RESUMEN
Background: Sodiumâglucose cotransporter-2 (SGLT2) inhibitors offer glycaemic and cardiorenal benefits in the early stage of chronic kidney disease (CKD). However, the use of SGLT2 inhibitors may increase the risk of genitourinary tract infection (GUTI). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may also cause deterioration of kidney function. The long-term follow-up of cardiorenal outcomes and GUTI incidence in patients with advanced CKD receiving SGLT2 inhibitors combined with ACEIs/ARBs should be further investigated. Methods: We analysed data from 5,503 patients in Taiwan's Taipei Medical University Research Database (2016-2020) who were part of a pre-end-stage renal disease (ESRD) program (CKD stages 3-5) and received ACEIs/ARBs. SGLT2 inhibitor users were matched 1:4 with nonusers on the basis of sex, CKD, and program entry duration. Results: The final cohort included 205 SGLT2 inhibitor users and 820 nonusers. SGLT2 inhibitor users experienced a significant reduction in ESRD/dialysis risk (aHR = 0.35, 95% CI = 0.190.67), and SGLT2 inhibitor use was not significantly associated with acute kidney injury or acute kidney disease risk. Among SGLT2 inhibitor users, those with a history of cardiovascular disease (CVD) had greater CVD rates. Conversely, those without a CVD history had lower rates of congestive heart failure, arrhythmia, acute pulmonary oedema, and acute myocardial infarction, although the differences were not statistically significant. Notably, SGLT2 inhibitor usage was associated with a greater GUTI incidence (aHR = 1.78, 95% CI = 1.122.84) shortly after initiation, irrespective of prior GUTI history status. Conclusion: Among patients with CKD stages 3-5, SGLT2 inhibitor use was linked to increased GUTI incidence, but it also significantly reduced the ESRD/dialysis risk without an episodic AKI or AKD risk. Clinical physicians should consider a personalized medicine approach by balancing GUTI episodes and cardiorenal outcomes for advanced CKD patients receiving SGLT2 inhibitors.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Taiwán/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Incidencia , Anciano , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiologíaRESUMEN
Background: Studies on middle-aged or individuals with cognitive or cardiovascular impairments, have established that intensive blood pressure (BP) control reduces cognitive decline risk. However, uncertainty exists on differential effects between antihypertensive medications (AHM) classes on this risk, independent of BP-lowering efficacy, particularly in community-dwelling hypertensive older adults. Methods: A post-hoc analysis of the ASPREE study, a randomized trial of low-dose aspirin in adults aged 70+ years (65+ if US minorities) without baseline dementia, and followed for two years post-trial. Cox proportional-hazards regression models were used to estimate associations between baseline and time-varying AHM exposure and incident dementia (an adjudicated primary trial endpoint), in participants with baseline hypertension. Subgroup analyses included prespecified factors, APO ε4 carrier status and monotherapy AHM use. Results: Most hypertensive participants (9,843/13,916; 70.7%) used AHMs. Overall, 'any' AHM use was not associated with lower incident dementia risk, compared with untreated participants (HR 0.84, 95%CI 0.70-1.02, p=0.08), but risk was decreased when angiotensin receptor blockers (ARBs) were included (HR 0.73, 95%CI 0.59-0.92, p=0.007). ARBs and ß-blockers decreased dementia risk, whereas angiotensin-converting enzyme inhibitors (ACEIs) and diuretics increased risk. There was no association with RAS modulating or blood-brain-barrier crossing AHMs on dementia risk. Conclusions: Overall, AHM exposure in hypertensive older adults was not associated with decreased dementia risk, however, specific AHM classes were with risk direction determined by class; ARBs and ß-blockers were superior to ACEIs and other classes in decreasing risk. Our findings emphasize the importance of considering effects beyond BP-lowering efficacy when choosing AHM in older adults.
RESUMEN
Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensive drugs. However, the impact that the use of ACEI and ARB drugs will have on the survival of patients with hypertension and cancer is still unclear. Therefore, the present study aimed to investigate the effects of ACEI and ARB use on the survival of patients with cancer. The Embase, PubMed and Web of Science databases were used to systematically analyze the survival of hypertensive patients with cancer treated with ACEIs or ARBs. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the association between ACEI and ARB use and patient survival. The relationship between the survival of patients with certain types of cancer and ACEI and ARB use was evaluated using the calculated HRs. Patients with ovarian, pancreatic, prostate, hepatocellular, lung, esophageal, gastric, colon, nasopharyngeal, head and neck tumors, gallbladder and rectal cancers that used ACEI and ARB analogs had significantly increased survival times, except for patients with breast cancer (HR, 1.04; 95% CI, 0.90-1.19; P<0.01) and uroepithelial carcinoma (HR, 1.15; 95% CI, 0.69-1.94; P<0.01), who had significantly decreased survival times, when compared with patients who did not use these drugs. Analysis of the relationship between the use of ACEIs or ARBs alone or in combination on the overall survival of hypertensive patients with cancer demonstrated that the use of ACEIs alone (HR, 1.00; 95% CI, 0.93-1.08; P<0.01) did not have a significant effect on the survival of these patients. By contrast, the survival time was increased in hypertensive patients with cancer who used either ARBs alone (HR, 0.89; 95% CI, 0.84-0.94; P<0.01) or a combination of ACEIs and ARBs (HR, 0.84; 95% CI, 0.78-0.91; P<0.01). The present meta-analysis demonstrated the potential effects of ACEI and ARB use on the overall survival of patients with cancer. Therefore, investigation of the underlying mechanisms of action of ACEIs and ARBs, as well as the identification of specific groups of patients who may benefit from these interventions, could potentially lead to novel therapeutic options and improve the prognosis of patients with cancer in the future.
RESUMEN
Background/Objectives: Chronic subdural hematoma (cSDH) is a common disease of growing significance due to the increasing use of antithrombotic drugs and population aging. There exists conflicting observational evidence that previous treatment with angiotensin-converting enzyme (ACE) inhibitors reduces the rate of cSDH recurrence. This study assesses the hypothesis that ACE inhibitors may affect recurrence rates by altering hematoma membrane formation. Methods: All patients with chronic subdural hematoma who were operated upon in a single university hospital between 2015 and 2020 were considered for inclusion. Hematomas were classified according to their structural appearance in computed tomography (CT) imaging into one of eight subtypes. Patients' own medication, prior to hospitalization for cSDH treatment, was noted, and the use of ACI-inhibitors was identified. Results: Of the included 398 patients, 142 (35.9%) were treated with ACE inhibitors before admission for cSDH treatment. Of these, 115 patients (81.0%) received ramipril, 13 received patients lisinopril (11.3%), and 11 patients (9.6%) received enalapril. Reflecting cardiovascular comorbidity, patients on ACE inhibitors were more often simultaneously treated with antithrombotics (63.4% vs. 42.6%; p ≤ 0.001). Hematomas with homogenous hypodense (OR 11.739, 95%CI 2.570 to 53.612; p = 0.001), homogenous isodense (OR 12.204, 95%CI 2.669 to 55.798; p < 0.001), and homogenous hyperdense (OR 9.472, 95%CI 1.718 to 52.217; p < 0.001) architectures, as well as the prior use of ACE inhibitors (OR 2.026, 95%CI 1.214 to 3.384; p = 0.007), were independently associated with cSDH recurrence. Conclusions: Once corrected for hematoma architecture, type of surgery, and use of antithrombotic medication, preoperative use of ACE inhibitors was associated with a twofold increase in the likelihood of hematoma recurrence.
RESUMEN
Objective: This study assessed the patterns and clinical significance of potential drug-drug interactions (pDDIs) in patients with diseases of the cardiovascular system. Methods: Electronic health records (EHRs), established in 2018-2023, were selected using the probability serial nested sampling method (n = 1030). Patients were aged 27 to 95 years (65.0% men). Primary diagnosis of COVID-19 was present in 17 EHRs (1.7%). Medscape Drug Interaction Checker was used to characterize pDDIs. The Mann-Whitney U test and chi-square test were used for statistical analysis. Results: Drug numbers per record ranged from 1 to 23 in T-List and from 1 to 20 in P-List. In T-List, 567 drug combinations resulted in 3781 pDDIs. In P-List, 584 drug combinations resulted in 5185 pDDIs. Polypharmacy was detected in 39.0% of records in T-List versus 65.9% in P-List (p-value < 0.05). The rates of serious and monitor-closely pDDIs due to 'aspirin + captopril' combinations were significantly higher in P-List than in T-List (p-value < 0.05). The rates of serious pDDIs due to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations were significantly lower in P-List compared with the corresponding rates in T-List (p-value < 0.05). Serious pDDIs due to administration of aspirin with fosinopril, perindopril, and ramipril were detected less frequently in T-List (p-value < 0.05). Conclusions: Obtained data may suggest better patient adherence to 'aspirin + enalapril' and 'aspirin + lisinopril' combinations, which are potentially superior to the combinations of aspirin with fosinopril, perindopril, and ramipril. An abundance of high-order pDDIs in real-world clinical practice warrants the development of a decision support system aimed at reducing pharmacotherapy-associated risks while integrating patient pharmacokinetic, pharmacodynamic, and pharmacogenetic information.
RESUMEN
BACKGROUND: Poststroke epilepsy (PSE) is a common complication after ischemic stroke. This study investigates the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and the risk of PSE in patients with ischemic stroke. METHODS AND RESULTS: A population-based retrospective cohort study was conducted using Taiwan's National Health Insurance Research Database between 2000 and 2015. Patients with hypertension with a history of ischemic stroke were classified into prevalent, new, and nonusers according to their use of ACEIs/ARBs. Prevalent ACEI/ARB users were further classified into continuing or discontinued users, based on their poststroke medication adherence. We used multivariate Cox regression models, adjusted for demographics and comorbidities, to assess the risk of PSE among different ACEI/ARB user groups. There were 182 983 ACEI/ARB users and 38 365 nonusers included. There were 7387 patients diagnosed with PSE, whereas 213 961 were not. Nonusers exhibited a higher risk of PSE (adjusted hazard ratio [aHR], 1.72 [95% CI, 1.63-1.82]). Both prevalent and nonusers had higher risks compared with new ACEI/ARB users, with respective aHRs of 1.33 (95% CI, 1.25-1.41) and 2.00 (95% CI, 1.87-2.14). Discontinued ACEI/ARB users showed the highest risk of PSE (aHR, 2.34 [95% CI, 2.15-2.54]), suggesting the importance of continuing ACEI/ARB use after stroke. Treatment-by-age interaction was significant among patients with or without ACEI/ARB use before stroke (P value for interaction 0.004 and <0.001, respectively), suggesting a stronger beneficial association in younger patients. CONCLUSIONS: The use of ACEIs/ARBs after ischemic stroke in patients with hypertension is associated with a reduced risk of PSE, especially among younger patients.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Epilepsia , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Accidente Cerebrovascular Isquémico/epidemiología , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/prevención & control , Estudios Retrospectivos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , Anciano , Taiwán/epidemiología , Persona de Mediana Edad , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Factores de Riesgo , Medición de Riesgo , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Hipertensión/complicaciones , Bases de Datos Factuales , Anciano de 80 o más Años , Factores ProtectoresRESUMEN
Background: Cardioprotective drugs have not been previously shown to improve the prognosis in patients with fulminant myocarditis presentation (FMP). We aimed to investigate whether cardioprotective drugs, including angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) and ß-blocker, administered during hospitalization improved the prognosis in patients with FMP. Methods and Results: This multicenter cohort study conducted in Japan included 755 patients with clinically diagnosed FMP. Those who died within 14 days of admission were excluded, and 588 patients (median age 53 [37-65] years and 40% female) were evaluated. The primary outcome was the composite of 90-day mortality or heart transplantation. The patients were divided into 4 groups according to whether they were administered ACEI/ARB or ß-blocker during hospitalization. Administration of ACEI/ARB without ß-blocker improved the overall patient outcomes (log-rank test [vs. ACEI/ARB - and ß-blocker -]: ACEI/ARB + and ß-blocker -, P<0.001; ACEI/ARB - and ß-blocker +, P=0.256). Subsequently, a matched cohort of 146 patient pairs was generated for patients with or without ACEI/ARB administration during hospitalization. The outcome-free survival at 90 days was significantly higher in the ACEI/ARB administration group than in the non-administration group (hazard ratio 0.37; 95% confidence interval 0.19-0.71). Conclusions: Administration of ACEI or ARB during hospitalization was associated with favorable outcomes in terms of 90-day mortality and heart transplantation events in patients with clinically diagnosed FMP.
RESUMEN
AIM: Although sodium glucose cotransporter2 inhibitor (SGLT-2I) is widely used in clinical practice, sufficient renin-angiotensin system (RAS) inhibition remains the cornerstone of diabetic kidney disease (DKD) treatment. The aim of this single-center study was to evaluate the efficacy and safety of dual RAS blockade compared with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) monotherapy in non-elderly DKD patients with preserved eGFR (WHO Standard, < 60y). METHODS: This single-center study was registered in Chinese Clinical Trial Registry (ChiCTR1900024752), and approved by the ethical committee (KY201994). In this study, we recruited non-elderly type 2 diabetes volunteers with initial diagnosis of DKD to receive dual RAS blockade or monotherapy. 150 non-elderly DKD patients with preserved eGFR were recruited. The patients were randomly divided into dual RAS blockade group and monotherapy group. The dual RAS blockade group treatment regimen was an 80 mg valsartan plus a 4 mg perindopril tert-butylamine per day. At the same time, monotherapy group patients who received the 8 mg perindopril tert-butylamine or 160 mg valsartan monotherapy. The clinical data of the three groups were compared at baseline and collected during the follow-up period of 12 months. RESULTS: The baseline of patients who received dual RAS blockade was similar to that of monotherapy group. After 12 months of treatment, the median level of proteinuria in the dual RAS blockade group was significantly lower than that in the monotherapy group. There was no significant difference in the estimated glomerular filtration rate (eGFR) level, potassium, blood pressure and no serious adverse reactions. CONCLUSIONS: In non-elderly DKD patients with preserved eGFR, dual RAS blockade is superior to control proteinuria, and does not increase the probability of adverse reactions such as hyperkalemia, hypotension and acute kidney injury in 12 months.
RESUMEN
This dataset demonstrates the use of computational fragmentation-based and machine learning-aided drug discovery to generate new lead molecules for the treatment of hypertension. Specifically, the focus is on agents targeting the renin-angiotensin-aldosterone system (RAAS), commonly classified as Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Blockers (ARBs). The preliminary dataset was a target-specific, user-generated fragment library of 63 molecular fragments of the 26 approved ACEI and ARB molecules obtained from the ChEMBL and DrugBank molecular databases. This fragment library provided the primary input dataset to generate the new lead molecules presented in the dataset. The newly generated molecules were screened to check whether they met the criteria for oral drugs and comprised the ACEI or ARB core functional group criterion. Using unsupervised machine learning, the molecules that met the criterion were divided into clusters of drug classes based on their functional group allocation. This process led to three final output datasets, one containing the new ACEI molecules, another for the new ARB molecules, and the last for the new unassigned class molecules. This data can aid in the timely and efficient design of novel antihypertensive drugs. It can also be used in precision hypertension medicine for patients with treatment resistance, non-response or co-morbidities. Although this dataset is specific to antihypertensive agents, the model can be reused with minimal changes to produce new lead molecules for other health conditions.
RESUMEN
Cancer therapy-related cardiac dysfunction (CTRCD) is a complication of selected cancer therapy agents associated with decline in left ventricular ejection fraction (LVEF). Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have established benefits in heart failure with reduced ejection fraction, but their efficacy for preventing CTRCD remains controversial. This narrative systematic review assessed the efficacy and safety of ACEI/ARB in the prevention of cancer therapy LVEF decline. We systematically searched PubMed, Embase and Cochrane from January 1980 to June 2022. Studies of interest were randomised controlled trials of patients with normal LVEF and active malignancy receiving cancer therapy, randomised to receive either an ACEI or ARB compared with a control group. The outcome was the change in LVEF from baseline to the end of the follow-up period. Death, clinical heart failure and adverse drug reactions were recorded. A total of 3731 search records were screened and 12 studies were included, comprising a total of 1645 participants. Nine studies assessed the prevention of anthracycline-induced LVEF decline, of which five showed a beneficial effect (1%-14% higher LVEF in treated groups), whereas four studies showed no effect. Three studies assessed the prevention of trastuzumab-induced LVEF decline, of which one showed a beneficial effect (4% higher LVEF) in a subset of participants. There are mixed data regarding the efficacy of ACEI/ARB in preventing the LVEF decline in patients undergoing anthracycline or trastuzumab therapy, with evidence suggesting no clinically meaningful benefit observed in recent studies.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Antraciclinas , Antineoplásicos , Volumen Sistólico , Trastuzumab , Disfunción Ventricular Izquierda , Humanos , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antraciclinas/efectos adversos , Antineoplásicos/efectos adversos , Cardiotoxicidad/etiología , Cardiotoxicidad/prevención & control , Neoplasias/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Volumen Sistólico/efectos de los fármacos , Trastuzumab/efectos adversos , Disfunción Ventricular Izquierda/inducido químicamente , Disfunción Ventricular Izquierda/prevención & control , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
Background: The PARADIGM HF trial showed sacubitril/valsartan (SV) to be superior to enalapril in patients with reduced ejection fraction (HFrEF). Since its publication, several other randomized trials have compared SV to either an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) in HFrEF which showed conflicting results regarding mortality, hospitalizations, and quality of life scoring. Objective: To review randomized comparative trials of SV to either ACEI or ARB in patients with HFrEF. Methods: PubMed and Embase databases were used to identify randomized comparative trials. The text terms sacubitril, angiotensin neprilysin, and LCZ696 were used for both searches. Meta-analysis, retrospective, adhoc, and cohort studies were excluded. Results: 1476 and 3983 citations were reviewed on PubMed and Embase, respectively. Of these, 11 randomized comparative trials to either ACEI or ARB were included for analysis. The mortality/quality of life benefits of SV over enalapril in the PARADIGM HF were not corroborated in any of the other trials. The effect of hospitalizations for heart failure was inconsistent among trials. Exercise tolerance was not improved with SV versus enalapril. Conclusion: The results of the PARADIGM HF trial have largely not been confirmed in subsequent randomized comparative trials.
RESUMEN
In this editorial, we comment on the article by Meng et al published in the World Journal of Clinical Cases. We comprehensively review immunoglobulin A nephropathy (IgAN), including epidemiology, clinical presentation, diagnosis, and management. IgAN, also known as Berger's disease, is the most frequent type of primary glomerulonephritis (GN) globally. It is mostly found among the Asian population. The presentation can be variable, from microscopic hematuria to a rapidly progressive GN. Around 50% of patients present with single or recurring episodes of gross hematuria. An upper respiratory infection and tonsillitis often precede these episodes. Around 30% of patients present microscopic hematuria with or without proteinuria, usually detected on routine examination. The diagnosis relies on having a renal biopsy for pathology and immunofluorescence microscopy. We focus on risk stratification and management of IgAN. We provide a review of all the landmark studies to date. According to the 2021 KDIGO (kidney disease: Improving Global Outcomes) guidelines, patients with non-variant form IgAN are first treated conservatively for three to six months. This approach consists of adequate blood pressure control, reduction of proteinuria with renin-angiotensin system blockade, treatment of dyslipidemia, and lifestyle modifications (weight loss, exercise, smoking cessation, and dietary sodium restrictions). Following three to six months of conservative therapy, patients are further classified as high or low risk for disease progression. High-risk patients have proteinuria ≥ 1 g/d or < 1 g/d with significant microscopic hematuria and active inflammation on kidney biopsy. Some experts consider proteinuria ≥ 2 g/d to be very high risk. Patients with high and very high-risk profiles are treated with immunosuppressive therapy. A proteinuria level of < 1 g/d and stable/improved renal function indicates a good treatment response for patients on immunosuppressive therapy.
RESUMEN
PURPOSE: The objective of this meta-analysis is to determine how sacubitril/valsartan (SV) compares to equivalent and sub-equivalent angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEI) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: The databases of PubMed and EMBASE were used to identify those randomized controlled trials which compared SV to ARB/ACEI in patients with HFrEF. Only those trials that reported outcomes regarding total mortality, cardiovascular mortality, and worsening heart failure were considered. Meta-analysis was performed separately in those patients receiving equivalent doses of ARB/ACEI and those receiving sub-equivalent doses. Equivalent doses were SV 97/103 = valsartan 160 mg twice daily = enalapril 20 mg twice daily = ramipril 5 mg twice daily. Meta-analyses were performed using Review Manager 5.4. RESULTS: Twelve randomized trials were identified involving 17,484 patients: 11,291 in the sub-equivalent group (8 trials) and 6193 in the equivalent group (4 trials). Meta-analyses showed there were no statistical differences regarding the outcomes of total mortality, cardiovascular mortality, and worsening heart failure in the equivalent dosing group. However, SV reduced total mortality (risk ratio (RR) = 0.85, 95% confidence interval (CI) = 0.78-0.93, p < 0.001), cardiovascular mortality (RR = 0.81, 95% CI = 0.73-0.90, p ≤ 0.001) and worsening heart failure (RR = 0.77, 95% CI = 0.64-0.92, p = 0.005) in the sub-equivalent group. CONCLUSION: When compared to equivalent doses of ARB/ACEI, SV is not superior in reducing mortality and worsening heart failure. SV is superior when compared to sub-equivalent doses of ACEI.
Asunto(s)
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Compuestos de Bifenilo , Insuficiencia Cardíaca , Tetrazoles , Valsartán , Humanos , Aminobutiratos/administración & dosificación , Aminobutiratos/uso terapéutico , Aminobutiratos/efectos adversos , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Compuestos de Bifenilo/administración & dosificación , Compuestos de Bifenilo/uso terapéutico , Combinación de Medicamentos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Volumen Sistólico/efectos de los fármacos , Tetrazoles/administración & dosificación , Tetrazoles/uso terapéutico , Valsartán/administración & dosificaciónRESUMEN
Previous work comparing safety and effectiveness outcomes for new initiators of angiotensin converting-enzyme inhibitors (ACEi) and thiazides demonstrated more favorable outcomes for thiazides, although cohort definitions allowed for addition of a second antihypertensive medication after a week of monotherapy. Here, we modify the monotherapy definition, imposing exit from cohorts upon addition of another antihypertensive medication. We determine hazard ratios (HR) for 55 safety and effectiveness outcomes over six databases and compare results to earlier findings. We find, for all primary outcomes, statistically significant differences in effectiveness between ACEi and thiazides were not replicated (HRs: 1.11, 1.06, 1.12 for acute myocardial infarction, hospitalization with heart failure and stroke, respectively). While statistical significance is similarly lost for several safety outcomes, the safety profile of thiazides remains more favorable. Our results indicate a less striking difference in effectiveness of thiazides compared to ACEi and reflect some sensitivity to the monotherapy cohort definition modification.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Hipertensión , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/efectos adversos , Diuréticos/efectos adversos , Hipertensión/tratamiento farmacológico , Inhibidores de los Simportadores del Cloruro de Sodio/efectos adversos , Tiazidas/efectos adversosRESUMEN
Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.
Asunto(s)
Insuficiencia Cardíaca , Neoplasias , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Neoplasias/epidemiologíaRESUMEN
BACKGROUND: This study aimed to evaluate the patient survival rates based on the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) in a large cohort of patients undergoing maintenance hemodialysis (HD). METHODS: Data from a national HD quality assessment program were used in this retrospective study. The patients were classified into four groups based on the use of renin-angiotensin system blockers (RASBs) as follows: No group, patients without a prescription of any anti-hypertensive drugs including RASBs; Other group, patients with a prescription of anti-hypertensive drugs excluding RASBs; ACEI group, patients with a prescription of an ACEI; and ARB group, patients with a prescription of an ARB. RESULTS: The 5-year survival rates in the no, other, ACEI, and ARB groups were 68.6%, 67.8%, 70.6%, and 69.2%, respectively. The ACEI group had the best patient survival trend among the four groups. In multivariable Cox regression analyses, no differences were observed between the ACEI and ARB groups. Among young patients and patients without diabetes or heart disease, the ACEI group had the best patient survival among the four groups. However, among patients with DM or heart disease, the ARB group had the best patient survival. CONCLUSIONS: Our study found that patients receiving ACEI and ARB had comparable survival. However, patients receiving ARB had better survival in the subgroups of patients with DM or heart disease, and patients receiving ACEI had better survival in the subgroup of young patients or patients without diabetes or heart disease.
Asunto(s)
Diabetes Mellitus , Cardiopatías , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Estudios Retrospectivos , Antihipertensivos , Estudios de Cohortes , Diálisis Renal , Diabetes Mellitus/inducido químicamente , Cardiopatías/inducido químicamenteRESUMEN
OBJECTIVE: Whether angiotensin II blockade is an effective medical treatment for abdominal aortic aneurysms (AAAs) has not been established. This systematic review and meta-analysis aimed to determine the association between angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) prescription and AAA growth and events. DATA SOURCES: MEDLINE, Embase, Scopus, Web of Science, and the Cochrane Library databases were searched from their inception to 4 January 2024, with no language restrictions. REVIEW METHODS: The five databases were searched for randomised controlled trials (RCTs) and observational studies reporting the association between ACEi or ARB prescription and AAA growth, repair, or rupture. The primary outcome was AAA growth, with secondary outcomes of AAA rupture, AAA repair, and AAA related events (rupture and repair combined). Risk of bias was assessed using the Risk of Bias 2 tool for RCTs and with a modified Newcastle-Ottawa scale for observational studies. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Random effects models were used for meta-analyses. RESULTS: Eleven studies (two RCTs, eight observational studies, and one meta-analysis of individual patient data from seven populations) involving 58 022 patients were included. ACEi prescription was not associated with a statistically significant reduction in AAA growth (standard mean difference 0.01 mm/year, 95% confidence interval [CI] -0.26 - 0.28; p = .93; I2 = 98%) or AAA repair (odds ratio [OR] 0.73, 95% CI 0.50 - 1.09; p = .65; I2 = 61%), but was associated with a statistically significantly lower risk of AAA rupture (OR 0.87, 95% CI 0.81 - 0.93; p < .001; I2 = 26%) and AAA related events (OR 0.82, 95% CI 0.72 - 0.95; p = .006; I2 = 80%). ARB prescription was not associated with significantly reduced AAA growth or a lower risk of AAA related events. The two RCTs had a low risk of bias, with one observational study having low, seven moderate, and one high risk of bias. All of the findings had a very low certainty of evidence based on the GRADE analysis. CONCLUSION: There was no association between ACEi or ARB prescription and AAA growth, but ACEi prescription was associated with a reduced risk of AAA rupture and AAA related events with very low certainty of evidence.
Asunto(s)
Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Aneurisma de la Aorta Abdominal , Aneurisma de la Aorta Abdominal/epidemiología , Humanos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/efectos adversos , Rotura de la Aorta/prevención & control , Rotura de la Aorta/etiología , Rotura de la Aorta/epidemiología , Progresión de la Enfermedad , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Formation of adhesion bands is a frequent clinical complication after tendon injury or surgery with limited treatment options. This study investigates the repurposing of Angiotensin-Converting-Enzyme Inhibitor (ACEI) in attenuating post-operative tendon-sheath adhesion bands in an Achilles tendon rat model. METHODS: Structural, mechanical, histological, and biochemical characteristics of the Achilles tendons were compared in the presence and absence of oral ACEI (enalapril) using the Achilles tendon adhesion (TA) model in rats. Inflammation and total fibrosis of tendon tissues were compared between groups using molecular investigations along with macroscopic and histological scoring methods. RESULTS: ACEI significantly alleviated the severity, length, and density of Achilles TAs. Moreover, histopathological changes, recruitment of inflammatory cells, and inflammation were significantly decreased in post-operative tissue samples as quantified with the Moran scoring model. We showed that ACEI treatment elicits a potent anti-fibrotic effect on tendon tissue samples, as illustrated by decreasing the severity and extent of the formed fibrotic tissue and collagen accumulation at the site of surgery when scored either by Tang or Ishiyama grading systems. The H&E staining showed no histopathological changes or damage to the principal organs. CONCLUSION: Our results showed that ACEI is a safe and effective therapeutic candidate with potent immunomodulatory and anti-fibrotic features to alleviate surgery-induced development of fibrotic adhesive tissue. However, its efficacy needs to be further validated in clinical studies.