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Renin–angiotensin–aldosterone system inhibitors (RAASi) are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the data on the response to treatment and tumour-based endpoints across different tumour types are unknown. We carried out a retrospective study at two tertiary referral centres in Taiwan. All adult patients treated with ICIs between January 2015 and December 2021 were included. The primary outcome was overall survival and the secondary outcomes were progression-free survival (PFS) and clinical benefit rates. In total, 734 patients were enrolled in our study, of which 171 were RAASi users and 563 were non-users. Compared with non-users, RAASi users had a longer median overall survival [26.8 (interquartile range 11.3–not reached) versus 15.2 (interquartile range 5.1–58.4) months, P < 0.001] and PFS [12.2 (interquartile range 3.9–34.5) versus 5.0 (interquartile range 2.2–15.2) months, P < 0.001]. In univariate Cox proportional hazard analyses, the use of RAASi was associated with a 40% reduction in the risk of mortality [hazard ratio 0.58 (95% confidence interval 0.44–0.76), P < 0.001] and disease progression [hazard ratio 0.62 (95% confidence interval 0.50–0.77), P < 0.001]. The association remained significant after adjusting for underlying comorbidities and cancer therapy in multivariate Cox analyses. A similar trend was observed for PFS. Furthermore, RAASi users experienced a greater clinical benefit rate than non-users (69% versus 57%, P = 0.006). Importantly, the use of RAASi before ICI initiation was not associated with improved overall survival and PFS. RAASi were not associated with an increased risk of adverse events. The use of RAASi is associated with improved survival outcomes, treatment response and tumour-based endpoints in patients undergoing immunotherapy. • RAASi were associated with improved clinical outcomes across a broad range of cancer patients receiving ICI. • Subgroup analysis showed that ARB were associated with improved clinical outcomes in patients undergoing immunotherapy. • The use of RAASi before immune checkpoint blockade was not associated with improved survival. • RAASi were not associated with increased risk of adverse events among cancer patients receiving ICI. [ABSTRACT FROM AUTHOR]

The chronic receipt of renin-angiotensin-aldosterone system (RAAS) inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been assumed to be associated with a significant decrease in overall gynecologic cancer risks. This study aimed to investigate the associations of long-term RAAS inhibitors use with gynecologic cancer risks. A large population-based case-control study was conducted from claim databases of Taiwan's Health and Welfare Data Science Center (2000–2016) and linked with Taiwan Cancer Registry (1979–2016). Each eligible case was matched with four controls using propensity matching score method for age, sex, month, and year of diagnosis. We applied conditional logistic regression with 95% confidence intervals to identify the associations of RAAS inhibitors use with gynecologic cancer risks. The statistical significance threshold was p < 0.05. A total of 97,736 gynecologic cancer cases were identified and matched with 390,944 controls. The adjusted odds ratio for RAAS inhibitors use and overall gynecologic cancer was 0.87 (95% CI: 0.85–0.89). Cervical cancer risk was found to be significantly decreased in the groups aged 20–39 years (aOR: 0.70, 95% CI: 0.58–0.85), 40–64 years (aOR: 0.77, 95% CI: 0.74–0.81), ≥65 years (aOR: 0.87, 95% CI: 0.83–0.91), and overall (aOR: 0.81, 95% CI: 0.79–0.84). Ovarian cancer risk was significantly lower in the groups aged 40–64 years (aOR: 0.76, 95% CI: 0.69–0.82), ≥65 years (aOR: 0.83, 95% CI: 0.75–092), and overall (aOR: 0.79, 95% CI: 0.74–0.84). However, a significantly increased endometrial cancer risk was observed in users aged 20–39 years (aOR: 2.54, 95% CI: 1.79–3.61), 40–64 years (aOR: 1.08, 95% CI: 1.02–1.14), and overall (aOR: 1.06, 95% CI: 1.01–1.11). There were significantly reduced risks of gynecologic cancers with ACEIs users in the groups aged 40–64 years (aOR: 0.88, 95% CI: 0.84–0.91), ≥65 years (aOR: 0.87, 95% CI: 0.83–0.90), and overall (aOR: 0.88, 95% CI: 0.85–0.80), and ARBs users aged 40-64 years (aOR: 0.91, 95% CI: 0.86–0.95). Our case-control study demonstrated that RAAS inhibitors use was associated with a significant decrease in overall gynecologic cancer risks. RAAS inhibitors exposure had lower associations with cervical and ovarian cancer risks, and increased endometrial cancer risk. ACEIs/ARBs use was found to have a preventive effect against gynecologic cancers. Future clinical research is needed to establish causality. [ABSTRACT FROM AUTHOR]

Background Mortality after myocardial infarction (MI) among patients undergoing dialysis is high. However, studies investigating the use of secondary prevention medications after MI and clinical outcomes in dialysis patients are lacking. This study aimed to examine the association of the number of guideline-recommended medications (antiplatelets, β-blockers, statins and renin–angiotensin–aldosterone system inhibitors) with all-cause mortality after MI in hemodialysis (HD) patients. Methods We conducted a nationwide cohort study of incident HD patients who were admitted for MI between 1 January 2010 and 31 December 2014 and were followed up until 31 December 2015, using Taiwan's national health insurance research database. Results Of 1471 patients (mean age 68 years, 41.9% women) included in the analysis, 281 (19.1%) were treated with one cardioprotective medication, 406 (27.6%) with two, 490 (33.3%) with three and 294 (20%) with four. During a median follow-up of 1.0 years, 458 (31.1%) patients died. In a multivariable Cox model, each additional use of guideline-recommended therapies was associated with a significant 12% reduction in the risk of mortality {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.80–0.97]}. Similar results were obtained in the analysis with the inverse probability of treatment weighting [HR 0.84 (95% CI 0.77–0.92)] and in the propensity score–matched subcohort [HR 0.87 (95% CI 0.77–0.98)]. The decreased mortality risk was consistently observed across all subgroups. Conclusions The use of more evidence-based medications for secondary prevention after MI was associated with a lower risk of all-cause mortality in HD patients. [ABSTRACT FROM AUTHOR]

• Acute kidney injury (AKI) during the aging process is particularly of significant concern. • Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. • Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the AKI risk. Aging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics. A case-crossover study utilized two sets of longitudinal data from Taiwan's National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1–7 days and 181–187 days prior to the index date served as the case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying case and control period lengths. The study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70–4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47–5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15–26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82–66.64). NSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI. [ABSTRACT FROM AUTHOR]

Objectives: Renal replacement therapy-requiring acute kidney injury frequently occurs in ICUs, which require evidence-based medical attention. However, in the postacute kidney injury patient population, the evidence regarding effective therapies to improve patient outcomes is lacking. Therefore, we aimed to examine whether the renin-angiotensin-aldosterone system blockade is effective in improving renal outcomes in postacute kidney injury patients who experienced temporary renal replacement therapy and have hypertension.Design: A retrospective cohort study.Setting: A nationwide database in Taiwan.Patients: From January 1, 2000, to December 31, 2013, we identified 8,558 acute kidney injury patients with hypertension in the national registry database. All these patients experienced an acute kidney injury episode, which required temporary renal replacement therapy for at least once.Interventions: Users (n = 3,885) and nonusers (n = 4,673) of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers.Measurements and Main Results: We used Cox proportional hazards regression models to analyze hazard ratios for the commencement of end-stage renal disease and all-cause mortality for angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users (n = 3,885) and nonusers (n = 4,673).In a median follow-up of 4.3 years, 5,880 patients (68.7%) required long-term dialysis, and 4,841 patients (56.6%) died. Compared with postacute kidney injury patients who did not use angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users are marginally less likely to progress to end-stage renal disease (adjusted hazard ratio 0.95; 95% CI 0.90-1.01; p = 0.06) and significantly less likely to suffer from all-cause mortality (adjusted hazard ratio 0.93; 95% CI 0.87-0.98; p = 0.011).Conclusions: In patients who experienced renal replacement therapy-requiring acute kidney injury and have hypertension, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use is associated with better survival outcomes compared with nonuser. [ABSTRACT FROM AUTHOR]

Some cohort studies showed the possibility of renin-angiotensin-aldosterone system (RAAS) blockade in preventing future osteoporotic fractures. The study aimed to evaluate the association between angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and future osteoporotic fracture in a hypertensive population. We queried the Taiwan Longitudinal Health Insurance Database between 2001 and 2012. We used propensity score matching and the total cohort was made up of 57,470 participants (28,735 matched-pairs using or not using RAAS blockers). The mean follow-up period was 6 years. The number of incident fractures was 3757. Hazard ratios (HRs) [95% confidence interval (CI)] of ACEIs and ARBs use with incident fractures were calculated. The incidence of future osteoporotic fracture was significantly lower in the ACEI and ARB user groups but not in the group using an ACEI plus ARB concomitantly, when compared with RAAS blocker nonusers. Comparing ACEI users with RAAS blocker non-users and ARB users with RAAS blocker non-users, the HRs for composite fractures were 0.70 (0.62–0.79) and 0.58 (0.51–0.65), respectively. Sensitivity analysis confirmed a lower incidence of future osteoporotic fracture in patients taking an ACEI for >55 cumulative defined daily doses (cDDDs) and those who received an ARB for >90 cDDDs. These results suggested a lower incidence of future osteoporotic fracture in a hypertensive population who were using an ACEI or ARB compared with RAAS blocker nonusers but not in the group taking an ACEI and ARB concomitantly. • The incidence of future osteoporotic fracture was lower in the ACEI and ARB groups. • The phenomenon was not observed in the group taking an ACEI and ARB concomitantly. • A lower incidence of future osteoporotic fracture was noted if using ACEI >55 cDDDs. • A lower incidence of future osteoporotic fracture was noted if using ARB >90 cDDDs. [ABSTRACT FROM AUTHOR]

Background: Secondary prevention therapy for patients with coronary artery disease using an antiplatelet agent, β-blocker, renin-angiotensin system blocker (RASB), or statin plays an important role in the reduction of coronary events after coronary artery bypass grafting (CABG) surgery or percutaneous coronary intervention (PCI). We analyzed the status and effects of secondary prevention after coronary revascularization in Taiwan. Methods: This national population-based cohort study was conducted by analyzing the Longitudinal Health Insurance Database 2000 from the National Health Insurance Research Database of Taiwan. Patients who underwent CABG or PCI from 2004 to 2009 were included in the analysis. The baseline characteristics of the patients and ACC/AHA class I medication use at 12 months were analyzed. The primary endpoints were a composite of major adverse cardiac and cerebrovascular events. Results: A total of 5544 patients comprising 895 CABG and 4649 PCI patients were evaluated. CABG patients had more comorbidities and a higher rate of major adverse event during the follow-up period. However, use of antiplatelet agents and RASB at 12 months was significantly lower in CABG patients than in PCI patients (44.2% vs. 50.9% and 38.6% vs. 48.9%, both p < 0.01). Age, diabetes, and chronic kidney disease were independent risk factors while statin use was a protective factor for the primary endpoints in both PCI and CABG groups. Conclusion: There is still much room to improve class I medication use in secondary prevention for patients after revascularization in Taiwan. Statin could be an effective treatment to improve the outcomes. [ABSTRACT FROM AUTHOR]

Two or more antihypertensive agents are required to achieve blood pressure control for the most hypertensive patients. However, comparison of clinical outcomes between fixed-dose combinations (FDC) and free-equivalent combinations of renin-angiotensin system (RAS) inhibitor and thiazide diuretic is lacking nowadays. Patients who were newly diagnosed with hypertension between July 1st, 2008 and December 31st, 2011 and prescribed with FDC (n = 13 176) or free combinations of RAS inhibitors and thiazide diuretic (n = 4392) were identified from the National Health Insurance Research Database of Taiwan and matched in 3:1 ratio using the propensity score method. The primary end point was major adverse cardiovascular events (MACE). The secondary end points were hospitalization of heart failure, new diagnosis of chronic kidney disease, and the initiation of dialysis. Compared with he FDC group was associated with better medication adherence compared with the free combination group. FDC of RAS inhibitor and thiazide diuretic reduced MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.74-0.97; P = 0.017), hospitalization for heart failure and initiation of dialysis compared with the free combination regimens. The outcome benefits of FDC was mainly driven by reduced cardiovascular and renal events in the patients with proportion of days covered <80%. In this retrospective claims database analysis, compared with the free combination regimens, the use of FDC of RAS inhibitor and thiazide diuretic was associated with improved medication compliance and clinical outcomes in the management of hypertension, particularly in the patients with poor medication adherence. [ABSTRACT FROM AUTHOR]

Aims Heart failure is among the most frequent complications of patients on long-term haemodialysis. The benefits of renin–angiotensin system (RAS) blockade on the outcomes of these patients have yet to be determined. Methods and results We conducted a nationwide observational study using data from the Taiwan National Health Insurance claims database, between 1999 and 2010. We enrolled patients aged ≥35 years with new-onset heart failure [diagnosed by International Classification of Diseases, 9th revision, clinical modification (ICD-9-CM) codes] under treatment with medications. New users of a RAS blocker (RASB; i.e. an ACE inhibitor or an ARB used as monotherapy or dual therapy) were selected to compare with non-RASB users. We used Cox proportional hazards regression with and without propensity score adjustment to compare the risk of 3-year all-cause and cardiovascular mortality. Stratified analyses and RASB therapy duration as a time-dependent covariate were also performed. In all, 4771 were treated with an RASB (n = 3024) or without an RASB (n = 1747). RASB users had a higher prevalence of hypertension and diabetes, and a higher number of hospitalization. Among RASB users, 1148 deaths (38.0%) occurred during 5272 person-years of follow-up compared with 734 deaths (42.0%) among non-RASB users during 2683 person-years of follow-up. Three-year mortality rates were 45.4% and 49.1% for patients receiving and those not receiving an RASB, respectively (log-rank test, P < 0.001). Adjusted hazard analysis revealed that RASB therapeutic effects remained significant on all-cause [hazard ratio (HR) 0.8; 95% confidence interval (CI) 0.72–0.89; P < 0.001] and cardiovascular mortality (HR 0.76; 95% CI 0.64–0.90; P < 0.01). Conclusions RASB therapy reduced all-cause and cardiovascular mortality in heart failure patients on long-term haemodialysis. [ABSTRACT FROM AUTHOR]