title: Factors influencing blood pressure response to trandolapril add-on therapy in patients taking verapamil SR (from the International Verapamil SR/Trandolapril [INVEST] Study).
abstract: Factors such as age and race/ethnicity might influence blood pressure (BP) response to drugs. Therapeutic response to the angiotensin-converting enzyme inhibitor trandolapril used as add-on therapy to stable calcium channel blocker therapy with verapamil sustained release 240 mg was addressed in a racially/ethnically diverse group of 1,832 hypertensive patients with coronary artery disease. Furthermore, the association with a polymorphism (1166A-->C) in the angiotensin II type 1 receptor gene (AGTR1) was tested. BP response was compared between groups using analysis of covariance after adjustment for covariates associated with BP response. Genotyping was performed using polymerase chain reaction and pyrosequencing. Trandolapril decreased mean unadjusted systolic and diastolic BPs by -9.1 +/- 17.3 (SD) and -4.1 +/- 10.1 mm Hg, respectively. The percentage of patients with BP under control (<140/90 mm Hg) increased from 6.7% to 41.3% (p <0.0001). Adjusted BP response was significantly associated with age and baseline systolic and diastolic BP (p <0.0001). Whereas the decrease in systolic BP was more pronounced in younger patients, the opposite was observed for diastolic BP decrease. Diastolic BP response was also significantly associated with race. Specifically, the adjusted diastolic BP decrease was significantly smaller in Hispanics and blacks than whites (p = 0.0032 and p = 0.0069, respectively). However, Hispanics achieved a decrease in systolic BP and an increase in BP control similar to the other ethnic groups. There was no genetic association between AGTR1 1166A-->C genotype and BP response. In conclusion, trandolapril add-on therapy was effective in increasing BP control, with age and baseline BP associated with both systolic and diastolic BP response. Race was associated with diastolic BP response, although the difference is likely not to be clinically significant and AGTR1 genotype was not associated with BP response.
authors.affiliation: Department of Pharmacy Practice, College of Pharmacy, University of Florida, Gainesville, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Brunner
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Cooper-DeHoff
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.forename: Jason H
authors.initials: JH
authors.lastname: Karnes
authors.forename: Taimour Y
authors.initials: TY
authors.lastname: Langaee
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.forename: Julie A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D015986:Confounding Factors, Epidemiologic; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000208:ethnology / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005260:Female; D005787:Gene Frequency / Q000187:drug effects / Q000235:genetics; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000208:ethnology / Q000503:physiopathology; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000187:drug effects; D011647:Puerto Rico / Q000208:ethnology; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000235:genetics; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007211:Indoles; D044140:Receptor, Angiotensin, Type 1; C052035:trandolapril; D014700:Verapamil