THE USE OF SPECIFIC ANTIHYPERTENSIVE MEDICATION AND SKIN CANCER RISK: A SYSTEMATIC REVIEW OF THE LITERATURE AND META-ANALYSIS

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Objectives:
The use of hydrochlorothiazide has recently been linked to skin cancer in observational studies. This may be explained by its photosensitizing properties, but photosensitivity has also been reported for other antihypertensive drugs. We conducted a systematic review and meta-analysis to compare skin cancer risk among antihypertensive drug classes and between individual blood pressure lowering drugs.

Methods:
We searched Medline, Embase, Cochrane and the Web of Science to 9th of February 2022 and included studies that investigated the association between antihypertensive medication exposure and non-melanoma skin cancer (NMSC) or cutaneous malignant melanoma (CMM). We combined the extracted adjusted odds ratios (OR) using a random effects model. We performed sensitivity analyses comparing study type, population and studies with and without correction for important covariates.

Results:
We included 43 studies. Diuretics (n = 17,729,595), in particular hydrochlorothiazide (n = 17,710,679), and calcium channel blockers (CCB, n = 8,413,919) were examined more frequently than beta-blockers (n = 94,872) or renin-angiotensin system inhibitors (n = 2,019,786). Exposure to diuretics (OR 1.30, 95% CI [1.12-1.52]) and CCB (OR 1.06, 95% CI [1.04-1.09]) was associated with an increased risk for NMSC. No antihypertensive drug class was associated with an increased risk for CMM. Within every drug class, at least 1 individual drug was associated with an increased risk for NMSC: nifedipine, hydrochlorothiazide, sotalol, verapamil, enalapril and bendroflumethiazide. Increased NMSC risk was only observed in case-control studies and in studies that did not correct for important covariates. No increased NMSC risk was observed in cohort studies and studies that did correct for the covariates sun exposure, skin phototype or smoking. (Figure) Only 2 out of 43 studies provided information about antihypertensive co-medication. Eggers test revealed a significant publication bias for the subgroup of diuretics and hydrochlorothiazide concerning NMSC (both p < 0.001).
Conclusion: Of all antihypertensive drugs, diuretics and calcium channel blockers may be associated with an increased risk of NMSC, but causal inferences remain difficult to make because of aforementioned substantial limitations in available data and evidence of publication bias. Background: Diabetes mellitus (DM) is associated with increased risks of cancers, cardiovascular disease (CVD), liver disease and death. In recent years, cardiovascular and metabolic medications have been developed for reducing cardiovascular events and mortality. We examined mortality statistics by cause of in-hospital death in patients with DM and patients without DM and we analyzed the effects of cardiovascular and metabolic medications on the lifespans of patients in a Japanese community general hospital during the past decade.

Methods:
We performed a retrospective analysis of cause of death in hospitalized patients at Anan Medical Center, a community general hospital in Tokushima, Japan, during the period from 2011 to 2020. Information on clinical characteristics of the patients including age at death, cause of death, complications and medications used was obtained from medical records. Statistical comparisons were performed in patients with DM and those without DM. Multivariate analysis was also carried out to determine the effects of medications on age at death.

Results:
A total of 2336 deaths were recorded during the 10-year period. The mean age at death was not significantly different between diabetic and nondiabetic patients for both sexes (78.9 (DM) vs. 79.6 (non DM) years in males and 82.5 (DM) vs. 83.6 (non DM) years in females). The rates of hepato-pancreatic cancer and cardio-renal failure as a cause of death were significantly higher in patients with DM than in patients without DM (p < 0.01 and p < 0.05, respectively). The incidences of hepato-renal failure, CVD, hypertension and dyslipidemia as comorbidities were significantly higher in diabetic patients than in nondiabetic patients (all p < 0.01). The percentages of patients taking antihypertensive, antiplatelet, diuretic and statin medications were higher in diabetic patients than in nondiabetic patients (all p < 0.01). Multivariate analysis of medications for determinants of age at death showed that insulin was a negative contributor in diabetic patients. On the other hand, the use of an angiotensin receptor blocker (ARB)/angiotensin-converting enzyme inhibitor (ACEi) or Ca antagonists was a positive correlator for longevity in all of the subjects including diabetic and nondiabetic patients.

Conclusions:
In our community general hospital, DM had no influence on age at death. It is possible that comprehensive treatment for DM and its complications eliminates the difference between lifespans of individuals with DM and those without DM. In addition, treatment of hypertension with ARB/ACEi or Ca antagonists was positively associated with the longevity of Japanese community subjects.