2-Amino­pyridinium 5-(5-chloro-2,4-dinitro­phen­yl)-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra­hydro­pyrimidin-6-olate

In the title mol­ecular salt, C5H7N2 +·C12H8ClN4O7 −, the dihedral angle between the aromatic rings of the anion is 51.88 (6)°. One of the nitro groups is disordered over two orientations in a 0.710 (6):0.290 (6) ratio. In the crystal, the cations and anions are linked by N—H⋯O hydrogen bonds, generating infinite ribbons extending along [100] which incorporate R 4 4(22) ring motifs. Weak C—H⋯O inter­actions also occur

Triethyl­ammonium [2-eth­oxy­carbonyl-2-(2-methyl­benz­yl)-6,9-dinitro-3-oxo­bicyclo­[3.3.1]non-6-en-8-yl­idene]azinate

In the title salt, C6H16N+·C20H20N3O9 −, the cations and anions are connected by N—H⋯O hydrogen bonds. The structure is consolidated by weak C—H⋯O inter­actions

Renin–Angiotensin–Aldosterone System inhibitors in patients with Covid-19

No abstract available

Prevention of heart failure events with sodium-glucose co-transporter 2 inhibitors across a spectrum of cardio-renal-metabolic risk

Aims Trials have tested the safety and efficacy of sodium-glucose co-transporter 2 inhibitors (SGLT2i) across various disease states. We performed a meta-analysis of randomized controlled trials (RCTs) to estimate the relative and absolute effects of SGLT2i in the prevention of heart failure (HF) events across different risk groups. Methods and results We conducted a systematic review and meta-analysis of large, placebo-controlled RCTs with >1000 participants evaluating HF hospitalization and the composite of cardiovascular (CV) death or HF hospitalization. Due to varying durations of therapeutic exposure and follow-up, absolute risk reductions and number needed to treat were calculated based on incidence rates (per 100 patient-years). Across 71 553 patients enrolled in 10 late-phase RCTs, SGLT2i reduced the risk of HF hospitalization by 31% [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.64-0.74; I-2 = 0%] and the composite outcome of CV death or HF hospitalization by 24% (HR 0.76, 95% CI 0.72-0.80; I-2 = 1.4%) compared with placebo. The number of patient-years of treatment exposure needed to prevent one CV death or HF hospitalization ranged from 19-26 (established HF) to 72-125 (chronic kidney disease) to 96-400 (high-risk type 2 diabetes). In mixed-effects meta-regression analyses, the benefits of SGLT2i on HF hospitalizations or the composite outcome (CV death or HF hospitalization) were not influenced by age, sex, or change in intermediate markers (glycated haemoglobin, systolic blood pressure, and body weight) (all P >= 0.10). Conclusion Despite wide variation in baseline risks and disease states evaluated, SGLT2i demonstrated comparable relative risk reductions in preventing HF events. Patients at highest baseline risk derived the greatest absolute benefits in preventing HF events. These composite estimates may help guide targeted implementation of SGLT2i for the prevention of HF events in type 2 diabetes and chronic kidney disease and in the treatment of HF

Identification of Hibernating Myocardium: Comparative Accuracy of Myocardial Contrast Echocardiography, Rest-Redistribution Thallium-201 Tomography and Dobutamine Echocardiography

AbstractObjectives. We sought to evaluate the comparative accuracy of myocardial contrast echocardiography (MCE), quantitative rest-redistribution thallium-201 (Tl-201) tomography and low and high dose (up to 40 μg/kg body weight per min) dobutamine echocardiography (DE) in identifying myocardial hibernation.Background. Myocardial contrast echocardiography can assess myocardial perfusion and may therefore be useful in predicting myocardial hibernation. However, its accuracy in comparison to myocardial perfusion scintigraphy and to that of high dose DE remains to be investigated.Methods. Eighteen patients (aged [±SD] 57 ± 10 years) with stable coronary artery disease and ventricular dysfunction underwent the above three modalities before coronary revascularization. Myocardial contrast echocardiography was achieved with intracoronary Albunex. Rest echocardiographic and Tl-201 studies were repeated ≥6 weeks after revascularization.Results. Of 109 revascularized segments with severe dysfunction, 46 (42%) improved. Left ventricular ejection fraction increased from 38 ± 14% to 45 ± 13% at follow-up (p = 0.003). Rest Tl-201 uptake and the ratio of peak contrast intensity of dysfunctional to normal segments with MCE were higher (p < 0.01) in segments that recovered function compared with those that did not. Myocardial contrast echocardiography, thallium scintigraphy and any contractile reserve during DE had a similar sensitivity (89% to 91%) with a lower specificity (43% to 66%) for recovery of function. A biphasic response during DE was the most specific (83%) and the least sensitive (68%) (p < 0.01). The best concordance with MCE was Tl-201 (80%, kappa 0.57). Changes in ejection fraction after revascularization related significantly to the number of viable dysfunctional segments by all modalities (r = 0.54 to 0.65).Conclusions. In myocardial hibernation, methods evaluating rest perfusion (MCE, Tl-201) or any contractile reserve have a similar high sensitivity but a low specificity for predicting recovery of function. A limited contractile reserve (biphasic response) increases the specificity of DE. Importantly, the three techniques identified all patients who had significant improvement in global ventricular function.(J Am Coll Cardiol 1997;29:985–93)© 1997 by the American College of Cardiolog

Estimated Lifetime Benefit of Combined RAAS and SGLT2 Inhibitor Therapy in Patients with Albuminuric CKD without Diabetes

Background and objectives: Despite high rates of complications in patients with CKD without diabetes, the implementation of proven therapies in this group remains low. Expressing the clinical benefitofatherapyin terms of extra years free from the disease or death may facilitate implementation. We estimated lifetime survival free of kidney failure for patients with albuminuric CKD without diabetes treated with the combination therapy of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and sodium-glucose cotransporter-2 (SGLT2) inhibitors relative to patients not treated. Design, setting, participants, & measurements: We used trial-level estimates of the effect of treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ramipril/benazepril; n=690) and SGLT2 inhibitors (dapagliflozin; n=1398) compared with placebo to derive the effect of combination therapy versus no treatment. Using this effect, we estimated treatment effect of combination therapy to the active treatment group of patients with albuminuric CKD without diabetes participating in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial (n=697) and projected eventfree and overall survival for those treated and not treated with combination therapy. We also performed our calculations anticipating lower adherence and less pronounced benefits than were observed in the clinical trials. The primary outcome was a composite of doubling of serum creatinine, kidney failure, or death. Results: The aggregate estimated hazard ratio comparing combination therapy with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitor versus no treatment for the primary end point was 0.35 (95% confidence interval, 0.30 to 0.41). For a 50-year-old patient until the age of 75 years, the estimated survival free from the primary composite end point was 17.0 (95% confidence interval, 12.4 to 19.6) years with the combination therapy and 9.6 years (95% confidence interval, 8.4 to 10.7) with no treatment with any of these agents, corresponding to a gain in eventfree survival of 7.4 (95% confidence interval, 6.4 to 8.7) years. When assuming lower adherence and less pronounced efficacy of combination therapy, the gain in eventfree survival ranged from 5.3 years (95% confidence interval, 4.4 to 6.1) to 5.8 years (95% confidence interval, 4.8 to 6.8). Conclusions: Treatment with the combination of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and SGLT2 inhibitor in patients with albuminuric CKD without diabetes is expected to substantially increase kidney failure–free survival. Clinical Trial registry name and registration number: Benazepril for Advanced Chronic Renal Insufficiency, NCT00270426, and a Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients with Chronic Kidney Disease (Dapa-CKD), NCT03036150

The rise and fall of aspirin in the primary prevention of cardiovascular disease

Aspirin is one of the most frequently used drugs worldwide and is generally considered effective for the secondary prevention of cardiovascular disease. By contrast, the role of aspirin in primary prevention of cardiovascular disease is controversial. Early trials evaluating aspirin for primary prevention, done before the turn of the millennium, suggested reductions in myocardial infarction and stroke (although not mortality), and an increased risk of bleeding. In an effort to balance the risks and benefits of aspirin, international guidelines on primary prevention of cardiovascular disease have typically recommended aspirin only when a substantial 10-year risk of cardiovascular events exists. However, in 2018, three large randomised clinical trials of aspirin for the primary prevention of cardiovascular disease showed little or no benefit and have even suggested net harm. In this narrative Review, we reappraise the role of aspirin in primary prevention of cardiovascular disease, contextualising data from historical and contemporary trials