FDA Requests Marketing Suspension of Trasylol

[audovichenko]

По-моему, где-то уже обсуждался трасилол после кардиохирургических операций. Темку не нашла, а инфа интересная...

FDA Requests Marketing Suspension of Trasylol
BETHESDA, MD -- November 5, 2007 -- The U.S. Food and Drug Administration (FDA) today announced that, at the agency's request, Bayer Pharmaceuticals Corp. has agreed to a marketing suspension of Trasylol, a drug used to control bleeding during heart surgery, pending detailed review of preliminary results from a Canadian study that suggested an increased risk for death.

FDA requested the suspension in the interest of patient safety based on the serious nature of the outcomes suggested in the preliminary data. FDA has not yet received full study data but expects to act quickly with Bayer, the study's researchers at the Ottawa Health Research Institute, and other regulatory agencies to undertake a thorough analysis of data to better understand the risks and benefits of Trasylol.

There are not many treatment options for patients at risk for excessive bleeding during cardiac surgery. Thus, FDA is working with Bayer to phase Trasylol out of the marketplace in a way that does not cause shortages of other drugs used for this purpose.

Until FDA can review the data from the terminated study it is not possible to determine and identify a population of patients undergoing cardiac surgery for which the benefits of Trasylol outweigh the risks. Understanding that individual doctors may identify specific cases where benefit outweighs risk, FDA is committed to exploring ways for those doctors to have continued, limited access to Trasylol.

Two weeks ago, FDA was notified that researchers with the Ottawa Health Institute stopped a study on Trasylol because the drug appeared to increase the risk for death compared to two other antifibrinolytic drugs used in the study. Antifibrinolytic drugs help slow the breakdown of blood clots and subsequent excessive bleeding. The preliminary data from this terminated study also suggested that fewer patients receiving the drug experienced serious bleeding events.

On Oct. 26, FDA issued an Early Communication about an Ongoing Safety Review of Trasylol in response to the Canadian study's termination. In 2006, FDA revised the labeling for Trasylol to strengthen its safety warning and limit its approved usage to patients at an increased risk for blood loss and blood transfusion during coronary bypass graft surgery.


SOURCE: U.S. Food and Drug Administration

[rsp]

Сообщение от audovichenko

По-моему, где-то уже обсуждался трасилол после кардиохирургических операций. Темку не нашла, а инфа интересная...

было-было, в топике акш.факты.ваш взгляд. Действительно инфа интересная. Пока создается впечатление (не исключаю что ложное), что трасилол в целом не такой уж полезный препарат.
В продолжение этой же темы, я не удержался и без особого фанатизма поискал данные по другому дорогостоящему чудо препарату НовоСевен, который также используется для предотвращения послеоперационных кровотечений. Вот выдержка из ревью по этому препарату:

One other very important question that remains to be answered is the safety of this agent in patients who have severe intractable bleeding status post coronary artery bypass grafting. The risk for thrombosis with rFVIIa in these patients is not know but theoretically may be increased due to circulating tissue factor and atherosclerotic plaque in other coronary arteries. At this time, there are no randomized controlled trials examining the efficacy and safety versus standard
treatments for excessive bleeding associated with cardiac surgery.

Recommendations for the Off-Label Use of rFVIIa (Novoseven®)

Severe, intractable bleeding associated with cardiac surgery.

(3C-no randomized controlled trials evaluating safety and benefit). Standard/conventional treatments for bleeding cessation should be exhausted prior to consideration/utilization of this therapy.

a. There are very limited data in using rFVIIa as a rescue intervention in patients having CABG surgery.

The risk for graft thrombosis is not known but may be increased. Additionally, the thromboembolic

risk in these patients with atherosclerotic plaques in other coronary arteries is not known but may be increased.

[Gilarov]

А апротинин и трасилол - одно и тоже?

[Igor73]

The Effect of Aprotinin on Outcome after Coronary-Artery Bypass Grafting

Andrew D. Shaw
[Ссылки доступны только зарегистрированным пользователям ]
Background Aprotinin has recently been associated with adverse outcomes in patients undergoing cardiac surgery. We reviewed our experience with this agent in patients undergoing cardiac surgery at Duke University Medical Center.
Methods We retrieved data on 10,275 consecutive patients undergoing surgical coronary revascularization at Duke between January 1, 1996, and December 31, 2005. We fit data to a logistic-regression model predicting each patient's likelihood of receiving aprotinin on the basis of preoperative characteristics and to models predicting long-term survival (up to 10 years) and decline in renal function, as measured by increases in serum creatinine levels.
Results A total of 1343 patients (13.2%) received aprotinin, 6776 patients (66.8%) received aminocaproic acid, and 2029 patients (20.0%) received no antifibrinolytic therapy. All patients underwent coronary-artery bypass grafting, and 1181 patients (11.5%) underwent combined coronary-artery bypass grafting and valve surgery. In the risk-adjusted model, survival was worse among patients treated with aprotinin, with a main-effects hazard ratio for death of 1.32 (95% confidence interval [CI], 1.12 to 1.55) for the comparison with patients receiving no antifibrinolytic therapy (P=0.003) and 1.27 (95% CI, 1.10 to 1.46) for the comparison with patients receiving aminocaproic acid (P=0.004). As compared with the use of aminocaproic acid or no antifibrinolytic agent, aprotinin use was also associated with a larger risk-adjusted increase in the serum creatinine level (P<0.001) but not with a greater risk-adjusted incidence of dialysis (P=0.56).
Conclusions Patients who received aprotinin had a higher mortality rate and larger increases in serum creatinine levels than those who received aminocaproic acid or no antifibrinolytic agent.

[Igor73]

Aprotinin during Coronary-Artery Bypass Grafting and Risk of Death

Sebastian Schneeweiss
[Ссылки доступны только зарегистрированным пользователям ]
Background Aprotinin (Trasylol) is used to mitigate bleeding during coronary-artery bypass grafting (CABG). Accumulating evidence suggests that this practice increases mortality.
Methods Using electronic administrative records of the Premier Perspective Comparative Database, we studied hospitalized patients with operating-room charges for the use of aprotinin (33,517 patients) or aminocaproic acid (44,682 patients) on the day CABG was performed. We tabulated the numbers of patients with a hospital-discharge status of death and performed three types of analyses: a multivariable logistic-regression analysis (primary analysis); propensity-score matching in the highly selected subcohort of patients who received full amounts of the study drug, who underwent CABG by surgeons who performed 50 or more CABG surgeries during the study period, and for whom information on 10 additional covariates was available because the surgery occurred on hospital day 3 or later; and an instrumental-variable analysis of data from patients whose surgeons showed a strong preference for one of the two study drugs.
Results In all, 1512 of the 33,517 aprotinin recipients (4.5%) and 1101 of the 44,682 aminocaproic acid recipients (2.5%) died. After adjustment for 41 characteristics of patients and hospitals, the estimated risk of death was 64% higher in the aprotinin group than in the aminocaproic acid group (relative risk, 1.64; 95% confidence interval [CI], 1.50 to 1.78). In the first 7 days after surgery, the adjusted relative risk of in-hospital death in the aprotinin group was 1.78 (95% CI, 1.56 to 2.02). The relative risk in a propensity-score–matched analysis was 1.32 (95% CI, 1.08 to 1.63). In the instrumental-variable analysis, the use of aprotinin was found to be associated with an excess risk of death of 1.59 per 100 patients (95% CI, 0.14 to 3.04). Postoperative revascularization and dialysis were more frequent among recipients of aprotinin than among recipients of aminocaproic acid.
Conclusions Patients who received aprotinin alone on the day of CABG surgery had a higher mortality than patients who received aminocaproic acid alone. Characteristics of neither the patients nor the surgeons explain the difference, which persisted through several approaches to control confounding.