Associations between initiating antihypertensive regimens on stage I–III colorectal cancer outcomes: A Medicare SEER cohort analysis

Balkrishnan, Rajesh; Desai, Raj Piyush; Narayan, Aditya; Camacho, Fabian; Flausino, Lucas E; Chammas, Roger

doi:10.1002/cam4.4088

Cited by 11 publications

(7 citation statements)

References 73 publications

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“…Our findings would require a larger and more diverse cohort of patients with CCB medication to draw any general conclusions. Balkrishnan et al 38 who evaluated the association between antihypertensive treatment and mortality in a cohort of 13,982 CRC patients reported a protective effect of these drugs; however, patients using CCB were not included in the analysis. Similarly, Peng et al 39 reported a beneficial impact of antihypertensives on the prognosis of 713 CRC patients, although their results were not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

The risk of second primary malignancies in colorectal cancer patients using calcium channel blockers

Halámková

Bohovicová

Pehalová

et al. 2023

Sci Rep

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Calcium channel blockers are among the most commonly used agents in the treatment of cardiovascular diseases. There are several known side-effects associated with their long-term use, whereas other potential adverse effects are yet to be proven. This study aims to evaluate the association between calcium channel blockers exposure and the incidence of second primary malignancy. We established a cohort of 1401 patients with colorectal cancer diagnosed in our institution between January 2003 and December 2016. Patients were followed-up until December 2020. The tumor characteristics and basic clinical data including medication information were obtained from the hospital information system database. Second malignancy was detected in 301 patients (21.5%), and occurred in 27.8% of patients who used calcium channel blockers compared to only 19.9% among non-users. Their use was associated with an increased incidence of bladder cancer in particular. Subanalysis of patients with second malignancy displayed a higher proportion of right-sided colon cancer compared to rectal carcinoma in non-users. Survival analysis revealed significantly better outcomes in early-stage colorectal cancer patients without a history of calcium channel blockers treatment or second primary malignancy.

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Section: Discussionmentioning

confidence: 99%

The risk of second primary malignancies in colorectal cancer patients using calcium channel blockers

Halámková

Bohovicová

Pehalová

et al. 2023

Sci Rep

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“…A detailed analysis showed a positive effect on survival of all study drug groups (ACEIs, beta blockers, diuretics), except for ARBs. Due to data availability, the analysis excluded, however, patients below 65 years old, and those using antihypertensive drugs before the diagnosis of colorectal cancer [ 32 ]. On the other hand, Holmes et al and Cardwell et al in two population studies, showed no such correlation in other groups of patients with colorectal cancer (n = 3967 and n = 4762, respectively) [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Risk factors for long-term survival in patients with ypN+ M0 rectal cancer after radical anterior resection

et al. 2022

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Background Regional lymph node metastases are the main adverse prognostic factor in patients with rectal cancer without distant metastases. There are discrepancies, however, regarding additional risk factors in the group of ypN + M0 patients. The purpose of the study was to assess clinical and pathological factors affecting long-term oncological outcomes in the group of ypN + M0 patients after radical rectal anterior resection. Methods 112 patients with ypN + M0 rectal cancer after neoadjuvant therapy and radical anterior resection were subject to a retrospective analysis. The effect of potential factors on survival was assessed with the use of Kaplan–Meier curves together with a log-rank test and multiple factor Cox proportional hazards model. Results In the multiple factor Cox analysis, adverse factors affecting disease-free survival (DFS) were: the use of angiotensin-converting enzyme inhibitors (ACEIs) (hazard ratio HR: 3.11, 95% CI 1.01–9.56, p = 0.047), presence of perineural invasion (HR: 7.27, 95% CI 2.74–19.3, p < 0.001) and occurrence of postoperative complications (HR: 6.79, 95% CI 2.09–22.11, p = 0.001), while a positive factor was the negative lymph node (NLN) count > 7 (HR: 0.33, 95% CI 0.12–0.88, p = 0.026). In the disease-specific survival (DSS) analysis, an adverse factor was the use of ACEIs (HR: 4.275, 95% CI 1.44–12.694, p = 0.009), while a positive effect was caused by NLN > 5 (HR: 0.22, 95% CI 0.082–0.586, p = 0.002). Conclusions The use of ACEIs may have a negative effect on long-term treatment outcomes in patients with ypN + M0 rectal cancer. In this group of patients, the NLN count seems to be an important prognostic factor, as well.

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“…A correlation between adherence to therapy with anti-hypertensives and decreased specific mortality due to CRC was also seen. It was therefore suggested that these drugs could be used as supplements to the anti-tumor therapy for the treatment of CRC in stages I-III [22]. In another example, Morris et al [23] evaluated patients with rectal cancer treated with neoadjuvant radiotherapy or chemo-radiotherapy followed by surgical resection and found that there was a significant positive correlation between taking ACEi/ARB anti-hypertensives and increased regression and lower tumor grade.…”

Section: Crc and Anti-hypertensivesmentioning

confidence: 99%

“…As discussed above, the use of ACEi is likely associated with a better outcome in CRC [21][22][23][24][25] but the mechanisms responsible are not fully understood and it is not yet clear whether the benefit to the patient observed in ACEi users is linked to MDSCs. ACE expression in myeloid cells is reported as a fundamental requirement for normal myelopoiesis, but ACE could also be responsible for myeloid cell modulation during the process of differentiation.…”

Section: Therapies Targeting Mdscsmentioning

confidence: 99%

Alternative Chemotherapies: Angiotensin-Converting Enzyme Inhibitors Reduce Myeloid-Derived Suppressor Cells to Benefit Older Patients with Colorectal Cancer

Bueno¹,

Forones²,

Pawelec³

2023

Front. Biosci. (Landmark Ed)

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Older individuals are more likely to develop solid cancers, but at the same time are more sensitive to the side effects of chemotherapy. In addition, older adults are more likely to present with chronic diseases (comorbidities) and immunosenescence that may decrease immunosurveillance against cancer. Clinical outcomes for the older patient with cancer are different from the younger patient and require different research and treatment approaches. Thus, alternative therapeutic approaches tailored specifically to the older patients are required. Colorectal cancer (CRC) has a high incidence in older individuals and is the third leading cause of cancer death globally. Anti-hypertensives are used by a large proportion of older patients and some studies have pointed to a positive impact of angiotensinconverting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) on CRC outcomes. As we have previously shown in a mouse model, lung metastases express ACE and contain many infiltrating myeloid-derived suppressor cells (MDSC); particularly high levels of MDSC are also present in the blood of older patients with CRC and other cancers, and are associated with disease severity. In this Commentary, we hypothesize that one mechanism responsible for the positive impact of ACEi or ARB on the outcome of CRC is the modulation of myeloid cells contributing to their maturation to non-suppressive neutrophils/monocytes and diverting them away from retaining an immature MDSC phenotype.

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Associations between initiating antihypertensive regimens on stage I–III colorectal cancer outcomes: A Medicare SEER cohort analysis

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 11 publications

References 73 publications

The risk of second primary malignancies in colorectal cancer patients using calcium channel blockers

The risk of second primary malignancies in colorectal cancer patients using calcium channel blockers

Risk factors for long-term survival in patients with ypN+ M0 rectal cancer after radical anterior resection

Alternative Chemotherapies: Angiotensin-Converting Enzyme Inhibitors Reduce Myeloid-Derived Suppressor Cells to Benefit Older Patients with Colorectal Cancer

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