Adherence to BP Meds Tied to Reduced Mortality Risk in the Elderly

Erik Greb

June 15, 2020

Good adherence to antihypertensive treatment is linked to a significant reduction in mortality risk among the elderly, even for the frailest of these patients, new research shows.

Investigators found that among individuals who had good clinical status, high adherence to antihypertensive treatment was associated with a 44% reduction in all-cause mortality, compared with very low adherence. Adherence was also associated with reduced risk for cardiovascular mortality.

The findings suggest "that antihypertensive treatment is beneficial in frail old patients, but that the extent of the benefit may be less than that achieved by healthier old individuals," the investigators, with lead author Giuseppe Mancia, MD, emeritus professor of medicine at the University of Milano-Bicocca in Milan, Italy, write.

The study was published online June 8 in Hypertension.

Previous Selection Bias

Previous randomized trials have demonstrated that treatment of hypertension reduces the risk for cardiovascular morbidity or fatal events related to hypertension.

Many of these trials, however, excluded patients with serious comorbidities. Reflecting this state of the evidence, hypertension guidelines emphasize that the effect of hypertensive medication on outcomes in frail, elderly patients is unclear.

To assess the relationship between adherence to antihypertensive medication regimens and death in frail vs nonfrail elderly patients, the investigators developed a multisource comorbidity score using databases from various Italian regions. The score predicts time to death in an unselected population of people aged 50 years or older with high sensitivity.

The investigators used this score to evaluate the protective effect of adherence to antihypertensive medication among elderly patients with different life expectancies.

The investigators obtained data from the Healthcare Utilization databases of Lombardy, Italy. Information included drug prescriptions, hospitalizations, and death certificates.

Eligible participants were aged 65 years or older, were beneficiaries of Italy's National Health Service, and had received at least three consecutive prescriptions for antihypertensive drugs between 2011 and 2012.

Patients with fewer than 6 months' follow-up and those who were institutionalized in long-term residential facilities were excluded.

Using the multisource comorbidity score, Mancia and colleagues categorized participants as having good, medium, poor, or very poor clinical status.

They conducted a case-control study of all patients who received antihypertensive medication. The two sets of case patients included those who died of any cause and those who died of a cardiovascular cause.

The researchers randomly matched case patients with control patients in accordance with sex, age at entry, date of entry, and clinical status.

They defined adherence to therapy as the cumulative number of days during which antihypertensive medication was available, divided by the number of days of follow-up. The resulting number was the proportion of days covered by prescriptions.

The analysis included 1,283,602 patients. Of this population, 255,228 patients died. The incidence of death ranged from 16% among patients with good clinical status to 64% in those with very poor clinical status.

Of the 255,228 case patients, 254,778 were matched with control patients. Case patients were more likely to have been taking only one antihypertensive drug at the index date, to have been taking other drugs more frequently, and to have more comorbidities, compared with control patients.

Compared with patients with very low adherence, for those with very high adherence, all-cause mortality was reduced by 44%, 43%, 40%, or 33%, depending on whether their baseline clinical status was good, medium, poor, or very poor, respectively.

Moreover, compared with patients with very low adherence, among those with very high adherence, cardiovascular mortality was reduced by 41%, 34%, 23%, and 14% for patients of good, medium, poor, and very poor clinical status, respectively.

The benefit of adherence persisted in the investigators' sensitivity analysis. This finding makes it unlikely that the progressive reduction in mortality observed with progressive increase in adherence results from other factors, despite the study's observational design, the investigators note.

In a statement, Mancia said clinicians should do their best "to encourage and support patients to take their medications, because adherence is crucial to getting the benefits. Medications do nothing if people don't take them."

Robust Research

Commenting on the study for Medscape Medical News, Bruce Ovbiagele, MD, professor of neurology and associate dean at the University of California, San Francisco, who was not involved in the research, said the investigators used "rigorous methodology in a large, unselected population to properly clarify the impact of adherence to antihypertensive treatment on risk of dying in frail elderly individuals.

"Previous studies on this topic have revealed conflicting results and were generally not conducted in as robust a manner as the current study," he said.

However, he added, the fact that the study is based on an administrative dataset is a limitation because "transient changes in use, type, or dose of antihypertensive medications during the study period could not be captured, and information on initial and subsequent blood pressure values was not available for analysis."

The investigators could have compensated for this shortcoming by assessing the data for interaction effects between age, frailty, and medication adherence on mortality outcome.

"It would have been interesting to know if these protective benefits are similar in a frail 65-year-old vs a frail 90-year-old," said Ovbiagele.

"The big message here is for clinicians (and patients and caregivers) to aim for high adherence (≥75%) to antihypertensive treatments in all elderly patients, regardless of their level of frailty, with the goal of significantly reducing mortality risk," he added.

The Italian Ministry of Education, University, and Research and the Italian Ministry of Health supported this study. Mancia has received honoraria for participation as speaker or chairman in national or international meetings from Bayer, Boehringer Ingelheim, CVRx, Daiichi Sankyo, Ferrer, Medtronic, Menarini Int, Merck, Novartis, Recordati, and Servier. Ovbiagele has disclosed no relevant financial relationships.

Hypertension. Published online June 9, 2020. Abstract

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