Quality of care after acute coronary syndromes in a prospective cohort with reasons for non-prescription of recommended medications

BACKGROUND Adherence to guidelines is associated with improved outcomes of patients with acute coronary syndrome (ACS). Clinical registries developed to assess quality of care at discharge often do not collect the reasons for non-prescription for proven efficacious preventive medication in Continental Europe. In a prospective cohort of patients hospitalized for an ACS, we aimed at measuring the rate of recommended treatment at discharge, using pre-specified quality indicators recommended in cardiologic guidelines and including systematic collection of reasons for non-prescription for preventive medications. METHODS In a prospective cohort with 1260 patients hospitalized for ACS, we measured the rate of recommended treatment at discharge in 4 academic centers in Switzerland. Performance measures for medication at discharge were pre-specified according to guidelines, systematically collected for all patients and included in a centralized database. RESULTS Six hundred and eighty eight patients(54.6%) were discharged with a main diagnosis of STEMI, 491(39%) of NSTEMI and 81(6.4%) of unstable angina. Mean age was 64 years and 21.3% were women. 94.6% were prescribed angiotensin converting enzyme inhibitors/angiotensin II receptor blockers at discharge when only considering raw prescription rates, but increased to 99.5% when including reasons non-prescription. For statins, rates increased from 98% to 98.6% when including reasons for non-prescription and for beta-blockers, from 82% to 93%. For aspirin, rates further increased from 99.4% to 100% and from to 99.8% to 100% for P2Y12 inhibitors. CONCLUSIONS We found a very high adherence to ACS guidelines for drug prescriptions at discharge when including reasons for non-prescription to drug therapy. For beta-blockers, prescription rates were suboptimal, even after taking into account reason for non-prescription. In an era of improving quality of care to achieve 100% prescription rates at discharge unless contra-indicated, pre-specification of reasons for non-prescription for cardiovascular preventive medication permits to identify remaining gaps in quality of care at discharge.

Management of ST-elevation myocardial infarction according to European and American guidelines.

AIMS To highlight differences between the most recent guidelines of the European Society of Cardiology (ESC) and the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) on the management of ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS ESC 2012 and ACCF/AHA 2013 guidelines on the management of STEMI were systematically reviewed for consistency. Recommendations were matched, directly compared in terms of class of recommendation and level of evidence, and classified as "identical", "overlapping", or "different". Out of 32 recommendations compared, 26 recommendations (81%) were classified as identical or overlapping, and six recommendations (19%) were classified as different. Most diverging recommendations were related to minor differences in class of recommendation between the two documents. This applies to recommendations for reperfusion therapy >12 hours after symptom onset, immediate transfer of all patients after fibrinolytic therapy, rescue PCI for patients with failed fibrinolysis, and intra-aortic balloon pump use in patients with cardiogenic shock. More substantial differences were observed with respect to the type of P2Y12 inhibitor and duration of dual antiplatelet therapy. CONCLUSIONS The majority of recommendations for the management of STEMI according to ESC and ACCF/AHA guidelines were identical or overlapping. Differences were explained by gaps in available evidence, in which case expert consensus differed between European and American guidelines due to divergence in interpretation, perception, and culture of medical practice. Systematic comparisons of European and American guidelines are valuable and indicate that interpretation of available evidence leads to agreement in the vast majority of topics. The latter is indirect support for the process of review and guideline preparation on both sides of the Atlantic.

Antiplatelet therapy for secondary prevention of coronary artery disease.

The choice and duration of antiplatelet therapy for secondary prevention of coronary artery disease (CAD) is determined by the clinical context and treatment strategy. Oral antiplatelet agents for secondary prevention include the cyclo-oxygenase-1 inhibitor aspirin, and the ADP dependent P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor. Aspirin constitutes the cornerstone in secondary prevention of CAD and is complemented by clopidogrel in patients with stable CAD undergoing percutaneous coronary intervention. Among patients with acute coronary syndrome, prasugrel and ticagrelor improve net clinical outcome by reducing ischaemic adverse events at the expense of an increased risk of bleeding as compared with clopidogrel. Prasugrel appears particularly effective among patients with ST elevation myocardial infarction to reduce the risk of stent thrombosis compared with clopidogrel, and offered a greater net clinical benefit among patients with diabetes compared with patients without diabetes. Ticagrelor is associated with reduced mortality without increasing the rate of coronary artery bypass graft (CABG)-related bleeding as compared with clopidogrel. Dual antiplatelet therapy should be continued for a minimum of 1 year among patients with acute coronary syndrome irrespective of stent type; among patients with stable CAD treated with new generation drug-eluting stents, available data suggest no benefit to prolong antiplatelet treatment beyond 6 months.

Echicetin coated polystyrene beads: a novel tool to investigate GPIb-specific platelet activation and aggregation.

von Willebrand factor/ristocetin (vWF/R) induces GPIb-dependent platelet agglutination and activation of αIIbβ3 integrin, which also binds vWF. These conditions make it difficult to investigate GPIb-specific signaling pathways in washed platelets. Here, we investigated the specific mechanisms of GPIb signaling using echicetin-coated polystyrene beads, which specifically activate GPIb. We compared platelet activation induced by echicetin beads to vWF/R. Human platelets were stimulated with polystyrene beads coated with increasing amounts of echicetin and platelet activation by echicetin beads was then investigated to reveal GPIb specific signaling. Echicetin beads induced αIIbβ3-dependent aggregation of washed platelets, while under the same conditions vWF/R treatment led only to αIIbβ3-independent platelet agglutination. The average distance between the echicetin molecules on the polystyrene beads must be less than 7 nm for full platelet activation, while the total amount of echicetin used for activation is not critical. Echicetin beads induced strong phosphorylation of several proteins including p38, ERK and PKB. Synergistic signaling via P2Y12 and thromboxane receptor through secreted ADP and TxA2, respectively, were important for echicetin bead triggered platelet activation. Activation of PKG by the NO/sGC/cGMP pathway inhibited echicetin bead-induced platelet aggregation. Echicetin-coated beads are powerful and reliable tools to study signaling in human platelets activated solely via GPIb and GPIb-triggered pathways.

Clinical impact of gastrointestinal bleeding in patients undergoing percutaneous coronary interventions.

BACKGROUND The risk factors and clinical sequelae of gastrointestinal bleeding (GIB) in the current era of drug-eluting stents, prolonged dual antiplatelet therapy, and potent P2Y12 inhibitors are not well established. We determined the frequency, predictors, and clinical impact of GIB after percutaneous coronary interventions (PCIs) in a contemporary cohort of consecutive patients treated with unrestricted use of drug-eluting stents. METHODS AND RESULTS Between 2009 and 2012, all consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Bleeding Academic Research Consortium (BARC) GIB and cardiovascular outcomes were recorded within 1 year of follow-up. Among 6212 patients, 84.1% received new-generation drug-eluting stents and 19.5% received prasugrel. At 1 year, GIB had occurred in 65 patients (1.04%); 70.8% of all events and 84.4% of BARC ≥3B events were recorded >30 days after PCI. The majority of events (64.4%) were related to upper GIB with a more delayed time course compared with lower GIB. Increasing age, previous GIB, history of malignancy, smoking, and triple antithrombotic therapy (ie, oral anticoagulation plus dual antiplatelet therapy) were independent predictors of GIB in multivariable analysis. GIB was associated with increased all-cause mortality (adjusted hazard ratio, 3.40; 95% confidence interval, 1.67-6.92; P=0.001) and the composite of death, myocardial infarction, or stroke (adjusted hazard ratio, 3.75; 95% confidence interval, 1.99-7.07; P<0.001) and was an independent predictor of all-cause mortality during 1 year. CONCLUSIONS Among unselected patients undergoing PCI, GIB has a profound effect on prognosis. Triple antithrombotic therapy emerged as the single drug-related predictor of GIB in addition to patient-related risk factors within 1 year of PCI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291.

Safety of Prasugrel Loading Doses in Patients Pre-Loaded With Clopidogrel in the Setting of Primary Percutaneous Coronary Intervention: Results of a Nonrandomized Observational Study.

OBJECTIVES The aim of this study was to assess the safety of the concurrent administration of a clopidogrel and prasugrel loading dose in patients undergoing primary percutaneous coronary intervention. BACKGROUND Prasugrel is one of the preferred P2Y12 platelet receptor antagonists for ST-segment elevation myocardial infarction patients. The use of prasugrel was evaluated clinically in clopidogrel-naive patients. METHODS Between September 2009 and October 2012, a total of 2,023 STEMI patients were enrolled in the COMFORTABLE (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI]) and the SPUM-ACS (Inflammation and Acute Coronary Syndromes) studies. Patients receiving a prasugrel loading dose were divided into 2 groups: 1) clopidogrel and a subsequent prasugrel loading dose; and 2) a prasugrel loading dose. The primary safety endpoint was Bleeding Academic Research Consortium types 3 to 5 bleeding in hospital at 30 days. RESULTS Of 2,023 patients undergoing primary percutaneous coronary intervention, 427 (21.1%) received clopidogrel and a subsequent prasugrel loading dose, 447 (22.1%) received a prasugrel loading dose alone, and the remaining received clopidogrel only. At 30 days, the primary safety endpoint was observed in 1.9% of those receiving clopidogrel and a subsequent prasugrel loading dose and 3.4% of those receiving a prasugrel loading dose alone (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.25 to 1.30, p = 0.18). The HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) bleeding score tended to be higher in prasugrel-treated patients (p = 0.076). The primary safety endpoint results, however, remained unchanged after adjustment for these differences (clopidogrel and a subsequent prasugrel loading dose vs. prasugrel only; HR: 0.54 [95% CI: 0.23 to 1.27], p = 0.16). No differences in the composite of cardiac death, myocardial infarction, or stroke were observed at 30 days (adjusted HR: 0.66, 95% CI: 0.27 to 1.62, p = 0.36). CONCLUSIONS This observational, nonrandomized study of ST-segment elevation myocardial infarction patients suggests that the administration of a loading dose of prasugrel in patients pre-treated with a loading dose of clopidogrel is not associated with an excess of major bleeding events. (Comparison of Biomatrix Versus Gazelle in ST-Elevation Myocardial Infarction [STEMI] [COMFORTABLE]; NCT00962416; and Inflammation and Acute Coronary Syndromes [SPUM-ACS]; NCT01000701).

Republished: Antiplatelet therapy for secondary prevention of coronary artery disease

The choice and duration of antiplatelet therapy for secondary prevention of coronary artery disease (CAD) is determined by the clinical context and treatment strategy. Oral antiplatelet agents for secondary prevention include the cyclo-oxygenase-1 inhibitor aspirin, and the ADP dependent P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor. Aspirin constitutes the cornerstone in secondary prevention of CAD and is complemented by clopidogrel in patients with stable CAD undergoing percutaneous coronary intervention. Among patients with acute coronary syndrome, prasugrel and ticagrelor improve net clinical outcome by reducing ischaemic adverse events at the expense of an increased risk of bleeding as compared with clopidogrel. Prasugrel appears particularly effective among patients with ST elevation myocardial infarction to reduce the risk of stent thrombosis compared with clopidogrel, and offered a greater net clinical benefit among patients with diabetes compared with patients without diabetes. Ticagrelor is associated with reduced mortality without increasing the rate of coronary artery bypass graft (CABG)-related bleeding as compared with clopidogrel. Dual antiplatelet therapy should be continued for a minimum of 1 year among patients with acute coronary syndrome irrespective of stent type; among patients with stable CAD treated with new generation drug-eluting stents, available data suggest no benefit to prolong antiplatelet treatment beyond 6 months.

Comparison of prasugrel and clopidogrel-treated patients with acute coronary syndrome undergoing percutaneous coronary intervention: A propensity score-matched analysis of the Acute Myocardial Infarction in Switzerland (AMIS)-Plus Registry

OBJECTIVE The purpose of this study was to investigate outcomes of patients treated with prasugrel or clopidogrel after percutaneous coronary intervention (PCI) in a nationwide acute coronary syndrome (ACS) registry. BACKGROUND Prasugrel was found to be superior to clopidogrel in a randomized trial of ACS patients undergoing PCI. However, little is known about its efficacy in everyday practice. METHODS All ACS patients enrolled in the Acute Myocardial Infarction in Switzerland (AMIS)-Plus registry undergoing PCI and being treated with a thienopyridine P2Y12 inhibitor between January 2010-December 2013 were included in this analysis. Patients were stratified according to treatment with prasugrel or clopidogrel and outcomes were compared using propensity score matching. The primary endpoint was a composite of death, recurrent infarction and stroke at hospital discharge. RESULTS Out of 7621 patients, 2891 received prasugrel (38%) and 4730 received clopidogrel (62%). Independent predictors of in-hospital mortality were age, Killip class >2, STEMI, Charlson comorbidity index >1, and resuscitation prior to admission. After propensity score matching (2301 patients per group), the primary endpoint was significantly lower in prasugrel-treated patients (3.0% vs 4.3%; p=0.022) while bleeding events were more frequent (4.1% vs 3.0%; p=0.048). In-hospital mortality was significantly reduced (1.8% vs 3.1%; p=0.004), but no significant differences were observed in rates of recurrent infarction (0.8% vs 0.7%; p=1.00) or stroke (0.5% vs 0.6%; p=0.85). In a predefined subset of matched patients with one-year follow-up (n=1226), mortality between discharge and one year was not significantly reduced in prasugrel-treated patients (1.3% vs 1.9%, p=0.38). CONCLUSIONS In everyday practice in Switzerland, prasugrel is predominantly used in younger patients with STEMI undergoing primary PCI. A propensity score-matched analysis suggests a mortality benefit from prasugrel compared with clopidogrel in these patients.

Reasons for discontinuation of recommended therapies according to the patients after acute coronary syndromes.

BACKGROUND The prescription of recommended medical therapies is a key factor to improve prognosis after acute coronary syndromes (ACS). However, reasons for cardiovascular therapies discontinuation after hospital discharge are poorly reported in previous studies. METHODS We enrolled 3055 consecutive patients hospitalized with a main diagnosis of ACS in four Swiss university hospitals with a prospective one-year follow-up. We assessed the self-reported use of recommended therapies and the reasons for medication discontinuation according to the patient interview performed at one-year follow-up. RESULTS 3014 (99.3%) patients were discharged with aspirin, 2983 (98.4%) with statin, 2464 (81.2%) with beta-blocker, 2738 (90.3%) with ACE inhibitors/ARB and 2597 (100%) with P2Y12 inhibitors if treated with coronary stent. At the one-year follow-up, the discontinuation percentages were 2.9% for aspirin, 6.6% for statin, 11.6% for beta-blocker, 15.1% for ACE inhibitor/ARB and 17.8% for P2Y12 inhibitors. Most patients reported having discontinued their medication based on their physicians' decision: 64 (2.1%) for aspirin, 82 (2.7%) for statin, 212 (8.6%) for beta-blocker, 251 (9.1% for ACE inhibitor/ARB) and 293 (11.4%) for P2Y12 inhibitors, while side effect, perception that medication was unnecessary and medication costs were uncommon reported reasons (<2%) according to the patients. CONCLUSIONS Discontinuation of recommended therapies after ACS differs according the class of medication with the lowest percentages for aspirin. According to patients, most stopped their cardiovascular medication based on their physician's decision, while spontaneous discontinuation was infrequent.

Platelet receptors and patient responses: The contributions of Professor Stan Heptinstall to platelet research.

Stan Heptinstall's contributions to platelet research covered organising meetings at the national and European level as well as starting and maintaining the journal "Platelets". The major part of his research addressed problems of inhibition of platelet receptors and the effects of this on patient health. In particular, the effects of P2Y12 inhibitors on patients with acute cardiovascular problems were a major focus. Other studies included the effects of feverfew (Tanacetum parthenium) extracts on platelets, of direct anti-IIb/IIIa receptor (αIIbβ3) inhibitors and of prostanoids on platelet function. Recently, methods for assessing the effectiveness of platelet inhibition were investigated.