Clinical trial NCT03453268: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Keywords: Blood pressure
Aged
Frailty
Polypharmacy
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2018-03-05
Enrollment: 1126
Sex: ALL
Minimum age (years): 80
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Therapeutic strategies: reduction of the antihypertensive treatment (intervention arm) vs. usual treatment (control arm)
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause mortality
timeFrame: up to 48 months
Secondary outcomes:
measure: Blood pressure analysis
timeFrame: up to 48 months
measure: Cause of deaths
timeFrame: up to 48 months
measure: Evaluation of frailty
timeFrame: up to 48 months
measure: Evaluation of autonomy
timeFrame: up to 48 months
measure: Evaluation of cognitive function
timeFrame: up to 48 months
measure: Number of falls
timeFrame: up to 48 months
measure: Medications
timeFrame: up to 48 months
measure: Evaluation of Quality of Life
timeFrame: up to 48 months
measure: Onset of cardiac decompensation , fatal or not fatal and monitoring of evolution in blood pressure
timeFrame: up to 48 months
measure: Number of patients at high risk for the onset of cardiac decompensation
timeFrame: up to 48 months
Other outcomes:
Locations:
city: Nancy
country: France
facility: Gériatrie - CHRU de Nancy
Study officials:
affiliation: CHRU NANCY - Pôle Gérontologie
name: Athanase BENETOS, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: