Adding New Hypertensive May Be More Potent Than Upping Doses

Adding a new medication rather than increasing the dose of an existing one may be slightly more effective at lowering blood pressure for older adults with uncontrolled hypertension, albeit with a tradeoff, a large study suggests.

Guidelines usually recommend starting a combination of medications at low doses when initiating hypertension treatment, but it’s less clear which strategy is best for older adults needing further treatment intensification to reach target blood pressure, Carole E. Aubert, MD, MSc, Bern University Hospital, Switzerland, explained in a video accompanying the study, published online October 5 in Annals of Internal Medicine.

Among 178,562 treated veterans with systolic blood pressure (SBP) above 130 mm Hg and at least one antihypertensive drug not at full dose, the investigators found that only 25.5% received a new medication and 74.5% maximized their dose to intensify treatment. Adding a new medication was more likely with younger age and higher baseline systolic blood pressure.

At 3 months, however, fewer patients adhered to the new medication than to the maximized dose (49.8% vs 65.0%).

In contrast, mean SBP was lower by 0.8 mm Hg at 3 months and by 1.1 mm Hg at 12 months with the added new medication than with maximizing dose.

“Adding a new medication was associated with greater SBP reduction but less frequent sustained intensification, possibly suggesting that adverse drug events might be more common or patients less willing to take additional medications,” Aubert and her colleagues conclude.

“When adapting antihypertensive medication regimens, it is important to consider not only BP control but also the risk–benefit ratio of each antihypertensive medication in light of all comorbid conditions and co-medications and the added complexity of adding an additional medication, particularly in older patients with multiple comorbid conditions, who are more vulnerable to adverse effects of medication and frequently receive multiple medications,” they caution.

The study, which emulated a clinical trial, was limited by incomplete medication intake available in pharmacy records, fewer than 2% of participants were women, it relied on unstandardized office BP measurements, and the data were collected from 2011 to 2013, before more tolerable or potent drugs were available, the investigators acknowledge.

An accompanying editorial suggests that the main shortcoming of the study lies in the broad spectrum of situations that prompted treatment intensification, including baseline number and doses of antihypertensive drugs, number of pills per day, BP level, and clinical condition, such as comorbid conditions and fitness.

“Encompassing such a heterogeneous case mix prevents definitive conclusions on how best to intensify treatment in patients with uncontrolled hypertension, in general or in any given situation,” writes Olivier Steichen, MD, PhD, Hôpital Tenon, Paris.

Nonetheless, two results must be stressed, she says. “First, whatever the chosen strategy, treatment intensification leads to large BP decreases in patients who need it the most.” The 12-month decrease in SBP averaged about 8 mm Hg for patients with baseline readings between 140 and 160 mm Hg and about 20 mm Hg in those with a baseline SBP above 160 mm Hg.

Second, she notes, that the two intensification strategies are associated with similar 12-month BP decreases in the emulated intention-to-treat analysis.

“In this analysis, mean BP decrease is the compound result of persistence and BP lowering potency,” Steichen says. “A similar mean BP decrease despite lower persistence is, therefore, confirmatory evidence that drug addition is more potent than dose maximization in those who persist. When a large BP decrease is needed, drug addition should be preferred together with promoting persistence — for example, with [single-pill combinations] SPCs and patient education.”

The study was funded by the National Institute on Aging and the Veterans Health Administration. Aubert reports support from the Swiss National Science Foundation. Steichen reports no relevant financial relationships.

Ann Intern Med. Published online October 4, 2021. Abstract, Editorial

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