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Frequency of adverse events in patients with poor anticoagulation: a meta-analysis
Natalie Oake1, Dean A Fergusson, Alan J Forster
1Department of Medicine, University of Ottawa, Ottawa, Ont. noake@ohri.ca
Insights
Optimizing anticoagulant therapy by keeping international normalized ratios (INRs) within the therapeutic range could prevent nearly half of all related adverse events, including hemorrhages and thromboemboli.
Area of Science:
- Pharmacology
- Clinical Medicine
- Medical Informatics
Background:
- Long-term oral anticoagulant therapy frequently results in international normalized ratios (INRs) outside the target therapeutic range.
- Suboptimal anticoagulation control is associated with increased rates of hemorrhagic and thromboembolic events.
- Understanding the proportion of adverse events occurring outside the therapeutic INR range is crucial for assessing the impact of improved anticoagulation management.
Purpose of the Study:
- To determine the proportion of anticoagulant-associated hemorrhagic and thromboembolic events that occur when INRs fall outside the established therapeutic range.
- To quantify the potential benefit of enhanced anticoagulation control on patient safety.
Main Methods:
- A meta-analysis was conducted on studies reporting hemorrhagic and thromboembolic events in patients on oral anticoagulants.
- Studies were identified through MEDLINE and EMBASE databases (1966-2006).
- Inclusion criteria required a therapeutic INR range of 1.8-2 to 3-3.5 and recorded INR at the time of the event.
Main Results:
- The analysis included 45 studies with a total of 71,065 patients.
- Approximately 44% of hemorrhages and 48% of thromboemboli occurred with INRs outside the therapeutic range.
- Events occurring outside the therapeutic range were more frequent in studies with shorter mean follow-up durations (< 1 year).
Conclusions:
- A significant proportion of adverse events related to oral anticoagulation occur when INR levels are suboptimal.
- Improving anticoagulation control, by maintaining INRs within the therapeutic range, has the potential to reduce nearly half of all associated adverse events.
- Enhanced anticoagulation management strategies could significantly improve patient outcomes and reduce healthcare burden.
Background:
Patients taking anticoagulants orally over the long term have international normalized ratios (INRs) outside the individual therapeutic range more than one-third of the time. Improved anticoagulation control will reduce hemorrhagic and thromboembolic event rates. To gauge the potential effect of improved anticoagulation control, we undertook to determine the proportion of anticoagulant-associated events that occur when INRs are outside the therapeutic range.
Methods:
We conducted a meta-analysis of all studies that assigned hemorrhagic and thromboembolic events in patients taking anticoagulants to discrete INR ranges. We identified studies using the MEDLINE (1966-2006) and EMBASE (1980-2006) databases. We included studies reported in English if the majority of patients taking oral anticoagulants had an INR range with a lower limit between 1.8 and 2 and an upper limit between 3 and 3.5, and their INR at the time of the hemorrhagic or thromboembolic event was recorded.
Results:
The final analysis included results from 45 studies (23 that reported both hemorrhages and thromboemboli; 14 that reported hemorrhages only; and 8, thromboemboli only) involving a median of 208 patients (limits of interquartile range [25th-75th percentile] 131-523 subjects; total n = 71 065). Of these studies, 64% were conducted at community practices; the remainder, at anticoagulation clinics. About 69% of the studies were classed as having moderate or high quality. Overall, 44% (95% confidence interval [CI] 39%-49%) of hemorrhages occurred when INRs were above the therapeutic range, and 48% (95% CI 41%-55%) of thromboemboli took place when below it. The mean proportion of events that occurred while the patient's INR was outside the therapeutic range was greater for studies with a short mean follow-up (< 1 yr). Between-study heterogeneity was significant (p < 0.001).
Interpretation:
Improved anticoagulation control could decrease the likelihood of almost half of all anticoagulant-associated adverse events.
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