The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI-Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65-0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52-0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions.

UNASSIGNED: To assess the characteristics of patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mid-range ejection fraction (HFmrEF), as well as the current application of guideline-directed medical therapy (GDMT) in Palestine.
UNASSIGNED: This retrospective cohort study involved a population of heart failure (HF) patients who visited cardiology clinics at An-Najah National University Hospital and the National Hospital, Palestine. The primary outcome measures of interest were the proportions of patients prescribed guideline-based cardiovascular medications (GBCMs), such as angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), β-blockers, and mineralocorticoid receptor antagonists (MRAs), and the corresponding optimized doses at ≥ 50 % of targets and the reasons underlying the non-prescription of GDMT.
UNASSIGNED: A total of 70.5%, 56.6%, and 88.6% of patients were on ACEIs/ARBs, MRAs, and β-blockers, respectively. Of all patients, 38.7% were on the triple GDMT regimen.
UNASSIGNED: Less than half the patients received the triple combination treatment. Age, diabetes mellitus, chronic renal disease, and admission to the hospital for HF all had significant independent relationships with the reduced utilization and inadequate dosage of GDMT.

OBJECTIVE: It is unknown whether safety and clinical endpoints by use of sacubitril/valsartan (an angiotensin receptor-neprilysin inhibitor [ARNI]) are affected by mineralocorticoid receptor antagonists (MRA) in high-risk myocardial infarction (MI) patients. The aim of this study was to examine whether MRA modifies safety and clinical endpoints by use of sacubitril/valsartan in patients with a MI and left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion.
RESULTS: Patients (n = 5661) included in the PARADISE MI trial (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) were stratified according to MRA. Primary outcomes in this substudy were worsening heart failure or cardiovascular death. Safety was defined as symptomatic hypotension, hyperkalaemia >5.5 mmol/L, or permanent drug discontinuation. A total of 2338 patients (41%) were treated with MRA. Safety of ARNI compared to ramipril was not altered significantly by ± MRA, and both groups had similar increase in symptomatic hypotension with ARNI. In patients taking MRA, the risk of hyperkalaemia or permanent drug discontinuation was not significantly altered by ARNI (p > 0.05 for all comparisons). The effect of ARNI compared with ramipril was similar in those who were and were not taking MRA (hazard ratio [HR]MRA 0.96, 95% confidence interval [CI] 0.77-1.19 and HRMRA- 0.87, 95% CI 0.71-1.05, for the primary endpoint; p = 0.51 for interaction [Clinical Endpoint Committee adjudicated]); similar findings were observed if investigator-reported endpoints were evaluated (p = 0.61 for interaction).
CONCLUSIONS: Use of a MRA did not modify safety or clinical endpoints related to initiation of ARNI compared to ramipril in the post-MI setting in patients with LVSD and/or congestion.

Fabry disease (FD) is a rare genetic disorder caused by a deficiency in the α-galactosidase A enzyme, which results in the globotriaosylceramide accumulation in many organs, including the kidneys. Nephropathy is a major FD complication that can progress to end-stage renal disease if not treated early. Although enzyme replacement therapy and chaperone therapy are effective, other treatments such as ACE inhibitors and angiotensin receptor blockers can also provide nephroprotective effects when renal damage is also established. Recently, SGLT2 inhibitors have been approved as innovative drugs for treating chronic kidney disease. Thus, we plan a multicenter observational prospective cohort study to assess the effect of Dapagliflozin, a SGLT2 inhibitor, in FD patients with chronic kidney disease (CKD) stages 1-3. The objectives are to evaluate the effect of Dapagliflozin primarily on albuminuria and secondarily on kidney disease progression and clinical FD stability. Thirdly, any association between SGT2i and cardiac pathology, exercise capacity, kidney and inflammatory biomarkers, quality of life, and psychosocial factors will also be evaluated. The inclusion criteria are age ≥ 18; CKD stages 1-3; and albuminuria despite stable treatment with ERT/Migalastat and ACEi/ARB. The exclusion criteria are immunosuppressive therapy, type 1 diabetes, eGFR < 30 mL/min/1.73 m2, and recurrent UTIs. Baseline, 12-month, and 24-month visits will be scheduled to collect demographic, clinical, biochemical, and urinary data. Additionally, an exercise capacity and psychosocial assessment will be performed. The study could provide new insights into using SGLT2 inhibitors for treating kidney manifestations in Fabry disease.

暂无摘要。

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) are commonly prescribed to patients with hypertension. These drugs are cardioprotective in addition to their blood pressure-lowering effects. However, it is debatable whether hypertensive patients who present for non-cardiac surgery should continue or discontinue these drugs preoperatively. Continuing the drugs entails the risk of perioperative refractory hypotension and/or angioneurotic oedema, while discontinuing the drugs entails the risk of rebound hypertension and myocardial ischaemia. The aim of this study is to evaluate the effect of continuation vs withholding of ACEIs/ARBs on mortality and other major outcomes in hypertensive patients undergoing elective non-cardiac surgery.
METHODS: The continuing vs withholding of ACEIs/ARBs in patients undergoing non-cardiac surgery is a prospective, multi-centric, open-label randomised controlled trial. Two thousand one hundred hypertensive patients receiving ACEIs/ARBs and planned for elective non-cardiac surgery will be enrolled. They will be randomised to either continue the ACEIs/ARBs including on the day of surgery (group A) or to withhold it 24-36 h before surgery (group B). The primary endpoint will be the difference in the composite outcome of all-cause in-hospital/30-day mortality and major adverse cardiovascular and non-cardiovascular events. Secondary endpoints will be to evaluate the differences in perioperative hypotension, angioneurotic oedema, myocardial injury, ICU and hospital stay. The impact of the continuation vs withholding of the ACEIs/ARBs on the incidence of case cancellation will also be studied.
CONCLUSIONS: The results of this trial should provide sufficient evidence on whether to continue or withhold ACEIs/ARBs before major non-cardiac surgery.
BACKGROUND: Clinical Trials Registry of India CTRI/2021/01/030199. Registered on 4 January 2021.

Hyperkalemia after starting renin-angiotensin system inhibitors has been shown to be subsequently associated with a higher risk of cardiovascular and kidney outcomes. However, whether to continue or discontinue the drug after hyperkalemia remains unclear.
Data came from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, which included a run-in period where all participants initiated angiotensin-converting enzyme inhibitor-based therapy (a fixed combination of perindopril and indapamide). The study population was taken as patients with type 2 diabetes with normokalemia (serum potassium of 3.5 to <5.0 mEq/L) at the start of run-in. Potassium was remeasured 3 weeks later when a total of 9694 participants were classified into hyperkalemia (≥5.0 mEq/L), normokalemia, and hypokalemia (<3.5 mEq/L) groups. After run-in, patients were randomized to continuation of the angiotensin-converting enzyme inhibitor-based therapy or placebo; major macrovascular, microvascular, and mortality outcomes were analyzed using Cox regression during the following 4.4 years (median).
During active run-in, 556 (6%) participants experienced hyperkalemia. During follow-up, 1505 participants experienced the primary composite outcome of major macrovascular and microvascular events. Randomized treatment of angiotensin-converting enzyme inhibitor-based therapy significantly decreased the risk of the primary outcome (38.1 versus 42.0 per 1000 person-years; hazard ratio, 0.91; 95% confidence interval, 0.83 to 1.00; P=0.04) compared with placebo. The magnitude of effects did not differ across subgroups defined by short-term changes in serum potassium during run-in (P for heterogeneity =0.66). Similar consistent treatment effects were also observed for all-cause death, cardiovascular death, major coronary events, major cerebrovascular events, and new or worsening nephropathy (P for heterogeneity ≥0.27).
Continuation of angiotensin-converting enzyme inhibitor-based therapy consistently decreased the subsequent risk of clinical outcomes, including cardiovascular and kidney outcomes and death, regardless of short-term changes in serum potassium.
Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), NCT00145925.

To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes.
We considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III) an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups. Over the follow-up period of 8 years, the proportion of subjects who developed MACE, type 2 diabetes mellitus and hyperuricemia, and the proportion of subjects needing for the intensification of antihypertensive treatment to improve blood pressure control were statistically different among the predefined groups (P < 0.05).
Combined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone.

Evaluate the associations between patients taking ACE inhibitors and angiotensin receptor blockers (ARBs) and their clinical outcomes after an acute viral respiratory illness (AVRI) due to COVID-19.
Retrospective cohort.
The USA; 2017-2018 influenza season, 2018-2019 influenza season, and 2019-2020 influenza/COVID-19 season.
People with hypertension (HTN) taking an ACEi, ARB or other HTN medications, and experiencing AVRI.
Change in hospital admission, intensive care unit (ICU) or coronary care unit (CCU), acute respiratory distress (ARD), ARD syndrome (ARDS) and all-cause mortality, comparing COVID-19 to pre-COVID-19 influenza seasons.
The cohort included 1 059 474 episodes of AVRI (653 797 filled an ACEi or ARB, and 405 677 other HTN medications). 58.6% were women and 72.9% with age ≥65. The ACEi/ARB cohort saw a larger increase in risk in the COVID-19 influenza season than the other HTN medication cohort for four out of five outcomes, with an additional 1.5 percentage point (pp) increase in risk of an inpatient stay (95% CI 1.2 to 1.9 pp) and of ICU/CCU use (95% CI 0.3 to 2.7 pp) as well as a 0.7 pp (0.1 to 1.2 pp) additional increase in risk of ARD and 0.9 pp (0.4 to 1.3 pp) additional increase in risk of ARDS. There was no statistically significant difference in the absolute risk of death (-0.2 pp, 95% CI -0.4 to 0.1 pp). However, the relative risk of death in 2019/2020 versus 2017/2018 for the ACEi/ARB group was larger (1.40 (1.36 to 1.44)) than for the other HTN medication cohort (1.24 (1.21 to 1.28)).
People with AVRI using ACEi/ARBs for HTN had a greater increase in poor outcomes during the COVID-19 pandemic than those using other medications to treat HTN. The small absolute magnitude of the differences likely does not support changes in clinical practice.

UNASSIGNED: Survivors of acute kidney injury (AKI) are at a high risk for cardiovascular complications. An underrecognition of this risk may contribute to the low utilization of relevant guideline-based therapies in this population.
UNASSIGNED: We sought to assess accordance with guideline-based recommendations for survivors of AKI with diabetes, coronary artery disease (CAD), and preexisting chronic kidney disease (CKD) in a post-AKI clinic, and identify factors that may be associated with guideline accordance.
UNASSIGNED: Retrospective cohort study.
UNASSIGNED: Post-AKI clinics at 2 tertiary care centers in Ontario, Canada.
UNASSIGNED: We included adult patients seen in both post-AKI clinics between 2013 and 2019 who had at least 2 clinic visits within 24 months of an index AKI hospitalization.
UNASSIGNED: We assessed accordance to recommendations from the most recent North American and international guidelines available at the time of study completion for diabetes, CAD, and CKD.
UNASSIGNED: We compared guideline accordance between visits using the Cochran Mantel Haenszel test. We used multivariable Poisson regression to identify prespecified factors associated with accordance.
UNASSIGNED: Of 213 eligible patients, 192 (90%) had Kidney Disease Improving Global Outcomes Stage 2-3 AKI, 91 (43%) had diabetes, 76 (36%) had CAD, and 88 (41%) had preexisting CKD. From the first clinic visit to the second, there was an increase in angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACE-I/ARB) use across all disease groups-from 33% to 46% (P = .028) in patients with diabetes, from 30% to 57% (P = .002) in patients with CAD, and from 16% to 35% (P < .001) in patients with preexisting CKD. Statin use increased in patients with preexisting CKD from 64% to 71% (P = .034). Every 25 μmol/L rise in the discharge serum creatinine was associated with a 19% (95% confidence interval [CI], 8%-28%) and 12% (95% CI, 2%-21%) lower likelihood of being on an ACE-I/ARB in patients with diabetes and preexisting CKD, respectively.
UNASSIGNED: The study lacked a comparison group that received usual care. The small sample and multiple comparisons make false positives possible.
UNASSIGNED: There is room to improve guideline-based cardiovascular risk factor management in survivors of AKI, particularly ACE-I/ARB use in patients with an elevated discharge serum creatinine.
UNASSIGNED: Les survivants d’un épisode d’insuffisance rénale aiguë (IRA) courent un risque élevé de subir des complications cardiovasculaires. Une sous-reconnaissance de ce risque pourrait contribuer à la faible utilisation des thérapies pertinentes recommandées par les lignes directrices dans cette population.
UNASSIGNED: Évaluer la conformité aux recommandations des lignes directrices pour les survivants d’un épisode d’IRA souffrant de diabète, de maladie coronarienne et d’insuffisance rénale chronique (IRC) préexistante dans une clinique post-IRA, et identifier les facteurs pouvant être associés à la conformité aux recommandations.
UNASSIGNED: Étude de cohorte rétrospective.
UNASSIGNED: Les cliniques post-IRA de deux centres de soins tertiaires de l’Ontario (Canada).
UNASSIGNED: Nous avons inclus les patients adultes suivis dans les deux cliniques post-IRA entre 2013 et 2019 et ayant visité la clinique au moins deux fois dans les 24 mois suivant une hospitalisation pour IRA.
UNASSIGNED: Nous avons évalué la conformité aux recommandations des plus récentes lignes directrices nord-américaines et internationales disponibles pour le diabète, la maladie coronarienne et l’IRC au terme de l’étude.
UNASSIGNED: Nous avons comparé la conformité aux recommandations entre les visites à l’aide du test Cochran Mantel Haenszel. La régression multivariée de Poisson a servi à établir les facteurs préspécifiés associés à la conformité.
UNASSIGNED: Sur les 213 patients admissibles, 192 (90 %) présentaient une IRA de stade KDIGO 2-3, 91 (43 %) étaient diabétiques, 76 (36 %) présentaient une maladie coronarienne et 88 (41 %) une IRC préexistante. Entre la première et la deuxième visite à la clinique, l’utilisation des inhibiteurs de l’enzyme de conversion de l’angiotensine/antagonistes des récepteurs de l’angiotensine (IECA/ARA) a augmenté dans tous les groupes, soit de 33 à 46 % (p = 0,028) chez les diabétiques, de 30 à 57 % (p = 0,002) chez les patients souffrant de maladie coronarienne et de 16 à 35 % (p < 0,001) chez ceux qui avaient une IRC préexistante. L’utilisation des statines est passée de 64 à 71 % (p = 0,034) chez les patients avec une IRC préexistante. Chaque augmentation de 25 μmol/L de la créatinine sérique à la sortie de l’hôpital a été associée, chez les diabétiques et les patients avec une IRC préexistante, à une diminution de la probabilité d’être sous IEAC/ARA de 19 % (IC 95 %: 8-28 %) de 12 % (IC 95 %: 2-21 %) respectivement.
UNASSIGNED: L’étude ne comportait pas de groupe témoin recevant les soins habituels. Le faible échantillon et les multiples comparaisons rendent possibles les faux positifs.
UNASSIGNED: Il est possible d’améliorer la prise en charge fondée sur les lignes directrices des facteurs de risques cardiovasculaires chez les survivants d’un épisode d’IRA; particulièrement l’utilisation des IECA/ARA chez les patients dont la mesure de créatinine sérique est élevée à la sortie de l’hôpital.