#1
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Drotrecogin Alfa: ðåàëüíûé ðèñê ïðåâûøàåò ïîëüçó?
 ìàðòîâñêîì íîìåðå Intensive Care Medicine îïóáëèêîâàíû ðåçóëüòàòû äâóõ ïîñòìàðêåòèíãîâûõ îáñåðâàöèîííûõ èññëåäîâàíèé [1, 2], â êîòîðûõ ÷àñòîòà ðàçâèòèÿ ãåìîððàãè÷åñêèõ îñëîæíåíèé ïðè èñïîëüçîâàíèè àêòèâèðîâàííîãî ïðîòåèíà Ñ (ÀÏÑ) áûëà ñóùåñòâåííî âûøå (îêîëî 10%), ÷åì â ïðåäûäóùèõ ðàíäîìèçèðîâàííûõ èññëåäîâàíèÿõ (2.4% â [Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ] è [Ññûëêè äîñòóïíû òîëüêî çàðåãèñòðèðîâàííûì ïîëüçîâàòåëÿì ]).
Ýôôåêòèâíîñòü ÀÏÑ áûëà ïîêàçàíà òîëüêî â åäèíñòâåííîì ðàííåì èññëåäîâàíèè PROWESS (è òîëüêî ó ïîäãðóïïû íàèáîëåå òÿæåëûõ ïàöèåíòîâ ñ APACHE II ≥ 25, êîòîðàÿ, êñòàòè, íå ïðîâîäèëàñü ïðîñïåêòèâíî), íî ýòî íå áûëî ïîäòâåðæäåíî â áîëåå ïîçäíèõ èññëåäîâàíèÿõ (ADDRESS è RESOLVE ó äåòåé). Ó÷èòûâàÿ ýòî, àâòîðû ðåäàêöèîííîãî êîììåíòàðèÿ çàêëþ÷àþò, ÷òî íåîáõîäèìû äàëüíåéøèå ðàíäîìèçèðîâàííûå êîíòðîëèðóåìûå èññëåäîâàíèÿ, ÷òîáû ïîêàçàòü, âîçìîæíî ëè âûÿâèòü òåõ ïàöèåíòîâ, êîòîðûì ïîìîãàåò ÀÏÑ, è íàñêîëüêî ýòà ïîëüçà âåëèêà, ÷òîáû îïðàâäàòü èñïîëüçîâàíèå ÀÏÑ â êëèíè÷åñêîé ïðàêòèêå, ãäå ðèñê êðîâîòå÷åíèé ñóùåñòâåíåí [3]. 1. Kanji S, Perreault MM, Chant C, Williamson D, Burry L. Evaluating the use of Drotrecogin alfa (activated) in adult severe sepsis: a Canadian multicenter observational study. Intensive Care Med. 2007 Mar;33(3):517-23. 2. Bertolini G, Rossi C, Anghileri A, Livigni S, Addis A, Poole D. Use of Drotrecogin alfa (activated) in Italian intensive care units: the results of a nationwide survey. Intensive Care Med. 2007 Mar;33(3):426-34. 3. Eichacker PQ, Natanson C. Increasing evidence that the risks of rhAPC may outweigh its benefits. Intensive Care Med. 2007 Mar;33(3):396-9. |
#2
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Íåñêîëüêî êàðòèíîê èç ðåäàêòîðñêîãî êîìåíòàíðèÿ:
Incidence (percentage of patients) during rhAPC infusion of serious hemorrhage (top panel), a drug related fatal event (middle panel), or termination of treatment due to a drug-related adverse event (lower panel). |
#3
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Effect of rhAPC on the relative risk of death in three controlled trials.
Adult patients in the PROWESS and ADDRESS were stratified based on whether their admission APACHE-II scores were greater or less than 25 |
#4
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The mortality rate in patients treated with rhAPC, stratified by number of organs injured in the PROWESS trial, VHA/UHC survey, and Canadian survey. Despite similar numbers of injured organs, mortality rates were greater in patients treated with rhAPC in both clinical surveys compared with the PROWESS trial. Similar data was not available for analysis from the other controlled trials and clinical surveys.
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#5
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Our understanding of the relative size of the beneficial and adverse effects of rhAPC.
This is based on accumulating evidence from controlled trials and clinical surveys starting in 2001 following completion of the PROWESS trial and licensing of rhAPC for clinical use. Since the original beneficial effects of rhAPC have not been confirmed in subsequent trials, but the incidence of bleeding has persisted in trials and increased in clinical use, it is unclear presently whether the benefit of this agent outweighs its risks. |
#6
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Çàêîíîìåðíûé èòîã, êîãäà ïðåäøåñòâóþùèå èññëåäîâàíèÿ ïðîâîäèëèñü ñî ñìåùåííîé âûáîðêîé.
Âñïîìèíàþ 2001-2002 ãîäû, êîãäà åùå àêòèâíî ôóíêöèîíèðîâàëà e-mail ðàññûëêà CCU - ìíîãèå ñåòîâàëè íà íåêîððåêòíûé íàáîð ïàöèåíòîâ. Íàïîìíþ, ÷òî èññëåäîâàíèå ïî ÀÏÑ áûëî ïðåêðàùåíî äîñðî÷íî, ïî äîñòèæåíèþ íåîáõîäèìîãî óðîâíÿ çíà÷èìîñòè, è êàê ðåçóëüòàò - ïîäàâëÿþùàÿ ÷àñòü ïàöèåíòîâ îêàçàëàñü "óðîñåïòèêàìè" (ïîæèëûå ñ ôîðìàëüíî âûñîêèìè APACHE è îðãàííûìè ïîðàæåíèÿìè) èç øòàòîâ. ×òî æå, ïîñòìàðêåòèíãîâûå òðèàëû âûïðàâëÿþò ñèòóàöèþ. |
#7
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Öèòàòà:
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#8
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Ñîâåðøåííî âåðíî, è ýòî òîæå. Íåñêîëüêî êðóïíûõ öåíòðîâ áûñòðî íàáðàëè áîëüøå ïëàíèðóåìîãî ïàöèåíòîâ, ÷òî ïðèâåëî ê èçìåíåíèþ âûáîðêè. Áûëî áû ñìåøíî óïðåêàòü Lilly, ÷òî ôèðìà ñýêîíîìèëà äåñÿòîê ìèëëèîíîâ.
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