AIMS: To correlate inhibition of platelet aggregation (IPA) with bleeding events assessed by TIMI, GUSTO, and BleedScore scales in a large cohort of patients with coronary artery disease (CAD) and ischaemic stroke (IS) treated with chronic low-dose aspirin plus clopidogrel. Data from recent trials and registries suggest a link between increased risk of bleeding and cardiovascular mortality. However, the potential association of bleeding risk and IPA is not established. It may play a critical role for the safety of more aggressive platelet inhibition or/and individual tailoring of antiplatelet strategies. METHODS AND RESULTS: Secondary post hoc analyses of 5 microM ADP-induced IPA and bleeding complications assessed by TIMI, GUSTO, and BleedScore scales in a combined data set consisting of patients with documented CAD (n = 246) and previous IS (n = 117). Demographic characteristics differ substantially depending on the underlying vascular disease; however, IPA and bleeding risks were similar between CAD and IS. All three bleeding scales adequately captured serious haemorrhagic events, where the TIMI scale was the most exclusive, whereas BleedScore was the most inclusive. Over half of all patients experienced superficial event(s), most commonly occurring during two to three distinct bleeding episodes. There was no correlation between IPA and duration of antiplatelet therapy. Inhibition of platelet aggregation >50% strongly correlates with minor (r(2) = 0.58, P < 0.001; c-statistic = 0.92), but not severe (r(2) = 0.11, P = 0.038; c-statistic = 0.57), bleeding events. CONCLUSION: Chronic oral combination antiplatelet regimens are associated with a very high (56.5-60.7%) prevalence of superficial bleeding episodes, which are grossly underestimated in trials and registries. The role of such frequent mild complications for the overall benefit of antiplatelet therapy is entirely unknown, as is their effect on compliance. Although IPA is well suited for defining the risk of minor complications, prediction of more severe bleeding events may be challenging.

BACKGROUND: Patients receiving oral anticoagulation should be tested often enough to optimize control, but excessive testing increases burden and cost. We examined the relationship between the follow-up interval after an in-range (2.0-3.0) INR and anticoagulation control. METHODS: We studied 104,451 patients receiving anticoagulation from 100 anticoagulation clinics in the Veterans Health Administration (VA). Most patients (98,877) recorded at least one in-range INR followed by another INR within 56 days. For each such patient, we selected the last in-range INR and characterized the interval between this "index value" and the next INR. The independent variable was site mean follow-up interval after an in-range INR. The dependent variable was site mean risk-adjusted percent time in therapeutic range (TTR). RESULTS: Site mean interval varied from 25-38 days. As the mean site follow-up interval became longer, risk-adjusted TTR was worse (-0.51% per day, p = 0.004). This relationship persisted when the index value was the first consecutive in-range INR (-0.63%, p < 0.001), or the second (-0.58%, p < 0.001), but not the third or greater (-0.12%, p = 0.46). CONCLUSIONS: Sites varied widely regarding follow-up intervals after in-range INR (25-38 days). Shorter intervals were generally associated with better anticoagulation control, but after a third consecutive in-range value, this relationship was greatly attenuated and no longer statistically significant. Our results suggest that a maximum interval of 28 days after the first or second in-range value and consideration of a longer interval after the third or greater consecutive in-range value may be appropriate.