Risk of urothelial cancer death among people using antihypertensive drugs—a cohort study from Finland

Santala, Eerik E. E.; Kotsar, Andres; Veitonmäki, Thea; Tammela, Teuvo L.J.; Murtola, Teemu J.

doi:10.1080/21681805.2019.1634147

Cited by 6 publications

(16 citation statements)

References 12 publications

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“…While beta blockers represented the most common antihypertensives in our analysis, no impact on RFS, CSS or OS was found. This is in line with findings by Dal Moro et al (20 patients) and Santala et al (500 patients) [ 8 , 9 ].…”

Section: Discussionsupporting

confidence: 93%

“…A study evaluating the risk for urinary tract cancer development enrolling over 30,000 patients found no effect for ACEI, while ARB increased the risk [ 10 ]. Recently, a Finnish retrospective study evaluating the impact of antihypertensives on survival after bladder cancer diagnosis found no effect for ACEI, but an improved survival for ARB [ 9 ]. Of note, the positive ARB effect was only significant in the multivariate analysis for men, but not women.…”

Section: Discussionmentioning

confidence: 99%

“…Previously studied non-oncologic drugs and drug classes used for chronic therapy were selected based on their potential effect on UCB development, recurrence or known impact on other cancer entities [6,9,10,12,15,17,[23][24][25]. The following drug classes defined by anatomical therapeutical chemical code (ATC) were included: antihypertensives (ACEI (C09AA), ARB (C09CA), beta blockers (C07AB), CCB (C08)), drugs targeting blood coagulation (acetylsalicylic acid (ASA) (B01AC), vitamin-K-antagonists (B01AA), direct acting oral anticoagulants (DOAC) (B01AF)), antidiabetic drugs (metformin (A10BA02), sulfonylureas (A10BB), thiazolidinediones (A10BG), dipeptidylpeptidase 4 (DPP4)-Inhibitors (A10BH), insulin (A10A)) and miscellaneous (statins (C10AA), allopurinol (M04AA01)).…”

Section: Analyzed Drugs and Drug Classesmentioning

confidence: 99%

“…While some studies are available on the impact of drugs on the risk of UCB development [5], data regarding an impact on recurrence and survival are still limited. For instance, conflicting results have been found for firstline antihypertensives like angiotensin-converting-enzyme inhibitors (ACEI), angiotensin-receptor-blockers (ARB) and calcium-channel blockers (CCB) [6][7][8][9][10][11][12]. Although the precise mechanism remains unclear, the renin-angiotensin-aldosterone system potentially affects carcinogenesis and tumor progression [13].…”

Section: Introductionmentioning

confidence: 99%

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Retrospective evaluation of the impact of non-oncologic chronic drug therapy on the survival in patients with bladder cancer

et al. 2021

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Background Chronic drug therapy may impact recurrence and survival of patients with bladder cancer and thus be of concern regarding drug choice and treatment decisions. Currently, data are conflicting for some drug classes and missing for others. Objective To analyze the impact of common non-oncologic chronic drug intake on survival in patients with bladder cancer and radical cystectomy. Setting. Patients with bladder cancer and radical cystectomy (2004–2018) at the University Hospital Munich. Method Data from an established internal database with patients with bladder cancer and radical cystectomy were included in a retrospective study. Drug therapy at the time of radical cystectomy and survival data were assessed and follow-up performed 3 months after radical cystectomy and yearly until death or present. Impact on survival was analyzed for antihypertensive, antidiabetic, anti-gout, antithrombotic drugs and statins, using the Kaplan–Meier method, log-rank test and Cox-regression models. Main outcome measure Recurrence free survival, cancer specific survival and overall survival for users versus non-users of predefined drug classes. Results Medication and survival data were available in 972 patients. Median follow-up time was 22 months (IQR 7–61). In the univariate analysis, a significant negative impact among users on recurrence free survival (n = 93; p = 0.038), cancer specific survival (n = 116; p < 0.001) and overall survival (n = 116; p < 0.001) was found for calcium-channel blockers, whereas angiotensin-receptor-blockers negatively influenced overall survival (n = 96; p = 0.020), but not recurrence free survival (n = 73; p = 0.696) and cancer specific survival (n = 96; p = 0.406). No effect of angiotensin-receptor-blockers and calcium-channel blockers was seen in the multivariate analysis. None of the other studied drugs had an impact on survival. Conclusion There was no impact on bladder cancer recurrence and survival for any of the analyzed drugs. Considering our results and the controverse findings in the literature, there is currently no evidence to withhold indicated drugs or choose specific drug classes among the evaluated non-oncologic chronic drug therapies. Thus, prospective studies are required for further insight. Trail registration This is part of the trial DRKS00017080, registered 11.10.2019.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Analyzed Drugs and Drug Classesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Retrospective evaluation of the impact of non-oncologic chronic drug therapy on the survival in patients with bladder cancer

et al. 2021

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“…In a large nationwide Finnish cohort, the authors found a significant reduction in mortality due to breast cancer in RASB users, also featuring a dose-effect, suggesting a mechanistic association [ 84 ]. Similarly, concurring elements supported that urological cancer survival improved with RASB use [ 85 , 86 , 87 , 88 , 89 ]. In non-small-cell lung cancer, RASB use with platinum and taxol chemotherapy was associated with improved survival [ 90 , 91 ].…”

Section: Part 1: Renin–angiotensin System Blockers and Malignanciesmentioning

confidence: 84%

Renin–Angiotensin–Aldosterone System and Immunomodulation: A State-of-the-Art Review

Laghlam

Jozwiak

Nguyen

2021

Cells

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The renin–angiotensin system (RAS) has long been described in the field of cardiovascular physiology as the main player in blood pressure homeostasis. However, other effects have since been described, and include proliferation, fibrosis, and inflammation. To illustrate the immunomodulatory properties of the RAS, we chose three distinct fields in which RAS may play a critical role and be the subject of specific treatments. In oncology, RAS hyperactivation has been associated with tumor migration, survival, cell proliferation, and angiogenesis; preliminary data showed promise of the benefit of RAS blockers in patients treated for certain types of cancer. In intensive care medicine, vasoplegic shock has been associated with severe macro- and microcirculatory imbalance. A relative insufficiency in angiotensin II (AngII) was associated to lethal outcomes and synthetic AngII has been suggested as a specific treatment in these cases. Finally, in solid organ transplantation, both AngI and AngII have been associated with increased rejection events, with a regional specificity in the RAS activity. These elements emphasize the complexity of the direct and indirect interactions of RAS with immunomodulatory pathways and warrant further research in the field.

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Survival Benefit of Renin-Angiotensin System Blockers in Critically Ill Cancer Patients: A Retrospective Study

Laghlam,

Chaba,

Tarneaud

et al. 2023

Cancers

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Increasing evidence argues for the promotion of tumorigenesis through activation of the renin-angiotensin system pathway. Accordingly, a benefit of renin-angiotensin system blockers (RABs) treatments has been suggested in patients with solid cancers in terms of survival. We aimed to evaluate in-ICU survival and one-year survival in cancer patients admitted to the ICU with respect to the use of RABs. We conducted a retrospective observational single-center study in a 24-bed medical ICU. We included all solid cancer patients (age ≥ 18 years) requiring unplanned ICU admission. From 2007 to 2020, 1845 patients with solid malignancies were admitted (median age 67 years (59–75), males 61.7%). The most frequent primary tumor sites were the gastrointestinal tract (26.8%), the lung (24.7%), the urological tract (20.1%), and gynecologic and breast cancers (13.9%). RABs were used in 414 patients, distributed into 220 (53.1%) with angiotensin-receptor blockers (ARBs) and 194 (46.9%) with angiotensin-converting enzyme inhibitors (ACEis). After multivariate adjustment, ARBs use (OR = 0.62, 95%CI (0.40–0.92), p = 0.03) and ACEis use (OR = 0.52, 95%CI (0.32–0.82), p = 0.006) were both associated with improved in-ICU survival. Treatment with ARBs was independently associated with decreased one-year mortality (OR = 0.6, 95%CI (0.4–0.9), p = 0.02), whereas treatment with ACEis was not. In conclusion, this study argues for a beneficial impact of RABs use on the prognosis of critically ill cancer patients.

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Risk of urothelial cancer death among people using antihypertensive drugs—a cohort study from Finland

Cited by 6 publications

References 12 publications

Retrospective evaluation of the impact of non-oncologic chronic drug therapy on the survival in patients with bladder cancer

Retrospective evaluation of the impact of non-oncologic chronic drug therapy on the survival in patients with bladder cancer

Renin–Angiotensin–Aldosterone System and Immunomodulation: A State-of-the-Art Review

Survival Benefit of Renin-Angiotensin System Blockers in Critically Ill Cancer Patients: A Retrospective Study

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