Does Combination Therapy With SGLT2 Inhibitors and Renin-Angiotensin System Blockers Lead to Greater Reduction in Cardiorenal Events Among Patients With Type 2 Diabetes?
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ABSTRACT:
SUBMITTER: Zhao LM
PROVIDER: S-EPMC8131654 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Does Combination Therapy With SGLT2 Inhibitors and Renin-Angiotensin System Blockers Lead to Greater Reduction in Cardiorenal Events Among Patients With Type 2 Diabetes?
Zhao Li-Min LM Zhang Miao M Zhan Ze-Lin ZL Qiu Mei M
Frontiers in cardiovascular medicine 20210505
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Project description:IntroductionAlthough several studies suggest that the prognosis of hypertensive dialysis patients can be improved by using antihypertensive drug therapy, it is unknown whether the prescription of a particular class or combination of antihypertensive drugs is beneficial during hemodialysis.MethodsWe performed a propensity score matching study to compare the effectiveness of various classes of antihypertensive drugs on cardiovascular (CV) mortality in 2518 incident hemodialysis patients in Spain. The patients had initially received antihypertensive therapy with a renin-angiotensin system (RAS) blocker (728 patients), a ß-blocker (679 patients), antihypertensive drugs other than a RAS blocker or a ß-blocker (787 patients), or the combination of a ß-blocker and a RAS inhibitor (324 patients). These patients were followed for a maximum of 5 years (median: 2.21 yr; range: 1.04-3.34 yr).ResultsAfter adjustment for baseline CV risk covariates, no significant differences were observed in the risk of CV mortality between patients taking a RAS blocker and patients treated with ß-blocker-based antihypertensive therapy. The combination of a RAS blocker with a ß-blocker was associated with better CV survival than either agent alone (RAS blocker: hazard ratio [HR]: 1.68; 95% confidence interval [CI] 1.05-2.69; ß-blocker: HR: 1.59; 95% CI: 1.01-2.50; antihypertensive medication other than a RAS blocker or ß-blocker: HR: 1.67; 95% CI: 1.08-2.58).DiscussionOur data suggested that the combination of a RAS blocker and a ß-blocker could improve survival in hemodialysis patients. Further prospective randomized controlled trials are necessary to confirm the beneficial effects of this combination of antihypertensive drugs in patients undergoing hemodialysis.
| S-EPMC5678679 | biostudies-literature
Project description:Several pharmacological agents to prevent the progression of diabetic kidney disease (DKD) have been tested in patients with type 2 diabetes mellitus (T2DM) in the past two decades. With the exception of renin-angiotensin system blockers that have shown a significant reduction in the progression of DKD in 2001, no other pharmacological agent tested in the past two decades have shown any clinically meaningful result. Recently, the sodium-glucose cotransporter-2 inhibitor (SGLT-2i), canagliflozin, has shown a significant reduction in the composite of hard renal and cardiovascular (CV) endpoints including progression of end-stage kidney disease in patients with DKD with T2DM at the top of renin-angiotensin system blocker use. Another SGLT-2i, dapagliflozin, has also shown a significant reduction in the composite of renal and CV endpoints including death in patients with chronic kidney disease (CKD), regardless of T2DM status. Similar positive findings on renal outcomes were recently reported as a top-line result of the empagliflozin trial in patients with CKD regardless of T2DM. However, the full results of this trial have not yet been published. While the use of older steroidal mineralocorticoid receptor antagonists (MRAs) such as spironolactone in DKD is associated with a significant reduction in albuminuria outcomes, a novel non-steroidal MRA finerenone has additionally shown a significant reduction in the composite of hard renal and CV endpoints in patients with DKD and T2DM, with reasonably acceptable side effects.
| S-EPMC9329844 | biostudies-literature
Project description:Renin-angiotensin-aldosterone system (RAAS) is hypothesized to be in the center of COVID pathophysiology as the angiotensin converting enzyme 2 (ACE2) represents the main entrance of the virus, thus there is a need to address the effect of chronic use of RAAS blockers, as in case of treatment of cardiovascular diseases, on the expression of ACE2. Accordingly, this study aimed to clarify the effect of ACE inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on ACE2 and to assess the correlation between ACE2 and several anthropometric and clinic-pathological factors. A total of 40 healthy controls and 60 Egyptian patients suffering from chronic cardiovascular diseases were enrolled in this study. Patients were divided into 40 patients treated with ACEIs and 20 patients treated with ARBs. Serum ACE2 levels were assessed by ELISA. Assessment of serum ACE2 level in different groups showed a significant difference between ACEIs and healthy groups and ACEIs and ARBs group, while there was no difference between ARBs and healthy. Multivariate analysis using ACE2 level as constant and age, female sex, ACEIs use and myocardial infarction (MI) showed that there was a significant effect of female sex and ACEIs use on ACE2 level with no effect of age, MI and diabetes. ACE2 levels varied between ACEIs and ARBs. It tends to be lower in ACEIs group and there is a strong positive association between ACE2 level and the female sex. This needs to be considered in Future studies to further understand the relationship between gender, sex hormones and ACE2 level. Retrospectively registered ClinicalTrials.gov ID: NCT05418361 (June 2022).
| S-EPMC10103030 | biostudies-literature
Project description:IntroductionUse of certain antihypertensive medications has been an area of interest during the COVID-19 pandemic, and several hypotheses have been developed regarding the effects of renin-angiotensin system blockers as well as calcium channel blockers in those infected with COVID-19. We seek to determine the association between exposure to ACEI, ARB, and CCB and outcomes in those admitted to the hospital with COVID-19 infection.MethodsThis retrospective cohort study included 841 adult patients hospitalized with COVID-19 infection at the University of Chicago Medical Center between March 25 and June 22, 2020. Out of these 841, 453 patients had a personal history of hypertension. For the first part, we evaluated primary outcomes of in-hospital mortality and ICU admission in hospitalized COVID-19 patients based on their exposure to particular medications regardless of a personal history of hypertension and compared them with those who were not on these medications. For the second part, we evaluated the aforementioned outcomes in 453 patients with a personal history of hypertension based on their medication exposure. Secondary outcomes of length of stay, readmission rate, and new-onset dialysis requirement were also compared across the study groups.ResultsOut of 841 patients, 111 (13.19%) were on ACEI/ARB (median age: 66.1, SD 15.4; 52.25% females) and 730 (86.80%) were not on them (median age: 56.6, SD 20.3; 50.14% females), while 277 (32.93%) used CCB (median age: 64.6, SD 15.2; 57.04% females) and 564 (67.06%) did not use CCB (median age: 54.6, SD 21.2; 47.16% females). After adjusting for demographics and covariates, neither ACEI/ARB nor CCB exposure was associated with any effect on mortality, but ACEI/ARB exposure was associated with 42% reduction in risk of ICU admissions (OR 0.58, 95% CI [0.35, 0.95], p value 0.03). In addition, combined use of ACEI/ARB and CCB was associated with statistically significant (45%) reduction in ICU admission (OR 0.55, 95% CI [0.32, 0.94], p value 0.029). Out of 453 patients with a personal history of hypertension, 85 (18.76%) were taking ACEI/ARB (median age 65, SD 15.6; 56.47% females) and 368 (81.24%) were not on ACEI/ARB (median age 62.8, SD 16.4; 54.89% females), while 208 (45.92%) out of 453 were on CCB (median age 65; SD 14.8; 60.1% females) and 245 (54.08%) were not on CCB (median age 61.7, SD 17.3; 51.02% females). In the fully adjusted model in this group, ACEI use was associated with 71% reduction in in-house mortality (OR 0.29, 95% CI [0.09, 0.93], p value 0.03).Discussion/conclusionAmong all hospitalized patients with COVID-19 infection, exposure to ACEI/ARB, as well as combined exposure to ACEI/ARB and CCB, were associated with reduced incidence of ICU admissions. In those admitted patients who had a personal history of hypertension, there was a trend towards reduced in-hospital mortality in those exposed to ACEI.
| S-EPMC8089461 | biostudies-literature
Project description:Severe acute respiratory syndrome coronavirus 2, which is responsible for the current coronavirus disease 2019 pandemic, uses angiotensin-converting enzyme 2 as a gateway into host cells. In this review, we summarise the biology of this enzyme, which plays a key role in cardiovascular homeostasis. Blockers of the renin-angiotensin system modify the expression and activity of angiotensin-converting enzyme 2 in different ways. The effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the expression and enzyme activity of angiotensin-converting enzyme 2 are reviewed, and the consequences of these treatments for the severity of coronavirus disease 2019 infection are discussed.
| S-EPMC7430243 | biostudies-literature
Project description:BackgroundA potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.MethodsWe carried out a population-based case-control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients' clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.ResultsAmong both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.ConclusionsIn this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.
| S-EPMC7206933 | biostudies-literature
Project description:IntroductionDiscontinuation of renin-angiotensin-aldosterone system inhibitor (RAASi) is common after hyperkalemia. We evaluated the risk of kidney and mortality outcomes associated with RAASi discontinuation among patients with chronic kidney disease (CKD) and hyperkalemia.MethodsWe identified adult patients with CKD (eGFR <60 mL/min/1.73 m2) who experienced new-onset hyperkalemia (potassium ≥5.0 mEq/L) between 2016 and 2017 from Kaiser Permanente Southern California and followed them through 2019. We defined treatment discontinuation as having ≥90-day gap in refills of all RAASi within 3 months after hyperkalemia. We used multivariable Cox proportional hazards models to evaluate the association between RAASi discontinuation and the primary composite outcome of kidney (≥40% eGFR decline, dialysis, kidney transplant) or all-cause mortality. We evaluated cardiovascular events and recurrence of hyperkalemia as secondary outcomes.ResultsAmong 5,728 patients (mean age 76 years), 13.5% discontinued RAASi within 3 months after new-onset hyperkalemia. During the median 2 years of follow-up, 29.7% had the primary composite outcome (15.5% with ≥40% eGFR decline, 2.8% dialysis or kidney transplant, 18.4% all-cause mortality). Patients who discontinued RAASi had a higher all-cause mortality compared with those who continued RAASi (26.7% vs. 17.1%) but had no differences in kidney outcomes, cardiovascular events, and recurrence of hyperkalemia. RAASi discontinuation was associated with a higher risk of kidney or all-cause mortality composite outcome (adjusted hazard ratio [aHR] 1.21, 95% CI: 1.06, 1.37) mainly driven by all-cause mortality (aHR: 1.34, 95% CI: 1.14, 1.56).ConclusionRAASi discontinuation after hyperkalemia was associated with worsened mortality, which may underscore the benefits of continuing RAASi among patients with CKD.
| S-EPMC10623389 | biostudies-literature
Project description:Objective To examine long term cardiorenal outcomes associated with increased concentrations of creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment.Design Population based cohort study using electronic health records from the Clinical Practice Research Datalink and Hospital Episode Statistics.Setting UK primary care, 1997-2014.Participants Patients starting treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers (n=122 363).Main outcome measures Poisson regression was used to compare rates of end stage renal disease, myocardial infarction, heart failure, and death among patients with creatinine increases of 30% or more after starting treatment against those without such increases, and for each 10% increase in creatinine. Analyses were adjusted for age, sex, calendar period, socioeconomic status, lifestyle factors, chronic kidney disease, diabetes, cardiovascular comorbidities, and use of other antihypertensive drugs and non-steroidal anti-inflammatory drugs.Results Among the 2078 (1.7%) patients with creatinine increases of 30% or more, a higher proportion were female, were elderly, had cardiorenal comorbidity, and used non-steroidal anti-inflammatory drugs, loop diuretics, or potassium sparing diuretics. Creatinine increases of 30% or more were associated with an increased adjusted incidence rate ratio for all outcomes, compared with increases of less than 30%: 3.43 (95% confidence interval 2.40 to 4.91) for end stage renal disease, 1.46 (1.16 to 1.84) for myocardial infarction, 1.37 (1.14 to 1.65) for heart failure, and 1.84 (1.65 to 2.05) for death. The detailed categorisation of increases in creatinine concentrations (<10%, 10-19%, 20-29%, 30-39%, and ≥40%) showed a graduated relation for all outcomes (all P values for trends <0.001). Notably, creatinine increases of less than 30% were also associated with increased incidence rate ratios for all outcomes, including death (1.15 (1.09 to 1.22) for increases of 10-19% and 1.35 (1.23 to 1.49) for increases of 20-29%, using <10% as reference). Results were consistent across calendar periods, across subgroups of patients, and among continuing users.Conclusions Increases in creatinine after the start of angiotensin converting enzyme inhibitor/angiotensin receptor blocker treatment were associated with adverse cardiorenal outcomes in a graduated relation, even below the guideline recommended threshold of a 30% increase for stopping treatment.
| S-EPMC5421447 | biostudies-literature
Project description: Not available
| S-EPMC7489985 | biostudies-literature
Project description:Background Renin-angiotensin system blockers (RASBs) have well-validated benefit in patients with hypertension, coronary artery disease, and left ventricular systolic dysfunction. Their use in the perioperative period, however, has been controversial, including in patients undergoing cardiac surgery, who often have a strong indication for their use. In the current study, we explore the impact of RASB use with 30-day and 1-year mortality after cardiac surgery. Methods and Results The Veterans Affairs Surgical Quality Improvement Program and Corporate Data Warehouse were data sources for this retrospective cohort study. A total of 37 197 veterans undergoing elective coronary artery bypass grafting and or valve repair or replacement over a 10-year period met inclusion criteria and were stratified into 4 groups by preoperative exposure (preoperative exposure versus no preoperative exposure) and postoperative continuing exposure (current exposure versus no current exposure) to RASBs. After adjusting for all baseline covariates, the preoperative exposure/current exposure group had lower 30-day and 1-year mortality than the preoperative exposure/no current exposure (30-day hazard ratio [HR], 0.25; 95% CI, 0.19-0.33 [P<0.001] and 1-year HR, 0.40; 95% CI, 0.33-0.48 [P<0.001] or no preoperative exposure/no current exposure (30-day HR, 0.44; 95% CI, 0.32-0.60 [P<0.001] and 1-year HR, 0.72; 95% CI, 0.62-0.84 [P<0.001] groups. The no preoperative exposure/current exposure group had significantly lower 30-day (HR, 0.31; 95% CI, 0.14-0.71 [P=0.006]) and 1-year (HR, 0.64; 95% CI, 0.53-0.77 [P<0.001]) mortality than the no preoperative exposure/no current exposure group. Conclusions Continuation of preoperative RASBs and initiation before discharge is associated with decreased mortality in veterans undergoing cardiac surgery. Given these findings, continuation of preoperative RASBs or initiation in the early postoperative period should be considered in patients undergoing cardiac surgery.
| S-EPMC8200704 | biostudies-literature