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

BackgroundTreatment 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.MethodsParticipants 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.ResultsWe 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.ConclusionsFurther work to examine whether antihypertensive treatment modifies frailty as measured by the FI should be explored.Trial registrationClinicalTrials.gov NCT00122811 (July 2005)Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0328-1) contains supplementary material, which is available to authorized users.

What Should Be the Target Blood Pressure in Elderly Patients With Diabetes?

“…The Hypertension in the Very Elderly Trial (HYVET) documented the benefits of lowering BP in persons $80 years of age: after 2 years of follow-up, mean BP was 15/6 mmHg lower in subjects receiving active treatment than in those receiving the placebo, and this difference led to a significant reduction in total mortality (21%), fatal stroke (39%), fatal and nonfatal stroke (30%), CV disease (23%), and heart failure (64%) (40). A more recent reanalysis of HYVET showed no evidence of interaction between the beneficial effect of lowering BP and frailty (41). This reanalysis suggests that frail and healthy individuals gain the same benefit from lowering BP.…”

Prescribing for frail older people

“…[6][7][8][22][23][24][25] The observational studies highlight the effects of polypharmacy, the use of drugs that increase the risk of falls, and drugs recommended by guidelines for secondary prevention of cardiovascular disease. They suggest that frail older people are more susceptible than non-frail to adverse outcomes, such as falls, institutionalisation and death with drug use.…”

“…The Hypertension in the Very Elderly Trial (HYVET) suggests benefit with antihypertensive therapy irrespective of frailty status. 25 In the Systolic Blood Pressure Intervention Trial (SPRINT) of adults aged 75 years or older, treating to a systolic blood pressure target of less than 120 mmHg compared with a target of less than 140 mmHg resulted in significantly lower rates of fatal and nonfatal major cardiovascular events and all-cause mortality. 24 Frailty did not appear to modify this relationship, although the trial was not powered to assess this.…”

Frailty and Cardiovascular Disease

“…The exclusion criteria for HYVET and SPRINT raise concern that their indings may not be generalizable to frail patients [43]. A subgroup analysis of patients enrolled in HYVET addressed this concern [44]. Participants in both the control and treatment groups were given a frailty index according to 60 diferent variables.…”