#1
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Ïî âòîðîìó êðóãó?
Ìëàäøîé ñîáðàò òðèìåòàçèäèíà - ðàíîëàçèí òîæå ïîêàçàë íóëåâîé ðåçóëüòàò ïðè ëå÷åíèè ÎÊÑ:
The Metabolic Efficiency with Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes Thrombolysis in MI-36 (MERLIN TIMI-36) was a multinational, double-blind, randomized, placebo-controlled trial designed to evaluate the efficacy and safety of ranolazine during acute and long-term treatment in around 6500 patients with NSTE ACS treated with standard therapy. The results show that the study drug ranolazine failed to reduce time to cardiovascular death, myocardial infarction, and/or recurrent ischemia compared with placebo in patients with non-ST segment elevation acute coronary syndrome. Îäíàêî, ó÷èòûâàÿ íàëè÷èå îòñóòñòâèÿ ýêñöåññîâ ñìåðòíîñòè è àðèòìèé, ïðåïàðàò ïîõîæå ìîæåò ïîëó÷èòü ñòàòóñ "àìåðèêàíñêîãî ïðåäóêòàëà": However, the study sponsor CV Therapeutics reports that there was no adverse trend in death or arrhythmias in patients on ranolazine. If these findings are borne out in the full results, they could support approval of ranolazine as first-line chronic angina therapy, as agreed in a Special Protocol Assessment with the US Food and Drug Administration. Ranolazine is currently indicated for the second-line treatment of chronic angina, in combination with amlodipine, beta-blockers, or nitrates, in patients who have not achieved an adequate response with other anti-anginal drugs. Concerns that the drug could lead to arrhythmias by prolonging the QT interval have restricted its use in this way. Ïî ìàòåðèàëàì ACC 2007 congress in New Orleans, Louisiana
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Èñêðåííå, Âàäèì Âàëåðüåâè÷. |
#2
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Èíòåðåñíî, ÷òî äîêàæåò MILSS-1 ñ àíàëîãè÷íûì äèçàéíîì äëÿ ìèëäðîíàòà...
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#3
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íó íå çíàþ, ïàöèåíòà
Öèòàòà:
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#4
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Ìåíÿ áîëüøå âñåãî çàèíòåðåñîâàëî
> Ïî ìàòåðèàëàì ACC 2007 congress in New Orleans, Louisiana Êîíãðåññà-òî åùå íå áûëî. Óæå îïóáëèêîâàíû ìàòåðèàëû? |
#5
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[Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ]
[Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ] [Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ] [Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ] [Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ] [Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ] [Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ] |
#6
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Ñîãëàñåí, ýòî áûë àíîíñ, ãäå èçëîæåí îñíîâíîé ðåçóëüòàò; ïîäðîáíîñòè áóäóò ïðåäñòàâëåíû íà ÀÑÑ'07
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Èñêðåííå, Âàäèì Âàëåðüåâè÷. |
#7
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Ôðàçà äíÿ òåêóùåãî...
Cochair of the late-breaking clinical-trial session at which the MERLIN study was presented, Dr Salim Yusuf (McMaster University, Hamilton, ON), agreed that the results supported the use of ranolazine in stable disease. Continuing his campaign against the use of angioplasty in stable coronary disease patients, he quipped: “Ranolazine actually looks as good as PCI in this indication.”
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Èñêðåííå, Âàäèì Âàëåðüåâè÷. |
#8
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Ìåæäó ðàíîëàçèíîì è ïðåäóêòàëîì êàê îêàçûâàåòñÿ íåò íè÷åãî îáùåãî. Ñåé÷àñ êîìïàíèÿ ïðåäñòàâèëà â FDA ìåõàíèç äåéñòâèÿ, êîòîðûé ïîäòâåðæäåí ïðîöåíòîâ íà 98%. Ñ÷èòàâøèéñÿ èçíà÷àëüíî ìåõàíèçì óãíåòåíèÿ áåòòà îêèñëåíèÿ íå ïîäòâåðäèëñÿ. Ïðåïàðàò óãíåòàåò ïîçäíèå íàòðèåâûå êàíàëû, êîòîðûå ñîîòâåñòâåííî ðàáîòàþò â äèàñòîëó è ïðèâîäèò ê ñíèæåíèþ êîíöåíòðàöèè êàëüöèÿ â êëåòêå. Ïîêà ýòî åäèíñòâåííûé ïðåïàðàò íåãåìîäèíàìè÷åñêîãî äåéñòâèÿ ðàáîòàþùèé â äèàñòîëó è èìåþùèé êëèíè÷åñêóþ ýôôåêòèâíîñòü (ëå÷åíèå ñòåíîêàðäè). Ó ìåíÿ åñòü ïðèìåðíî 10 ïàöèåíòîâ, ïîëó÷àþùèõ åãî ñ íåïëîõèìè ðåçóëüòàòàìè.  MERLIN îòìå÷àëñÿ ïðåêðàñíûé ïðîôèëü áåçîïàñíîñòè ïðåïàðàòà, ÷òî äëÿ ìåíÿ î÷åíü âàæíî. Òåïåðü ïîêàçàíèÿ äëÿ íåãî ìîãóò çíà÷èòåëüíî ðàñøèðÿòüñÿ. Ïðåïàðàò íàâåðíÿêà ïîëó÷èò ïîääåðæêó ñî ñòîðîíû VA, êàê áîëåå ýôôåêòèâíûé è äåøåâûé ñïîñîá ëå÷åíèÿ õðîíè÷åñêîé ñòåíîêàðäèè. Ïðè åãî ïðèìåíåíèè îòìå÷àåòñÿ òàêæå ðÿä èíòåðåñíûõ ýôôåêòîâ, î çíà÷èìîñòè êîòîðûõ ãîâîðèòü ïîêà ðàíî (ñíèæåíèå A1c ïðèìåðíî íà 0.7%, ÷òî ïðèìåðíî ñîîòâåòñòâóåò ïî ýôôåêòèâíîñòè áîëüøèíñòâó èìåþùèõñÿ ñðåäñòâ, è â òîì ÷èñòå Byetta, ïðîòèâîàðèòìè÷åñêèé ýôôåêò (áûë ïîêàçàí â MERLIN, õîòÿ è íå èìåë êëèíè÷åñêîé çíà÷èìîñòè ñ òî÷êè çðåíèÿ èñõîäîâ, çà èñêëþ÷åíèåì ãðóïïû ñ TIMI 6-7). Êðîìå ýòîãî èíòåðåñåí ýôôåêò íà ñêåëåòíûå ìûøöû è êîíå÷íî íà ñêîðîñòü ïàññèâíîãî äèàñòîëè÷åñêîãî ðàññëàáëåíèÿ ËÆ (E`) ïî òêàíåâîìó äîïïëåðó. Îäíèì ñëîâîì ïðåïàðàò èíòåðåñíûé è çàñëóæèâàåò äàëüíåéøåãî èçó÷åíèÿ ïðåæäå âñãî áëàãîäàðÿ ñâîåé ýôôåêòèâíîñòè (ïî ëå÷åíèþ ñèìïòîìîâ) è îòëè÷íîé áåçîïàñíîñòè (êàê ïîêàçàë MERLIN).
Åñëè êòî-òî âçüìåòñÿ äåëàòü èññëåäîâàíè ïî ýòîìó ïðåïàðàòó, òî âêëþ÷àòü íóæíî ñàìûõ âûñîêîðèñêîâûõ ïàöèåíòîâ ñ ACS è âîçìîæíî ñ TWA (àëüòåðíàöèÿ Ò âîëíû íà ÝÊÃ). Òàêæå áûëî áû èíòåðåñíî ïðîñëåäèòü ýôôåêò ïðåïàðàòà ó ïàöèåíòîâ ñ èøåìè÷åñêîé êàðäèîìèîïàòèåé, âûñîêèì ðèñêîì âíåçàïíîé ñìåðòè, AICD è ÑÍ III-IV íà ôîíå èìåþùåéñÿ íåèðîãîðìîíàëüíîé òåðàïèè - äàâëåíèå òî îí íå áðîñàåò. Óâåðåí, ÷òî â áëèæàéøèå íåñêîëüêî ëåò ìû åùå óñëûøèì ìíîãî íåãàòèâíîãî è íàäåþñü ÷òî-íèáóäü ïîçèòèâíîå ïî ýòîìó ëåêàðñòâó. Stay tuned... |
#9
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Íàïðàñíî, óâàæàåìûé Àëåêñàíäð, Âû îáèäåòü òðèìåòàçèäèí õîòèòå...
 íåäàâíåé ðàáîòå èç Àíãëèè íè òðèìåòàçèäèí íè ðàíîëàçèí íå óãíåòàþò ôåðìåíò long-chain 3-ketoacyl CoA thiolase, îñíîâíîé â áåòà-îêèñëåíèè æèðíûõ êèñëîò: The antianginal agent trimetazidine does not exert its functional benefit via inhibition of mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2003 Aug 8;93(3):e26-32. [Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ] îòòþëü: Trimetazidine and ranolazine failed to demonstrate inhibitory activity of LC 3-KAT at concentrations 10-fold greater than the concentrations used to demonstrate functional benefit in the working heart model. Ïðåäïîëàãàåìûå ìåõàíèçìû äåéñòâèÿ: Trimetazidine’s mechanism of action remains ill-defined, with (1) direct effects on cardiac sodium current,17 (2) reducing the production of superoxide free radicals,18 (3) synthesis and turnover of complex lipids,19 and (4) binding to a mitochondrial transition pore binding site20 all having been subject to investigation. Âîò ýâèäåíñ, ÷òî è òðèìåòà ñíèæàåò êîíöåíòðàöèþ èîíîâ êàëüöèÿ â êëåòêå ïóòåì âëèÿíèÿ íà èîííûå êàíàëû: Renaud JF. Internal pH, Na+, and Ca2+ regulation by trimetazidine during cardiac cell acidosis. Cardiovasc Drugs Ther. 1988 Mar;1(6):677-86. Kiyosue T, Nakamura S, Arita M. Effects of trimetazidine on action potentials and membrane currents of guinea-pig ventricular myocytes. J Mol Cell Cardiol. 1986 Dec;18(12):1301-11. Coetzee WA, Enous R, Opie LH. Trimetazidine: effects on delayed afterdepolarizations (DADs) and upstroke velocity of the action potential. Cardiovasc Drugs Ther. 1990 Aug;4 Suppl 4:806-7.
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Èñêðåííå, Âàäèì Âàëåðüåâè÷. |