China
Africa
Explore chapters and articles related to this topic
Heart failure with preserved ejection fraction in older adults
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
Bharathi Upadhya, Dalane W. Kitzman
Sitaxsentan is an orally active, selective endothelin-A receptor antagonist that provided a modest increase in treadmill exercise time, but did not improve any of the secondary endpoints, such as LV mass or diastolic function, in a small trial with stable HFpEF patients (183). Advanced glycation end products (AGEs) are formed when glucose interacts nonenzymatically with proteins. AGEs can cause increased stiffness of the extracellular matrix directly by cross-linking collagen or elastin and indirectly by stimulating the production of collagen and depleting NO, thereby increasing oxidative stress (184). In a small open-label study with stable HFpEF, alagebrium chloride (AGE breaker), was associated with slightly reduced LV mass and improved diastolic filling and QOL; however, there were no changes in the peak VO2 (185). Interleukin-1 (alpha and beta) are potent proinflammatory cytokines implicated in adverse VV remodeling (186). Interleukin-1 blockade with anakinra for 14 days in a double-blind, randomized, placebo-controlled, crossover trial (Diastolic HF Anakinra Response Trial [D-HART-Pilot]) significantly reduced the systemic inflammatory response and improved aerobic exercise capacity in patients with HFpEF and elevated plasma C-reactive proteins levels. Currently, the D-HART2, phase 2 clinical trial testing anakinra for improving cardiorespiratory fitness, diastolic dysfunction, and elevated inflammation in patients with HFpEF, is underway (NCT01542502).
Pulmonary hypertension: Hemodynamic assessment and response to vasodilators
Published in Debabrata Mukherjee, Eric R. Bates, Marco Roffi, Richard A. Lange, David J. Moliterno, Nadia M. Whitehead, Cardiovascular Catheterization and Intervention, 2017
Myung H. Park, Vallerie V. Mclaughlin
The incidence of hepatic transaminase elevation more than three times the upper limit of normal was 0.8% for patients receiving ambrisentan.127 This was further investigated in a recently published study of 36 patients who did not tolerate bosentan or sitaxsentan because of hepatic transaminase increases and were placed on ambrisentan therapy.128 Ambrisentan therapy was tolerated well in this group. Peripheral edema is another side effect of the ERA class and was reported in mild to moderate severity in the clinical trials.127 An increased incidence of peripheral edema during postmarketing use prompted the FDA to issue a labeled warning for elderly patients.129 The mechanisms behind this observed edema is currently undergoing evaluation. No drug interaction was found with sildenafil.129 Ambrisentan is teratogenic. Monthly blood tests for liver function and pregnancy tests for women of child-bearing age are required (Table 10.5).
Large animal models for translational research in acute kidney injury
Published in Renal Failure, 2020
Balamurugan Packialakshmi, Ian J. Stewart, David M. Burmeister, Kevin K. Chung, Xiaoming Zhou
Increase of blood flow to the kidney by vasodilation through increasing either nitric oxide bioavailability, endothelin inhibition, or administration of hormone and neurotransmitter analogues has been shown to ameliorate AKI in LAM. By preserving nitric oxide bioavailability and preventing regional hypoxia, Sildenafil attenuates IRI in canine and swine kidneys [100,186]. Sitaxsentan, an endothelin receptor antagonist, improves hypoxia during AKI in a porcine model [99]. Sodium nitroprusside, a nitric oxide donor, in combination with N-acetyl cysteine and phosphormidon, an endothelin-1 converting enzyme inhibitor, improves renal function after I/R injury in a canine model [188]. Fenoldopam, a synthetic D1 dopamine receptor agonist, demonstrated a prophylactic benefit against the reduction in renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs [193]. Fenoldopam has also been shown to attenuate I/R-induced AKI in a porcine model [123]. Fenoldopam was found to be beneficial in the prevention or treatment of AKI in postoperative or intensive care patients [200], but a recent review only found that its renoprotective effect is transient [201]. Both atrial natriuretic peptide and brain natriuretic peptide relax vascular smooth muscles and improve blood flow and urine output in dogs [182]. Limited clinical trials suggest that low dose of atrial natriuretic peptide might be effective in preventing or treating AKI [202].
A Bayesian network meta-analysis on the efficacy and safety of eighteen targeted drugs or drug combinations for pulmonary arterial hypertension
Published in Drug Delivery, 2018
Sumei Wang, Miao Yu, Xiangchun Zheng, Shangjuan Dong
As the first network meta-analysis which directly evaluated the common specific targeted therapies, instead of the drug category, on a more comprehensive dimension with twelve aspects relating to efficacy or safety, it reduced the significant variance within drug groups. Although bosentan and sitaxsentan, both belonging to the ERAs, owned the same target, the former one was more effective in lowering PVR, while sitaxsentan demonstrated no superiority over placebo in terms of PVR change and was much less effective than bosentan (placebo vs. sitaxsentan, MD: 160, 95% CrI −9.7 to 320; bosentan vs. sitaxsentan, MD: −593.24, 95% CrI −783.18 to −401.25). This dilemma was not an exception, for withdrawal, two PDE-5i treatments, vardenafil and treprostinil acted out opposite as well (vardenafil vs. treprostinil, OR: 0.03, 95% CrI 0.01–0.23), under this tricky situation, grouping by individual drugs overweighed by the mechanism. However, the consequent problem was the inevitable error posed by the poor quality and limited size of included trials and small probability events. Therefore, more valuable data of RCTs should be included to update this analysis.
Advances in the available non-biological pharmacotherapy prevention and treatment of acute mountain sickness and high altitude cerebral and pulmonary oedema
Published in Expert Opinion on Pharmacotherapy, 2018
K.E. Joyce, S.J.E. Lucas, C.H.E. Imray, G.M Balanos, A. D. Wright
Research has demonstrated that the ETA antagonist sitaxentan reduces pulmonary vascular resistance (PVR) in both acute and chronic hypoxia with such changes in PVR being correlated with restorations in VO2max [133]. Increases in PVR associated with hypoxia may be a contributing factor to the reductions in VO2max observed in hypoxia. Thus, sitaxentan may offer an alternative option to existing pharmacotherapies, especially, when exercise performance at altitude is a priority. In vivo models have shown sitaxentan reduces high-altitude-induced cerebral vascular leakage by 40%, but its effect on altitude illnesses remains uninvestigated [65].