Matteo Franchi’s research while affiliated with Università degli Studi di Milano-Bicocca and other places

Objective Several meta-analyses have examined whether antihypertensive drugs alter the risk of cancer. However, in most studies follow-up was relatively short and adherence to antihypertensive drugs was not accounted for. We analysed the relationship between long-term exposure to antihypertensive drugs and risk of cancer. Design and method Retrospective population-based cohort study based on healthcare utilization databases of Lombardy Region (Italy). We selected all individuals aged 40 - 85 years newly dispensed with at least one antihypertensive drug from between 2009 and 2011, and with no previous history of cancer. Exposure to angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), calcium channel blockers (CCB), beta-blockers (BB), thiazides/thiazide-likes, loop diuretics and mineralocorticoid receptor antagonists (MRA) was evaluated by using an “as-treated” approach, according to which each cohort member was classified based on the duration of exposure to each class of drugs. Patients were followed-up from the date of the first dispensation of antihypertensive drug and ended at the earliest date between onset of cancer, migration, death or December 31, 2020. The association between the duration of exposure to each class of drug (considered as a time-dependent covariate) and cancer risk was evaluated by Cox regression models, adjusted for sex, age and the Multisource Comorbidity Score, and mutually adjusted for the exposure to each class of drugs. Results The study cohort included 339,842 new users of antihypertensive drugs (median age 59 years, 49.5% males). During a median follow-up of 10.2 years, 36,778 cancers occurred. There was no evidence of consistent significant associations of the risk of cancer with ACEI, ARB and thiazides. An increasing but weak risk was associated to a medium-long term exposure to CCB and with a long-term exposure to BB. With the limit that the number of users was much smaller, exposure to MRA was associated to a significant increase in the risk of cancer at all exposure levels. Conclusions In our study, treatment adherence allowed a more accurate evaluation of true exposure to a potentially carcinogenic drug influence. The results showed an increased risk with the exposure to some antihypertensive agents, in particular with the MRA.

Objective Data from randomized clinical trials showed that new-onset hypertension is a common side effect of anti-angiogenic drugs. We compared the cumulative incidence of new-onset hypertension in cancer patients treated with either anti-angiogenic based therapy (AAG) or other chemotherapy only, and in patients who did not received antineoplastic agents (untreated). Design and method Retrospective population-based cohort study based on the healthcare utilization databases of Lombardy Region (Italy). We identified the cohort of patients aged 40 years or older with a new diagnosis of cancer between 2009 and 2017. We excluded patients with antihypertensive treatment in the five years before cancer diagnosis. We 1:1:1 matched each patient who started a therapy with AAG (index case) with one patient treated with other chemotherapy only and with one untreated patient by date of cancer diagnosis, tumoral site and date of start of antineoplastic therapy. We followed-up each of the three matched patients from the date of start of AAG of the index case until the first date between onset of antihypertensive treatment with at least 3 prescriptions (the outcome of interest), death, migration or 2 years after the start of follow-up. We estimated the incidence cumulative function by considering death as competing event and we fitted a Fine and Grey regression model, adjusted for age, sex and Cancer Multimorbidity Score, in order to estimate the association between treatment and new-onset hypertension. Results The final cohort included 3,333 1:1:1 matched patients (median age 62 years; 43.6% males). The cumulative incidence of new-onset hypertension was higher among patients treated with AAG, as compared to others. The cumulative incidence rapidly increased 1 year (26.3%) after starting therapy with AAG. The adjusted hazard ratios were 3.73 (95% CI 3.34 to 4.15) and 4.00 (3.56 to 4.48), when compared to patients treated with other chemotherapy and with those untreated, respectively. Moreover, patients treated with AAG also showed a significant increased risk of major cardiovascular events compared to others. Conclusions Cancer patients treated with AAG showed a markedly higher risk of new-onset hypertension. The risk rapidly increased 1 year after the start of therapy.

Introduction: Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia. The objective of this analysis was to compare the efficacy and adverse effects of extended release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on biomarkers PTH, calcium and Phosphate in patients with non-dialysis CKD (ND CKD). Methods: A systematic literature research (SLR) was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting. Results: Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on two overlapping networks, due to non-reporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared to ERC (0.2 mg/dl increase, 95% CI: -0.37 to -0.05 mg/dl). No differences in effects on phosphate were observed. Conclusion: This NMA showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well tolerated treatment option for the management of SHPT in patients with ND CKD.