An Expert Opinion From the European Society of Hypertension–European Union Geriatric Medicine Society Working Group on the Management of Hypertension in Very Old, Frail Subjects
2016; Lippincott Williams & Wilkins; Volume: 67; Issue: 5 Linguagem: Inglês
10.1161/hypertensionaha.115.07020
ISSN1524-4563
AutoresAthanase Bénétos, Christopher J. Bulpitt, Mirko Petrović, Andrea Ungar, Enrico Agabiti Rosei, Antonio Cherubini, Josep Redón, Tomasz Grodzicki, Anna F. Dominiczak, Timo Strandberg, Giuseppe Mancia,
Tópico(s)Cardiovascular Health and Disease Prevention
ResumoHomeHypertensionVol. 67, No. 5An Expert Opinion From the European Society of Hypertension–European Union Geriatric Medicine Society Working Group on the Management of Hypertension in Very Old, Frail Subjects Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessResearch ArticlePDF/EPUBAn Expert Opinion From the European Society of Hypertension–European Union Geriatric Medicine Society Working Group on the Management of Hypertension in Very Old, Frail Subjects Athanase Benetos, Christopher J. Bulpitt, Mirko Petrovic, Andrea Ungar, Enrico Agabiti Rosei, Antonio Cherubini, Josep Redon, Tomasz Grodzicki, Anna Dominiczak, Timo Strandberg and Giuseppe Mancia Athanase BenetosAthanase Benetos From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). , Christopher J. BulpittChristopher J. Bulpitt From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). , Mirko PetrovicMirko Petrovic From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). , Andrea UngarAndrea Ungar From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). , Enrico Agabiti RoseiEnrico Agabiti Rosei From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). , Antonio CherubiniAntonio Cherubini From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). , Josep RedonJosep Redon From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). , Tomasz GrodzickiTomasz Grodzicki From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). , Anna DominiczakAnna Dominiczak From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). , Timo StrandbergTimo Strandberg From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). and Giuseppe ManciaGiuseppe Mancia From the Department of Geriatrics and FHU CARTAGE, CHU de Nancy and INSERM 1116, Université de Lorraine, Nancy, France (A.B.); Department of Medicine Imperial College, London, United Kingdom (C.J.B.); Department of Geriatrics, Ghent University Hospital, and Ghent University, Ghent, Belgium (M.P.); Geriatric Cardiology and Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Firenze, Italy (A.U.); Clinica Medica, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy (E.A.R.); Geriatria ed Accettazione Geriatrica d'Urgenza, IRCCS-INRCA, Ancona, Italy (A.C.); Department of Internal Medicine Hospital Clínico de Valencia, INCLIVA Research Institute, University of Valencia, CIBERObn ISCiii, Madrid, Spain (J.R.); Department of Internal Medicine and Geriatrics, Jagiellonian University, Cracow, Poland (T.G.); College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom (A.D.); University of Helsinki, and Helsinki University Central Hospital, Geriatrics, Helsinki, and Center for Life Course Health Research, University of Oulu, Oulu, Finland (T.S.); and Department of Clinical Medicine, University of Milano-Bicocca, Milan, Italy (G.M.). Originally published14 Mar 2016https://doi.org/10.1161/HYPERTENSIONAHA.115.07020Hypertension. 2016;67:820–825Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2016: Previous Version 1 Two years after the publication of the 2013 guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC),1 the ESH and the European Union Geriatric Medicine Society have created a common working group to examine the management of hypertensive subjects aged >80 years. The general term hypertension in the elderly is not sufficiently accurate because it mixes younger old patients (60–70 years) with the oldest old. Our group believes that the management of hypertension in individuals aged ≥80 years should be specifically addressed. Although arbitrary, this cutoff value identifies a population that is expanding faster than any other age group with a 50% increase of life expectancy during the past 50 years2,3; furthermore, the incidence and prevalence of comorbidities, frailty, and loss of autonomy greatly increases after the age of 80 years4; finally, although there is limited evidence on the management of hypertension in this age group, the latest clinical studies indicate that in these patients, treatment may not be the same as in patients in the lower age strata.The aim of this Working Group was to discuss more in-depth treatment aspects of hypertensive patients aged ≥80 years or older, with special focus on the difficulties and uncertainties posed by very old frail individuals. We focused, in particular, on the following points of the 2013 ESH/ESC guidelines:Benefits of treatment.Blood pressure (BP) thresholds and targets.The choice of treatment.Benefits of TreatmentThe 2013 ESH/ESC guidelines1 reported the results of the Hypertension in the Very Elderly Double Blind Trial (HYVET). This showed that in hypertensive patients aged ≥80 years, the administration of the thiazide-like diuretic indapamide supplemented, if necessary, by the angiotensin-converting enzyme inhibitor perindopril led to a significant reduction in the risk of major cardiovascular events and all-cause death when compared with placebo.2 From this, the guidelines concluded that there is evidence that antihypertensive treatment is beneficial in octogenarians in whom BP is elevated and that, therefore, BP-lowering interventions can be strongly recommended within this age range. However, both the ESH/ESC guidelines1 and other publications5–8 also point out limitations in the demonstration that treatment is beneficial in octogenarians and this need to be addressed. First, the HYVET is to date the only randomized clinical trial that has addressed this important issue, making confirmation by a second trial highly desirable. Second, the age of the HYVET patients was for the most part closer to 80 years (73% in the 80–84 and 22% in the 85–89 range), leaving the effect of treatment in patients close to or >90 years of age largely unexplored. Third, because the trial was prematurely interrupted by the Safety Monitoring Board (because of the evidence of protective effect of BP reduction in the treated group), the follow-up was rather short (median, 1.8 years). Despite the observation that in the HYVET patients the rate of events remained lower in the originally treated group 1 year after the trial termination,9 this requires the duration of benefit to be determined. Finally, the 2013 ESH/ESC guidelines state that the HYVET deliberately recruited patients in good physical and mental conditions and excluded ill and frail individuals, who are common among octogenarians, and also excluded patients with clinically relevant orthostatic hypotension,1 thereby emphasizing probably the most important limitation of the available information, ie, leaving out of consideration the influence of patients' general health, concomitant medication, and frailty on the decision about antihypertensive treatment implementation.Post hoc analysis of the HYVET trial did not find a relationship between the benefit of antihypertensive treatment and patients' frailty.10 This is reassuring for community-dwelling older hypertensives, but it is worth remembering that the HYVET did not include very frail patients and that patients with multiple morbidities and clinically significant cognitive impairment were also excluded. Indeed, both recent observational studies and registries show an important influence of the frailty status on the relationship between BP and outcomes, especially in treated hypertensives. This can be exemplified by studies that show the association between BP and mortality to vary according to the walking speed,11 cognitive function, assessed with the Mini Mental State Examination and disability, measured using the activity of daily living.12 Indeed, Odden et al11 showed that systolic BP in faster walkers was positively correlated with mortality, whereas no relationship between BP and mortality was observed among slower walkers. Moreover, in patients unable to complete the walk test, BP was negatively associated with the risk of death.6 In the Milan Geriatrics study,12 higher systolic BP values were related to lower mortality among individuals aged ≥75 years who had an impaired Mini Mental State Examination (<25 points) or activity of daily living (<6 points). Also, the Predictive Value of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population (PARTAGE) study has shown that what applies to middle-aged patients does not necessarily apply to old (≥80 years) nursing home residents,13–15 ie, the frailest oldest patients. Actually, in this very old frail population, values of BP recorded with clinical standard procedures were similar to those obtained with multiple 3-day morning and evening measurements,13 and the negative relationship between the main end point of the study (total mortality and major cardiovascular events) and systolic BP (SBP) was observed with BP measured by a clinician, or self-measured.14 Interestingly, in this study, the highest mortality rate was observed in patients with SBP<130 mm Hg, who were treated with ≥2 antihypertensive drugs, at variance from what was seen in those treated with 1 antihypertensive agent or not receiving any antihypertensive drug at all.15 Likewise, Mossello et al16 found a more pronounced cognitive decline in treated old hypertensive patients having mild cognitive impairment or dementia in whom SBP was low (<128 mm Hg). Such an effect was not observed in subjects with low SBP but without antihypertensive treatment.It is important to remember that both low BP and orthostatic hypotension are associated with syncope, falls, and related injuries and fractures.17–19 Therefore, both the benefits (including preserving autonomy) and the risks of antihypertensive therapy should be considered before starting treatment in the very frail older population. This population is the one at the highest risk of not only hypertension-related cardiovascular events but also hypotension-related events.19–21 Hypotension-related events are likely to be more common in real life than in clinical trials in which treatment is delivered by expert physicians and patients are followed up closely. In a recent analysis of a large real-life database, very old individuals showed a significant increase in hospitalizations for hip fracture over the 30 days after initiation of antihypertensive drug treatment.22 This has been previously observed in patients with a mean age of 80 years (between 86 and 100 years; 26%) over the 45 days after antihypertensive treatment initiation.19BP Thresholds and TargetsBecause in the HYVET, patients were recruited if their entry SBP was ≥160 mm Hg, this is the SBP value recommended by the 2013 ESH/ESC guidelines at which drug treatment in octogenarians should be started.1 The threshold for treatment has been set at a lower SBP level (≥150 mm Hg) in the US 2014 guidelines,5 but because octogenarians with entry SBP values <160 mm Hg have never been studied in randomized clinical trials or shown to have beneficial effects of BP-lowering interventions in subgroup data from trials addressing a larger age range, this does not seem to be based on solid evidence. Thus, it remains unsubstantiated whether in this very old patient category grade 1 hypertension, ie, a SBP between 140 and 159 mm Hg, might benefit from antihypertensive drugs.Evidence on the BP goals for treatment in octogenarians is also limited. Both the 2013 ESH/ESC1 and the US guidelines5 recommend adopting the goal set by the HYVET, ie, <150 mm Hg SBP but neither addresses the question of the SBP value below which the treatment may interfere with patients' safety. This is a critical issue because, as mentioned above, (1) observational studies have repeatedly shown that in the very old population, low BP values are associated with an increased morbidity and mortality, (2) somewhat statistically underpowered, randomized Japanese trials have not found clear benefits of SBP reductions <140 mmHg,23,24 and (3) a SBP reduction to 75 years. However, in the SPRINT, the number of patients aged ≥80 years has not been reported and may be substantially lower than the 28% (2600) patients aged ≥75 years. Furthermore, interpretation of several aspects of the SPRINT data (lack of beneficial effect on stroke, masking effect of diuretics on signs and symptoms of >3 drug heart failure, BP measuring approach, etc) are still under discussion.28,29 Finally, and more importantly, patients with advanced frailty, cognitive decline, loss of autonomy, and living in nursing home were excluded from the trial. Exclusion from trial extended to patients with decompensated heart failure, history of stroke, and diabetes mellitus, ie, conditions commonly associated with hypertension in aged individuals in whom they represent a common cause of death. This is a crucial issue also because in SPRINT, the aggressively treated group showed a substantial increase of hypotension, syncope, electrolyte abnormalities, and renal failure, ie, adverse reactions that are likely to be magnified in very old patients, even more so if frail. Thus, application of the SPRINT results in this population cannot be done unconditionally, also considering that other studies including frail people have not obtained similar results. Although potentially useful to robust old hypertensives, these results may have a limited transferability to frail, very old patients in whom the treatment strategies and the treatment goals should be largely driven by their functional status and comorbidities.Choice of TreatmentOn the basis of trials performed in patients aged ≥60 years, both the 2013 ESH/ESC1 guidelines and the US guidelines2 recommend that the antihypertensive treatment to be implemented in old hypertensive subjects to use the same drug classes that are recommended for younger patients, ie, diuretics, angiotensin receptor antagonists, angiotensin-converting enzyme inhibitors, and calcium channel blockers, with an extension to β-blockers in the ESH/ESC guidelines.1 On the basis of large meta-analyses, they also consider the above 5 classes similarly protective in old hypertensive individuals although indicating diuretics and calcium channel blockers as the preferred choice in isolated systolic hypertension given the preferential use of these 2 drugs in trials on this condition. Neither the European nor the US guidelines mention any difference in the type of treatment in hypertensive patients aged ≥80 years when compared with patients aged <80 years. In the HYVET, the drugs used were the thiazide-like diuretic indapamide complemented by perindopril in ≈70% of the patients, suggesting a possible preference for a treatment based on a diuretic-angiotensin-converting enzyme inhibitor combination. However, in a prespecified secondary analysis of a Japanese study30 on hypertensive patients aged 75 to 84 years, those receiving an angiotensin receptor antagonist/calcium channel blocker combination showed a reduction in the risk of stroke when compared with patients receiving an angiotensin receptor antagonist/diuretic combination. Given the evidence that the benefit of treatment largely depends on BP lowering per se,31 ie, regardless how it is obtained, the opinion of this Working Group is that in principle the large number of antihypertensive drug classes recommended for younger age strata are suitable for use also in the oldest-old individuals. Except when required for specific clinical conditions (eg, angina pectoris, previous myocardial infarction, and heart failure), the use of β-blockers in these very old hypertensive individuals remains controversial, however.32,33In the 2013 ESH/ESC guidelines,1 the suggestion is made to consider initiation of antihypertensive treatment with a 2-drug combination if cardiovascular risk is high, with no distinction between younger and older patients. However, in octogenarians, initial administration of 2 antihypertensive drugs, even when administered at low doses, may put subjects at an unwarranted risk of hypotension, given that homeostatic mechanisms that maintain BP against gravity and other challenges undergo a progressive impairment as age advances.34 Furthermore, increasing the number of the prescribed drugs may increase the probability of adverse drug, drug–drug, and drug–dise
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