Impact of the Reduction in Antihypertensive Treatment on Total Mortality in Frail Subjects With Low Systolic Blood Pressure: Study in Subjects Over 80 Years Living in Nursing Homes

Study Overview
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Brief Summary
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The investigators hypothesize that a gradual reduction in antihypertensive treatment in nursing home (NH) patients with low systolic blood pressure (SBP) can improve survival through a controlled increase in SBP and a decrease in secondary morbidity due to 'overmedication'. Accordingly, the investigators propose a randomized, case/control trial in NH patients ≥ 80 years with a SBP<130 mmHg with >1 anti-Htn drugs. This trial will consist of two parallel arms: the intervention arm will entail antihypertensive drug step-down, while the control arm will comprise the standard anti-hypertensive treatment.

Detailed Description
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High blood pressure (BP), principally systolic hypertension, is a common condition in older people and is considered a major determinant not only of cardiovascular morbidity and mortality, but also of several other age-related diseases, including frailty, cognitive decline and loss of autonomy. The Hypertension in the Very Elderly Treatment (HYVET) study showed the beneficial effect of antihypertensive treatment in patients ≥ 80 years. More recently, the Systolic Blood Pressure Intervention Trial (SPRINT) study showed that even in subjects 75 years and older, CVD outcomes and total mortality were reduced with intensive treatment as compared to the standard therapeutic strategies. However, both HYVET and SPRINT were conducted in selected populations since they excluded the most frail subjects, those with clinically significant cognitive decline and dementia, those with several cardiovascular and other co-morbidities, as well as patients living in nursing homes. Interestingly, observational studies in these frail people, have shown no or even an inverse relationship between BP and morbidity and mortality. The PARTAGE longitudinal study was performed in 1130 subjects ≥ 80 years living in nursing homes (NHs). These subjects were receiving at mean 7.1 drugs/day; 2/3 of them were under antihypertensive drugs (mean 2.2 drugs/day). The PARTAGE study showed an over-mortality in hypertensive subjects with low SBP (<130 mmHg) treated with 2 or more antihypertensive drugs. These individuals, who represented 20% of the total studied population, exhibited 80% increase in mortality compared to all other groups, even after adjustment for several comorbidities. The recent European guidelines for hypertension indicate that in people ≥ 80 years with SBP≥160 mmHg there is evidence to recommend reducing SBP to between 150 and 140 mmHg. However, no recommendation exists on which strategy to follow if treatment decreases SBP to lower levels (ex: 120 mmHg) especially on the more frail and polymedicated patients of that age. Thus, in this case, physicians can either continue the same treatment of reduce the number of drugs. These contrasting results in old hypertensives reflects the enormous functional heterogeneity among individual of this age-group and clearly show that functional status rather than chronological age should guide therapeutic strategies. Thus, the guidelines for robust older individuals cannot be extrapolated to very old, frail individuals, who have been completely excluded from the above-mentioned clinical trials. The only way is to conduct a controlled clinical trial.

Official Title
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Impact of the Reduction in Antihypertensive Treatment on Total Mortality in Frail Subjects With Low Systolic Blood Pressure: Randomized, Controlled Study in Subjects Over 80 Years Living in Nursing Homes

Conditions
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Hypertension

Intervention / Treatment
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* Other: STEP DOWN strategy
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient 80 years or older Patient living in a NH SBP <130 mmHg, as measured (with an electronic device with recorder) in nursing homes by nurses (average of 3 measurements after 10 min of rest). These SBP values should be recorded in the absence of any acute illness or condition inducing acute BP drop Patient treated for hypertension with 2 or more antihypertensive drugs Stable antihypertensive treatment (3 weeks for an introduction or stop and 2 weeks for a posology change) Mandatory enrollment in a social security plan Patient (or legal representative if applicable) having signed an informed consent. Exclusion Criteria: Patient in which none of antihypertensive drugs can be stopped because of simultaneous indications for other cardiovascular diseases. Patient with estimated life expectancy <3 months. Patient who has already been included in this study

Ages Eligible for Study
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Minimum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Therapeutic strategies: reduction of the antihypertensive treatment (intervention arm) vs. usual treatment (control arm)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1: Interventional (drug reduction)<br>STEP DOWN strategy. Proposition of reduction of the number of antihypertensive medication according to: the systolic blood pressure levels, co-morbidities | Other: STEP DOWN strategy<br>* reduction of the number of antihypertensive medication according to: the systolic blood pressure levels, co-morbidities<br>|
| Other: 2: Control<br>Usual treatment | Other: Control<br>* usual treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | during a follow up period of 24 months minimal to 48 months maximal | up to 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood pressure analysis | Systolic BP, diastolic BP, pulse pressure (PP) in sitting position and then in upright position during the follow up period of 24-48 months | up to 48 months | 
| Cause of deaths | Major cardiovascular (CV) events (myocardial infarction, hospitalization for heart failure, stroke and any other serious CV complications requiring specific treatment or hospitalization) during the follow up period of 24-48 months | up to 48 months | 
| Evaluation of frailty | assessed by muscular force and Short Physical Performance Battery every 6 months | up to 48 months | 
| Evaluation of autonomy | assessed by scale Activites of Daily Living scale every 6 months | up to 48 months | 
| Evaluation of cognitive function | assessed by Mini Mental Status Evaluation (MMSE) every 6 months | up to 48 months | 
| Number of falls | Number of falls and recording of fractures during the follow up period of 24-48 months | up to 48 months | 
| Medications | Total number of medications, number of anti-hypertensive drugs during the follow up period of 24-48 months | up to 48 months | 
| Evaluation of Quality of Life | Indices of Quality of Life (EQ 5D) yearly | up to 48 months | 
| Onset of cardiac decompensation , fatal or not fatal and monitoring of evolution in blood pressure | Onset of cardiac decompensation , fatal or not fatal and monitoring of evolution in blood pressure during the follow un of 24 months to 48 months | up to 48 months | 
| Number of patients at high risk for the onset of cardiac decompensation | Number of patients at high risk for the onset of cardiac decompensation during the follow up of 24 months to 48 months | up to 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure, Aged, Frailty, Polypharmacy