RESUMO
Ovarian cancer (OC) has a poor prognosis. Hypertension may be a prognostic factor for OC, but it is unclear whether antihypertensive (anti-HT) drug use of modifies OC prognosis. We performed a population-based analysis assessing the effect of anti-HT drug use on OC mortality. A cohort of 12,122 women identified from the Finnish Cancer Registry with OC in 1995-2013 was combined with information on their anti-HT drug use during the same time period. Use of each anti-HT drug was analysed as a time-dependent variable. Analyses were run for five, ten and full follow-up (19-year) mortality with cardiovascular morbidity risk evaluated in competing risk analysis. No anti-HT drug group was associated with OC survival within five years after OC diagnosis. At ten years, a dose-dependent association was observed between pre-diagnostic ACE-inhibitor use and improved OC survival. With full follow-up, post-diagnostic high-intensity use associated with reduced OC death risk for multiple anti-HT drug groups. In competing risk analysis, only the post-diagnostic use of ACE-inhibitors associated with increased OC survival. Anti-HT drugs were not associated with survival benefits within five years after OC diagnosis. ACE-inhibitors may confer survival benefits in women with OC, but further confirmatory studies are needed.
RESUMO
BACKGROUND: Breast cancer incidence has been associated with hypertension, which might worsen disease prognosis, but few nationwide studies have investigated the association between antihypertensive drug use and breast cancer prognosis. METHODS: A cohort of 73,170 women diagnosed with breast cancer during 1995-2013 identified from the Finnish Cancer Registry was combined with information on antihypertensive drug use during the same time period from a national prescription database. Antihypertensive drugs were analyzed in groups categorized by mechanism of action. Usage of antihypertensive drugs, statins, antidiabetic, and anticoagulative drugs was analyzed as time-dependent exposure to model for simultaneous use of multiple drug groups. Influence of protopathic bias was evaluated in lag-time analyses. RESULTS: In prediagnostic use, only angiotensin receptor (ATR)-blockers were associated with decreased risk of breast cancer death as compared with nonusers (HR: 0.76, 95% confidence interval, CI: 0.69-0.82), and there was an inverse association with cumulative dose of use. Postdiagnostic use of ATR-blockers, angiotensin-converting enzyme (ACE)-inhibitors, beta-blockers, and calcium-channel blockers was dose dependently associated with better breast cancer survival compared with nonusers. The risk decrease was strongest for ATR-blockers (HR: 0.69, 95% CI: 0.63-0.75) and remained for exposures occurring up to 3 years earlier. CONCLUSIONS: Only ATR-blockers were associated with improved breast cancer survival in both prediagnostic and postdiagnostic use. The association was dose dependent and supported by a biological rationale as a causal explanation. In postdiagnostic use, similar reduction was found also for other antihypertensives, supporting a prognostic role of hypertension control. IMPACT: Inhibition of angiotensin receptor subtype 1 (AT1) could be a promising novel way to affect breast cancer progression.
Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/farmacologia , Neoplasias da Mama/mortalidade , Estudos de Coortes , Feminino , Finlândia , Humanos , Análise de SobrevidaRESUMO
Background: To analyse the association between antihypertensive (anti-HT) drug use and risk of urothelial cancer (UC) death. UC occurs as bladder cancer (BCa) and upper tract urothelial carcinomas (UTUCs). Hypertension is a suggested risk factor for BCa and may impair disease prognosis. However, it's unclear if use of anti-HT drugs could improve the prognosis of UC.Materials and methods: This study evaluated the association between use of anti-HT drugs and UC survival among 14,065 participants diagnosed with BCa and 1080 with UTUC during 1995-2012 in Finland. It analyzed data using the multivariable adjusted conditional Cox regression model.Results: Angiotensin-receptor (ATR) blocker use before BCa diagnosis was associated with slightly decreased risk of BCa death (HR = .81, CI = .71-0.93). The association was dose-dependent and it decreased in association with elevated intensity of ATR-blocker use. Post-diagnostic use of ATR-blockers was similarly associated with better survival compared to non-users (HR = .81, CI = .71-0.92. Interestingly, use of calcium-channel blockers also associated with better survival and the risk of BCa death decreased with increasing intensity of use (HR = .67, CI = .52-0.86 for highest intensity).Conclusions: This large population-based cohort suggests decreased risk of BCa death among ATR-blocker and calcium-channel blocker users. The risk association among ATR-blockers and calcium-channel blockers was dose-dependent suggesting a causal explanation. Similar risk associations are not observed for other anti-HT drug users, which may suggest a direct effect of ATR blocker or calcium-channel blocker use. Further studies are needed to elucidate the potential anticancer mechanism.