title: No evidence that frailty modifies the positive impact of antihypertensive treatment in very elderly people: an investigation of the impact of frailty upon treatment effect in the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over.
abstract: BACKGROUND
  Treatment for hypertension with antihypertensive medication has been shown to reduce stroke, cardiovascular events, and mortality in older adults, but there is concern that such treatment may not be appropriate in frailer older adults. To investigate whether there is an interaction between effect of treatment for hypertension and frailty in older adults, we calculated the frailty index (FI) for all available participants from the HYpertension in the Very Elderly Trial (HYVET) study, a double-blind, placebo-controlled study of antihypertensives in people with hypertension aged 80 and over, and obtained frailty adjusted estimates of the effect of treatment with antihypertensive medication on risk of stroke, cardiovascular events, and mortality.
  
  
  METHODS
  Participants in HYVET were randomised 1:1 to active treatment with indapamide sustained release 1.5 mg ± perindopril 2 to 4 mg or to matching placebo. Data relating to blood pressure, comorbidities, cognitive function, depression, and quality of life were collected at entry into the study and at subsequent follow-up visits. The FI was calculated at entry, based on 60 potential deficits. The distribution of FI was similar to that seen in population studies of adults aged 80 years and above (median FI, 0.17; IQR, 0.11-0.24). Cox regression was used to assess the impact of FI at entry to the study on subsequent risk of stroke, total mortality, and cardiovascular events. Models were stratified by region of recruitment and adjusted for sex and age at entry. Extending these models to include a term for a possible interaction between treatment for hypertension and FI provided a formula for the treatment effect as a function of FI. For all three models, the point estimates of the hazard ratios for the treatment effect decreased as FI increased, although to varying degrees and with varying certainty.
  
  
  RESULTS
  We found no evidence of an interaction between effect of treatment for hypertension and frailty as measured by the FI. Both the frailer and the fitter older adults with hypertension appeared to gain from treatment.
  
  
  CONCLUSIONS
  Further work to examine whether antihypertensive treatment modifies frailty as measured by the FI should be explored.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00122811 (July 2005).
authors.affiliation: Warwick Clinical Trials Unit, Division of Health Sciences, Warwick Medical School, University of Warwick, Gibbet Hill Campus, Coventry, CV4 7AL, UK. j.warwick@warwick.ac.uk.
authors.forename: Jane
authors.initials: J
authors.lastname: Warwick
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK. e.falaschetti@imperial.ac.uk.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Falaschetti
authors.affiliation: Geriatric Medicine, Dalhousie University, Queen Elizabeth II Health Sciences Centre, 1421-5955 Veterans' Memorial Lane, Halifax, B3H 1C6, Nova Scotia, Canada. kenneth.rockwood@dal.ca.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rockwood
authors.affiliation: Department of Medicine, Dalhousie University, Centre for Health Care of the Elderly, 1421-5955 Veterans' Memorial Lane, Halifax, B3H 2E1, Nova Scotia, Canada. arnold.mitnitski@dal.ca.
authors.forename: Arnold
authors.initials: A
authors.lastname: Mitnitski
authors.affiliation: Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Campus Sint Rafaël, Kapucijnenvoer 35, Box 7001, BE-3000, Leuven, Belgium. lutgarde.thijs@med.kuleuven.be.
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Thijs
authors.affiliation: Department of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK. n.beckett@imperial.ac.uk.
authors.forename: Nigel
authors.initials: N
authors.lastname: Beckett
authors.affiliation: Department of Medicine, Imperial College London, Hammersmith Campus, London, W12 0NN, UK. c.bulpitt@imperial.ac.uk.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bulpitt
authors.affiliation: Imperial Clinical Trials Unit, School of Public Health, Faculty of Medicine, Imperial College London, St Mary's Campus, Norfolk Place, London, W2 1PG, UK. r.peters@imperial.ac.uk.
authors.forename: Ruth
authors.initials: R
authors.lastname: Peters
mesh_terms: D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D015897:Comorbidity; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D016330:Frail Elderly; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000453:epidemiology; D015994:Incidence; D007190:Indapamide / Q000627:therapeutic use; D008297:Male; D020913:Perindopril / Q000627:therapeutic use; D011788:Quality of Life; D020521:Stroke / Q000453:epidemiology
chemical_list: D000959:Antihypertensive Agents; D007190:Indapamide; D020913:Perindopril