Clinical trial NCT06964217: Immediate Fracture Risk After Antihypertensive Drug Initiation
Official title: Overall Fracture Risk Immediately After Anti-hypertensive Medication Initiation and Temporal Trend in Initial Pharmacotherapy Regimens: An Observational Study
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Hypertension
Fracture
Lead sponsor: Ajou University School of Medicine
Sponsor class: OTHER
First posted: 2025-05-09
Enrollment: 10000000
Sex: ALL
Minimum age (years): 50
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Community-dwelling patients who are new users of antihypertensive medication, defined as individuals with no prior antihypertensive exposure in the 365 days prior to the index date

Brief summary: This retrospective observational study aims to evaluate the short-term fracture risk associated with anti-hypertensive medication initiation using a self-controlled case series (SCCS) design and investigate temporal trends of initial anti-hypertensive regimen (monotherapy vs combination therapy) and subsequent fracture incidence. The investigators use the Korean Health Insurance Review and Assessment (HIRA) database to identify adults aged ≥65 with a new prescription for anti-hypertensive therapy and at least one incident non-traumatic fracture.

In the SCCS analysis, the investigators estimate the within-person incidence rate of overall fractures during the 30-day period following anti-hypertensive initiation compared to control periods. Temporal trends will be recorded through 2013 - 2022.

The primary outcome is overall non-traumatic fracture occurrence; the secondary outcome is incident proximal hip fracture. These outcomes are defined using diagnostic and procedural codes validated for use in claims data. This study aims to quantify both the immediate temporal association between treatment initiation and fracture risk, and the comparative safety of different initial anti-hypertensive regimens.


Eligibility criteria: Inclusion Criteria:

* Individuals with at least 365 days of continuous observation prior to the index date (defined as the date of first antihypertensive medication prescription), with no prior antihypertensive use during that period
* At least one diagnosis of hypertension (ICD-10 codes I10-I13, I15) recorded within 180 days before the index date

Exclusion Criteria (main cohort):

* Any of the following occurring in the 365 days prior to the index date: Hospitalization (inpatient admission, including long-term care facility), transport-related trauma (ICD-10 codes V01-V99), Intentional self-harm (ICD-10 codes X60-X84, Y87), History of pathological fractures (e.g., M84.4, M90.7), Evidence of end-stage renal disease (ESRD), dialysis, kidney transplant, renal osteodystrophy

Primary outcomes:
measure: Overall fracture risk
timeFrame: 45 days after initiation of antihypertensive medication
Secondary outcomes:
measure: Hip fracture
timeFrame: 45 days after initiation of antihypertensive medication
Other outcomes:
Locations:
Study officials:
affiliation: Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea
name: Rae Woong Park, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Butt DA, Mamdani M, Austin PC, Tu K, Gomes T, Glazier RH. The risk of hip fracture after initiating antihypertensive drugs in the elderly. Arch Intern Med. 2012 Dec 10;172(22):1739-44. doi: 10.1001/2013.jamainternmed.469.
citation: Dave CV, Li Y, Steinman MA, Lee SJ, Liu X, Jing B, Graham LA, Marcum ZA, Fung KZ, Odden MC. Antihypertensive Medication and Fracture Risk in Older Veterans Health Administration Nursing Home Residents. JAMA Intern Med. 2024 Jun 1;184(6):661-669. doi: 10.1001/jamainternmed.2024.0507.