Deprescribing Antihypertensive Agents in the OPTIMISE Trial

This research highlights the potential role for deprescribing anti-hypertensive agents in older adults (aged at least 80 years) who do not have a major cardiovascular comorbidity. While this is an important step forward for the deprescribing field, there are still several important questions related to the role of deprescribing that require further elucidation in future studies.

  1. Which patients are appropriate for deprescribing? In the OPTIMISE study1 participants were selected by primary care physicians based on their opinion about who they believed were safe for and could potentially benefit from deprescribing. Consequently, just 10% of individuals who were screened were enrolled in the study.1 In addition, the vast majority (97.7%) of participants were white. This highlights the potential challenges of recruiting patients for deprescribing studies and supports the need for larger-scale population-based studies of deprescribing given feasibility and safety shown here.
  2. Which antihypertensive medications should be deprescribed? It is not known whether safety differed according to which drugs were deprescribed. Future deprescribing studies that focus on the safety of deprescribing selected agents are warranted. Future studies may additionally benefit from explicitly incorporating the patient into decisions about which agent to deprescribe based on perceived side effects and negative impact on quality of life.
  3. How do the outcomes of this study1 apply to clinical practice? These results suggest that in adults aged at least 80 years without major cardiovascular comorbidity and with reasonable blood pressure control (systolic blood pressure less than 150) who take multiple anti-hypertensive agents, deprescribing may be a reasonable strategy. While the number of participants with reasonable blood pressure control (systolic blood pressure below 150) did not differ between the groups, there was an increase in systolic blood pressure of 3.4 mmHg and a numerical increase in adverse events in the intervention group. While the adverse events are not fully explained by the small increase in blood pressure, these are aspects that will be important to include in shared decision-making discussions regarding medication management and deprescribing. This also supports the need for close safety monitoring in the setting of deprescribing. The observation that 66 participants from the intervention arm had their antihypertensive medication reinstated based on the safety monitoring algorithm further supports this concept. Given this, it is worth emphasizing that deprescribing is defined as medication discontinuation under supervision.2 Finally, it is important to note that this study only examined outcomes at 12 weeks; additional long-term data are needed to further guide the potential value of deprescribing, with focus on both clinical events and quality of life.


Optimizing cardiovascular pharmacotherapy is about ensuring that the right patients are on the right drugs at the right time. Inherent to this, is the need to prescribe the right meds and deprescribe inappropriate or harmful medications. This study has taken important steps toward developing an evidence base toward the latter and has laid the groundwork for future researchers to study additional aspects of deprescribing.

Study Questions
Cardiovascular clinical practice guidelines have helped to standardize care; however, most clinical practice guidelines do not address the care of older adults with multiple co-morbidities resulting in polypharmacy. The researchers of this study1 aimed to establish whether reduction of one antihypertensive medication in adults over the age of 80, on two or more antihypertensive agents was possible without significant changes in systolic blood pressure control at 12 week follow up, or adverse events.

A total of 569 patients aged at least 80 years old from 69 primary care sites in England were enrolled in this non-inferiority open-label randomized controlled trial. All patients were taking two or more antihypertensive drugs and were considered to be under good blood pressure control (below 150/80) as defined by UK NIH target blood pressure for adults older than 80. Notably, patients with history of myocardial infarction (MI), heart failure, or stroke were excluded. Of those enrolled, 282 patients were randomized to a strategy of removal of one antihypertensive drug (intervention group), and 287 were randomized to continue usual care (control group). Blood pressures were assessed at 4 weeks in the intervention group, and then again at 12 weeks for both groups. The primary outcome was maintenance of systolic blood pressure below 150 at 12-week follow-up. Secondary outcomes included differences in systolic blood pressure, frailty, quality of life, adverse effects (including reported symptoms such as dizziness), adverse events non-resulting in hospitalization or death (such as elevated blood pressure), and serious adverse events resulting in hospitalization or death (such as acute coronary syndrome).

This study found that 86.4% of the patients in the intervention group and 87.7% of the patients in the control group had a systolic blood pressure less than 150 at 12 weeks, with an adjusted relative risk ratio of .98 (p=0.07). The mean increase in systolic blood pressure was 3.4 mm hg (95 %CI, [1.1- 5.8 mmHg], p=0.005) higher in the intervention group compared to control. There were no statistically significant differences between groups in frailty, quality of life, adverse effects, or serious adverse events at follow up. The number of patients experiencing at least one adverse event was significantly higher in the intervention group (adjusted RR 1.28 [95% CI, 1.06 to 1.54]).

This study found that among patients aged at least 80 years (without a history heart failure, history of MI, or stroke) who were on at least two antihypertensive medications, a strategy of antihypertensive medication reduction was non-inferior compared to usual care with regard to maintaining blood pressure below 150 systolic at 12 weeks.


  1. Sheppard 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;323:2039-51.

Clinical Topics: Acute Coronary Syndromes, Geriatric Cardiology

Keywords: Geriatrics, Antihypertensive Agents, Blood Pressure, Physicians, Primary Care, Control Groups, Quality of Life, Risk, Acute Coronary Syndrome, Follow-Up Studies, Feasibility Studies

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