MARRIAGE: A Randomized Trial of Moxonidine Versus Ramipril or in Combination With Ramipril in Overweight Patients With Hypertension and Impaired Fasting Glucose or Diabetes Mellitus. Impact on Blood Pressure, Heart Rate and Metabolic Parameters.

BACKGROUND: Moxonidine, an imidazoline I1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic. AIMS: This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes. METHODS: Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment. RESULTS: Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, p = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters. CONCLUSION: Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment.

Investigating the Relationship Between Acne and Vasodilatory Medications in a Hospital-Wide Adult Population.

Acne vulgaris is a common chronic dermatological condition characterized by obstruction and inflammation of pilosebaceous units. Recent research on a different dermatologic condition has demonstrated that the use of vasodilatory medications is associated with a decreased relative risk of rosacea. This finding is significant due to the overlapping inflammatory pathways involved in rosacea and acne. Herein, a retrospective cohort study was designed to determine the correlation between vasodilator usage and the risk of developing acne within 5 years, contrasting it with thiazide diuretics, chosen as a control due to its non-vasodilatory antihypertensive mechanism and availability of data. Angiotensin-converting enzyme (ACE) inhibitors (RR, 0.775; 95% CI, 0.727-0.826; P<0.05), angiotensin receptor blockers (ARBs) (RR, 0.739; 95% CI, 0.685-0.797; P<0.05), beta-blockers (BB) (RR, 0.829; 95% CI, 0.777-0.885; P<0.05), and calcium channel blockers (CCB) usage (RR, 0.821, 95% CI, 0.773-0.873; P<0.05) were associated with a significantly lower risk of developing acne within 5 years of initiating therapy compared to thiazide diuretics. It is unclear if thiazide diuretics are more likely to cause acne within the adult population or if vasodilators are protective against the development of acne. Finding mechanisms and therapeutics that lower the risk of developing acne is of significant public health interest, and this study provides a step toward this endeavor. Further research is required to uncover the underlying mechanisms for this reduction in the development of acne.  J Drugs Dermatol. 2024;23(6):446-449.     doi:10.36849/JDD.8362.

Preoperative use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and diuretics increases the risk of dehydration after ileostomy formation: population-based cohort study.

BACKGROUND: Readmission rates following ileostomy formation are high. Dehydration and consecutive renal failure are common causes of readmission, potentially pronounced by drugs affecting the homeostasis. The aim of the study was to assess the risk of dehydration after ileostomy formation in patients treated with angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) or diuretics. METHOD: This nationwide population-based cohort study used data derived from the Colorectal Cancer Data Base of several Swedish healthcare registers. The study included all patients operated on with elective anterior resection and temporary ileostomy for rectal cancer clinically staged I-III in Sweden in 2007-2016. Exposure was at least two dispensations of ACEI, ARB or diuretics within 1 year prior to surgery. Outcome was 90-day readmission due to dehydration including acute renal failure. RESULTS: In total, 3252 patients were included with 1173 (36.1%) exposed to ACEI, ARB or diuretics. The cumulative incidence for 90-day readmission due to dehydration was 29.0% (151 of 520) for exposed versus 13.8% (98 of 712) for unexposed. The proportion of readmissions due to any reason was 44.3% (520 of 1173) for exposed compared to 34.2% (712 of 2079) for unexposed. The incidence rate ratio for readmission due to dehydration was 2.83 (95% c.i. 2.21 to 3.63, P < 0.001). The hazard rate ratio was 2.45 (95% c.i. 1.83 to 3.27, P < 0.001) after adjusting for age, gender and comorbidity. CONCLUSION: Medication with ACEI, ARB or diuretics defines a vulnerable patient group with increased risk of readmission due to dehydration after ileostomy formation.

ACE inhibitors and angiotensin receptor blockers differentially alter the response to angiotensin II treatment in vasodilatory shock.

BACKGROUND: Angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blockers (ARB) medications are widely prescribed. We sought to assess how pre-admission use of these medications might impact the response to angiotensin-II treatment during vasodilatory shock. METHODS: In a post-hoc subgroup analysis of the randomized, placebo-controlled, Angiotensin Therapy for High Output Shock (ATHOS-3) trial, we compared patients with chronic angiotensin-converting enzyme inhibitor (ACEi) use, and patients with angiotensin receptor blocker (ARB) use, to patients without exposure to either ACEi or ARB. The primary outcome was mean arterial pressure after 1-h of treatment. Additional clinical outcomes included mean arterial pressure and norepinephrine equivalent dose requirements over time, and study-drug dose over time. Biological outcomes included baseline RAS biomarkers (renin, angiotensin-I, angiotensin-II, and angiotensin-I/angiotensin-II ratio), and the change in renin from 0 to 3 h. RESULTS: We included n = 321 patients, of whom, 270 were ACEi and ARB-unexposed, 29 were ACEi-exposed and 22 ARB-exposed. In ACEi/ARB-unexposed patients, angiotensin-treated patients, compared to placebo, had higher hour-1 mean arterial pressure (9.1 mmHg [95% CI 7.6-10.1], p < 0.0001), lower norepinephrine equivalent dose over 48-h (p = 0.0037), and lower study-drug dose over 48-h (p < 0.0001). ACEi-exposed patients treated with angiotensin-II showed similarly higher hour-1 mean arterial pressure compared to ACEi/ARB-unexposed (difference in treatment-effect: - 2.2 mmHg [95% CI - 7.0-2.6], pinteraction = 0.38), but a greater reduction in norepinephrine equivalent dose (pinteraction = 0.0031) and study-drug dose (pinteraction < 0.0001) over 48-h. In contrast, ARB-exposed patients showed an attenuated effect of angiotensin-II on hour-1 mean arterial pressure versus ACEi/ARB-unexposed (difference in treatment-effect: - 6.0 mmHg [95% CI - 11.5 to - 0.6], pinteraction = 0.0299), norepinephrine equivalent dose (pinteraction < 0.0001), and study-drug dose (pinteraction = 0.0008). Baseline renin levels and angiotensin-I/angiotensin-II ratios were highest in ACEi-exposed patients. Finally, angiotensin-II treatment reduced hour-3 renin in ACEi/ARB-unexposed and ACEi-exposed patients but not in ARB-exposed patients. CONCLUSIONS: In vasodilatory shock patients, the cardiovascular and biological RAS response to angiotensin-II differed based upon prior exposure to ACEi and ARB medications. ACEi-exposure was associated with increased angiotensin II responsiveness, whereas ARB-exposure was associated with decreased responsiveness. These findings have clinical implications for patient selection and dosage of angiotensin II in vasodilatory shock. Trial Registration ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

Evaluating prescription of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in patients with diabetes and albuminuria.

AIM: Although guidelines recommend the use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) in patients with diabetes, hypertension, and albuminuria, their use remains suboptimal in several developed countries. Limited data are available on ACEi/ARB use in developing countries. Here, we assessed the use of ACEi/ARB and identified factors contributing to their underutilization at Hatyai Hospital, Thailand. MATERIALS AND METHODS: This retrospective cross-sectional study was conducted using data from the Hatyai Hospital database. Adult patients with diabetes, hypertension, and albuminuria were included. Clinical data and laboratory results were extracted. Furthermore, this study recorded pre-specified conditions that influenced physicians' decisions regarding the prescription of ACEi/ARBs in patients who did not adhere to guidelines. RESULTS: Of 4,655 eligible patients, 500 patients were selected. The average age of the patients was 66.3 years, and 59.6% were female. The adherence rate was 72.4%. Multivariate logistic regression analysis found a significant association between non-adherence and chronic kidney disease (CKD) stage (OR = 1.29, 95% CI: 1.04 - 1.60, p = 0.019). The most common pre-specified condition contributing to non-adherence was "no condition identified" (69.8%). Among the cases of non-adherence, 21.7% were due to ACEi/ARB discontinuation after acute kidney injury, followed by hyperkalemia (5.1%) and a moderate increase in serum creatinine (4.3%). CONCLUSION: ACEi/ARB therapy was suboptimal in patients with diabetes, hypertension, and albuminuria. Non-adherence was associated with CKD stage, possibly because of concerns about adverse events and healthcare-related factors.

Should renin-angiotensin system inhibitors be held prior to major surgery?

Many patients undergoing surgical procedures have a history of hypertension, diabetes mellitus, heart failure, or a combination. Often, these conditions involve the chronic use of a renin-angiotensin system inhibitor, including angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Observational studies have suggested that continuing ACEIs/ARBs before major noncardiac surgery can increase the risk of intraoperative hypotension, which might drive postoperative complications such as acute kidney injury, myocardial injury, or stroke. Strong recommendations on how to manage ACEIs/ARBs before surgery are, however, lacking owing to insufficient evidence, mostly limited to data from observational studies. Recently, the SPACE trial investigated the impact of preoperative management of ACEIs/ARBs on postoperative myocardial injury. Myocardial injury occurred in 48.3% patients randomised to discontinue and 41.3% patients randomised to continue ACEI/ARB (odds ratio for continuing: 0.77, 95% confidence interval 0.45-1.31). Patients randomised to the 'Stop' group experienced more postoperative hypertension. In a post hoc analysis, patients randomised to the 'Continue' group with low preoperative NT-proBNP concentrations (<100 pg ml-1) experienced less myocardial injury after surgery than the 'Stop' group, whereas no significant difference was observed in patients with elevated preoperative NT-proBNP concentrations. The SPACE trial provides important and new reassuring data on the safety of continuing ACEIs/ARBs before major surgery, challenging previous beliefs.

Tolerability of Antihypertensive Medications: The Influence of Age.

INTRODUCTION: Despite high prevalence of hypertension, few studies have analysed the adverse effects (AEs) of antihypertensive medications, especially in older patients. AIM: To investigate the prevalence and associated factors of antihypertensive-related AEs, focusing on the influence of age on treatment tolerability. METHODS: We retrospectively investigated antihypertensive-related AEs in patients evaluated at the Hypertension Clinic of Careggi Hospital, Florence, Italy, between January 2017 and July 2020. Multivariable regression models were generated to analyse variables associated with AEs in the overall sample and in participants ≥75 years. RESULTS: Among 622 subjects (mean age 64.8 years, 51.4% female), the most frequently reported AEs were calcium-channel blockers (CCB)-related ankle swelling (26.8%) and ACEi-induced cough (15.1%). Ankle swelling was more common in older patients (35.7% vs 22.3%, p = 0.001; odds ratio [OR] 1.94, 95%CI 1.289-2.912) and was independently associated with Body Mass Index (BMI, adjOR 1.073) and angiotensin-receptor antagonists (adjOR 1.864). The association with BMI was confirmed in older patients (adjOR 1.134). ACEi-induced cough showed similar prevalence in younger and older patients (13.9% vs 15.6%, p = 0.634), being independently associated with female sex (adjOR 2.118), gastroesophageal reflux disease (GERD, adjOR 2.488) and SNRI therapy (adjOR 8.114). The association with GERD was confirmed in older patients (adjOR 3.238). CONCLUSIONS: CCB-related ankle swelling and ACEi-induced cough represent the most common antihypertensive-related AEs, also at old age. Older patients showed a two-fold increased risk of ankle swelling, that was also independently associated with BMI. ACEi-induced cough had similar prevalence at younger and old ages, being independently associated with GERD.

Preoperative beta blockers and other drugs in relation to anastomotic leakage after anterior resection for rectal cancer.

AIM: Previous research has indicated that preoperative beta blocker therapy is associated with a decreased risk of complications after surgery for rectal cancer. This is thought to arise because of the anti-inflammatory activity of the drug. These results need to be reproduced and analyses extended to other drugs with such properties, as this information might be useful in clinical decision-making. The main aim of this work was to replicate previous findings of beta blocker use as a prognostic marker for postoperative leakage. We also investigated whether drug exposure might induce anastomotic leaks. METHOD: This is a retrospective multicentre cohort study, comprising 1126 patients who underwent anterior resection for rectal cancer between 2014 and 2018. The use of any preoperative beta blocker was treated as the primary exposure, while anastomotic leakage within 12 months of surgery was the outcome. Secondary exposures comprised angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins and metformin. Using multivariable regression, we performed a replication analysis with a predictive aim for beta blockers only, while adjustment for confounding was done in more causally oriented analyses for all drugs. We estimated incidence rate ratio (IRR) and relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Anastomotic leakage occurred in 20.6% of patients. Preoperative beta blockers were used by 22.7% of the cohort, while the leak distribution was almost identical between exposure groups. In the main replication analysis, no association could be detected (IRR 0.95, 95% CI 0.68-1.33). In the causally oriented analyses, only metformin affected the risk of leakage (RR 1.59, 95% Cl 1.31-1.92). CONCLUSION: While previous research has suggested that preoperative beta blocker use could be prognostic of anastomotic leakage, this study could not detect any such association. On the contrary, our results indicate that preoperative beta blocker use neither predicts nor causes anastomotic leakage after anterior resection for rectal cancer.

Comparative safety and effectiveness of angiotensin converting enzyme inhibitors and thiazides and thiazide-like diuretics under strict monotherapy.

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.

Management of Hyperkalemia in Renin-Angiotensin-Aldosterone System Inhibitor: Strategies to Maintain Chronic Kidney Disease Patients with Type II Diabetes on Therapy.

BACKGROUND: According to the Centers for Disease Control and Prevention (CDC), diabetes affects approximately 37.3 million individuals in the USA, with another estimated 96 million people having a prediabetic state. Furthermore, one or two out of three adult Americans exhibit metabolic syndrome or an insulin-resistant state, depending on their age group. SUMMARY: Chronic kidney disease (CKD) represents a complication often associated with type II diabetes or the insulin-resistant condition, typically identifiable through proteinuria. Proteinuria serves as both a marker and a contributing factor to kidney damage, and it significantly heightens the risk of cardiovascular (CV) events, including atherosclerosis, heart attacks, and strokes. Renin-angiotensin-aldosterone system inhibitors (RAASis) have demonstrated clinical efficacy in lowering blood pressure, reducing proteinuria, and slowing CKD progression. However, hyperkalemia is a common and serious adverse effect associated with using RAASi. KEY MESSAGES: It is imperative to establish personalized management strategies to enable patients to continue RAASi therapy while effectively addressing hyperkalemia risk. Healthcare professionals must be careful not to inadvertently create a low renal perfusion state, which can reduce distal nephron luminal flow or luminal sodium concentration while using RAASi. Nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), such as finerenone, are demonstrated to delay CKD progression and reduce CV complications, all while mitigating the risk of hyperkalemia. Additionally, maintaining a routine monitoring regimen for serum potassium levels among at-risk patients, making dietary adjustments, and considering the adoption of newer potassium-binding agents hold promise for optimizing RAASi therapy and achieving more effective hyperkalemia management.

Effects of the valsartan recall on heart failure patients: A nationwide analysis.

BACKGROUND: Valsartan is commonly used for cardiac conditions. In 2018, the Food and Drug Administration recalled generic valsartan due to the detection of impurities. Our objective was to determine if heart failure patients receiving valsartan at the recall date had a greater likelihood of unfavorable outcomes than patients using comparable antihypertensives. METHODS: We conducted a cohort study of Optum's de-identified Clinformatics® Datamart (July 2017-January 2019). Heart failure patients with commercial or Medicare Advantage insurance who received valsartan were compared to persons who received non-recalled angiotensin receptor blockers (ARBs) and angiotensin converting enzyme-inhibitors (ACE-Is) for 1 year prior and including the recall date. Outcomes included a composite for all-cause hospitalization, emergency department (ED), and urgent care (UC) use and a measure of cardiac events which included hospitalizations for acute myocardial infarction and hospitalizations/ED/UC visits for stroke/transient ischemic attack, heart failure or hypertension at 6-months post-recall. Cox proportional hazard models with propensity score weighting compared the risk of outcomes between groups. RESULTS: Of the 87 130 adherent patients, 15% were valsartan users and 85% were users of non-recalled ARBs/ACE-Is. Valsartan use was not associated with an increased risk of all-cause hospitalization/ED/UC use six-months post-recall (HR 1.00; 95% CI 0.96-1.03), compared with individuals taking non-recalled ARBs/ACE-Is. Similarly, cardiac events 6-months post-recall did not differ between individuals on valsartan and non-recalled ARBs/ACE-Is (HR 1.04; 95% CI 0.97-1.12). CONCLUSIONS: The valsartan recall did not affect short-term outcomes of heart failure patients. However, the recall potentially disrupted the medication regimens of patients, possibly straining the healthcare system.

Investigating the use of finerenone in children with chronic kidney disease and proteinuria: design of the FIONA and open-label extension studies.

INTRODUCTION: Proteinuria is a modifiable risk factor for chronic kidney disease (CKD) progression in children. Finerenone, a selective, non-steroidal, mineralocorticoid receptor antagonist (MRA) has been approved to treat adults with CKD associated with type 2 diabetes mellitus (T2DM) following results from the phase III clinical trials FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049). In a pre-specified pooled analysis of both studies (N = 13,026), finerenone was shown to have an acceptable safety profile and was efficacious in decreasing the risk of adverse kidney and cardiovascular outcomes and of proteinuria. OBJECTIVE: FIONA and the associated open-label extension (OLE) study aim to demonstrate that combining finerenone with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) is safe, well-tolerated, and effective in sustainably reducing urinary protein excretion in children with CKD and proteinuria. DESIGN: FIONA (NCT05196035; Eudra-CT: 2021-002071-19) is a randomized (2:1), double-blind, placebo-controlled, multicenter, phase III study of 6 months' duration in approximately 219 pediatric patients. Patients must have a clinical diagnosis of CKD (an eGFR ≥ 30 mL/min/1.73 m2 if ≥ 1 to < 18 years or a serum creatinine level ≤ 0.40 mg/dL for infants 6 months to < 1 year) with significant proteinuria despite ACEi or ARB usage. The primary objective is to demonstrate that finerenone, added to an ACEi or ARB, is superior to placebo in reducing urinary protein excretion. FIONA OLE (NCT05457283; Eudra-CT: 2021-002905-89) is a single-arm, open-label study, enrolling participants who have completed FIONA. The primary objective of FIONA OLE is to provide long-term safety data. FIONA has two primary endpoints: urinary protein-to-creatinine ratio (UPCR) reduction of ≥ 30% from baseline to day 180 and percent change in UPCR from baseline to day 180. A sample size of 198 participants (aged 2 to < 18 years) in FIONA will provide at least 80% power to reject the null hypothesis of either of the two primary endpoints. CONCLUSION: FIONA is evaluating the use of finerenone in children with CKD and proteinuria. Should safety, tolerability, and efficacy be demonstrated, finerenone could become a useful additional therapeutic agent in managing proteinuria and improving kidney outcomes in children with CKD. TRIAL REGISTRATION: ClinicalTrials.gov NCT05196035. Registered on 19 January 2022.

Non-steroidal anti-inflammatory drugs, renin-angiotensin system blockade or diuretics and risk of acute kidney injury: A case-crossover study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Effect of continuing angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers on the day of surgery on myocardial injury after non-cardiac surgery: A retrospective cohort study.

STUDY OBJECTIVE: To evaluate the effect of continuing of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) prescriptions 24 h before surgery on postoperative myocardial injury and blood pressure in patients undergoing non-cardiac surgery. DESIGN: A single-center, retrospective study. SETTING: Operating room and perioperative care area. PATIENTS: 42,432 patients who had been taking chronic ACEI/ARB underwent non-cardiac surgery from January 2012 to June 2022. INTERVENTIONS: Patients who discontinued ACEI/ARB 24 h before surgery (withheld group, n=31,055) and those who continued ACEI/ARB 24 h before surgery (continued group, n=11,377). MEASUREMENTS: Primary outcome was myocardial injury after non-cardiac surgery (MINS) within 7 days postoperatively. MINS was defined as an elevated postoperative cardiac troponin measurement above the 99th percentile of the upper reference limit with a rise/fall pattern. Perioperative blood pressure and clinical outcomes were secondary outcomes. MAIN RESULTS: Among 42,432 patients, MINS occurred in 2848 patients (6.7%) and was the all-cause of death within 30 days in 122 patients (0.3%). Incidence of MINS was significantly higher in the continued group than the withheld group (847/11,377 [7.4%] vs. 2001/31,055 [6.4%]; OR [95% CI] 1.17 [1.07-1.27]; P<0.001). After 1:1 propensity score matching, 11,373 patients were included in each group. There was still a significant difference for the occurrence of MINS between two groups in matched cohort (7.4% vs. 6.6%, OR [95% CI] 1.14 [1.03-1.26]; P=0.015). Time-average weight of mean arterial pressure <65 mmHg during surgery was significantly higher in the continued group (mean 0.11 vs. 0.09 [95% CI of mean difference] [0.01-0.03]; P<0.001). However, there was no significant difference in other clinical outcomes and mortality. CONCLUSIONS: Withholding ACEI/ARB before surgery was associated with a reduced risk of intraoperative hypotension and postoperative myocardial injury, but it did not affect overall clinical outcomes in patients undergoing non-cardiac surgery.

The risk of common hypoglycemic and antihypertensive medications and COVID-19: A 2-sample Mendelian randomization study.

BACKGROUND: It has been reported that diabetes and hypertension increase the adverse outcomes of coronavirus disease 2019 (COVID-19). Aside from the inherent factors of diabetes and hypertension, it remains unclear whether antidiabetic or antihypertensive medications contribute to the increased adverse outcomes of COVID-19. The effect of commonly used antidiabetic and antihypertensive medications on COVID-19 outcomes has been inconsistently concluded in existing observational studies. Conducting a systematic study on the causal relationship between these medications and COVID-19 would be beneficial in guiding their use during the COVID-19 pandemic. METHODS: We employed the 2-sample Mendelian randomization approach to assess the causal relationship between 5 commonly used antidiabetic medications (SGLT-2 inhibitors, Sulfonylureas, Insulin analogues, Thiazolidinediones, GLP-1 analogues) and 3 commonly used antihypertensive medications (calcium channel blockers [CCB], ACE inhibitors, ß-receptor blockers [BB]), and COVID-19 susceptibility, hospitalization, and severe outcomes. The genetic variations in the drug targets of the 5 antidiabetic medications and 3 antihypertensive medications were utilized as instrumental variables. European population-specific genome-wide association analysis (GWAS) data on COVID-19 from the Host Genetics Initiative meta-analyses were obtained, including COVID-19 susceptibility (n = 2597,856), COVID-19 hospitalization (n = 2095,324), and COVID-19 severity (n = 1086,211). The random-effects inverse variance-weighted estimation method was employed as the primary assessment technique, with various sensitivity analyses conducted to evaluate heterogeneity and pleiotropy. RESULTS: There were no potential associations between the genetic variations in the drug targets of the 5 commonly used antidiabetic medications (SGLT-2 inhibitors, Sulfonylureas, Insulin analogues, Thiazolidinediones, GLP-1 analogues) and the 3 commonly used antihypertensive medications (CCBs, ACE inhibitors, BBs) with COVID-19 susceptibility, hospitalization, and severity (all P > .016). CONCLUSION: The findings from this comprehensive Mendelian randomization analysis suggest that there may be no causal relationship between the 5 commonly used antidiabetic medications (SGLT-2 inhibitors, Sulfonylureas, Insulin analogues, Thiazolidinediones, GLP-1 analogues) and the 3 commonly used antihypertensive medications (CCBs, ACE inhibitors, BBs) with COVID-19 susceptibility, hospitalization, and severity.

Statins, ACE/ARBs drug use, and risk of pneumonia in hospitalized older patients: a retrospective cohort study.

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.

Tranexamic acid for angiotensin converting enzyme inhibitor induced angioedema: A retrospective multicenter study.

BACKGROUND: Angiotensin converting enzyme inhibitors (ACE-Is) prevent the breakdown of bradykinin and can lead to life threatening angioedema. Tranexamic acid is an antifibrinolytic that inhibits formation of precursors involved in bradykinin synthesis and, in case reports, has been described as a potential treatment for ACE-I angioedema. METHODS: This retrospective study included patients who presented to the emergency department (ED) from January 2018 to August 2021 with angioedema while taking an ACE-I. Patients who received tranexamic acid (treatment group) were compared with patients who did not receive tranexamic acid (control group). Primary outcome was length of stay (LOS). Secondary outcomes evaluated included ICU admissions, intubations, and safety events. RESULTS: A total of 262 patients were included in this study (73 treatment; 189 control). Overall, the median ED LOS was longer in the treatment group than controls (20.9 h vs 4.8 h, p < 0.001). ICU admission rates were higher in the treatment group (45% vs 16%, p < 0.001). More patients were intubated in the treatment group (12% vs 3%, p = 0.018). No difference was seen between the treatment group and the controls for return within 7 days, complications related to thrombosis, and death. In patients presenting with severe angioedema symptoms who were admitted to the hospital, median LOS was not different between the two groups (58.7 h vs 55.7 h, p = 0.61). CONCLUSIONS: Patients who received tranexamic acid had increased ED LOS, rates of ICU admission, and need for intubation. This finding may be related to the severity of presentation. Administration of tranexamic acid appears safe to use in ACE-I angioedema. Prospective randomized controlled studies should be considered to determine whether tranexamic acid is an effective treatment for ACE-I angioedema.