Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin, and Amoxicillin
Abstract
:1. Introduction
1.1. Background
1.2. Objective
2. Method
2.1. Data Sources and Covariates
- (1)
- The Danish Register of Chronic Obstructive Pulmonary Disease DrCOPD-Data were collected from all COPD outpatients across Denmark. Numerous beneficial variables are available. These variables include the Medical Research Council Dyspnea Scale (MRC), which measures respiratory distress; Forced Expired Volume in the first second (FEV1), a critical measure of lung function; Body Mass Index (BMI), reflecting patients’ nutritional and health status; along with the dates of outpatient visits, providing insights into healthcare utilization patterns. Additionally, demographic details such as age and gender, alongside crucial life events such as the date of death, were also captured. The Danish Register of Chronic Obstructive Pulmonary Disease (DrCOPD) is an important resource, meticulously crafted to strengthen the capacities of healthcare professionals, researchers, and policymakers in their quest to comprehend and tackle COPD with greater efficacy in the Danish context. Within this rich database lie invaluable variables, each offering a unique lens through which the complexities and severity of COPD can be discerned and categorized. The integrity and depth of this data repository are upheld through the diligent contributions of physicians and nurses operating within outpatient clinics, ensuring a robust and reliable foundation for advancing COPD care and research initiatives.
- (2)
- The Danish National Patient Registry (DNPR)—we had access to all of the patient’s hospital admissions in Denmark registered with ICD-10. They are divided into A and B diagnoses. We used the A diagnosis to find the cardiovascular event admissions registered after each patient study entry. We used the B diagnosis to find the patient’s comorbidities. We looked at the 10-year prior baseline for the comorbidities. The Danish National Patient Registry is a comprehensive medical database that collects data on all hospital admissions and outpatient visits in Denmark, offering invaluable insights for healthcare research and policy-making by tracking patient diagnoses, treatments, and outcomes since its inception in 1977. The outpatient visits have been recorded since 1995.
- (3)
- The Danish National Health Service Prescription Database (DNHSPD)- we obtained all of the patient’s prescriptions. Each prescription is named by its Anatomical Therapeutic Chemical ATC) classification system. The following ATC codes were used for the four groups: amoxicillin ‘J01CA04’, azithromycin ‘J01FA10’, clarithromycin ‘J01FA09’, and roxithromycin ‘J01FA06’. The Danish National Health Service Prescription Database meticulously records all prescriptions dispensed at Danish pharmacies, providing a detailed overview of medication use patterns across the population. This extensive database is instrumental in pharmaceutical research and healthcare policy development, enabling the study of prescription trends, drug safety, and adherence. Data have been registered since 2004.
- (4)
- With the Danish National Death Registry, we can now identify the reason for death for each patient. The Danish National Death Registry is a resource that compiles information on all deaths occurring within Denmark, including causes and dates. This registry plays a vital role in epidemiological studies and public health planning, offering insights into mortality trends, life expectancy, and the impact of specific health interventions.
2.2. Study Design
2.3. Exposure to Antibiotics
2.4. Outcome
2.5. Statistical Analysis
2.6. Patient and Public Involvement
3. Results
3.1. Participants
3.1.1. Primary Outcome
3.1.2. Secondary Outcome
4. Discussion
Strengths and Limitations
5. Conclusions
6. Future Perspectives
7. Ethical Considerations
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Appendix A
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All | Amoxicillin | Azithromycin | Clarithromycin | Roxithromycin | |
---|---|---|---|---|---|
Number of subjects, n (%) | 10,153 (100.0) | 2241 (22.1) | 2322 (22.9) | 1025 (10.1) | 4565 (45.0) |
Females, n (%) | 5843 (57.5) | 1158 (51.7) | 1366 (58.8) | 596 (58.1) | 2723 (59.6) |
FEV1, % of expected, median (IQR) | 48.0 (35.0–63.0) | 47.0 (34.0–62.0) | 45.0 (32.0–60.0) | 49.0 (36.0–63.0) | 50.0 (36.0–64.0) |
Age | 69.69 (40–98) | 70.85 (40–98) | 68.96 (40–92) | 69.39 (40–93) | 69.55 (40–96) |
Asprin | 2989 | 722 | 646 | 305 | 1316 |
Renin-Angiotension-System (RAS)-inhibitors | 2954 | 698 | 604 | 300 | 1352 |
Novel oral anticoagulants (NOAC) | 451 | 98 | 115 | 47 | 191 |
Beta-blockers, n (%) | 2604 | 675 | 523 | 258 | 1148 |
Amount prescriptions of antibiotic courses: | |||||
≤2 | 8621 | 1998 | 1677 | 925 | 4021 |
>2 | 1532 | 243 | 645 | 100 | 544 |
MRC, median (IQR) | 3.0 (2.0–4.0) | 3.0 (2.0–4.0) | 3.0 (2.0–4.0) | 3.0 (2.0–4.0) | 3.0 (2.0–4.0) |
BMI, n (%), kg/m² | 25.0 (21.0–29.0) | 25.0 (21.0–29.0) | 24.8 (21.0–28.4) | 25.0 (21.2–29.0) | 25.0 (22.0–29.0) |
Peripheral vascular disease, n (%) | 1149 (11.3) | 284 (12.7) | 233 (10.0) | 118 (11.5) | 514 (11.3) |
Ischaemic heart disease, n (%) | 902 (8.9) | 241 (10.8) | 186 (8.0) | 98 (9.6) | 377 (8.3) |
Heart failure, n (%) | 1430 (14.1) | 375 (16.7) | 285 (12.3) | 139 (13.6) | 631 (13.8) |
Diabetes without complications, n (%) | 1266 (12.5) | 278 (12.4) | 261 (11.2) | 132 (12.9) | 595 (13.0) |
Diabetes with complications, n (%) | 411 (4.0) | 92 (4.1) | 72 (3.1) | 45 (4.4) | 202 (4.4) |
Stroke, n (%) | 1115 (11.0) | 266 (11.9) | 214 (9.2) | 126 (12.3) | 509 (11.2) |
Renal disease, n (%) | 415 (4.1) | 115 (5.1) | 74 (3.2) | 52 (5.1) | 174 (3.8) |
Rheumatological disease, n (%) | 460 (4.5) | 99 (4.4) | 108 (4.7) | 50 (4.9) | 203 (4.4) |
Paraplegia, n (%) | 46 (0.5) | 12 (0.5) | 12 (0.5) | 7 (0.7) | 15 (0.3) |
Antibiotic Groups | End of Follow-Up N (%) | Stroke N (%) | AMI ** N (%) | Cardiovascular Death N (%) | Cause of Death * N (%) | Antibiotic Switch N (%) | Total (n) |
---|---|---|---|---|---|---|---|
Amoxicillin | 1092 (48.73) | 74 (3.30) | 37 (1.65) | 84 (3.75) | 502 (22.40) | 452 (20.17) | 2241 |
Azithromycin | 1329 (57.24) | 58 (2.50) | 41 (1.77) | 63 (2.71) | 473 (20.37) | 358 (15.42) | 2322 |
Clarithromycin | 553 (53.95) | 29 (2.83) | 13 (1.27) | 38 (3.71) | 183 (17.85) | 209 (20.39) | 1025 |
Roxithromycin | 2568 (56.25) | 128 (2.80) | 78 (1.71) | 174 (3.81) | 1007 (22.06) | 610 (13.36) | 4565 |
Total | 5542 (54.58) | 289 (2.85) | 169 (1.66) | 359 (3.54) | 2165 (21.32) | 1629 (16.04) | 10,153 |
Adjusted | IPTW | |||||
---|---|---|---|---|---|---|
Treatment Groups | Hazard Ratio | 95% Confidential Interval | p Value | Hazard Ratio | 95% Confidential Interval | p Value |
Azithromycin | 1.01 | 0.81–1.25 | 0.96 | 0.94 | 0.76–1.16 | 0.54 |
Clarithromycin | 0.99 | 0.75–1.30 | 0.91 | 1.03 | 0.79–1.35 | 0.82 |
Roxithromycin | 1.02 | 0.85–1.22 | 0.86 | 1.00 | 0.83–1.19 | 0.97 |
Amoxicillin | 1.00 | ref | ref | 1.00 | ref | ref |
Adjusted | IPTW | |||||
---|---|---|---|---|---|---|
Treatment Groups | Hazard Ratio | 95% Confidential Interval | p Value | Hazard Ratio | 95% Confidential Interval | p Value |
Azithromycin | 1.06 | 0.94–1.19 | 0.37 | 0.98 | 0.88–1.11 | 0.78 |
Clarithromycin | 0.95 | 0.81–1.11 | 0.51 | 0.93 | 0.80–1.08 | 0.31 |
Roxithromycin | 0.98 | 0.89–1.09 | 0.70 | 0.98 | 0.88–1.08 | 0.63 |
Amoxicillin | 1.00 | ref | ref | 1.00 | ref | ref |
Adjusted | IPTW | |||||
---|---|---|---|---|---|---|
Treatment Groups | Hazard Ratio | 95% Confidential Interval | p Value | Hazard Ratio | 95% Confidential Interval | p Value |
Azithromycin | 0.96 | 0.70–1.33 | 0.82 | 0.87 | 0.64–1.19 | 0.40 |
Clarithromycin | 1.16 | 0.79–1.69 | 0.45 | 1.22 | 0.85–1.74 | 0.27 |
Roxithromycin | 1.12 | 0.87–1.45 | 0.37 | 1.1 | 0.85–1.40 | 0.48 |
Amoxicillin | 1.00 | ref | ref | 1.00 | ref | Ref |
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Alispahic, I.A.; Eklöf, J.; Sivapalan, P.; Jordan, A.R.; Harboe, Z.B.; Biering-Sørensen, T.; Jensen, J.-U.S. Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin, and Amoxicillin. J. Clin. Med. 2024, 13, 1987. https://doi.org/10.3390/jcm13071987
Alispahic IA, Eklöf J, Sivapalan P, Jordan AR, Harboe ZB, Biering-Sørensen T, Jensen J-US. Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin, and Amoxicillin. Journal of Clinical Medicine. 2024; 13(7):1987. https://doi.org/10.3390/jcm13071987
Chicago/Turabian StyleAlispahic, Imane Achir, Josefin Eklöf, Pradeesh Sivapalan, Alexander Ryder Jordan, Zitta Barrella Harboe, Tor Biering-Sørensen, and Jens-Ulrik Stæhr Jensen. 2024. "Risk of Mortality and Cardiovascular Events in Patients with Chronic Obstructive Pulmonary Disease Treated with Azithromycin, Roxithromycin, Clarithromycin, and Amoxicillin" Journal of Clinical Medicine 13, no. 7: 1987. https://doi.org/10.3390/jcm13071987