Immediate Fracture Risk After Antihypertensive Drug Initiation

NCT ID: NCT06964217

Last Updated: 2025-05-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 10000000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2025-07-31

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.

Conditions

Hypertension; Fracture

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Monotherapy

Community-dwelling patients who get prescription of per oral anti-hypertensive drug (AHD) at an outpatient visit for hypertension diagnosis, without an exposure to any antihypertensive medication in the preceding year.

Monotherapy

Intervention Type: DRUG

Antihypertensive medications, regardless of dose or formulation, will be classified by their pharmacologic class. A total of eight drug classes will be considered: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, dihydropyridine calcium channel blockers (DHP-CCBs), non-dihydropyridine calcium channel blockers (non-DHP-CCBs), loop diuretics, thiazide and thiazide-like diuretics, and potassium-sparing diuretics.

Exposure groups will be defined as follows:

• Monotherapy: prescription of a single antihypertensive drug class on the index date.
• Dual therapy: prescription of two ore more antihypertensive drug classes on the same index date.

To qualify for group assignment, all drugs must be initiated on the same day, and the drug of interest is limited to the class described in group/cohort.

Out of the two, this intervention will be monotherapy.

Combination therapy

Community-dwelling patients who get prescription of per oral antihypertensive pill/pills with two or more drug classes of AHDs - on a same day at an outpatient visit for hypertension diagnosis, without an exposure to any antihypertensive medication in the preceding year.

Combination therapy

Intervention Type: DRUG

Antihypertensive medications, regardless of dose or formulation, will be classified by their pharmacologic class. A total of eight drug classes will be considered: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, dihydropyridine calcium channel blockers (DHP-CCBs), non-dihydropyridine calcium channel blockers (non-DHP-CCBs), loop diuretics, thiazide and thiazide-like diuretics, and potassium-sparing diuretics.

Exposure groups will be defined as follows:

• Monotherapy: prescription of a single antihypertensive drug class on the index date.
• Dual therapy: prescription of two or more antihypertensive drug classes on the same index date.

To qualify for group assignment, all drugs must be initiated on the same day, and the drug of interest is limited to the class described in group/cohort.

Out of the two, this intervention will be combination therapy.

Interventions

Monotherapy

Antihypertensive medications, regardless of dose or formulation, will be classified by their pharmacologic class. A total of eight drug classes will be considered: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, dihydropyridine calcium channel blockers (DHP-CCBs), non-dihydropyridine calcium channel blockers (non-DHP-CCBs), loop diuretics, thiazide and thiazide-like diuretics, and potassium-sparing diuretics.

Exposure groups will be defined as follows:

• Monotherapy: prescription of a single antihypertensive drug class on the index date.
• Dual therapy: prescription of two ore more antihypertensive drug classes on the same index date.

To qualify for group assignment, all drugs must be initiated on the same day, and the drug of interest is limited to the class described in group/cohort.

Out of the two, this intervention will be monotherapy.

Intervention Type: DRUG

Combination therapy

Antihypertensive medications, regardless of dose or formulation, will be classified by their pharmacologic class. A total of eight drug classes will be considered: angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers, dihydropyridine calcium channel blockers (DHP-CCBs), non-dihydropyridine calcium channel blockers (non-DHP-CCBs), loop diuretics, thiazide and thiazide-like diuretics, and potassium-sparing diuretics.

Exposure groups will be defined as follows:

• Monotherapy: prescription of a single antihypertensive drug class on the index date.
• Dual therapy: prescription of two or more antihypertensive drug classes on the same index date.

To qualify for group assignment, all drugs must be initiated on the same day, and the drug of interest is limited to the class described in group/cohort.

Out of the two, this intervention will be combination therapy.

Intervention Type: DRUG

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

• 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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ajou University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Jong Min Lee

Teaching Assistant (M.D)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rae Woong Park, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Republic of Korea

Central Contacts

Jong Min Lee, M.D.

Role: CONTACT

jongmin.lee.35@gmail.com

+82-10-5443-3196

References

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.

Reference Type: BACKGROUND

PMID: 23165923 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38648065 (View on PubMed)

Other Identifiers

AJOUIRB-EX-2025-198

Identifier Type: -

Identifier Source: org_study_id