Adding new antihypertensive to current therapy may reduce BP more than maximizing dose

Adding a new medication to older adults’ antihypertension treatment regimen produced a slightly greater reduction in systolic BP than maximizing dosage, according to findings published in Annals of Internal Medicine.

However, increasing the dosage of current medication correlated with sustained treatment intensification.

“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 comedications 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,” Carole E. Aubert, MD, MSc, a primary care physician and clinical researcher in the department of general internal medicine at Bern University Hospital in Switzerland, and colleagues wrote.

The researchers conducted a large-scale, population-based, retrospective cohort study of veterans aged 65 years or older with hypertension (systolic BP of 130 mm Hg or higher) and a prescription of at least one antihypertensive medication taken at less than the maximum dose. They compared the observational effectiveness of adding a new medication or maximizing the dosage of current medication in patients who had not reached their target BP. The sustainability of both treatment methods was based on inverse probability weighting and systolic BP at 3 months and 12 months of follow up.

The analysis included data on 178,562 patients who had a clinical encounter through the Veterans Health Administration between July 1, 2009, and June 30, 2013. Their mean age was 75.8 years and 98.1% were men.

New medication vs. increased dosage

Among the study cohort, 25.5% of patients were given a new medication to add to their treatment regimen while 74.5% had the dosage of their current medication maximized.

Patients who received a new medication were less likely to have sustained treatment intensification at 3 months and 12 months, with an average reduction of about 15 percentage points compared with maximizing dosage, according to Aubert and colleagues. Yet, adding a new medication correlated with systolic BP decreases of 4.6 mm Hg (95% CI, 5-4.2) at 3 months and 5.6 mm Hg (95% CI, 1.6-0.6) at 12 months compared with 3.8 mm Hg (95% CI, 4-3.6) and 4.5 mm Hg (95% CI, 4.8-5.3) for maximizing dosage.

Overall, the researchers reported that adding a new medication achieved a “slightly larger reduction” in patients’ average systolic BP by 0.8 mm Hg (95% CI, 1.2-0.4) at 3 months and 1.1 mm Hg (95% CI, -1.6 to -0.6) at 12 months compared with maximizing dosage.

The researchers suggested that maximizing dosage “might be simpler to maintain in older adults, but with a tradeoff.”

“Adding a new medication was associated with a slightly greater reduction in systolic BP than maximizing dose, even after adjustment for total dose increase, which is likely to affect follow-up systolic BP,” Aubert and colleagues wrote.

However, older patients or their prescribers might prefer maximizing dosage to avoid increasing the risk or difficulty of a patient’s treatment plan. This could explain why maximizing dosage was three times more common than adding a new medication, according to the researchers.

Study limitations

In a related editorial, Olivier Steichen, MD, PhD, a professor of internal medicine at Assistance Publique-Hôpitaux de Paris in France, noted the limitations of the study, writing that the “results remain vulnerable to bias and confounding”

“The main shortcoming of the study lies in the broad spectrum of baseline situations,” he wrote.

Differences in baseline factors, including the number of antihypertensive medications, daily dosage, BP level and clinical conditions, among the study cohort may have biased the results “in unpredictable ways,” according to Steichen.

Still, he highlighted two key takeaways from the study:

Treatment intensification leads to large reductions in BP among patients who most need it, no matter the intensification method.

In an emulated intention-to-treat analysis, both intensification strategies were linked to similar reductions in BP at 12 months.

“When a large BP decrease is needed, drug addition should be preferred together with promoting persistence,” he added.

References:

Aubert CE, et al. Ann Intern Med. 2021;doi:10.7326/M21-1456.

Steichen O. Ann Intern Med. 2021;doi:10.7326/M21-3648.