Anticoagulant After Implantation of Biological Aortic Valve Comparing With Aspirin

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Nikolaj B. Lilleoer, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier:
NCT01452568
First received: September 22, 2009
Last updated: August 28, 2013
Last verified: August 2013

September 22, 2009
August 28, 2013
June 2005
March 2012   (final data collection date for primary outcome measure)
  • Haemorrhagic complications due to anticoagulant therapy and treatment with Aspirin [ Time Frame: 2006 - 2011 (5 years) ] [ Designated as safety issue: Yes ]
  • Thromboembolic complications due to anticoagulant therapy and treatment with Aspirin [ Time Frame: 2006-2011 (5 years) ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT01452568 on ClinicalTrials.gov Archive Site
  • Echocardiographic findings before surgery, before discharge and 3 months after implantation [ Time Frame: 2006 - 2011 (5 years) ] [ Designated as safety issue: No ]
  • Registration of surgical data and postoperative complications [ Time Frame: 2006-2011 (5 years) ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Anticoagulant After Implantation of Biological Aortic Valve Comparing With Aspirin
Can Anticoagulant Therapy After Implantation of Biological Aortic Valve be Replaced by Treatment With Aspirin for Three Months ? A Prospective, Randomised Study

After implantation of a biological stentet aortic valve, it is recommented routine to give the patient anticoagulant therapy for 3 months according to international guidelines (1, 2).

The evidence for treatment with anticoagulant therapy for 3 months is weak we have found out that there exist no randomised investigations.

The recommendations are based on few, older, retrospective statements in small patient populations. Several centers in USA and in Europe have decided not to threat the patients with 3 months anticoagulant therapy, on regular routine, although these centres know that there is no documentation.

An increasing number of investigations predict that 3 months anticoagulant therapy with Warfarin to INR-level 2,0-3,0 is connected with more complications than earlier assumed In a recently published meta-analysis (8), they found higher rate of haemorrhagical com-plications, 7.2 per 100 patients/year and mortality because of bleeding on 1.3 per 100 pa-tients/year. The incidence of haemorrhagic complications was considerable higher in the first 3 months after beginning of anticoagulant therapy compared with the period 3 months up to 1 year.

Bleeding complications are more frequently in elderly patients, this means patients above 80 years of age and in this age it is expected that the anticoagulant therapy is more diffi-cult to control due to lower compliance. This is confirmed in an investigation of anticoagu-lant treatment (7). The only group with increased risk of haemorrhagic complications and increased mortality due to haemorrhagic complications was the group of patients older than 80 years.

The purpose of this investigation is to clarify if treatment with Aspirin 150 mg daily for 3 months can replace the conventional anticoagulant therapy for patients who receive a biological aortic valve prosthesis.

After implantation of a biological stentet aortic valve, it is recommented routine to give the patient anticoagulant therapy for 3 months according to international guidelines (1, 2).

The evidence for treatment with anticoagulant therapy for 3 months is weak and after going through the literature in this area, we have found out that there exist no randomised investigations.

The recommendations are based on few, older, retrospective statements in small patient populations. Heras et al (3) concluded that anticoagulant therapy should be initiated im-mediately after the implantation of the valve, the therapy should last for 3 months, and the effect was most successful in patients with mitral valve implants.

Babell-Ebell (4) published a retrospective investigation on the results after implantation of biological aortic valve in 57 patients without use of conventional anticoagulant therapy or therapy with aspirin. After 3 months the rate of thrombo-embolization was 1,75% corresponding to 3,5 per 100 patients per year. This was compared to a risk of 4,6% for serious haemorrhagic complications due to conventional INR-treatment with INR between 2,5-4,0. On this background they concluded that there was no advantage of oral anticoagulant therapy.

Moinuddeen et al (5) published a retrospective investigation with a comparison between 109 patients treated with Warfarin in 3 months to INR 2,0-3,0 with a group of 76 patients that neither got anticoagulant therapy nor platelet inhibitor therapy. The neurological complications after 3 months were not different between the 2 groups. They also com-pared haemorrhagic complications, echocardiographic findings and survival, but did not find differences. The conclusion was that anticoagulant therapy after implantation of a biological aortic valve was not necessary.

Medtronic has in a seven-year clinical compendium of the Mosaic Aortic and Mosaic Mi-tral prostheses (6) found that only 36,4% of the patients were treated with regular antico-agulant therapy while 37,3% were treated with aspirin. 11,5% was not treated at all, and 14,8% of the patients received other treatments.

On this background several centers in USA and in Europe have decided not to threat the patients with 3 months anticoagulant therapy, on regular routine, although these centres know that there is no documentation.

An increasing number of investigations predict that 3 months anticoagulant therapy with Warfarin to INR-level 2,0-3,0 is connected with more complications than earlier assumed In a recently published meta-analysis (8), they found higher rate of haemorrhagical complications, 7.2 per 100 patients/year and mortality because of bleeding on 1.3 per 100 patients/year. The incidence of haemorrhagic complications was considerable higher in the first 3 months after beginning of anticoagulant therapy compared with the period 3 months up to 1 year.

Bleeding complications are more frequently in elderly patients, this means patients above 80 years of age and in this age it is expected that the anticoagulant therapy is more difficult to control due to lower compliance. This is confirmed in an investigation of anticoagulant treatment (7). The only group with increased risk of haemorrhagic complications and increased mortality due to haemorrhagic complications was the group of patients older than 80 years.

This means, that several investigations indicate that the risk of severe haemorrhagic complications because of 3 months anticoagulant treatment is higher than the risk of thromboembolic complications without anticoagulant treatment

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Thromboembolism
  • Bleeding
  • Drug: Aspirin
    150mg/daily for three months, starting day after surgery
    Other Name: Magnyl, Acetyl salicylic acid
  • Drug: Warfarin
    Warfarin daily dosage to obtain an INR in between 2,0 to 3,0. Started the day after surgery and continued for three months.
    Other Name: marevan
  • Experimental: Aspirin
    Aspirin 150mg daily, starting day 1 after surgery, for three months.
    Intervention: Drug: Aspirin
  • Active Comparator: Warfarin
    Warfarin daily dosage to International normalized ratio(INR) value between 2,0 to 3,0.
    Intervention: Drug: Warfarin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
370
March 2012
March 2012   (final data collection date for primary outcome measure)

Inclusion criteria:

  • Patients with aortic valve disease where there is indication for implantation of a biological stentet aortic valve with or without coronary bypass surgery.
  • Age 60 years Sinus rhythm

Exclusion Criteria:

  • Patients planned for double valve surgery
  • Patients with active endocarditis
  • Patients with atrial fibrillation/flutter
  • Patients in anticoagulation treatment of other reason.
  • Patients with previous cerebrovascular accidents or insults.
  • Patients with TCI
  • Patients with hyper-coagulable conditions, disseminated intervascular coagulation, haemophilia or any other blood coagulapathy or related condition, whereby the blood coagulation process is not radily controllable
  • Patients with pacemaker
  • Any other disease than valve disease that will considerably increase the operative risk and increase the probability that the patient dies within one year after the op-eration, for example because of terminal cancer
  • Patients that is HIV-positive or have active AIDS
  • Patients that are known drug abuser
  • Patients in chronic haemodialysis or other types of dialysis
Both
60 Years and older
Yes
Contact information is only displayed when the study is recruiting subjects
Not Provided
 
NCT01452568
01-080/04, (KF) 01-080/04
No
Nikolaj B. Lilleoer, Rigshospitalet, Denmark
Rigshospitalet, Denmark
Not Provided
Principal Investigator: Peter S Olsen, MD, DMSc Cardiothoracic Surgery, Rigshospitalet, University of Copenhagen
Principal Investigator: Nikolaj B Lilleør Cardiothoracic Surgery, Rigshospitalet, University of Copenhagen
Study Chair: Sulman Rafiq Cardiothoracic Surgery, Rigshospitalet, University of Copenhagen
Rigshospitalet, Denmark
August 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP