Our study reviewed 16 RCTs comparing POCD testing to routine anticoagulation monitoring care in a hospital or laboratory. Of those, 11 compared the use of POCDs for self-management and self-monitoring with routine anticoagulation monitoring. The latter comparison is the most relevant from the perspective of patient’s convenience of care, and the data in these trials suggest that POCDs result in significantly fewer major thromboembolic events. The odds ratio for major hemorrhage was 0.78, but the 95% confidence interval crossed 1 and therefore must be considered similar between the 2 groups. Insufficient data were provided in these studies to determine whether these differences were related to duration of time that the patient was over-anticoagulated or under-anticoagulated in respective groups. All results were unchanged regardless of the subgroup analysis performed. For all analyses, the comparison of percentage time in range between the POCD group and the control group demonstrated superiority with POCD use.
To test the robustness of the data we performed several subgroup analyses. One included only patients who had been on OAT for ≥ 3 months. We were initially concerned that including patients who were not yet stable on OAT could bias the results against the use of POCDs, given the known interactions with heparin and the difficulty in first achieving INR control.61
Our subgroup analysis showed that the results were essentially the same, regardless of the time that patients were on OAT at baseline. The odds ratios were also similar whether we included all studies (i.e.
, any POCD testing compared to routine INR testing) or just self-test plus self-management comparisons. The outcomes were unchanged regardless of who performed the dosing in the POCD groups. The summary data suggest that POCDs are advantageous. However, in all studies, the frequency of INR monitoring was higher in the POCD group than with routine anticoagulation monitoring. In most cases, the frequency of testing was dictated by the study protocol. It remains unknown whether similar frequent monitoring in routine care would eliminate these differences. It is also unknown whether this rigorous frequency of monitoring using POCDs would persist outside the study setting. It is possible that patients who self-manage may lose regular contact with their physician. The implications of this are unknown, but when assessed against the critical endpoint of death, it does not seem to be a disadvantage. It should be noted that we calculated odds ratios to approximate the relative risk, since the event rates were relatively “rare” (some take this as < 10%), and so the odds ratio approximation of the relative risk is good. The odds ratio will always be further from the neutral point of 1 than the relative risk (i.e.
, it is a less conservative measure), so the results should be interpreted with this in mind.
These findings are subject to certain limitations. First, the study methods were found to be less than ideal. The highest-quality score for any of the publications was 3, no study was double-blinded, and in many studies it was impossible to categorize what happened to the patients who withdrew. In all studies, the withdrawal rates of the POCD testing groups were higher than those of the routine testing groups. In most studies, thromboembolic events were not evaluated in a blinded and objective manner. This introduces the risk that the summary estimates may be biased. However, it is perhaps unreasonable to suggest in studies of this nature that double-blinding would be possible, and therefore in our analysis we categorized studies with a Jadad score of at least 3 as “high quality.”
Second, the criteria for patients’ eligibility for inclusion into the individual clinical trials and the high withdrawal rates are such that it is difficult to determine generalizability. It seems that the inclusion–exclusion criteria for the individual trials resulted in the exclusion of many patients deemed unsuitable for POCD self-testing before randomization, in addition to many such patients declining the invitation to participate. Perhaps more importantly, many patients failed to complete POCD training, and many who completed training subsequently dropped out. An upper bound of 24% of OAT patients could be eligible for self-testing or self-management with POCD.36
Consequently, the results of our meta-analysis may apply only to selected patients.
Third, the INR test frequency was much higher in the POCD testing strategies: INRs were performed approximately weekly versus monthly in the standard group. Furthermore, the POCD group underwent 3 2-hour, small-group education sessions in most studies, whereas no special education was provided to the standard care groups.
The final limitation of these studies is that there is no description of the frequency with which warfarin was withdrawn for surgical procedures or other interventions. As such, we have no way of knowing how many of the thromboembolic or hemorrhagic events could have been related to this phenomenon. It has been clearly documented that hospitalization creates the greatest risk of poor anticoagulation control, and there is a suggestion that the risk of thrombosis and hemorrhage is highest around the time of hospitalization of patients on oral anticoagulant therapy. Although these studies are all randomized, without this information it is difficult to know if there are discrepancies between the POCD group and the routine care group.64
These limitations make it impossible to determine what effects the frequency of monitoring, patient education, the POCD, or the patient selection may have on the outcomes.60
Although information on quality of life and patient satisfaction with the POCDs was collected, we were unable to provide quantitative summary measures of these factors. A qualitative analysis of the data suggest that, in general, patients were at least as satisfied with self-management using a POCD as with receiving care at an anticoagulation clinic, and that some preferred using a POCD. These patients were good candidates for using a POCD, having been self-selected or selected by a health care researcher.
This report is not the first systematic review to compare POCD testing with laboratory testing for the management of patients on OAT. Five systematic reviews have been published, but all have limitations.22, 24, 62, 63
The most recent analysis by Heneghan and colleagues suggests that POCD testing resulted in significantly fewer major hemorrhages, thromboembolic events, and deaths than conventional INR testing.61
The Heneghan analysis involved the examination of 14 studies, included 3 that we considered to be ineligible: one compared POCD testing only with other POCD testing (i.e., inappropriate comparison for their analysis), one did not use POCD test results for OAT management, and the third followed patients for only 8 weeks.21, 27, 43
Our report also included 5 articles that were either excluded or not yet published at the time of Heneghan’s analysis.45, 46, 54, 58
Finally, the summary data used by these authors reported events per patient enrolled and not by length of follow-up, as we did. As such, the rates we report are more accurate and more relevant. With the additional studies and analysis we used, we came to similar conclusions with respect to the rate of all thromboembolic events, deaths and time in therapeutic range. Heneghan did not report separately on the more relevant outcome of major thromboembolic events. Contrary to Heneghan’s study our analysis did not detect a significant difference for the outcome of major hemorrhage.
Our meta-analysis suggests that using POCDs to manage OAT results in significantly fewer thromboembolic events and better INR control than laboratory-based INR testing. Under usual care, warfarin therapy requires regular laboratory monitoring of the INR, coupled with frequent physician–patient contact for dosage adjustment to ensure efficacy and safety.9
The usual-care method can be cumbersome and inconvenient for the patient and the physician. There is also a potential for dosing errors resulting from misinterpretation of information conveyed by the physician or delays in contacting the patient.9
This, plus faster test results, greater convenience and more frequent testing, are plausible reasons for the incremental health benefits observed with POCD use.
Unfortunately, the studies designed to date do not allow a determination of why POCD care is superior. Further randomized controlled trials are needed to determine whether it is patient education or frequency of testing that provides superior outcomes. Widespread adoption of POCD monitoring at this time would be premature.
Forest plot, major thromboembolic events
Forest plot, all thromboembolic events (major and minor)