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BACKGROUND: Performance metrics currently focus on the measurement of the application of guideline-indicated medications without considering the appropriate dosing of these drugs.
RESULTS: We studied 39 291 patients from the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) registry with non-ST-segment elevation acute coronary syndromes. We evaluated hospital variability in the composite use of American College of Cardiology/American Heart Association guideline-recommended therapies (adherence) and the proportion of treated patients with the recommended dose of heparins or a glycoprotein IIb/IIIa antagonist (safety), and its association with risk-adjusted in-hospital mortality and bleeding. The rates of composite guideline adherence (median, 85%; 25th, 75th percentile, 82, 88) and antithrombotic dosing safety (median, 53%; 25th, 75th percentile, 45%, 60%) varied among hospitals. Correlation between hospital composite adherence and safety metrics was significant but low (r=0.16, P=0.008). Risk-adjusted in-hospital mortality was inversely related to both guideline adherence (odds ratio-10% increment, 0.80; 95% confidence interval, 0.67-0.94) and safety metrics (odds ratio-10% increment, 0.90; 95% confidence interval, 0.83-0.98). Safety was inversely related to major bleeding (adjusted odds ratio-10% increment, 0.93; 95% confidence interval, 0.87-0.98). In comparison with hospitals with low adherence and safety (≤median performance) metrics, those with mixed performance metrics (high adherence and low safety, low adherence and high safety) had intermediate risk-adjusted mortality rates, whereas hospitals with above-average performance on both metrics (>median performance) had a trend for lowest risk adjusted mortality rates (odds ratio 0.83; 95% confidence interval, 0.68-1.01). Hospitals with high safety had lower bleeding rates in comparison to those with low safety.
CONCLUSIONS: Guideline adherence and dosing safety appeared to provide independent and complementary information on hospital bleeding and mortality, supporting the need for broader metrics of quality that should include measures of both guideline-based care and safety.

Optimal perioperative antiplatelet therapy in patients with coronary stents undergoing surgery still remains poorly defined and a matter of debate among cardiologists, surgeons and anaesthesiologists. Surgery represents one of the most common reasons for premature antiplatelet therapy discontinuation, which is associated with a significant increase in mortality and major adverse cardiac events, in particular stent thrombosis. Clinical practice guidelines provide little support with regard to managing antiplatelet therapy in the perioperative phase in the case of patients with non-deferrable surgical interventions and/or high haemorrhagic risk. Moreover, a standard definition of ischaemic and haemorrhagic risk has never been determined. Finally, recommendations shared by cardiologists, surgeons and anaesthesiologists are lacking. The present consensus document provides practical recommendations on the perioperative management of antiplatelet therapy in patients with coronary stents undergoing surgery. Cardiologists, surgeons and anaesthesiologists have contributed equally to its creation. On the basis of clinical and angiographic data, the individual thrombotic risk has been defined. All surgical interventions have been classified according to their inherent haemorrhagic risk. A consensus on the optimal antiplatelet regimen in the perioperative phase has been reached on the basis of the ischaemic and haemorrhagic risk. Aspirin should be continued perioperatively in the majority of surgical operations, whereas dual antiplatelet therapy should not be withdrawn for surgery in the case of low bleeding risk. In selected patients at high risk for both bleeding and ischaemic events, when oral antiplatelet therapy withdrawal is required, perioperative treatment with short-acting intravenous glycoprotein IIb/IIIa inhibitors (tirofiban or eptifibatide) should be taken into consideration.

There are no evidence-based guidelines for antithrombotic management in people with haemophilia (PWH) presenting with acute coronary syndrome (ACS). The aim of the study was to review the current European Society of Cardiology guidelines, and to consider how best they should be adapted for PWH. Structured communication techniques based on a Delphi-like methodology were used to achieve expert consensus on key aspects of clinical management. The main final statements are as follows: (i) ACS and myocardial revascularization should be managed promptly by a multidisciplinary team that includes a haemophilia expert, (ii) each comprehensive care centre for adult PWH should have a formal clinical referral pathway with a cardiology centre with an emergency unit and 24 h availability of percutaneous coronary intervention (PCI), (iii) PCI should be performed as soon as possible under adequate clotting factor protection, (iv) bare metal stents are preferred to drug-eluting stents, (v) anticoagulants should only be used in PWH after replacement therapy, (vi) minimum trough levels should not fall below 5-15% in PWH on dual antiplatelet therapy, (vii) the duration of dual antiplatelet therapy after ACS and PCI should be limited to a minimum, (viii) the use of GPIIb-IIIa inhibitors is not recommended in PWH other than in exceptional circumstances, (ix) the use of fibrinolysis may be justified in PWH when primary PCI (within 90 min) is not available ideally under adequate clotting factor management. It is hoped that the results of this initiative will help to guide optimal management of ACS in PWH.

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The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment.

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BACKGROUND: Glycoprotein (GP) IIb/IIIa inhibitors can improve outcomes in patients with non-ST-segment elevation acute coronary syndromes but raise the risk of bleeding, particularly if dosed in excess. The impact of GP IIb/IIIa dosing feedback on safety and major bleeding is unknown.
METHODS: Glycoprotein IIb/IIIa dosing feedback was added to the CRUSADE quarterly site reports in the first quarter of 2006. We describe GP IIb/IIIa use and dosing among 25,641 patients with non-ST-segment elevation acute coronary syndromes from the fourth quarter of 2005 to the fourth quarter of 2006.
RESULTS: Eleven thousand eight hundred forty-six patients received GP IIb/IIIa inhibitors, including 4,031 women and 2,609 elderly patients (age, ≥75 years). Among GP IIb/IIIa-treated patients, unadjusted rates of excess GP IIb/IIIa dosing declined overall (26.4%-22.4%, Ptrend=.01) and among the elderly (65.6%-52.1%, Ptrend<.001). After adjustment, declines in excess dosing remained significant only for the elderly, although more than half of GP IIb/IIIa-treated elderly patients continued to receive excess dosing at the end of the study period (64.1%-51.3%, Ptrend<.001). There were concurrent declines in unadjusted major bleeding rates overall (9.6%-8.0%, Ptrend=.02), but declines among women (14.4%-11.5%, Ptrend=.08) and the elderly (17.1%-11.0%, Ptrend=.05) did not reach statistical significance. After adjustment for baseline characteristics and excess dosing, declines in major bleeding rates were no longer significant overall or for any subgroup.
CONCLUSIONS: Within 9 months of initiating a safety feedback program, we observed early decreases in excess GP IIb/IIIa dosing among the elderly but minimal changes in excess dosing overall. Further work is needed to promote safe and effective medication use in vulnerable patients who are most at risk of harm.

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