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
  Purpose

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.


Condition Intervention Phase
Thromboembolism
Bleeding
Drug: Aspirin
Drug: Warfarin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Can Anticoagulant Therapy After Implantation of Biological Aortic Valve be Replaced by Treatment With Aspirin for Three Months ? A Prospective, Randomised Study

Resource links provided by NLM:


Further study details as provided by Rigshospitalet, Denmark:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 370
Study Start Date: June 2005
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aspirin
Aspirin 150mg daily, starting day 1 after surgery, for three months.
Drug: Aspirin
150mg/daily for three months, starting day after surgery
Other Name: Magnyl, Acetyl salicylic acid
Active Comparator: Warfarin
Warfarin daily dosage to International normalized ratio(INR) value between 2,0 to 3,0.
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

Detailed Description:

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

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01452568

Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
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
  More Information

No publications provided

Responsible Party: Nikolaj B. Lilleoer, Clinical Project Coordinator, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT01452568     History of Changes
Other Study ID Numbers: 01-080/04, (KF) 01-080/04
Study First Received: September 22, 2009
Last Updated: August 28, 2013
Health Authority: Denmark: Ethics Committee

Keywords provided by Rigshospitalet, Denmark:
Thromboembolic complications
Bleeding complications
Haemorrhagic complications
Anticoagulant therapy
Aspirin
biological Aorta Valve

Additional relevant MeSH terms:
Hemorrhage
Thromboembolism
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Aspirin
Salicylates
Warfarin
Anticoagulants
Salicylic Acid
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014