Multiple HTN Meds Can Present a Risk in Frail Elderly With "Low" Systolic BP

Marlene Busko

February 19, 2015

NANCY, FRANCE — A new study of more than 1000 frail people in their 80s and 90s living in nursing homes "raises a cautionary note regarding the safety of using combination antihypertensive therapy in frail elderly patients with low systolic blood pressure," according to lead author Dr Athanase Benetos (University Hospital of Nancy, France) and colleagues[1].

Specifically, the frail individuals with a systolic BP <130 mm Hg (low systolic BP) who also received two or more antihypertensive agents had a twofold higher risk of dying within 2 years compared with their peers. Merely having the low systolic BP alone did not up the risk.

These findings from the Predictive Values of Blood Pressure and Arterial Stiffness in Institutionalized Very Aged Population (PARTAGE) longitudinal study are published online February 16, 2015 in JAMA Internal Medicine.

Thus, clinicians need to be aware of risks of polypharmacy in very frail elderly people. "In nursing-home residents and frail elderly patients, it is advisable to conduct a more comprehensive assessment (eg, comorbidities, polymedication, and frailty) to optimize therapeutic decisions," Benetos and colleagues write.

Moreover, since clinical trials were done in robust seniors, "dedicated, controlled interventional studies are warranted to assess the corresponding benefit-to-risk ratio in this growing population."

Invited to comment, Dr Carl J Pepine (University of Florida, Gainesville), cochair of the writing committee of the ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly, agrees that "we should be cautious in combining antihypertensives in frail elderly."

Frail Elderly, Polypharmacy, and Intensive BP Lowering

The Hypertension in the Very Elderly Trial (HYVET)—which informs the current European and American recommendations—showed benefits of lowering BP to 140 mm Hg to 150 mm Hg in individuals over age 80, but that trial excluded frail people with major comorbidities living in nursing homes, Benetos and colleagues note.

PARTAGE enrolled 1127 frail individuals age 80 and older in 2007 to 2008 who were living in nursing homes in France and Italy. The participants had a mean age of 88, and 78% were women.

The researchers had previously shown that, compared with the other participants in PARTAGE, those in the lowest BP tertile (systolic BP <130 mm Hg) had a 30% higher all-cause mortality during a 2-year follow up.

In the current study, they aimed to determine whether this increase in mortality in patients with a low systolic BP was tied to the number of antihypertensives the patients were receiving.

Of the 227 patients (20.1%) who were receiving two or more antihypertensive drugs and had a mean systolic BP below 130 mm Hg, the mean number of drugs was 2.6 and mean systolic BP was 119 mm Hg. The other 900 patients were receiving 1.5 BP-lowering medications and had a mean systolic BP of 142 mm Hg.

A total of 78% of the participants with low systolic BP who were taking multiple antihypertensives had hypertension, and 70% of the others had hypertension.

At 2 years, 32.2% of the individuals with low systolic BP who were taking multiple antihypertensives had died (14.5% from cardiovascular causes), and 19.7% of the others had died (9.4% from cardiovascular causes).

Patients who had a low systolic BP and were taking two or more antihypertensives had an adjusted 78% increased risk of mortality at 2 years.

All-Cause Mortality in Frail Elderly People, Low Systolic BP Plus at Least 2 Antihypertensives vs All Others

Systolic BP and antihypertensives HR (95% CI)
Adjusted* 1.78 (1.34–2.37)*
Excluding cardiovascular comorbidities 1.73 (1.29–2.32)
Excluding patients without hypertension* 1.76 (1.28–2.41)
*Adjusted for age, male sex, BMI <25, Charlson Comorbidity Index score, and activities of daily living scale score
Low systolic BP: < 130 mm Hg

Little is known about whether systolic blood pressure below 130 mm Hg should prompt a reduction in the number of antihypertensive drugs, but these new findings "point to the potentially crucial issue of overtreatment in frail elderly individuals," according to Benetos and colleagues.

The reasons for the increased mortality in this group remain to be determined, they write. Orthostatic hypotension occurred at similar rates across all predefined subgroups. Very old, frail individuals with low BP more frequently develop hypoperfusion of key organs, such as the brain, kidneys, and heart, due to impaired autoregulation; but in this study, low systolic BP alone did not predict increased mortality.

The researchers acknowledge that this was an observational study, and they were not able to adjust for the severity of comorbidities.

Nevertheless, "physicians should be more cautious when implementing international guidelines," which are based on studies of more robust elderly individuals, Benetos and colleagues write.

Pepine concurs. "Although BP values below which vital organ perfusion is impaired in octogenarians are not known, [the 2011 ACCF/AHA consensus statement about hypertension in the elderly recommends that] systolic BP <130 and diastolic BP <65 should be avoided, whenever possible . . . based on data from INVEST in elderly patients with hypertension with CAD who received multiple antihypertension drugs."

The study was supported by the Programme Hospitalier de Recherche Clinique of the French Ministry and by the French Ministry of Health. The researchers also received support from the Center of Clinical Investigations, the Center of Clinical Epidemiology of the University Hospital of Nancy, and the Cardiovascular and Renal Clinical Trialists network. The authors and Pepine have reported no relevant financial relationships.

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