Generalizability of Blood Pressure Lowering Trials to Older Patients: Cross-Sectional Analysis.
Aged, 80 and over
Antihypertensive Agents
/ therapeutic use
Blood Pressure
Cross-Sectional Studies
Eligibility Determination
Female
Frailty
General Practice
/ statistics & numerical data
Humans
Hypertension
/ drug therapy
Male
Patient Selection
Randomized Controlled Trials as Topic
/ statistics & numerical data
cardiovascular disease
electronic health records
frailty
hypertension
randomized controlled trials
Journal
Journal of the American Geriatrics Society
ISSN: 1532-5415
Titre abrégé: J Am Geriatr Soc
Pays: United States
ID NLM: 7503062
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
06
04
2020
revised:
05
05
2020
accepted:
11
05
2020
pubmed:
9
9
2020
medline:
1
4
2021
entrez:
8
9
2020
Statut:
ppublish
Résumé
Randomized controlled trials are used to inform clinical guidelines on the management of hypertension in older adults, but it is unclear to what extent these trials represent the general population attending routine clinical practice. This study aimed to define the proportion and characteristics of patients eligible for hypertension trials conducted in older people. Cross-sectional study. A total of 24 general practices in England. Anonymized electronic health record data from all individuals aged 80 and older. Descriptive statistics were used to define the proportion and characteristics of patients eligible for two previous medication intensification trials (HYVET, SPRINT) and one medication reduction trial (OPTiMISE). A logistic regression model was constructed to estimate predictors of eligibility for each trial. Of 15,376 patients identified, 268 (1.7%; 95% confidence interval [CI] = 1.5-2.0%), 5,290 (34.4%; 95%CI = 33.7-35.2%), and 3,940 (25.6%; 95%CI = 24.9-26.3%) were eligible for the HYVET, SPRINT, and OPTiMISE trials, respectively. Between 5.6% and 30.7% of exclusions from each trial were due to eligibility criteria excluding those with high or uncontrolled blood pressure. Frailty (odds ratio [OR] = .44; 95%CI = .36-.54 [OPTiMISE]), cardiovascular polypharmacy (OR = .61; 95%CI = .55-.68 [SPRINT]) and multimorbidity (OR = .72; 95%CI = .64-.82 [SPRINT]) were associated with a lower likelihood of being eligible for one or more of the trials. A possible unintended consequence of blood pressure criteria used by trials attempting to answer different primary questions is that for many older patients, no trial evidence exists to inform treatment decisions in routine practice. Caution should be exercised when applying results from existing trials to patients with frailty or multimorbidity.
Sections du résumé
BACKGROUND/OBJECTIVES
Randomized controlled trials are used to inform clinical guidelines on the management of hypertension in older adults, but it is unclear to what extent these trials represent the general population attending routine clinical practice. This study aimed to define the proportion and characteristics of patients eligible for hypertension trials conducted in older people.
DESIGN
Cross-sectional study.
SETTING
A total of 24 general practices in England.
PARTICIPANTS
Anonymized electronic health record data from all individuals aged 80 and older.
MEASUREMENTS
Descriptive statistics were used to define the proportion and characteristics of patients eligible for two previous medication intensification trials (HYVET, SPRINT) and one medication reduction trial (OPTiMISE). A logistic regression model was constructed to estimate predictors of eligibility for each trial.
RESULTS
Of 15,376 patients identified, 268 (1.7%; 95% confidence interval [CI] = 1.5-2.0%), 5,290 (34.4%; 95%CI = 33.7-35.2%), and 3,940 (25.6%; 95%CI = 24.9-26.3%) were eligible for the HYVET, SPRINT, and OPTiMISE trials, respectively. Between 5.6% and 30.7% of exclusions from each trial were due to eligibility criteria excluding those with high or uncontrolled blood pressure. Frailty (odds ratio [OR] = .44; 95%CI = .36-.54 [OPTiMISE]), cardiovascular polypharmacy (OR = .61; 95%CI = .55-.68 [SPRINT]) and multimorbidity (OR = .72; 95%CI = .64-.82 [SPRINT]) were associated with a lower likelihood of being eligible for one or more of the trials.
CONCLUSION
A possible unintended consequence of blood pressure criteria used by trials attempting to answer different primary questions is that for many older patients, no trial evidence exists to inform treatment decisions in routine practice. Caution should be exercised when applying results from existing trials to patients with frailty or multimorbidity.
Substances chimiques
Antihypertensive Agents
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2508-2515Subventions
Organisme : Department of Health
ID : NIHR-RP-02-12-015
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 211182/Z/18/Z
Pays : United Kingdom
Organisme : Department of Health
ID : SPCR 335
Pays : United Kingdom
Organisme : Department of Health
ID : Oxford CLAHRC P2-501
Pays : United Kingdom
Organisme : Department of Health
ID : NIHR-RP-R2-12-015
Pays : United Kingdom
Organisme : Department of Health
ID : P2‐501
Pays : United Kingdom
Organisme : The Dunhill Medical Trust
ID : RTF107/0117
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2020 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.
Références
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903-1913.
Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387(10022):957-967.
Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358(18):1887-1898.
SPRINT Investigators. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103-2116.
Bejan-Angoulvant T, Saadatian-Elahi M, Wright JM, et al. Treatment of hypertension in patients 80 years and older: the lower the better? A meta-analysis of randomized controlled trials. J Hypertens. 2010;28(7):1366-1372.
Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure-lowering treatment on cardiovascular outcomes and mortality: 13 - benefits and adverse events in older and younger patients with hypertension: overview, meta-analyses and meta-regression analyses of randomized trials. J Hypertens. 2018;36(8):1622-1636.
Tinetti ME, Han L, Lee DS, et al. Antihypertensive medications and serious fall injuries in a nationally representative sample of older adults. JAMA Intern Med. 2014;174(4):588-595.
Mansfield KE, Nitsch D, Smeeth L, Bhaskaran K, Tomlinson LA. Prescription of renin-angiotensin system blockers and risk of acute kidney injury: a population-based cohort study. BMJ Open. 2016;6(12):e012690.
Benetos A, Labat C, Rossignol P, et al. Treatment with multiple blood pressure medications, achieved blood pressure, and mortality in older nursing home residents: the PARTAGE study. JAMA Intern Med. 2015;175(6):989-995.
Todd OM, Wilkinson C, Hale M, et al. Is the association between blood pressure and mortality in older adults different with frailty? A systematic review and meta-analysis. Age Ageing. 2019;48(5):627-635.
Pajewski NM, Berlowitz DR, Bress AP, et al. Intensive vs standard blood pressure control in adults 80 years or older: a secondary analysis of the systolic blood pressure intervention trial. J Am Geriatr Soc. 2020;68(3):496-504.
Rothwell PM. External validity of randomised controlled trials: “to whom do the results of this trial apply?”. Lancet. 2005;365(9453):82-93.
Supiano MA, Williamson JD. Applying the systolic blood pressure intervention trial results to older adults. J Am Geriatr Soc. 2017;65(1):16-21.
Tulner LR, Kuper IM, van Campen JP, et al. Treatment of hypertension in an elderly outpatient population in The Netherlands. Am J Geriatr Pharmacother. 2009;7(4):204-209.
Pajewski NM, Williamson JD, Applegate WB, et al. Characterizing frailty status in the systolic blood pressure intervention trial. J Gerontol A Biol Sci Med Sci. 2016;71(5):649-655.
Kulminski A, Yashin A, Ukraintseva S, et al. Accumulation of health disorders as a systemic measure of aging: findings from the NLTCS data. Mech Ageing Dev. 2006;127(11):840-848.
Romero-Ortuno R, Kenny RA. The frailty index in Europeans: association with age and mortality. Age Ageing. 2012;41(5):684-689.
Sheppard JP, Burt J, Lown M, et al. OPtimising Treatment for MIld Systolic hypertension in the Elderly (OPTiMISE): protocol for a randomised controlled non-inferiority trial. BMJ Open. 2018;8(9):e022930.
Bradley MC, Motterlini N, Padmanabhan S, et al. Potentially inappropriate prescribing among older people in the United Kingdom. BMC Geriatr. 2014;14:72.
Sato I, Akazawa M. Polypharmacy and adverse drug reactions in Japanese elderly taking antihypertensives: a retrospective database study. Drug Healthc Patient Saf. 2013;5:143-150.
Sterne JAC, White IR, Carlin JB, et al. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009;338:b2393.
Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol. 2017;71(19):2199-2269.
National Guideline Centre. National Institute for Health and Care Excellence. Hypertension in Adults: Diagnosis and Management [NICE Guideline 136]. London, UK: Royal College of Physicians; 2019.
Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104.
Nerenberg KA, Zarnke KB, Leung AA, et al. Hypertension Canada's 2018 guidelines for diagnosis, risk assessment, prevention, and treatment of hypertension in adults and children. Can J Cardiol. 2018;34(5):506-525.
Public Health England. National General Practice Profiles. 2018. https://fingertips.phe.org.uk/profile/general-practice. Accessed May 21, 2019.
Johnson KC, Whelton PK, Cushman WC, et al. Blood pressure measurement in SPRINT (systolic blood pressure intervention trial). Hypertension. 2018;71(5):848-857.
Clegg A, Bates C, Young J, et al. Development and validation of an electronic frailty index using routine primary care electronic health record data. Age Ageing. 2016;45(3):353-360.
Song X, Mitnitski A, Rockwood K. Prevalence and 10-year outcomes of frailty in older adults in relation to deficit accumulation. J Am Geriatr Soc. 2010;58(4):681-687.
Warwick J, Falaschetti E, Rockwood K, et al. 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. BMC Med. 2015;13:78.
Bress AP, Tanner RM, Hess R, Colantonio LD, Shimbo D, Muntner P. Generalizability of SPRINT results to the U.S. adult population. J Am Coll Cardiol. 2016;67(5):463-472.