Antihypertensive drugs and prostate cancer survival after radical prostatectomy in Finland—A nationwide cohort study

Abstract

Antihypertensive (anti-HT) drugs targeting renin-angiotensin-aldosterone (RAA)- system have been associated with improved prostate cancer (PCa)-specific survival. Challenge is that often multiple drugs are used simultaneously. We evaluated the association between use of anti-HT drugs and PCa survival among 14,422 surgically treated Finnish PCa patients. Information on drug purchases was obtained from a national prescription database. We used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of PCa death and initiation of androgen deprivation therapy (ADT) with adjustment for age, tumor extent, use of statins and for Charlson Comorbidity Index. Angiotensin-converting enzyme (ACE)- inhibitors, angiotensin- receptor (ATR)-blockers, diuretics, calcium-channel blockers, beta-blockers and other anti-HT drugs were analyzed as separate time-dependent variables to model simultaneous use. Overall anti-HT drugs were associated with an increased risk of PCa death. Conversely use of ATR-blockers was associated with decreased risk of PCa death (HR: 0.43, 95% CI: 0.26-0.72 and HR: 0.60, 95% CI 0.37-0.97 for pre- and post-diagnostic use). Similar risk decrease was not observed in other drug groups. Anti-HT drugs were also associated with an increased risk of starting ADT, with the exception of ATR-blockers (HR: 0.81 CI:0.71-0.92). ATR- blockers differ from other anti-HT drugs as the survival is better in users of this drug group. The result partly supports the role of RAA system in PCa progression. Nevertheless, the risk decrease was not observed in ACE-inhibitor users. Further research is needed to elucidate the molecular mechanism for the potential anticancer effect of ATR- blockers.

Calcium channel blockers therapy and the risk of prostate cancer death

“…Recently, a cohort study conducted by Santala et al . published in the International Journal of Cancer reported the association between prostate cancer survival after radical prostatectomy and antihypertensive drug use . We are interested in their findings that calcium channel blockers use before prostate cancer diagnosis was not significantly associated with the risk of prostate cancer death (multivariable adjusted hazard ratio = 0.84, 95% confidence interval = 0.51–1.40).…”

“…1 Recently, a cohort study conducted by Santala et al published in the International Journal of Cancer reported the association between prostate cancer survival after radical prostatectomy and antihypertensive drug use. 2 We are interested in their findings that calcium channel blockers use before prostate cancer diagnosis was not significantly associated with the risk of prostate cancer death (multivariable adjusted hazard ratio = 0.84, 95% confidence interval = 0.51-1.40). However, a case-control study conducted by Rotshild et al revealed that a positive association was detected between the risk of prostate cancer and calcium channel blockers use (odds ratio = 1.10, 95% confidence interval = 1.02-1.18).…”

Investigating the Role of Mineralocorticoid Receptor Signaling in Cancer Biology in the Genomic Era

“…Consistently, silencing of MR resulted in enhanced resistance to enzalutamide and AR activity [55]. Moreover, the effects of diverse antihypertensive medication on prostate cancer survival following radical prostatectomy were tested in the Finnish population, and overall, the antihypertensive treatment was associated with increased death risk [56]. These findings clearly establish the importance of AR and MR cross talk and complex ligand interactions in prostate cancer, which could be further studied in other cancers and cancer subtypes where AR signaling can play a role.…”

Reply to: Calcium channel blockers therapy and the risk of prostate cancer death

“…We are very pleased to answer the comments on our manuscript "Antihypertensive drugs and prostate cancer survival after radical prostatectomy in Finlanda nationwide cohort study." 1 Lai et al wonder whether androgens would be a potent confounding subject for prostate cancer (PCa) diagnosis. At first, it is important to consider that risk factors for PCa diagnosis might be different compared to risk factors for PCa death, as may also confounding subjects be.…”

“…We are very pleased to answer the comments on our manuscript “Antihypertensive drugs and prostate cancer survival after radical prostatectomy in Finland – a nationwide cohort study.”…”