The association between antihypertensive treatment and serious adverse events by age and frailty: A cohort study

Author summary Why was this study done? The benefits of blood pressure-lowering treatment have been widely studied, with recent reviews of the scientific literature suggesting increasing benefit as patients get older.The harms of blood pressure-lowering treatment are less well known, although another recent review of clinical trials showed that treatment is associated with acute kidney injury, hyperkalaemia (high blood potassium leading to medical complications), hypotension (low blood pressure) and syncope (fainting), but not falls or fracture.However, the trials included in these reviews are likely to have limited external validity, since participants are typically highly selected and diligently supported by trial teams in a way that does not reflect routine clinical practice.At present, there is little evidence to describe how the harms of antihypertensive treatment change as patients get older and develop frailty. What did the researchers do and find? This observational study utilised anonymised data from the electronic health records of patients in England. Those included were aged 40+ years, with high blood pressure, but had not previously been prescribed blood pressure-lowering treatment.A statistical analysis was undertaken to examine whether patients prescribed a blood pressure-lowering medication were more likely to experience a serious adverse event sooner, compared to those who were not prescribed such medications.In a total of 3,834,056 patients, blood pressure-lowering treatment was associated with an increased risk of hospitalisation or death from falls, hypotension, syncope (but not fracture), acute kidney injury, electrolyte abnormalities, and primary care consultations for gout.These risks were much higher in older patients and those with frailty. For example, in those aged 40 to 49 years, 3,501 patients would need to be treated for 5 years to cause a serious fall. However, for those aged 80 to 89 years, only 33 patients would need to be treated for the same period to cause a serious fall. What do these findings mean? Blood pressure-lowering treatment was found to be associated with an increased risk of serious adverse events.Across the whole population, the likelihood of experiencing this harm was very low.However, in older patients (aged 80+ years) and those with moderate to severe frailty, the risk of harm was notably increased.This analysis suggests that new prescription of blood pressure-lowering treatment in these older patients with frailty was just as likely to cause a serious fall, as it would prevent a stroke or heart attack. BackgroundAntihypertensives are effective at reducing the risk of cardiovascular disease, but limited data exist quantifying their association with serious adverse events, particularly in older people with frailty. This study aimed to examine this association using nationally representative electronic health record data. Methods and findingsThis was a retrospective cohort study utilising linked data from 1,256 general practices across England held within the Clinical Practice Research Datalink between 1998 and 2018. Included patients were aged 40+ years, with a systolic blood pressure reading between 130 and 179 mm Hg, and not previously prescribed antihypertensive treatment. The main exposure was defined as a first prescription of antihypertensive treatment. The primary outcome was hospitalisation or death within 10 years from falls. Secondary outcomes were hypotension, syncope, fractures, acute kidney injury, electrolyte abnormalities, and primary care attendance with gout. The association between treatment and these serious adverse events was examined by Cox regression adjusted for propensity score. This propensity score was generated from a multivariable logistic regression model with patient characteristics, medical history and medication prescriptions as covariates, and new antihypertensive treatment as the outcome. Subgroup analyses were undertaken by age and frailty. Of 3,834,056 patients followed for a median of 7.1 years, 484,187 (12.6%) were prescribed new antihypertensive treatment in the 12 months before the index date (baseline). Antihypertensives were associated with an increased risk of hospitalisation or death from falls (adjusted hazard ratio [aHR] 1.23, 95% confidence interval (CI) 1.21 to 1.26), hypotension (aHR 1.32, 95% CI 1.29 to 1.35), syncope (aHR 1.20, 95% CI 1.17 to 1.22), acute kidney injury (aHR 1.44, 95% CI 1.41 to 1.47), electrolyte abnormalities (aHR 1.45, 95% CI 1.43 to 1.48), and primary care attendance with gout (aHR 1.35, 95% CI 1.32 to 1.37). The absolute risk of serious adverse events with treatment was very low, with 6 fall events per 10,000 patients treated per year. In older patients (80 to 89 years) and those with severe frailty, this absolute risk was increased, with 61 and 84 fall events per 10,000 patients treated per year (respectively). Findings were consistent in sensitivity analyses using different approaches to address confounding and taking into account the competing risk of death. A strength of this analysis is that it provides evidence regarding the association between antihypertensive treatment and serious adverse events, in a population of patients more representative than those enrolled in previous randomised controlled trials. Although treatment effect estimates fell within the 95% CIs of those from such trials, these analyses were observational in nature and so bias from unmeasured confounding cannot be ruled out. ConclusionsAntihypertensive treatment was associated with serious adverse events. Overall, the absolute risk of this harm was low, with the exception of older patients and those with moderate to severe frailty, where the risks were similar to the likelihood of benefit from treatment. In these populations, physicians may want to consider alternative approaches to management of blood pressure and refrain from prescribing new treatment.

Automated summary

This study found that blood pressure-lowering treatment is associated with an increased risk of serious adverse events, particularly in older and frail patients. The analysis suggests that prescribing new treatment in these populations may be just as likely to cause a serious fall as it would prevent a stroke or heart attack.