AHA 2011 Scientific Sessions highlight key studies

Risks and Benefits of Antiplatelet Therapy in Uremic Patients

Connecting the C's: Coronaries, Creatinine, Compliance, CRUSADE

Relationship of Lipoproteins to Cardiovascular Events: The AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes)

Current guidelines recommend dual antiplatelet therapy (DAPT) that includes aspirin and the platelet P2Y12 ADP receptor antagonist clopidogrel after percutaneous coronary intervention (PCI). These recommendations are based on data that DAPT with the P2Y12 inhibitors clopidogrel reduces major adverse cardiac events after PCI in stable angina and acute coronary syndrome (ACS) patients when compared with aspirin, or aspirin in combination with warfarin.1 Despite treatment with DAPT, patients with ACS undergoing PCI are at elevated risk for recurrent ischemic events compared with stable angina patients in part because of increased platelet thrombotic activity in ACS. In addition, there is considerable interindividual variability in the degree of platelet inhibition achieved by clopidogrel, and high residual platelet activity in the setting of clopidogrel therapy (hyporesponsiveness) is associated with adverse cardiovascular (CV) events after PCI. Clopidogrel hyporesponsiveness is related to a variety of clinical and genetic factors that alter pharmacokinetics, and diabetes, congestive heart failure (CHF), and obesity are associated with reduced efficacy. Clopidogrel is a prodrug that requires conversion by the hepatic cytochrome P450 system (CYP) to an active metabolite, and it can take up to 6 hours for clopidogrel to have maximal effect after the loading dose. Genetic polymorphisms that reduce CYP activity result in decreased hepatic metabolism of clopidogrel. Among persons treated with clopidogrel, carriers of specific reduced function CYP2C19 alleles have impaired clopidogrel conversion, significantly lower levels of active metabolite, diminished platelet inhibition, and higher rates of adverse CV events and stent thrombosis after PCI.2 The prevalence of CYP2C19 polymorphisms ranges from 30% to 60% depending on ethnicity.2,3 Medications that inhibit CYP activity also reduce clopidogrel conversion, and some proton pump inhibitors (PPI) that reduce CYP function (eg, omeprazole) diminish clopidogrel metabolite levels and efficacy measured by platelet function testing. The interaction between clopidogrel and …

Response

792 Acute Coronary Syndrome in Patients With Normal or Non-Obstructive Coronary Artery Disease: Patient Characteristics and Long-Term Outcomes

Vascular Disease Burden and In-Hospital Outcomes Among Patients Undergoing Percutaneous Coronary Intervention in New York State

Management of Acute Coronary Syndromes

Introduction: The importance of the number of circulating low-density lipoprotein cholesterol (LDL-C) particles, in addition to the total level of LDL-C is increasingly recognized. The effects of Extended Release Niacin (ERN) on LDL-C particle number have not been studied. The primary objective of this study was to evaluate ERN’s effects on LDL-C particle number. ERN’s effect on high-density lipoprotein cholesterol (HDL-C) particle number was a secondary objective. Hypothesis : In patients with stable coronary artery disease (CAD) and LDL-C at goal, the addition of ERN will favorably alter LDL-C particle number. Methods: 60 patients with stable CAD and well-controlled LDL-C levels were randomly assigned to 3 months of ERN (1g/d) or placebo in addition to their baseline medications. Particle number was analyzed by proton nuclear magnetic resonance spectroscopy at baseline and after 3 months. Results: Baseline and follow up lipid values are shown in Table . Compared to baseline, while ERN had no significant effect on total LDL-C levels, it significantly decreased the mean number of medium and small very small LDL-C particles (p=0.005). The percent change in each of these particle numbers was significantly greater in the ERN group compared to placebo as well (p<0.05 for each) ERN therapy raised HDL-C levels and also significantly shifted from small to large HDL-C particles (p<0.001). There were no significant changes in lipid values or particle numbers in the placebo-treated patients ( Table ). Conclusion: In patients with stable CAD and well-controlled LDL-C levels, ERN significantly reduced the number of circulating particles of the more atherogenic subtypes of LDL-C, despite having no effect on total LDL-C levels. ERN also favorably altered particle numbers of HDL-C. These findings suggest that ERN-induced alterations in particle number may contribute to its anti-atherosclerotic effects, and that these effects may not be evident from the standard lipid profile.

oronary heart disease is the leading cause of mortality and morbidity in industrialized countries, in men as well as in women.Women have their first cardiac event 6 to 10 years later than men do.Whereas the cardiovascular death rates are declining in men, they remain constant in women.In cardiovascular studies with age limits, women are naturally the minority, amounting to Ͻ40%.It is well known that distinct gender differences exist in terms of presentation of symptoms, validity of diagnostic tests, drug side effects, and complications.With respect to cardiac risk factors, women have higher rates of diabetes and hypertension but are less frequently smokers.

Modern antithrombotic therapy for acute coronary syndromes rests on a growing body of basic and clinical evidence that rupture or erosion of the surface of a vulnerable plaque sets in motion a sequence of events culminating in thrombus formation in the culprit vessel.1 When the contents of a vulnerable plaque are exposed to the bloodstream, platelets adhere to the subendothelial matrix, release ADP and thromboxane A2, and amplify the generation of thrombin.2 As a result, a platelet aggregate begins to develop. In addition, the coagulation cascade is activated and fibrin strands are formed. Thrombin (factor IIa) plays a pivotal role in the processes described above because of its extensive procoagulant and prothrombotic actions.3 In addition to catalyzing the transformation of soluble fibrinogen into fibrin monomers and activating factor XIII to produce cross-linked fibrin, thrombin promotes clot formation by activating factors V and VIII. It is also one of the most potent agents responsible for platelet adhesion, activation, and aggregation. In vessels with a diseased endothelium, thrombin promotes the release of the vasoconstrictor endothelin 1. Importantly, thrombin also potentiates the proliferative effects of multiple growth factors and is a key mediator of early smooth muscle cell proliferation after arterial injury. There is now abundant evidence that thrombus formation can be prevented by direct or indirect inactivation of thrombin or by inhibition of thrombin production via the intrinsic or extrinsic limbs of the coagulation pathway.3 Unfractionated heparin, the standard antithrombotic agent in clinical practice, is a glycosaminoglycan, consisting of chains of alternating residues of d-glucosamine and uronic acid.4 Although familiar to the vast majority of clinicians, unfractionated heparin has several disadvantages: (1) a variable anticoagulant effect (necessitating frequent monitoring of activated partial thromboplastin time), (2) neutralization by platelet factor 4, (3) less effective inhibition …

Mortality in the TRACER and ATLAS ACS 2 Trials: Two More Reasons to Audit Vital Records in PLATO

Usefulness of Mean Platelet Volume as a Biomarker for Long-Term Outcomes After Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVESGender associations with acute coronary syndrome (ACS), remain inconsistent. Gender-specific data in the Saudi Project for Assessment of Coronary Events registry, launched in December 2005 and currently with 17 participating hospitals, were explored.DESIGN AND SETTINGSA prospective multicenter study of patient with ACS in secondary and tertiary care centers in Saudi Arabia were included in this analysis.PATIENTS AND METHODSPatients enrolled from December 2005 until December 2007 included those presented to participating hospitals or transferred from non-registry hospitals. Summarized data were analyzed.RESULTSOf 5061 patients, 1142 (23%) were women. Women were more frequently diagnosed with non ST-segment elevation myocardial infarction (NSTEMI [43%]) than unstable angina (UA [29%]) or ST-segment elevation myocardial infarction (STEMI [29%]). More men had STEMI (42%) than NSTEMI (37%) or UA (22%). Men were younger than women (57 vs 63 years) who had more diabetes, hypertension, and hyperlipidemia. More men had a history of coronary artery disease. More women received angiotensin receptor blockers (ARB) and fewer had percutaneous coronary intervention (PCI). Gender differences in the subset of STEMI patients were similar to those in the entire cohort. However, gender differences in the subset of STEMI showed fewer women given β-blockers, and an insignificant PCI difference between genders. Thrombolysis rates between genders were similar. Overall, in-hospital mortality was significantly worse for women and, by ACS type, was significantly greater in women for STEMI and NSTEMI. However, after age adjustment there was no difference in mortality between men and women in patients with NSTEMI. The multivariate-adjusted (age, risk factors, treatments, door-to-needle time) STEMI gender mortality difference was not significant (OR=2.0, CI: 0.7–5.5; P=.14).CONCLUSIONThese data are similar to other reported data. However, differences exist, and their explanation should be pursued to provide a valuable insight into understanding ACS and improving its management.

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