New Study Reveals How Age and Frailty Influence Association Between Antihypertensive Treatment and Serious Adverse Events

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Cardiovascular disease is a significant health concern, and its risk can be significantly reduced through antihypertensive treatment. Recent hypertension management guidelines have recommended more intensive blood pressure-lowering strategies based on trials demonstrating benefits across all age groups. However, antihypertensives are also commonly associated with adverse drug reactions, so physicians must carefully weigh the potential benefits against the potential harms when prescribing these medications. Despite these recommendations, limited empirical evidence describes the association between antihypertensive therapy and serious adverse events. 

A recent observational study published in PLOS Medicine involving 3.8 million patients, who were previously untreated and had raised systolic blood pressure, has shed light on the association between antihypertensive treatment and serious adverse events. The study, which spanned a decade, found that antihypertensive treatment was linked to an increased risk of hospitalization or death resulting from falls, hypotension, syncope, acute kidney injury, electrolyte abnormalities, and primary care consultations for gout. However, the risk of harm from treatment was shallow overall, and serious adverse events were rare.  

The study’s findings revealed that older patients aged 80 and above and those with moderate to severe frailty faced notably increased absolute risks of harm from antihypertensive treatment. In these subpopulations, the risk of harm from falls was similar to the likelihood of benefit from treatment. This suggests that prescribing antihypertensive treatment becomes more finely balanced in these cases. Consequently, recent calls to eliminate age-related blood pressure treatment thresholds from international guidelines should be approached with caution.  

These results provide crucial information for clinicians, enabling them to make individualized treatment decisions in partnership with their patients. While patient choice remains essential in treatment decisions, the study highlights that a more cautious approach may be warranted when considering antihypertensive treatment for individuals in advanced old age and with increasing frailty severity.  

This study is the most extensive population-based analysis, examining the serious adverse events associated with antihypertensive therapy. By utilizing nationally representative electronic health record data, the researchers could replicate population treatment effects observed in meta-analyses of randomized controlled trials. Moreover, the study is the first to demonstrate how an individual’s absolute risk of harm changes with increasing age and frailty, providing valuable insights for clinical practice.  

While previous studies have attempted to explore the relationship between antihypertensive treatment and adverse events, they have produced inconclusive findings. This study, however, overcomes previous limitations by analyzing a large, more generalizable population that includes a significant proportion of older patients and those with moderate to severe frailty. The results confirm the association between antihypertensive treatment and falls and reveal a notably higher absolute risk increase in the underrepresented populations of older and frailer individuals.  

The study’s strength lies in its use of electronic health records from two databases, covering over half the population in England, ensuring the data’s representativeness. The findings align with treatment effect estimates from meta-analyses of randomized controlled trials for most outcomes. However, some discrepancies may be attributed to differences in outcome measurement methods between the study and previous trials.  

Although the absolute risk of harm from antihypertensive treatment is low overall, this study’s insights emphasize the need to consider age and frailty when assessing the benefits and harms of treatment. The findings contribute to a growing body of evidence supporting personalized treatment decisions, with future research aiming to develop prediction models that estimate an individual’s risk and personalize treatment recommendations accordingly. In the meantime, these study results provide meaningful guidance for clinical practice and can inform health economic modeling to support evidence-based prescribing recommendations. 

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