Drug used for 35 days after THA reduced VTE rate by 80% vs. 12 ...

Tag : enoxaparin sodium

Kakkar presented results of the RECORD2 trial (Regulation ofCoagulation in Major Orthopaedic surgery reducing the Risk of DVTand PE) at the 9th European Federation of National Associations ofOrthopaedics and Traumatology Congress in Nice.
During the same session, Kakkar’s co-author for the RECORD2study, orthopaedist Bengt Eriksson, MD, of Gothenburg, presentedresults of a related trial, RECORD1. That study compared extendedprophylaxis (35±4 days) with rivaroxaban following total hiparthroplasty (THA) to treatment with enoxaparin sodium (Lovenox,Sanofi) for the same extended time period. Extended prophylaxis
Investigators for the double-blind RECORD2 trial involving 2,509patients undergoing elective THA explored the merits of usingextended prophylaxis to prevent patients from developing a VTEpostoperatively. Based on previous studies, they hypothesized thatextended prophylaxis (35±4 days) with the oral anticoagulantrivaroxaban might be more effective than short-term prophylaxis(10-14 days) with enoxaparin in preventing the occurrence ofpostoperative VTE.
Patients were randomized to receive rivaroxaban (10 mg once daily)starting 6 to 8 hours after surgery and continuing for 35 days(±4 days). Their results were compared to those of patientsrandomized to receive a subcutaneous injection of enoxaparin (40 mgonce daily) for 12±2 postoperative days starting the nightbefore surgery. Patients also received placebo tablets orinjections matching the rivaroxaban or enoxaparin doses,respectively.
All patients underwent mandatory bilateral venography the day afterthe last dose of study medication and were followed for anadditional 30-35 days. Primary, secondary endpoints
Both trials used the same endpoints. The primary efficacy endpointwas total VTE, defined as the composite of any DVT, nonfatal PE,and all-cause mortality up to 35±6 days after surgery.Secondary efficacy endpoints were major VTE (composite of proximalDVT, nonfatal PE and VTE-related death), any DVT, and symptomaticVTE.
Bleeding events, both major and non-major, were the safetyendpoints evaluated. In this trial, major bleeding was defined as ableed that was fatal, went into a critical organ or requiredreoperation, and any extra surgical site bleeding associated with adrop in hemoglobin of >2 dl or bleeds requiring a transfusion oftwo or more units of whole blood.
“Compared to short-duration thromboembolic prophylaxis withonly 12 days of enoxaparin followed by placebo, extended durationprophylaxis for up to 35 days was associated with a substantialreduction in the frequency of VTE events, a 79% reduction from 9.3%in the short-duration group to 2.0% in the extended-durationgroup,” Kakkar said.
For secondary endpoints, extended prophylaxis with rivaroxabansignificantly reduced the incidence of major VTE by 88%, from 5.1%in the short-term enoxaparin group to 0.6% in the group thatreceived extended rivaroxaban.
“But most importantly, if one looks at symptomatic eventsoccurring before the time of venography, we can see a similarreduction in the frequency of events, an 80% reduction from a 1.2%symptomatic VTE rate some 35 days after operation reduced to 0.2%,a highly significant difference,” Kakkar said. RECORD1 results
Eriksson presented the results of the RECORD1 trial, which involved4,541 patients.
Total VTE rates (the primary efficacy endpoint) were 3.7% inpatients treated with enoxaparin for 5 weeks, which comparedfavorably with the results from the other study, he said.“This was reduced to 1.1% with rivaroxaban and a significant Pvalue and you can see a relative reduction risk of 70%,”Eriksson said.
The reduction in total VTE was consistent with the significant andsubstantial reduction seen in the incidence of major VTE. “Itwas reduced substantially by the rivaroxaban drug from 2.0% to0.2%,” Eriksson said.
“This is the first study to compare extended prophylaxis for35 days with rivaroxaban vs. enoxaparin. The primary endpoint wasreduced by 70% with rivaroxaban compared to enoxaparin,” hesaid. “This was also consistent with the results seen formajor VTE … and there was no indication of any compromise insafety.”
For more information: Ajay K. Kakkar, PhD, FRCS, can be reached at the ThrombosisResearch Institute, Barts and the London School of Medicine andDentistry, Emmanuel Kaye Building, Manresa Road, London SW3 6LREngland; +44-171-35-8301; e-mail: akkakkar@tri-london.ac.ak . He received honoraria as a member of the Bayer Healthcare AGsteering committee and is a consultant to Bayer Healthcare AG. Bengt Eriksson, MD, can be reached at the Department ofOrthopaedics, Sahlgrenska University Hospital/Östra, SE-41685Gothenburg, Sweden; +46-31-343-4408; e-mail: b.eriksson@orthop.gu.se . He received an honorarium as a member of the RECORD1 and RECORD2Steering Committees and is a consultant to Bayer HealthCare AG.
References: Eriksson B, Borris L, Friedman R, et al. Comparison of oralrivaroxaban and subcutaneous enoxaparin for extendedthromboprophylaxis following total hip replacement: RECORD1. PaperF2. Kakkar AK, Brenner B, Dahl O, et al. An evaluation of the efficacyand safety of extended thromboprophylaxis with oral rivaroxabancompared with short-term subcutaneous enoxaparin following totalhip replacement (RECORD2: a phase III study). Paper F1. Bothpresented at the 9th European Federation of National Associationsof Orthopaedics and Traumatology Congress. May 29-June 1, 2008.Nice.