Bhatt DL Research Articles

Cangrelor Offers Protective Benefits in PCI Patients

Cangrelor, an intravenous, potent, direct-acting adenosine diphosphate (ADP) receptor antagonist, significantly reduced the composite endpoint of death, myocardial infarction (MI), ischemia-driven revascularization, and stent thrombosis in patients undergoing percutaneous coronary intervention (PCI) with no excess in severe bleeding compared with clopidogrel loading at the time of PCI. This article presents the results of the Clinical Trial Comparing Cangrelor to Clopidogrel Standard Therapy in Subjects Who Require Percutaneous Coronary Intervention [CHAMPION PHOENIX; Bhatt DL et al. N Engl J Med 2013] in a late-breaking clinical trial.

Prasugrel

Prasugrel

Adding omeprazole to clopidogrel reduced GI events and did not increase CV events

Source Citation Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363:1909-17. 20925534

Top Advances in Functional Genomics and Translational Biology for 2010

In recent years, major advances have been made in transcriptomics, metabolomics, proteomics, and particularly population genetics. More than 850 genome-wide association studies (GWAS) were published by the end of 2010, now covering a vast number of diseases and phenotypes and often incorporating tens of thousands of subjects or, in some cases, more than 100 000 subjects, increasing statistical power to identify and replicate contributing loci. Sequencing throughput advances and decreasing costs per sample have allowed the application of genome-wide genotyping and sequencing technology to larger DNA samples as well as transcriptome and epigenome features. This year was marked not only by continuing progress with GWAS, sequencing, and copy number variation studies but also by follow-up of GWAS and other findings with functional studies that uncover new molecular pathways contributing to disease and pave the way for future clinical applications. The American Heart Association Functional Genomics and Translational Biology Interdisciplinary Council (http://www.americanheart.org/presenter.jhtml?identifier=3016539) provides a forum for a multidisciplinary group of volunteers committed to making a substantial contribution to reduce the burden of heart disease and stroke through genetics, genomics, proteomics, and metabolomics research and translational science. With input from the Early Career Committee of the Council on Functional Genomics and Translational Biology, we considered many papers and selected 10 outstanding manuscript groups (15 articles) published in 2010 that reflect these advances, and we briefly summarize each below in chronological order.

Letter by Aboyans et al Regarding Article, “Smoking, Clopidogrel, and Mortality in Patients With Established Cardiovascular Disease”

HomeCirculationVol. 122, No. 3Letter by Aboyans et al Regarding Article, “Smoking, Clopidogrel, and Mortality in Patients With Established Cardiovascular Disease” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Aboyans et al Regarding Article, “Smoking, Clopidogrel, and Mortality in Patients With Established Cardiovascular Disease” Victor Aboyans, MD, PhD, Alexandre Le Guyader, MD and Philippe Lacroix, MD Victor AboyansVictor Aboyans Department of Thoracic and Cardiovascular Surgery and Vascular Medicine, Dupuytren University Hospital, Limoges, France Search for more papers by this author , Alexandre Le GuyaderAlexandre Le Guyader Department of Thoracic and Cardiovascular Surgery and Vascular Medicine, Dupuytren University Hospital, Limoges, France Search for more papers by this author and Philippe LacroixPhilippe Lacroix Department of Thoracic and Cardiovascular Surgery and Vascular Medicine, Dupuytren University Hospital, Limoges, France Search for more papers by this author Originally published20 Jul 2010https://doi.org/10.1161/CIRCULATIONAHA.109.931212Circulation. 2010;122:e394To the Editor:Berger and colleagues1 are commended for their interesting and hypothesis-generating posthoc analysis of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial published recently in Circulation. To better understand the potential pathways leading to an enhanced protective effect of clopidogrel in smokers, several issues need further discussion and analysis.First, the protective effect of clopidogrel in smokers in this report contrasts with the lack of interaction between smoking and antiplatelet strategies in the subgroups analysis in the first Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance trial report.2 This difference might be explained by a different definition of smoking in the current article1 (≥1 cigarette a day) compared with the original publication (>15 cigarettes a day). The authors should explain why they changed their definition and whether the number of cigarettes smoked daily may affect the beneficial effects of clopidogrel, as suggested recently by others.3Second, the authors repeatedly called the 2 therapeutic arms of the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance trial the “clopidogrel” group and the “placebo” group, even though both groups were also taking low-dose (75 to 160 mg) aspirin. Another hypothesis that has not been considered by the authors is that the protective effect observed in smokers in the “aspirin plus clopidogrel” group (compared with the “aspirin alone” group) might be related to the antiplatelet effect of clopidogrel in patients resistant to aspirin, the latter condition being strongly associated with smoking.4Last, the authors report higher rates of bleeding in smokers taking clopidogrel plus aspirin, but they did not detail the different localizations of bleeding. Smoking (along with aspirin) is a risk factor for gastrointestinal ulcers and their hemorrhagic complications.5 The higher rates of bleeding while taking clopidogrel in smokers versus nonsmokers not only might be related to a greater platelet inhibition by this drug in smokers, as suggested by the authors, but also may be due to an increased incidence of smoking-related gastrointestinal complications revealed by dual antiplatelet therapy. Similarly, the higher incidence of different types of cancers in smokers may contribute to this increased hemorrhagic risk.DisclosuresNone. References 1 Berger JS, Bhatt DL, Steinhubl SR, Shao M, Steg PG, Montalescot G, Hacke W, Fox KA, Lincoff AM, Topol EJ, Berger PB, for the CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) Investigators. Smoking, clopidogrel, and mortality in patients with established cardiovascular disease. Circulation. 2009; 120: 2337–2344.LinkGoogle Scholar2 Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry-Ribaudo L, Booth J, Topol EJ, for the CHARISMA Investigators. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med. 2006; 354: 1706–1717.CrossrefMedlineGoogle Scholar3 Desai NR, Mega JL, Jiang S, Cannon CP, Sabatine MS. Interaction between cigarette smoking and clinical benefit of clopidogrel. J Am Coll Cardiol. 2009; 53: 1273–1278.CrossrefMedlineGoogle Scholar4 Mirkhel A, Peyster E, Sundeen J, Greene L, Michelson AD, Hasan A, Domanski M. Frequency of aspirin resistance in a community hospital. Am J Cardiol. 2006; 98: 577–579.CrossrefMedlineGoogle Scholar5 Malfertheiner P, Chan FK, McColl KE. Peptic ulcer disease. Lancet. 2009; 374: 1449–1461.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 20, 2010Vol 122, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/CIRCULATIONAHA.109.931212PMID: 20644023 Originally publishedJuly 20, 2010 PDF download Advertisement SubjectsEpidemiologySecondary Prevention

Erratum

Diabetes, Obesity and MetabolismVolume 12, Issue 9 p. 833-833 Free Access Erratum This article corrects the following: Bariatric surgery vs. advanced practice medical management in the treatment of type 2 diabetes mellitus: rationale and design of the Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently trial (STAMPEDE) Sangeeta R. Kashyap, Deepak L. Bhatt, Philip R. Schauer, , Volume 12Issue 5Diabetes, Obesity and Metabolism pages: 452-454 First Published online: November 6, 2009 First published: 23 July 2010 https://doi.org/10.1111/j.1463-1326.2010.01246.xAboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In Kashyap et al. 1, ‘Bariatric surgery vs. advanced practice medical management in the treatment of type 2 diabetes mellitus: rationale and design of the Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently trial (STAMPEDE)’, there was an error in the figure 1 legend. It should have been: Figure 1. Illustration of the two bariatric procedures used in this trial. All procedures will be performed laparascopically. Surgical procedures in STAMPEDE trial. We apologize for the error. Reference 1 Kashyap SR, Bhatt DL, Schauer PR. Bariatric surgery vs. advanced practice medical management in the treatment of type 2 diabetes mellitus: rationale and design of the Surgical Therapy And Medications Potentially Eradicate Diabetes Efficiently trial (STAMPEDE). Diabetes Obes Metab 2010; 12: 452– 454. Wiley Online LibraryPubMedWeb of Science®Google Scholar Volume12, Issue9September 2010Pages 833-833 ReferencesRelatedInformation

Registries and Selection Bias

Outcomes researchers share a strong interest in determining what is being achieved in practice. In the quest to reveal what is actually being done in medicine, we are often in a position to use existing data about clinical practice and patient experience to answer relevant questions, rather than having to generate data de novo. Patient registries, with their size, scope, and focus on patients who represent those seen in clinical practice, have become an increasingly common source of data for outcomes researchers. There is much to like about patient registries. These organized collections of data about clinical practice are a vehicle by which we can assemble massive amounts of information about patients and use it to assess quality of care, identify patterns of care, facilitate real-world research, and improve performance. In cardiovascular medicine, registries capture information about patients with acute coronary syndromes and heart failure as well as those who undergo procedures related to cardiac catheterization, percutaneous coronary intervention, carotid stents, and internal cardioverter defibrillators. Federal agencies are turning to registries to provide information about quality and produce insights about how to best practice medicine through an emphasis on comparative effectiveness research. Outcomes research articles based on registry data are numerous, including those from NRMI, CRUSADE, GWTG-HF, …

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

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

Carotid Stenting in the Elderly

Elderly patients are at higher risk of procedural complications. Surgical revascularization has been performed successfully in selected octogenarians.1,2 Nevertheless, it is widely believed that percutaneous approaches are safer in the elderly. Indeed, percutaneous coronary intervention is now successfully being performed even in selected nonagenarians.3 Thus, it is tempting to presume that carotid revascularization in the elderly might be safer if done via endovascular means (Figure).4 Figure. Angiography before (A) and after (B) a right carotid artery stent in an 81-year-old man with amaurosis fugax. Article see p 2343 The data to date, however, have been conflicting, with several reports demonstrating very high rates of stroke or death with carotid stenting in octogenarians. Furthermore, although carotid stenting with embolic protection has been shown to be noninferior to carotid endarterectomy in patients at high surgical risk, whether carotid stenting is equivalent to carotid endarterectomy remains an open question in patients at low surgical risk.5–7 Additionally, especially for asymptomatic patients, the question arises whether a patient will live long enough to derive potential benefit from any procedure. This question becomes more pressing as the elderly population expands and the definition of elderly creeps upward, and also as clinical trials continue to underenroll the elderly. The cut point where appropriate clinical caution turns instead into preconceived notions and age-related bias is difficult to define. In this issue of Circulation , Chiam et al report on 142 consecutive patients aged 80 years or older who underwent carotid stenting.8 This series of patients has previously been reported, with the current article adding observations related to intermediate-term …

Intravenous Thrombolysis for Acute Ischemic Stroke

Marc Fisher MD Kennedy Lees MD Section Editors: On September 26, 2008, the New England Journal of Medicine published the results of the European Cooperative Stroke Study (ECASS) III,1 the first randomized, placebo-controlled trial to demonstrate safe and effective use of intravenous recombinant tissue plasminogen activator (rtPA) to treat patients with acute ischemic stroke (AIS) beyond 3 hours from stroke onset. The ECASS investigators studied the safety and efficacy of administering intravenous rtPA to patients with AIS 3 to 4.5 hours after AIS onset. Using the modified Rankin Scale score at 90 days after stroke occurrence as the primary end point of the study, the investigators demonstrated a modest, statistically significant increase in the likelihood of having normal or near normal recovery (modified Rankin Scale=0 or 1) in favor of rtPA treatment compared with placebo (unadjusted OR, 1.34; 95% CI, 1.02 to 1.76; P =0.04). So, what impact will the results of the study have on acute stroke management and stroke research in the United States and elsewhere? With regard to the first part of the question, the answer is complex. First, the ECASS III results will hopefully help to increase the number of thrombolysis eligible patients with AIS who receive rtPA. Twelve years after the US Food and Drug Administration approved the management of AIS within 3 hours of symptom onset as an indication for the use of intravenous rtPA, less than 5% of patients with AIS are being treated worldwide with rtPA within 3 hours of stroke onset. One of the major factors contributing to this parlous state of affairs has been disagreement among healthcare professionals about the validity of the results of the National Institutes of Neurological Disorders and Stroke (NINDS) trial of rtPA for acute stroke.2 In the late 1990s, the stroke community unexpectedly …

Mounting Evidence for Safety and Improved Outcomes of Drug-Eluting Stenting

Mounting Evidence for Safety and Improved Outcomes of Drug-Eluting Stenting

Primary Percutaneous Coronary Intervention With Drug-Eluting Stents

Primary percutaneous coronary intervention (P-PCI) is the preferred reperfusion strategy for patients with ST-segment elevation myocardial infarction if it can be performed rapidly by an experienced team.1 Compared with balloon angioplasty, routine bare-metal stent (BMS) implantation decreases risk for target vessel revascularization (TVR) and possibly reduces myocardial reinfarction rates but does not reduce mortality rates.2,3 Therefore, BMS has become the dominant P-PCI strategy, despite initial concern about increased stent thrombosis rates from delayed healing or inadequate late stent apposition due to initial thrombus trapping. Less established is the role of drug-eluting stents (DES) in P-PCI. DES have the potential to further decrease TVR rates but may increase risk for stent thrombosis. In fact, the risk of stent thrombosis might even be higher in P-PCI than in electively treated patients because of the combination of increased platelet activation, delayed healing, lack of endothelialization, and the proinflammatory and prothrombotic environment in the infarct artery.4 Article see p 103 Several relatively small randomized clinical trials have shown inconsistent efficacy for DES over BMS for P-PCI. Three meta-analyses of these trials have concluded that there is no difference in death or myocardial infarction rates, but TVR rates are decreased.5–7 Variably included were 12 studies that differed in trial design, inclusion criteria, end-point definitions, stent types, duration of clopidogrel treatment, and type of follow-up (angiographic versus clinical). They were limited by sample size and duration of follow-up and usually required angiographic documentation of stent thrombosis, which may have underestimated its true incidence. In this issue of Circulation: Cardiovascular Interventions , Kukreja et al8 report a single-center registry study that is an expanded version of a previous publication.9 Again including the 185 ST-segment elevation myocardial infarction patients treated with Sirolimus-eluting stents (SES) from April 2002 to February 2003, they compare …

Biomarker Release After Percutaneous Coronary Intervention

Cardiac biomarkers of necrosis provide clinicians with important “messages” from the heart. They are released into the interstitium of the myocardium after loss of the integrity of cardiac myocyte membranes. The pattern of the rise and fall of an individual biomarker (ie, its release kinetics) depends on its intracellular location in the myocyte, molecular weight, and clearance from the interstitium of the myocardium and ultimately the circulation.1 Cardiac biomarkers play an integral role in the clinical diagnosis of myocardial infarction (MI). Referring to the spontaneous occurrence of MI in patients, the World Health Organization required that at least 2 of the following be present to fulfill the criteria for MI: a history of ischemia-type chest discomfort, evolutionary changes on serially obtained ECG tracings, and a rise and fall in serum cardiac markers.2 Article see p 10 See Editorial Circulation . 2008;118:609–611 See Article Circulation . 2008;118:632–638 Several dramatic advances have occurred in the biomarker component of the diagnosis of MI. Analytes with greater specificity for the myocardium were introduced into clinical medicine, with creatine kinase-MB replacing total creatine kinase and subsequently cardiac-specific troponins replacing creatine kinase-MB as the biomarker of choice for diagnosing MI.3 Assay technology improved as clinical chemists moved from enzymatic activity assays for CK to highly specific immunoassays that can detect progressively smaller concentrations of cardiac troponins in the peripheral circulation.4 Although ST-elevation MI (STEMI) is easily identified on the 12-lead ECG, we now recognize that many patients previously diagnosed with unstable angina are more properly diagnosed as having non–ST-elevation MI (NSTEMI) on the basis of the detection of elevated levels of cardiac troponins in their blood.5 Cardiac biomarkers are used as a rough guide to the extent of myocardial necrosis. The higher the peak biomarker level after STEMI, the larger the …

Glucocorticoids in the prevention of in-stent restenosis: The role of inflammation

mechanisms of in-stent restenosis: a serial intravascular ultrasound study. Circulation 1996;94:1247–54. [6] Moreno PR, Palacios IF, Leon MN, Rhodes J, Fuster V, Fallon JT. Histopathologic comparison of human coronary in-stent and postballoon angioplasty restenotic tissue. Am J Cardiol 1999;84:462–6. [7] Assali AR, Moustapha A, Sdringola S, et al. Acute coronary syndrome may occur with in-stent restenosis and is associated with adverse outcomes (the PRESTO trial). Am J Cardiol 2006;98:729–33. [8] Bossi I, Klersy C, Black AJ, et al. In-stent restenosis: long term outcome and predictors of subsequent target lesion revascularization after repeat balloon angioplasty. J Am Coll Cardiol 2000;35:1569–76. [9] Chen MS, John JM, Chew DP, Lee DS, Ellis SG, Bhatt DL. Bare metal stent restenosis is not a benign clinical entity.AmHeart J 2006;151:1260–4. [10] Steinberg DH, Pinto Slottow TL, Buch AN, et al. Impact of in-stent restenosis on death and myocardial infarction. Am J Cardiol 2007;100:1109–13. [11] Iakovou I, Ge L, Michev I, et al. Clinical and angiographic outcome after sirolimus-eluting stent implantation in aorto–ostial lesions. J Am Coll Cardiol 2004;44:967–71. [12] Kumana CR, Cheung G, Lauder IJ, Cheung BM. Long-term combination therapy with aspirin and clopidogrel. J Cardiovasc Pharmacol Ther 2004;9:223–5. [13] Barlis P, Di Mario C. Still a future for the bare metal stent? Int J Cardiol 2007;121:1–3. [14] Pfisterer M, Brunner-La Rocca HP, Buser PT, et al. BASKET-LATE Investigators. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drugeluting versus bare-metal stents. J Am Coll Cardiol 2006;48:2584–91. [15] Kim HL, Park KW, Kwak JJ, et al. Stent-related cardiac events after noncardiac surgery: drug-eluting stent vs. bare metal stent. Int J Cardiol 2008;123:353–4. [16] Yagi S, Kimura T, Hayashi I, Nishiuchi T. Acute coronary syndrome due to hinge movement of a bare-metal stent. Int J Cardiol 2008;123:e64–6.

Is It Time to Definitely Abandon Neuroprotection in Acute Ischemic Stroke?

See related article, pages 1751–1758. Since the ischemic penumbra was discovered and since a therapeutic window for acute ischemic stroke has been postulated, stroke experts are looking for safe and effective drugs to treat as many acute ischemic stroke patients as possible. Maturation of ischemic damage is a complex process, triggered by hypoperfusion at critical levels and spontaneously evolving toward cell death. It is a self-perpetuating process in which some critical steps (such as ion pumps failure and iNOS production) maintain and enhance the process.1 Reperfusion may reverse the ischemic cascade but, at the same time, induces a further damage. The risk/benefit ratio of reperfusion depends on the amount of penumbral salvageable tissue, that is “individual” and only partially predictable.2,3 Spontaneous reperfusion may occur, and symptoms may reverse, partially or totally, but the percentages of spontaneous reperfusion so far reported account for approximately the 24% of all stroke cases.4 A review of published articles about cerebral angiography in stroke reported that the percentage of spontaneous reperfusion …

Addition of clopidogrel to aspirin may have increased risk for cardiovascular death in a primary prevention population

Source Citation Wang TH, Bhatt DL, Fox KA, et al. An analysis of mortality rates with dual-antiplatelet therapy in the primary prevention population of the CHARISMA trial. Eur Heart J. 2007;28:2200...

One-year cardiovascular event rates in outpatients with atherothrombosis. Steg PG, Bhatt DL, Wilson PW, et al; REACH Registry Investigators. JAMA. 2007;297: 1197-1206

available at http://jama.ama-assn.org/cgi/ content/full/297/11/1197.

Poststroke Care

See related article, pages 1899–1904. “Thinking is easy, acting is difficult, and to put one’s thoughts into action is the most difficult thing in the world”. — —Goethe (1749–1832) Major advances in acute stroke management have been seen over the past decade, including the use of thrombolysis, antithrombotic therapy, and organized in-hospital stroke care. However, relatively few studies have evaluated the effectiveness of these interventions in routine clinical practice, or have assessed issues related to delivery of services, access to care, and long-term care after discharge from stroke. In this issue of Stroke , Bravata et al1 contribute to our understanding of outcomes after stroke by analyzing readmissions and deaths in the first 5 years after a hospitalization for stroke. The target population included stroke survivors aged over 65 years who were Medicare beneficiaries and who were discharged from Connecticut acute care hospitals in 1995. This population was followed from discharge in 1995 through 2000 using Medicare claims and Social Security Administration mortality data. Among 2603 patients discharged alive, 40% were readmitted at least once within the first year of discharge, 53% had died or been readmitted within 1 year and only 15% survived admission-free for 5 years. Leading causes for readmission included pneumonia (8.2% to 9.0%), stroke (3.9% to 6.1%) and acute myocardial infarction (4.2% to 6.0%). There was no apparent association between length of hospital stay and readmission rate (unreported data kindly provided by the authors, 2007), and no information was available on potential patient and system factors associated with higher hospital readmission rates. Lower readmission rates of 25% to 27% within 1 year have been previously reported.2,3 These studies found that the average number of days of rehospitalization was 23.2 Stroke was the single most frequent reason for readmission followed by cardiac disease, …

Heritability, Platelet Function, and Aspirin

Platelets play a critical role in the pathophysiology of atherothrombotic disease. A pivotal event contributing to the understanding of platelet-dependent clot formation was the development of the platelet aggregometer in 1962.1 An aggregometer specifically measures the ability of platelets to adhere via glycoprotein IIb/IIIa (integrin αIIbβ3), and thousands of articles using this technique have been published, characterizing platelet function; however, the usefulness of these measurements remains unclear. Whereas the aggregometer and related techniques that measure platelet aggregation or glycoprotein expression have led to large amounts of data characterizing platelet function in various settings, the clinical importance of measurable differences in platelet function is still debated.2 The use of platelet function testing is established in rarer platelet abnormalities, such as the autosomal recessive bleeding disorder Glanzmann thrombasthenia,3 but no clear consensus has been reached on its usefulness for highly prevalent diseases caused by platelet-dependent thrombosis, such as myocardial infarction. A major factor for this discrepancy is that many of the platelet function defects that lead to bleeding are known to be caused by a single defect, whereas thrombosis in the setting of cardiovascular disease is presumed to be multifactorial. Article p 2490 The evolution of platelet function studies in various clinical settings has led to the realization that wide interindividual variability exists in the platelet activation response.4,5 What accounts for this variability? Only a few studies have systematically examined this question. Platelet function has been established as markedly dependent on the type of agonist used, the agonist concentration, and the concomitant use of antiplatelet therapy.6 In addition, in the large population-based Framingham Heart Study, O’Donnell and colleagues7 have demonstrated that heritable factors play a major role in determining platelet aggregation, as opposed to measured covariates. Less clear from the current literature is the direct …

CHARISMA: The Antiplatelet Saga Continues

To the Editor: We read with interest the Editorial by Norris and Barnett1 on the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial. They conclude that aspirin is still the first choice in the secondary prevention of stroke, that clopidogrel is only marginally more effective than aspirin in secondary prevention of vascular end points, and that there is no convincing evidence that clopidogrel (either alone or combined with aspirin) improves the outcome in patients presenting with TIA or stroke with a cost that is 80 times that of aspirin alone.1 The Canadian Cooperative Study Group already in 1978 had observed that among men the fewest events occurred …