One Less Pill in Elderly Hypertensive Patients Safe in the Short Term

Elderly adults with hypertension can trim back on their multiple antihypertensive drugs without sacrificing blood pressure control—at least over the short-term, results of the OPTIMISE trial suggest.

The findings help fill a knowledge gap about the safety of intensive BP-lowering therapies in elderly patients, who due to age cutoffs and comorbidities were typically excluded from the major trials that inform current guidelines, most notably the SPRINT trial and before that HYVET. The lack of data in this particular high-risk group has led to conflicting guidance from different groups and leaves open the question of whether it might be safe to pull back on pill burden in these patients.

“Our study was really trying to look at a different population to those who would have been enrolled in SPRINT and HYVET,” namely frail patients taking numerous medications for a range of other chronic conditions in addition to hypertension, lead author James P. Sheppard, PhD (University of Oxford, England), told TCTMD. “There are lots of studies which suggest that if you are taking a lot of medications you are more likely to end up in hospital with adverse events and adverse drug reactions. There’s a feeling that [if] you could reduce the number of medications, you reduce those risks of polypharmacy.”

The paper and an accompanying editorial were published last week in JAMA.

The OPTIMISE Dose

OPTIMISE, conducted at 69 primary care sites in England, randomized 569 patients aged 80 years or older to maintain their daily course of therapy using at least two antihypertensive meds or to have one medication removed at the doctor’s discretion. At 12 weeks, investigators saw no significant difference in the proportion of patients who had a systolic BP less than 150 mm Hg, which was 86.4% among patients who’d dropped one of their medications and 87.7% among those who did not. The reduced pill burden was maintained in more than two-thirds of patients in the intervention arm.

Mean systolic blood pressure crept higher in the deprescribing group over the follow-up period, but stayed relatively stable in the standard-care group, such that the change was 3.4-mm Hg greater in the intervention group at 12 weeks. Thus, write the authors, the “potential benefits of reducing medication need to be balanced against possible harms from increased risk of cardiovascular disease in the longer term.”

Of note, more patients in the pill-reduction group experienced at least one adverse event, and more than one-quarter of these events were deemed to be related to the withdrawal of treatment. That flies in the face of the key rationale for deprescribing in older adults: that doing so might lead to better quality of life and fewer side effects. However, there are a number of problems with interpreting the side effect/adverse event data in OPTIMISE, Sheppard noted. The trial was not blinded or placebo-controlled and patients in the deprescribing group also had an additional follow-up visit with their physician, he said, “so they had one extra opportunity to report an adverse event to their doctor, compared to the control group.”

Longer follow-up would be needed to see any of these kinds of signals of fewer adverse events, he said. “There are very few trials out there that have tried deprescribing as an intervention and so there's not much data out there of whether it’s safe, which is why we chose 3-month follow-up,” Sheppard explained to TCTMD. “Before you can justify a longer study you need to show that it's a safe thing to do in the short term.”

It’s “too early” to say that deprescribing antihypertensives in older adults can be encouraged on the basis of the noninferiority findings in OPTIMISE, he concluded. “We don’t even know if this is a beneficial thing to do and we don't really know if it’s harmful in the long term.” That said, if patients with their physicians, for a range of reasons, decide they want to reduce their pill burden, “our trial provides a good example about how you might go about doing it safely, at least in the short term,” Sheppard suggested.

Good Prescribing/Deprescribing

In their editorial, Eric D. Peterson, MD, MPH (Duke University Medical Center, Durham, NC), and Michael Rich, MD (Washington University School of Medicine, St. Louis, MO), write that Sheppard et al’s study provides “important” data supportive of prior studies and uses a pragmatic approach. With the caveats that the patients in OPTIMISE were highly selected (just one in 10 were ultimately enrolled in the study) and generally had well-controlled blood pressure at baseline, the study supports “good prescribing practice,” Peterson and Rich argue. Until larger, longer-term studies can establish safety and efficacy, they write, “clinicians should consider the fundamental concept inherent to deprescribing: that medications should continuously be reviewed to assure that their potential benefits outweigh potential risks. . . . In some cases, when treating an older patient with high BP, more medications (to achieve lower targets) may be beneficial; while in others, less medications (when safe) will truly be more.”

To TCTMD, Sheppard stressed a point intended for patients who come across this paper or any news coverage of its findings.

“It’s worth emphasizing that this was an intervention done by trained doctors who carefully monitored it so I wouldn’t want people to read our study and think, I can stop taking my blood pressure drugs now because this is safe,” he said. “I think deprescribing is definitely something you need to do with your consent and after carefully considering the potential benefits and harms.”