Study suggests ’yes,’ but deprescribing antihypertensives still not ready for prime time

In elderly patients with high blood pressure (BP), a BP medication reduction strategy was deemed noninferior to usual care in terms of controlling systolic BP at 12 weeks, but experts questioned the safety of the approach.

In the OPTIMISE trial, over 500 participants (mean ages 84.8 years) were randomized in a 1:1 ratio to a strategy of antihypertensive medication reduction (49.6%) by the removal of at least one drug, or to either usual care with no medication changes (50.4%) or remaining on at least two BP-lowering drugs, according to James P. Sheppard, PhD, of the University of Oxford in England, and co-authors.

Overall, 86.4% patients in the medication reduction group and 87.7% in the usual care group had a systolic BP <150 mmHg at 12-week follow-up (adjusted relative risk 0.98, 97.5% CI 0.92 to ∞), they reported in JAMA.

The medication reduction was maintained in 66.3% participants in the intervention group, Sheppard and co-authors added. But they also noted that change in systolic BP at 12 weeks was 3.4 mmHg (95% CI 1.0 mm to 5.8 mm) higher in the intervention group versus the usual care group, after correcting for baseline BP.

As a result, “potential benefits of reducing medication need to be balanced against possible harms from increased risk of cardiovascular disease in the longer term,” they cautioned.

“While the study demonstrated that deprescribing was achievable for antihypertensive therapy, it did not prove the strategy was safe,” observed Eric D. Peterson, MD, MPH, of Duke University Medical Center in Durham, N.C., and Michael W. Rich, MD, of Washington University School of Medicine in St. Louis, in an editorial accompanying the study.

They pointed out that although a 150 mmHg treatment threshold is consistent with U.K. guidelines, but the results would have been different if the U.S. guidelines of a more stringent 130 mmHg threshold had been applied.

“Had this been the outcome of the study, the deprescribing strategy would have failed to be considered noninferior to usual care,” Peterson and Rich stated, with an adjusted RR of 0.76 (97.5% CI 0.63 to ∞, P=0.98).

Nonetheless, the study “provides important data supporting the proof of concept of deprescribing in older adults,” they wrote. “In some cases, when treating an older patient with high blood pressure, more medications (to achieve lower targets) may be beneficial; while in others, less medications (when safe) will truly be more.”

OPTIMISE was conducted in 69 primary care sites across Central and Southern England among 569 elderly patients (48.5% women) who were on a median of two antihypertensive medications prescribed for at least 12 months prior to baseline. Nearly all of the patients (93.8%) completed the trial that ran from April 2017 to January 2019.

The authors excluded patients with a history of heart failure due to left ventricular dysfunction or myocardial infarction or stroke in the preceding 12 months, secondary hypertension, or lacking in capacity to consent.

The trial used an unblinded design with patients and investigators not masked to the randomization group. The primary outcome was systolic BP <150 mm Hg at 12-week follow-up. A prespecified noninferiority margin was an RR of 0.90.

Secondary outcomes included the proportion of participants maintaining medication reduction and differences in BP, frailty, quality of life, adverse effects, and serious adverse events (AEs).

Each patient’s medication regimen prior to baseline was reviewed by their primary care physician (PCP), who decided which antihypertensive drug would be removed if their patient was randomized to the intervention group.

There was little difference between the two groups in terms of the type of BP medications prescribed:

  • ACE inhibitor/angiotensin II receptor blocker: 84.4% in the intervention group and 84.7% in the usual care group.
  • Calcium channel blocker: 70.6% and 66.6%.
  • ß-blocker: 39.7% and 40.4%.
  • Thiazide and related diuretics: 38.7% for both groups.

Patients in the deprescribing group were monitored at a 4-week safety visit and treatment was reinstated if systolic BP was >150 mmHg or diastolic BP was >90 mmHg for more than 1 week (by patient self-monitoring), if AEs occurred, or signs of accelerated hypertension developed.

The authors reported that there was a higher, but statistically non-significant, incidence of serious AEs in the intervention group versus the usual care group (4.3% versus 2.4%, adjusted RR 1.72, 95% CI 0.7 to 4.3). Also, adverse cardiovascular events were reported in 7% of intervention group versus 2.8% in the usual care group.

However, only one-fourth of the events in the deprescribing group were considered possibly related to medication reduction, Sheppard’s group stated.

The authors reported there were no statistically significant differences between groups in frailty, quality of life, adverse effects, or serious AEs at 12-week follow-up.

Study limitations included the fact that participants were selected by PCPs, and only one in 10 screened were enrolled. Also, patients and investigators were aware of treatment allocation and study end points. The intervention group had at least one more physician consultation than the usual care group.

The short follow-up period meant that the study was underpowered to make reliable comparisons of AEs between groups, and the noninferiority margin was determined based on opinion of likely meaningfulness for physician and patient and not prior evidence, the authors explained.

Sheppard’s group called for more studies on long-term clinical outcomes, which Peterson and Rich agreed were necessary “before widespread adoption of deprescribing antihypertensive therapy in older adults.”

  1. Antihypertensive medication reduction may be achievable without substantial change in blood pressure (BP) control in some older adults taking multiple antihypertensive medications.

  2. Change in systolic BP at 12 weeks was 3.4 mmHg higher in the intervention group versus the usual care group (staying on at least two BP-lowering drugs, after correcting for baseline BP.

Shalmali Pal, Contributing Writer, BreakingMED™

OPTIMISE was funded by the NIHR CLAHRC at Oxford Health NHS Foundation Trust and the NIHR School for Primary Care Research.

Sheppard reported funding from an NIHR professorship, the Wellcome Trust/Royal Society via a Sir Henry Dale Fellowship, and an NIHR Oxford Biomedical Research Centre senior fellowship. Co-authors reported funding from NIHR professorship, NIHR senior investigator awards, NIHR School for Primary Care Research, NIHR Oxford Biomedical Research Centre, NIHR CLAHRC Oxford, and the NIHR for polypharmacy and medicines optimization research.

Peterson reported relationships with, and/or support from, Cerner, Livongo, AstraZeneca, Janssen, and Amgen. Rich reported no relationships relevant to the contents of this paper to disclose.

Cat ID: 6

Topic ID: 74,6,400,730,6,255,916