Improving Quality Measurement for Anticoagulation

Abstract

TTR and INR variabilities measure different characteristics of anticoagulation control.12 TTR reflects the achievement of appropriate intensity, and not necessarily the stability, of the anticoagulation regimen. Conversely, INR variability measures stability, but not intensity, of anticoagulation. One approach to strengthen our prediction about warfarin adverse events would be to combine these measures. Whether the use of both measures jointly will improve risk stratification for ultimate outcomes of interest, such as thrombotic events, bleeding events, or mortality, requires further exploration.Our study aimed to test whether using both measures will more accurately assign risk of warfarin therapy complications, such as ischemic strokes and major bleeding, among patients with atrial fibrillation. Improving intermediate outcome measures in anticoagulation will allow a more accurate reflection of the true quality of care received by patients.Background-Among patients receiving warfarin, percent time in therapeutic range (TTR) and international normalized ratio (INR) variability predict adverse events individually. Here, we examined what is added to the prediction of adverse events by using both measures together. Methods and Results-We included 40 404 patients anticoagulated for atrial fibrillation, aged 65+, within the Veterans Health Administration. TTR and log-transformed INR variability were calculated for each patient. Our study outcomes were ischemic stroke and major bleeding, defined using International Classification of Diseases-9 codes. We estimated the hazard ratios (HRs) for the study outcomes using 3 nested Cox regression models, including (1) TTR or log INR variability separately; (2) TTR and log INR variability together; and (3) both predictors together plus an interaction term. We divided TTR into 3 categories (high, >70%; moderate, 50% to 70%; low, <50%) and log INR variability into 2 categories (stable and unstable). The reference groups high TTR and stable anticoagulation each denote good control. Higher log INR variability (ie, unstable control) predicted ischemic stroke (HR=1.45, P<0.001) and major bleeding (HR=1.57, P<0.001) independently, regardless of TTR levels. Our model with interaction terms showed that High log INR variability predicted a significantly higher risk for ischemic stroke and major bleeding compared with low log INR variability, at moderate TTR levels (HR= 1.27 and HR=1.29, respectively) and at high TTR levels (HR=1.55 and HR=1.56, respectively), but not at low TTR levels. Conclusions-Unstable anticoagulation predicts warfarin adverse effects independent of TTR. Moreover, knowledge about anticoagulation stability further stratifies the risk for adverse events at given levels of TTR. (Circ Cardiovasc Qual Outcomes. 2014;7:664-669.)Key Words: anticoagulants ◼ healthcare quality ◼ international normalized ratio ◼ outcome ◼ warfarin

Comparison of the Abilities of Summary Measures of International Normalized Ratio Control to Predict Clinically Relevant Bleeding

“…10 In that study, as in ours, the 2 measures together provided additional, complementary information, as evidenced by better prediction than either one alone. 10 Still another study by Lind et al 17 found that INR variability was a much stronger predictor of outcomes than TTR. In that study, the predictive ability of TTR was so slight that it did not meaningfully add to that of INR variability when combined in one model.…”

“…4 Warfarin control is best understood as an intermediate outcome of care, in that control has been correlated with definitive outcomes, such as hemorrhage and stroke. [5][6][7][8][9][10][11] Intermediate outcomes of care are useful for quality assurance and research efforts because they can be assessed with smaller samples and briefer follow-up than are often needed to confidently assess rates of definitive outcomes. 12,13 Using the most predictive intermediate outcome will ensure that efforts to improve performance on intermediate outcomes can achieve the maximum possible benefit for patients.…”

“…12,13 Presently, the most commonly used summary measure of international normalized ratio (INR) control for research and quality assurance is percent time in therapeutic range (TTR). [5][6][7][8][9][10][11]14 In particular, we are referring to individual TTR, which is more tightly linked to outcomes than center-level TTR, as we have shown. 15 In addition to TTR, at least 1 other measure of control has been linked to definitive outcomes: INR variability.…”

“…15 In addition to TTR, at least 1 other measure of control has been linked to definitive outcomes: INR variability. 16,17 Studies on which of these 2 measures is more predictive of complications are divided with one study suggesting that INR variability is more predictive of complications, 18 another suggesting that TTR is more predictive, 10 and still another suggesting that they are similarly predictive. 6 Nevertheless, studies that have examined predictive ability have found that TTR and INR variability provide complementary information, such that their use together predicts complication events better than either one alone.…”

“…6 Nevertheless, studies that have examined predictive ability have found that TTR and INR variability provide complementary information, such that their use together predicts complication events better than either one alone. 6,10 There are other measures to summarize INR control that have not been formally compared with the measures in current use. Some of these measures, such as the proportion of INR values in range, have the advantage of being simpler to compute and understand; however, no study to our knowledge has evaluated whether simpler measures are as strongly associated with outcomes as TTR or other more commonly used measures.…”