Emulation of a Target Trial of Antihypertensive Medications on Weight Change
Pi-I D Lin1, Sheryl L Rifas-Shiman1, Joshua Petimar1,2
1Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
Background:
Weight gain after starting antihypertensive medications is a frequent concern for patients, but there is limited data on expected weight change after initiation of these medications. A comparative effectiveness trial to evaluate this outcome would not be feasible.
Objective:
To estimate and compare average weight change under initiating and adhering to commonly prescribed, first-line antihypertensive medications as monotherapy by emulating a target trial.
Design:
Retrospective observational cohort study over 24 months of follow-up using electronic health records (EHR).
Participants:
141,260 patients prescribed one of seven antihypertensives between 2010 and 2019 across 8 US health systems.
Main Outcome And Measures:
We examined mean weight change associated with initiation of and adherence to amlodipine, atenolol, hydrochlorothiazide, losartan, metoprolol, or propranolol, relative to lisinopril, at 6, 12, and 24 months after initiation. To adjust for baseline confounding and informative outcome measurement, we used inverse probability weighting with repeated outcome marginal structural models.
Key Results:
After baseline and time-varying covariate adjustment, initiation of and adherence to lisinopril were associated with mean weight loss at 6 months (- 0.69 kg, 95% CI - 0.92, - 0.47), 12 months (- 0.58 kg, 95% CI - 1.05, - 0.30), and 24 months (- 1.121 kg, 95% CI - 2.013, - 0.46). Compared to lisinopril, the estimated 6-month weight change was higher for patients prescribed hydrochlorothiazide (0.68 kg, 95% CI 0.31, 1.04), losartan (0.54 kg, 95% CI 0.17, 0.93), metoprolol (1.38 kg, 95% CI 0.95, 1.76), and propranolol (1.03 kg, 95% CI 0.346, 1.62). At 12 months, metoprolol (1.74 kg, 95% CI 1.03, 2.41) and propranolol (1.72 kg, 95% CI 0.06, 3.235) continued to show higher weight change compared to lisinopril.
Conclusion:
We observed small differences in weight change across antihypertensive medications, with lisinopril leading to weight loss and metoprolol and propranolol to modest weight gain. Clinicians should consider potential weight gain when selecting antihypertensive medications.
Insights
Weight changes vary among first-line antihypertensives. Lisinopril is associated with weight loss, while metoprolol and propranolol may cause modest weight gain. Consider these effects when prescribing blood pressure medications.
Area of Science:
- Cardiovascular medicine
- Pharmacology
- Public health
Background:
- Weight gain is a common patient concern with antihypertensive medications.
- Limited data exists on expected weight changes following initiation of these drugs.
- A comparative effectiveness trial for this outcome is not feasible.
Purpose of the Study:
- To estimate and compare average weight change associated with initiating and adhering to commonly prescribed, first-line antihypertensive medications.
- To emulate a target trial for evaluating weight change outcomes.
- To analyze weight changes for monotherapy treatments.
Main Methods:
- Retrospective observational cohort study using electronic health records (EHR).
- Follow-up period of 24 months.
- Included 141,260 patients prescribed one of seven antihypertensives between 2010 and 2019 across 8 US health systems.
- Used inverse probability weighting with repeated outcome marginal structural models to adjust for confounding.
Main Results:
- Lisinopril was associated with mean weight loss at 6, 12, and 24 months (-0.69 kg, -0.58 kg, and -1.121 kg, respectively).
- Compared to lisinopril, hydrochlorothiazide, losartan, metoprolol, and propranolol were associated with higher weight changes at 6 months.
- Metoprolol and propranolol showed higher weight changes compared to lisinopril at 12 months.
Conclusions:
- Small differences in weight change were observed across antihypertensive medications.
- Lisinopril use was linked to weight loss.
- Metoprolol and propranolol were associated with modest weight gain, suggesting clinicians consider weight effects in medication selection.
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