Primary Prevention of Hormonal Treatment-related Cardiovascular Events in High-Risk Prostate Cancer Patients

Abstract

<p>Introduction: Among men with prostate cancer, androgen deprivation therapy (ADT) therapy<br>frequently causes adverse cardiometabolic events, but data on primary prevention using statins or<br>metformin are scarce.<br>Aims: To investigate the effectiveness of statins and metformin against major adverse cardiovascular<br>events (MACE) in high-risk ADT-treated prostate cancer patients in Hong Kong.<br>Methods: This cohort study used electronic health records in Hong Kong. Men with prostate cancer<br>treated with ADT between 2004 and 2019, without a history but risk factors for atherosclerotic<br>cardiovascular disease were included. New users of statins or metformin within one year after ADT<br>initiation were compared with non-users using an index date one year after ADT initiation. Outcomes<br>were MACE and all-cause mortality over 10 years of follow-up. Cox regression was used to estimate<br>the hazard ratios (HR) and competing risks were accounted for using the Fine-Gray method to<br>estimate subdistribution HR.<br>Results: Among 11,457 eligible men, 235 statin users and 129 metformin users with high<br>cardiovascular risks were identified. After propensity score matching, incidence rates of MACE were<br>14.29 and 35.19 per 1000 person-years in statin and metformin new users, respectively. Neither<br>statin (HR 0.82, 95% confidence interval [CI] 0.39 – 1.70) nor metformin initiation (HR 1.27, 95% CI<br>0.65 – 2.47) was associated with a reduced risk of MACE. Statin initiation was associated with<br>reduced all-cause mortality (HR 0.53, 95% CI 0.40 – 0.68), but not metformin. Competing risk analysis<br>showed that statin initiation was associated with a reduced risk of MACE (sHR 0.49, 95% CI 0.26 –<br>0.92).<br>Conclusions: Statin initiation was associated with reduced cardiovascular risks and improved overall<br>survival among high-risk patients undergoing ADT for prostate cancer, but not metformin. Further<br>investigations are needed to validate the benefits of statins against cardiotoxicities of hormonal<br>treatment for prostate cancer.</p>