[Switching from acenocoumarol to phenprocoumon: step in personalised anticoagulation?] / Overstappen van acenocoumarol naar fenprocoumon.

Acenocoumarol and phenprocoumon are vitamin K antagonists (VKA) with average half-lives of 11 hours and 160 hours, respectively. They are used to treat and prevent thrombosis in mechanical cardiac valve replacement, atrial fibrillation and venous thromboembolism. There are historical regional differences in preferred VKA in the Netherlands. Safe and effective treatment requires the international normalized ratios (INRs) to be in the therapeutic range, and stable. Theoretically, the longer-acting phenprocoumon would yield a higher time in therapeutic range (TTR) and lower INR variability. In practice, switching from acenocoumarol to phenprocoumon eventually improves INR variability and in some patients TTR as well. However, during the preceding transition period, INRs are more often volatile and supratherapeutic. Furthermore, switching to an alternative VKA could weaken integrated care, as other healthcare providers are less experienced with it. Healthcare providers must coordinate an intended switch with the anticoagulation clinic.

Is the time in therapeutic range on coumarins predicted by previous time in therapeutic range?

BACKGROUND: The benefit of vitamin K antagonists depends on the time within the therapeutic range (TTR). A patient's previous TTR could be a factor in the decision to change the anticoagulation regimen. However, the predictive value of a previous TTR for a future TTR is not well established, nor is it clear which TTR should prompt action. OBJECTIVES: To investigate the predictive performance of a TTR and identify a threshold below which no recovery of TTR should be expected. PATIENTS/METHODS: From 18 031 patients who used acenocoumarol in a first-line anticoagulation clinic, a TTR was calculated over multiple periods of 90, 180, and 365 days each. We assessed the correlation between baseline and later TTR and the separation between groups by quintile of baseline TTR. We describe the proportion of patients who obtain a TTR≥ 70% conditional on baseline TTR. RESULTS: The correlation between baseline and later TTR was 0.25 (95% confidence interval [CI], 0.24-0.26), 0.27 (95% CI, 0.26-0.28) and 0.34 (95% CI, 0.32-0.35) for analyses over 90, 180, and 365 days. Corresponding c statistics for discrimination by baseline group were 0.60, 0.61, and 0.63. The probability to obtain a TTR ≥70% increased with baseline TTR: from 42% with a baseline TTR of 50%-65% when TTR was 100% (TTR calculated over 180 days). CONCLUSIONS: We conclude that a current TTR hardly predicts a future TTR. Physicians and patients should deliberate together which probabilities to accept, take measures to improve TTR, and consider potential alternatives.

Effect of switching from acenocoumarol to phenprocoumon on time in therapeutic range and INR variability: A cohort study.

BACKGROUND: Treatment with vitamin K antagonists (VKA) requires a high proportion of time in the therapeutic range (TTR) and a low international normalised ratio (INR) variability to be maximally safe and effective. Switching from short-acting acenocoumarol to long-acting phenprocoumon could improve VKA control. AIMS: We assessed whether switching from acenocoumarol to phenprocoumon improves the time in the therapeutic range (TTR) and INR variability. METHODS AND RESULTS: In a retrospective cohort with data on 236,957 patients-years of VKA management from two first-line anticoagulation clinics in the Netherlands, we identified 124 patients in target range 2-3, 269 patients in target range 2-3.5 and 98 patients in target range 2.5-3.5 who switched from acenocoumarol to phenprocoumon. They were matched in a 1:2 ratio to non-switching controls using propensity score matching. Over the first 180 days after a switch, switchers' TTR declined 5 (95% CI 1 to 10), 10 (95% CI 7 to 13) and 5 (95% CI 0 to 11) percentage points relative to non-switchers, in target ranges 2-3, 2-3.5 and 2.5-3.5. Anticoagulation was more often supra-therapeutic in switchers, and switchers had a higher INR variability. In the following 180 days, TTR in switchers became 1 (95% CI -4 to 6), 4 (95% CI 0 to 7) and 6 (95% CI 1 to 12) percentage points better than in non-switchers. Switchers' INRs were much more stable than non-switchers'. CONCLUSION: Eventually, a switch from acenocoumarol to phenprocoumon leads to a higher TTR and a lower INR variability. However, this is preceded by a transition period with opposite effects. An improved conversion algorithm could possibly shorten the transition period. Until then, physicians and patients should decide whether switching is worth the increased risk during the transition phase.

Quality of life after switching from well-controlled vitamin K antagonist to direct oral anticoagulant: Little to GAInN.

BACKGROUND: Direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) prevent thromboembolism in atrial fibrillation (AF). DOAC have a fixed dosing regimen and obviate INR monitoring. Therefore, DOAC presumably affect quality of life (QoL) less than VKA. However, some VKA users appreciate the monitoring. A high time in the therapeutic range (TTR) leads to a lower impact on QoL. We assessed the influence of switching from well-controlled VKA to a DOAC on QoL. METHODS: In the GAInN study, 241 patients with AF, a TTR ≥ 70%, and neither bleeding nor thrombosis while on VKA were randomised to switching to DOAC (n = 121) or continuing VKA (n = 120). Health-related (SF-36) and anticoagulation-related QoL (PACT-Q) was assessed at baseline and after six and twelve months of follow-up. RESULTS AND CONCLUSION: SF-36 development did not differ between groups. After one year, average PACT-Q Convenience improvement was 2.5 (0.3-4.7) higher on DOAC. DOAC users were 6percentage points (95%CI -4-16) more likely to improve >5 points on Convenience; 22 pp. (95%CI 1-43) in patients who scored <95/100 at baseline. The probability to meaningfully improve on PACT-Q Satisfaction was 12 pp. (95%CI 0-25) higher on DOAC. However, 5 (4.1%) and 4 (3.3%) DOAC users resumed VKA because of side-effects and patient preference. Switching from well-controlled VKA to DOAC for AF leads to a higher probability of improved PACT-Q convenience and satisfaction, but also to a higher risk of side-effects. Arguably only patients who are not satisfied with VKA should switch, because they have more to gain by switching.

An easy-to-use tool to flag patients at risk of poor INR control: A streak of subtherapeutic INRs.

INTRODUCTION: Vitamin K antagonist therapy is safest and most effective with a high time within the therapeutic range (TTR). The TTR is difficult to calculate in the consultation room, therefore physicians need an easier-to-use tool to predict poor VKA control. We explored the prognostic value of subtherapeutic INRs on future TTR in two settings: MATERIALS AND METHODS: Retrospective cohort of 17,711 patients from a dedicated thrombosis service, using acenocoumarol (target range 2.0-3.0), with a "streak" defined as four consecutive INRs <2.0. RESULTS AND CONCLUSIONS: Clinical review setting: The occurrence of any streak in the last 180 days or 1 year increased the odds of a TTR <45%: ORs 2.84 (95% CI 2.41-3.34) and 3.25 (95% CI 2.72-3.87), respectively. Day-to-day INR management setting: A current streak increases the odds of poor TTR over the next 90 days 3.58 (95% CI 2.64-4.87) fold. We conclude that a streak of four consecutive subtherapeutic INRs can aid physicians in flagging at-risk patients.

Clinical usefulness of the SAMe-TT2R2 score: A systematic review and simulation meta-analysis.

BACKGROUND: Vitamin K antagonist (VKA) therapy is safer and more effective when patients have a high time within the therapeutic range and low international normalised ratio variability. The SAMe-TT2R2 score aims to identify those at risk for poor VKA control. OBJECTIVES: To evaluate the predictive value and clinical usefulness of the SAMe-TT2R2 score to identify those at risk for poor VKA control. METHODS: We performed a systematic review in MEDLINE and Embase for original research papers assessing the SAMe-TT2R2's relation to poor TTR. We performed a meta-analysis where scores ≥ 2 and ≥ 3 predicting TTR < 70%. When studies evaluated other cutoffs for TTR or SAMe-TT2R2, they were harmonised by multiple simulations with patient characteristics from the individual studies, if the data were available. RESULTS: 16 studies were identified and used in the meta-analysis: 4 and 2 times directly, 8 and 8 times harmonised for scores ≥ 2 and ≥ 3, respectively (not all studies provided information about both cutoffs). The sensitivities and specificities were too heterogeneous to pool. The positive likelihood ratios were 1.25 (1.14-1.38) for a score ≥ 2, and 1.24 (1.09-1.40) for a score ≥ 3; the negative ones were 0.87 (0.82-0.93) and 0.96 (0.91-1.02), respectively. This shows that the post-test probabilities hardly differ from the prior probability (prevalence). CONCLUSION: The SAMe-TT2R2 score does predict low TTR, but the effect is small. Its effect on individual patients is too limited to be clinically useful.