Antihypertensive drug use and prostate cancer-specific mortality in Finnish men

Abstract

The aim of this study was to investigate pre-and post-diagnostic use of antihypertensive drugs on prostate cancer (PCa)-specific survival and the initiation of androgen deprivation therapy (ADT). The cohort investigated 8,253 PCa patients with 837 PCa-specific deaths during the median follow-up of 7.6 years after diagnosis. Information on drug use, cancer incidence, clinical features of PCa, and causes of death was collected from Finnish registries. Hazard ratios with 95% confidence intervals were calculated using Cox regression with antihypertensive drug use as a time-dependent variable. Separate analyses were performed on PCa survival related to pre-and post-diagnostic use of drugs and on the initiation of ADT. Antihypertensive drug use overall was associated with an increased risk of PCaspecific death (Pre-PCa: 1.21 (1.04-1.4), Post-PCa: 1.2 (1.02-1.41)). With respect to the separate drug groups, angiotensin II type 1 receptor (ATr) blockers, were associated with improved survival (Post-PCa: 0.81 (0.67-0.99)) and diuretics with an increased risk (Post-PCa: 1.25 (1.05-1.49)). The risk of ADT initiation was slightly higher among antihypertensive drug users as compared to non-users. In conclusion, this study supports anti-cancer effect of ATr blockers on PCa prognosis and this should be investigated further in controlled clinical trials.

Associations between Statin/Omega3 Usage and MRI-Based Radiomics Signatures in Prostate Cancer

“…ACEI is a type of renin–angiotensin system (RAS) inhibitor and is commonly used to treat hypertension. A few studies have analyzed the association between ACEI and prostate cancer [ 41 , 42 ]. These studies tend to suggest that ACEI has no effect on prostate cancer development or progression.…”

Pharmacoepidemiological Evaluation in Prostate Cancer—Common Pitfalls and How to Avoid Them

“…Other drugs that have been pharmacoepidemiological targets for prostate cancer development and progression are antihypertensive drugs as well as allopurinol and anticoagulants. Compounds inhibiting the renin–angiotensin–aldosterone system and beta-blockers have been the most widely investigated antihypertensive drugs [ 46 , 47 ]. Platelets have been suggested to play a role in promoting tumor metastasis, but the association between anticoagulant therapy and prostate cancer risk is controversial [ 48 , 49 ].…”

“…This eliminates follow-up time where a user would be falsely categorized as exposed before the actual start of usage. We used time-dependent variables and the start of follow-up from the beginning of exposure when the impact of commonly used drugs on prostate cancer risk or mortality is compared against that in non-users [ 46 , 60 ]. Use of these methods requires, at minimum, knowledge on starting dates of medication use.…”

“…The bias creates an illusion that non-users, who might have been users for a long time but discontinued usage shortly before cancer death, have more cancer deaths compared to those who have kept using the drug until the end of follow-up ( Figure 3 ). Our approach to avoid this bias while analyzing medication use as a time-dependent exposure is to keep the subjects as users after the first recorded usage, i.e., user status may change from non-user to user but will not change back to non-user even though the medication use has been later discontinued [ 46 ]. This effectively eliminates the selective discontinuation bias described above.…”

“…One example of this situation occurred when we investigated the association between use of antihypertensive drugs and the risk of prostate cancer death in a Finnish population-based cohort [ 46 ]. In the preliminary analysis, the use of diuretics was associated an increased risk of prostate cancer death compared to non-users (hazard ratio 2.61, 95% CI 2.22–3.06).…”