ATEMPTing to navigate between “lower is better” and “less is more”

Hypertension is a leading risk factor for dementia, cardiovascular disease, and death in older adults. Although intensive blood pressure control effectively reduces cardiovascular morbidity and mortality, older and frail adults might be more susceptible to adverse effects such as hypotension, falls, and electrolyte abnormalities. Most of the landmark hypertension trials that inform current clinical guidelines have excluded older adults or those with significant multimorbidity, polypharmacy, disability, or other factors that can limit life expectancy or the ability to strictly adhere to burdensome study protocols.1Sheppard JP Lown M Burt J et al.Generalizability of blood pressure lowering trials to older patients: cross-sectional analysis.J Am Geriatr Soc. 2020; 68: 2508-2515Crossref PubMed Scopus (34) Google Scholar These exclusion criteria have led to substantial uncertainty in the management of populations that are simultaneously at the highest risk of cardiovascular disease and the highest risk of medication-related adverse effects, leaving clinicians struggling to navigate between the results of the Systolic Blood Pressure Intervention Trial (SPRINT) supporting the notion that "lower is better" (ie, a lower systolic blood pressure target is more favourable in these populations),2Williamson JD Supiano MA Applegate WB et al.Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years.JAMA. 2016; 3152673Crossref PubMed Scopus (918) Google Scholar versus the "less is more" approach of The Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTiMISE) trial (ie, fewer blood pressure-lowering medications are more favourable in these populations).3Sheppard JP Burt J Lown M et al.Effect of antihypertensive medication reduction vs usual care on short-term blood pressure control in patients with hypertension aged 80 years and older: the OPTIMISE randomized clinical trial.JAMA. 2020; 323: 2039-2051Crossref PubMed Scopus (91) Google Scholar In The Lancet Healthy Longevity, Jeannette Majert and colleagues4Majert J Nazarzadeh M Ramakrishnan R et al.Efficacy of decentralised home-based antihypertensive treatment in older adults with multimorbidity and polypharmacy (ATEMPT): an open-label randomised controlled pilot trial.Lancet Health Longev. 2024; (published online Feb 8.)https://doi.org/10.1016/S2666-7568(23)00259-3Summary Full Text Full Text PDF Scopus (0) Google Scholar present the results of a pilot study, the Antihypertensive Treatment Evaluation in Multimorbidity and Polypharmacy Trial (ATEMPT), that specifically targeted adults aged 65 years or older with mild hypertension and evidence of multimorbidity or polypharmacy, or both. ATEMPT was a decentralised, open-label trial that randomly assigned participants in a stratified manner to a group targeting intensification and another targeting de-escalation of therapy, aiming to produce an average difference of two medications between these groups. Additionally, unlike most large-scale hypertension trials to date, the intervention in ATEMPT was delivered in the home environment, leveraging home-based blood pressure monitoring, an online participant portal, largely remote contact with study personnel and medical personnel, and home delivery of study medications. At 13 months of follow-up, the group randomly assigned to intensification of therapy had a mean decrease of –10·7 mm Hg (95% CI –17·5 to –4·0) in systolic blood pressure relative to the lower intensity group. No differences were observed in major cardiovascular events, cognitive function, frailty, or quality of life, although the trial was not powered for these outcomes. Consistent with the findings of SPRINT, ATEMPT illustrates that achieving improved blood pressure control in vulnerable older adults, on average slightly above a 120 mm Hg systolic blood pressure target, is feasible and typically entails the addition of 1 to 1·5 more antihypertensive medications. The primary innovation of ATEMPT is achieving this level of blood pressure control through a pragmatic home-based strategy, which was well received by participants. This approach could serve as a model for future trials of chronic disease management in community-dwelling older adults. However, one unanswered question is to what extent reductions in blood pressure managed in this manner would persist over multiple years, given the typical time to benefit from antihypertensive therapy5Chen T Shao F Chen K et al.Time to clinical benefit of intensive blood pressure lowering in patients 60 years and older with hypertension.JAMA Intern Med. 2022; 182: 660Crossref PubMed Scopus (18) Google Scholar and the ease with which more intensive blood pressure control can degrade over time.6Jaeger BC Bress AP Bundy JD et al.Longer-term all-cause and cardiovascular mortality with intensive blood pressure control: a secondary analysis of a randomized clinical trial.JAMA Cardiol. 2022; 7: 1138-1146Crossref PubMed Scopus (22) Google Scholar Additionally, it is certainly premature to assume that intensive blood pressure control is safe in this population without larger trials of longer duration, involving more sensitive measures of physical and cognitive function. An important decision moving forward will be how to balance the need for full characterisation of safety and ascertainment of geriatric constructs that are not consistently assessed in primary care,7Nicosia FM Spar MJ Steinman MA Lee SJ Brown RT Making function part of the conversation: clinician perspectives on measuring functional status in primary care.J Am Geriatr Soc. 2019; 67: 493-502Crossref PubMed Scopus (13) Google Scholar with the desire to use pragmatic methodology that eases the burden of participation. Another important result is the fact that deprescribing antihypertensive medications was generally unsuccessful. The group targeting reduced antihypertensive medications actually experienced a mean increase of 0·4 antihypertensive medications during follow-up. Despite the growing interest in deprescribing throughout geriatric medicine,8Reeve E Thompson W Boyd C Lundby C Steinman MA The state of deprescribing research: how did we get here?.Basic Clin Pharmacol Toxicol. 2023; 133: 657-660Crossref PubMed Scopus (1) Google Scholar these results reinforce the view that deprescribing in the context of chronic disease management is easier said than done. Patients might be, counterintuitively, more amenable to adding medications, rather than removing medications that they might have been taking for years, if not decades. As the authors point out, this observation is consistent with the rate of re-prescription observed in the OPTiMISE trial,3Sheppard JP Burt J Lown M et al.Effect of antihypertensive medication reduction vs usual care on short-term blood pressure control in patients with hypertension aged 80 years and older: the OPTIMISE randomized clinical trial.JAMA. 2020; 323: 2039-2051Crossref PubMed Scopus (91) Google Scholar as well as what has been observed with interventions targeting less intensive glycaemic control in older adults with type 2 diabetes and frailty or multimorbidity. Alternatively, the pragmatic nature of the trial might have allowed for differential effects of external factors that can influence antihypertensive prescribing, including overlapping indications for medication (eg, alpha blockers for benign prostatic hypertrophy) and inconsistent medication reconciliation. ATEMPT provides an important window into the feasibility of enrolling and retaining older patients in hypertension trials, including safely achieving intensive blood pressure control in the short term. Although a longer duration of follow-up across a larger trial population is needed to ultimately draw clinical conclusions, this study opens the door to improving hypertension management and outcomes in this often-neglected population. NMP was an investigator on the Systolic Blood Pressure Intervention Trial (SPRINT) and received funding from the US National Institutes of Health (R01 AG055606). The US National Institutes of Health does not bear any responsibility for the commentary or interpretations presented here. Efficacy of decentralised home-based antihypertensive treatment in older adults with multimorbidity and polypharmacy (ATEMPT): an open-label randomised controlled pilot trialRemotely delivered antihypertensive treatment substantially reduced systolic blood pressure in older adults who are often less represented in trials, with no increase in the risk of serious adverse events. The results of this trial will inform a larger clinical trial focusing on assessing major cardiovascular events, safety, physical functioning, and cognitive function that is currently in the planning stages. These results also underscore the efficiency of decentralised trial designs, which might be of broader interest in other settings. Full-Text PDF Open Access