifedipine GITS and Valsartan or Low-dose Combination in Uncontrolled Hypertension: the FOCUS Study.
abstract: Doubling the dose of antihypertensive drugs is necessary to manage hypertension in patients whose disease is uncontrolled. However, this strategy can result in safety issues. This study compared the safety and efficacy of up-titration of the nifedipine gastrointestinal therapeutic system (GITS) with up-titration of valsartan monotherapy; these were also compared with low-dose combinations of the two therapies.
  
  
  
  This prospective, open-label, randomized, active-controlled, multicenter study lasted 8 weeks. If patients did not meet the target blood pressure (BP) after 4 weeks of treatment with low-dose monotherapy, they were randomized to up-titration of the nifedipine GITS dose from 30 mg (N30) to 60 mg or valsartan from 80 mg to 160 mg or they were randomized to receive a low-dose combination of N30 and valsartan 80 mg for another 4 weeks. BP variability was assessed by using the SD or the %CV of the short-term BP measured at clinic.
  
  
  
  Of the 391 patients (20~70 years with stage II or higher hypertension) screened for study inclusion, 362 patients who had 3 BP measurements were enrolled. The reduction in the mean systolic/diastolic BP from baseline to week 4 was similar in both low-dose monotherapy groups with either N30 or valsartan 80 mg. BP variability (SD) was unchanged with either therapy, but the %CV was slightly increased in the N30 group. There was no significant difference in BP variability either in SD or %CV between responders and nonresponders to each monotherapy despite the significant difference in the mean BP changes. The up-titration effect of nifedipine GTS from 30 to 60 mg exhibited an additional BP reduction, but this effect was not shown in the up-titration of valsartan from 80 to 160 mg. Although the difference in BP was obvious between high-dose nifedipine GTS and valsartan, the BP variability was unchanged between the 2 drugs and was similar to the low-dose combinations. There was a low rate of adverse events in all treatment groups. In addition, escalating the dose of either nifedipine GITS or valsartan revealed a similar occurrence of adverse effects with low-dose monotherapy or the low-dose combination.
  
  
  
  Compared with up-titration of the angiotensin receptor blocker valsartan, up-titration of the calcium channel blocker nifedipine GITS provided no additional increased safety concerns and revealed better mean reductions in BP without affecting short-term BP variability. ClinicalTrials.gov identifier: NCT01071122.
authors.affiliation: Division of Cardiology, Cheil General Hospital, Dankook University College of Medicine, Seoul, South Korea. Electronic address: mdparkjb@gmail.com.
authors.forename: Jeong Bae
authors.initials: JB
authors.lastname: Park
authors.affiliation: Division of Cardiology, Ajou University Hospital, Gyeonggi, South Korea.
authors.forename: Joon-Han
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Division of Cardiology, Inje University Pusan Paik Hospital, Busan, South Korea.
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Division of Cardiology, The Catholic University of Korea, Seoul St. Mary׳s Hospital, Seoul, South Korea.
authors.forename: Ho-Joong
authors.initials: HJ
authors.lastname: Youn
authors.affiliation: Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea.
authors.forename: Seung Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Division of Cardiology, Korea University Anam Hospital, Seoul, South Korea.
authors.forename: Wan Joo
authors.initials: WJ
authors.lastname: Shim
authors.affiliation: Division of Cardiology, Korea University Guro Hospital, Seoul, South Korea.
authors.forename: Chang Gyu
authors.initials: CG
authors.lastname: Park
authors.affiliation: Division of Cardiology, Chungbuk National University Hospital, Chungbuk, South Korea.
authors.forename: Dong-Woon
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Seoul National University Bundang Hospital, Gyeonggi, Seoul, South Korea.
authors.forename: Dong-Ju
authors.initials: DJ
authors.lastname: Choi
authors.affiliation: Division of Cardiology, Gangnam Severance Hospital, Seoul, South Korea.
authors.forename: Se-Joong
authors.initials: SJ
authors.lastname: Rim
authors.affiliation: Division of Cardiology, Inje University IlsanPaik Hospital, Gyeonggi, South Korea.
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Chonnam National University Hospital, Gwangju, South Korea.
authors.forename: Ju-Han
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011446:Prospective Studies; D000068756:Valsartan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; D000068756:Valsartan; D009543:Nifedipine
keywords: BP variability; angiotensin receptor blocker; antihypertensive agents; calcium channel blocker; hypertension; safety