Abstract
The effect of sodium glucose cotransporter-2 inhibitors on mortality and cardiovascular outcomes of patients with prostate cancer receiving luteinizing hormone releasing hormone agonists.
Author
person
Zhiting Tang
Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, NY
info_outline
Zhiting Tang, Cho Han Chiang, Yu-Cheng Chang, Xin Ya See, Qian Wang, Kuan-Yu Chi, Cho Hung Chiang
Full text
Authors
person
Zhiting Tang
Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, NY
info_outline
Zhiting Tang, Cho Han Chiang, Yu-Cheng Chang, Xin Ya See, Qian Wang, Kuan-Yu Chi, Cho Hung Chiang
Organizations
Department of Medicine, Unity Hospital, Rochester Regional Health, Rochester, NY, Mount Auburn Hospital, Harvard Medical School, Cambridge, MA, Department of Medicine, Danbury Hospital, Danbury, CT, Unity Hospital, Rochester Regional Health, Rochester, NY, University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, OH, Department of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, National Taiwan University Hospital, Taipei, Taiwan
Abstract Disclosures
Research Funding
No funding sources reported
Background:
Luteinizing hormone releasing hormone agonists (LHRHa) are the standard of care treatment for prostate cancer but associated with an increased risk of cardiotoxicity. Recent studies suggest that sodium glucose cotransporter-2 inhibitors (SGLT2i), a class of antidiabetic drugs, reduce the risk of cardiovascular events compared to other glucose-lowering agents. We aim to investigate the potential cardioprotective effect of SGLT2i in prostate cancer patients with T2DM undergoing LHRHa therapy.
Methods:
We performed a retrospective, propensity score matched study using the TriNetX database, a network comprising deidentified data across more than 120 participating healthcare institutions. We included patients with prostate cancer and T2DM who were treated with LHRHa for prostate cancer and received either SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) for diabetes. The primary outcomes were all-cause mortality, incident hypertension, and incident major cardiovascular adverse events (MACE), which was defined as a composite of heart failure, myocardial infarction, and atrial fibrillation/flutter within 5 years of LHRHa initiation.
Results:
We matched 932 patients treated with an SGLT2i to patients treated with a DPP4i. The median age was 73 years for both cohorts. A total of 110 and 275 patients died in the SGLT2i and DPP4i cohorts, respectively. In Cox proportional hazard analyses, SGLT2i was associated with a reduction in the risk of all-cause mortality (Hazard ratio (HR), 0.65 [95% CI, 0.52 to 0.81]), hypertension (HR, 0.40 [95% CI: 0.22-0.70]) and major adverse cardiovascular events (HR, 0.70 [95% CI, 0.50 to 0.97]) compared to DPP4i. Similarly, SGLT2i was associated with a statistically significant reduction in heart failure and myocardial infarction. There appeared to be a tendency toward a lower risk of atrial fibrillation/flutter.
Conclusions:
The use of SGLT2i was associated with a lower risk of mortality, hypertension, and cardiovascular events in patients with prostate cancer and T2DM undergoing LHRHa therapy.
Outcomes
SGLT2i
DPP4i
Hazard Ratio
a
(95% CI)
P-value (Log-Rank)
No. of at Risk Patients
No. of Cases
No. of at Risk Patients
No. of Cases
All-cause mortality
932
110
932
275
0.65 (0.52-0.81)
<0.001
Hypertension
92
16
93
45
0.40 (0.22-0.70)
0.001
MACE
521
55
516
112
0.70 (0.50-0.97)
0.029
Heart failure
625
59
632
113
0.72 (0.53-0.99)
0.044
Myocardial infarction
793
23
823
72
0.53 (0.33-0.86)
0.009
Atrial fibrillation and flutter
706
28
711
66
0.68 (0.44-1.04)
0.073
a
After propensity score matching by incorporating variables: age, sex, metastatic disease, androgen deprivation therapy, radiation therapy, underlying comorbidities, use of cardiovascular and diabetes medications, smoking status, and hemoglobin A1c.
16 organizations
6 drugs
5 targets
Drug
LHRHaDrug
SGLT2iDrug
DPP4iTarget
SGLT2Organization
Unity HospitalOrganization
Rochester Regional Health SystemOrganization
Rochester, NYOrganization
Mount Auburn HospitalOrganization
Harvard Medical SchoolOrganization
Cambridge, MAOrganization
Danbury HospitalOrganization
Danbury, CTOrganization
Cleveland, OHOrganization
Jacobi Medical Center/North Central BronxOrganization
Albert Einstein College of MedicineOrganization
Bronx, NYOrganization
Taipei, Taiwan