Papers by Gilbert Gosselin
The Lancet, 2019
Background Patients with stable coronary artery disease and diabetes with previous percutaneous c... more Background Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population).
Previous studies have indicated that angiotensin-converting enzyme inhibitors may reduce the freq... more Previous studies have indicated that angiotensin-converting enzyme inhibitors may reduce the frequency of ventricular arrhythmias in patients with heart failure. These reports were mosti small and of short duration. We prospectively studi ecr 734 patients recruited in 11 universities for 1 year who were enrolled in the Studies of left Ventricular Dysfunction (SOLVD) to determine the long-term effects of enalapril and placebo on the frequency and complexity of ventricular arrhythmias in patients with symptomatic (treatment trial) or asymptomatic (prevention trial) heart failure and depressed left ventricular function (ejection fraction 535%). Five hundred fifty-three patients from the prevention trial and 18 1 from the treatment trial of SOLVD underwent ambulatory electrocardiographic monitoring at baseline, and then at 4 and 12 months Of double-blind therapy with either placebo or enala daily). The prospectively defin ecr ril(2.5 to 10 mg twice primary analysis was by intent-to-trea...
Archives Des Maladies Du Coeur Et Des Vaisseaux, 1990
: Two cases of coronary artery right ventricular fistula were diagnosed during the yearly check-u... more : Two cases of coronary artery right ventricular fistula were diagnosed during the yearly check-up of 38 of the 66 cardiac transplant patients of the Montreal Heart Institute between September 1982 and April 1989. In one case, the fistula involved the right anterior ventricular branch of the right coronary artery and in the other case, a septal branch of the left anterior descending artery. Histological examination of the biopsy fragments obtained before diagnosis of the fistula showed the presence of small calibre arteries, which was not the case in 10 control transplant patients. A review of the literature indicates that the risks of endomyocardial biopsy are minimal (less than or equal to 0.5%). However, the possibility of a coronary artery right ventricular fistula should be added to the list of known complications. The resulting shunt is negligible and has no haemodynamic consequences.
A case of Takayasu arteritis with left main disease is described. Intrastent restenosis occurred ... more A case of Takayasu arteritis with left main disease is described. Intrastent restenosis occurred one year after the first percutaneous coronary angioplasty (PCI) with a drug-eluting stent (everolimus). After suppression of the active disease with immunosuppressive therapy, and sirolimus added, a second PCI were performed with zotarolimusbased DES, after pre-dilatation with paclitaxel-based balloon angioplasty. Control coronary angiography with optic coherence tomography performed two months later confirmed no restenosis. This is the first case of effective local use of two different antiproliferative agents during angioplasty and effective systemic use of sirolimus in Takayasu’s disease with coronary involvement.
To determine whether calcium channel blockers influence the progression of coronary atheroscleros... more To determine whether calcium channel blockers influence the progression of coronary atherosclerosis, 383 patients age 65 years or less with 5-75% stenoses in at least four coronary artery segments were selected at random within 1 month of coronary arteriography to participate in double-blind therapy with a placebo or nicardipine 30 mg three times daily. Coronary events (5 deaths, 22 myocardial infarctions, and 28 unstable anginas) occurred in 28 of 192 nicardipine patients and 23 of 191 placebo patients (p=NS). At 24 months coronary arteriography was repeated in 335 patients. Progression, defined as a 10% or more worsening in diameter stenosis, measured quantitatively, was found in 147 of 1,153 lesions (12.7%) in 168 nicardipine patients and in 170 of 1,170 lesions (14.5%) in 167 placebo patients (p=NS). Ninety-two nicardipine patients (55%) and 95 placebo patients (57%) had progression at one or more sites (p=NS). Regression, that is, an improvement by l1o0 or more in diameter sten...
JACC: Cardiovascular Imaging
Percutaneous coronary intervention is a mainstay in the management of symptomatic or high-risk co... more Percutaneous coronary intervention is a mainstay in the management of symptomatic or high-risk coronary artery disease. The bulk of clinical evidence and experience underlying this fact relies, however, on relatively young patients. Indeed, few data of very limited quality are available which adequately define the risk-benefit and cost-benefit profile of coronary angioplasty and stenting in very old subjects, such as those of 90 years of age or older (i.e., nonagenarians). The aim of this review is to provide a concise, yet practical, synthesis of the available evidence on percutaneous coronary revascularization in the very elderly. The main arguments elaborated upon are to what extent we can extrapolate findings from studies including younger patients to nonagenarians, whether we should provide higher priority to prognosis or quality of life in such patients, and whether we can afford to allocate vast resources to care for such subjects in an era of financial constraints. Our review of 18 studies and 1082 patients suggest that percutaneous coronary intervention is feasible and associated with acceptable short-and long-term results in this population, which is nonetheless fraught with a high mortality risk irrespective of the revascularization procedure. Accordingly, the pros and cons of percutaneous coronary intervention should be carefully weighed when considering this treatment in nonagenarians.
Journal of the American College of Cardiology
The Lancet Diabetes & Endocrinology
Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovasc... more Background After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1•4-1•8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1−12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0•65-1•30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA 1c or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. Findings At study baseline, 5444 patients (28•8%) had diabetes, 8246 (43•6%) had prediabetes, and 5234 (27•7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2•20-2•28 mmol/L), after 4 months' treatment with alirocumab (0•80 mmol/L), or after 4 months' treatment with placebo (2•25-2•28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2•8 years was greater in patients with diabetes (16•4%) than in those with prediabetes (9•2%) or normoglycaemia (8•5%); hazard ratio (HR) for diabetes versus normoglycaemia 2•09 (95% CI 1•78-2•46, p<0•0001) and for diabetes versus prediabetes 1•90 (1•65-2•17, p<0•0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2•3%, 95% CI 0•4 to 4•2) than in those with prediabetes (1•2%, 0•0 to 2•4) or normoglycaemia (1•2%,-0•3 to 2•7; absolute risk reduction p interaction =0•0019). Among patients without diabetes at baseline, 676 (10•1%) developed diabetes in the placebo group, compared with 648 (9•6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1•00, 95% CI 0•89-1•11). HRs were 0•97 (95% CI 0•87-1•09) for patients with prediabetes and 1•30 (95% CI 0•93-1•81) for those with normoglycaemia (p interaction =0•11). Interpretation After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0•65-1•30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes. Funding Sanofi and Regeneron Pharmaceuticals.
Lancet (London, England), Jan 10, 2017
Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mo... more Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 m...
Archives of Cardiovascular Diseases Supplements
American heart journal, 2017
The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of... more The Universal Definition of Myocardial Infarction recommends the 99th percentile concentration of cardiac troponin in a normal reference population as part of the decision threshold to diagnose type 1 spontaneous myocardial infarction. Adoption of this recommendation in contemporary worldwide practice is not well known. We performed a cohort study of 276 hospital laboratories in 31 countries participating in the National Heart, Lung, and Blood Institute-sponsored International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial. Each hospital laboratory's troponin assay manufacturer and model, the recommended assay's 99th percentile upper reference limit (URL) from the manufacturer's package insert, and the troponin concentration used locally as the decision level to diagnose myocardial infarction were ascertained. Twenty-one unique troponin assays from 9 manufacturers were used by the surveyed hospital laboratories. The ratio of the trop...
On behalf of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (CO... more On behalf of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) Investigators, we wish to thank Drs Joshi, Tarantini, and colleagues for their letters to the editor regarding our article. 1 Many excellent comments were made that serve to clarify the COURAGE nuclear substudy. It is important to note that this study was devised to compare treatment effectiveness using nuclear quantification of ischemia as a surrogate outcome. The design of the substudy was based on the prognostic findings from observational registries of tens of thousands of patients undergoing stress myocardial perfusion single photon emission computed tomography (SPECT). 2-4 Importantly, no published data were available previously to suggest that significant relative risk reduction would be seen in patients with ischemia reduction. Therefore, this study was not powered to examine differences in prognosis but was designed to determine whether percutaneous coronary intervention (PCI) resulted in a greater reduction of objective ischemia than did optimal medical therapy alone, extending prior, small series that found serial changes in perfusion induced by an array of antiischemic therapies. 5 Thus, the interpretation of clinical outcomes from the COURAGE nuclear substudy should be viewed with caution, especially as risk-adjusted models did not show a prognostic benefit between ischemia reduction and risk reduction. Our preliminary data do suggest that there is potential risk reduction for those patients with significant ischemia reduction (ie, Ն5% of the myocardium) or minimal residual ischemia after intensive medical therapy with or without PCI. We believe, therefore, that the implication of Tarantini and colleagues that a study focused solely on patients with more extensive and severe ischemia as documented by nuclear imaging has merit. These authors suggest that had we limited enrollment to only patients with moderate-to-severe ischemia, a significant benefit in prognosis from PCI might have emerged. In this regard, in our subset of 105 patients with moderate-to-severe ischemia encumbering 10% or more of the myocardium, risk-adjusted analysis does reveal a trend toward improved survival rates for those with ischemia reduction (Pϭ0.082). When we review the risk-adjusted survival rate for the whole cohort, however, no significant differences were noted for those with and without ischemia reduction (Pϭ0.26). Importantly, in those exhibiting a significant reduction in ischemia, nearly 80% of patients receiving either treatment were free from angina, suggesting that many patients benefited from the intensive risk factor and lifestyle modifications and antiischemic therapeutic regimen with or without PCI. Finally, it is worth emphasizing that, with only a few prespecified exceptions, patients in the COURAGE trial were required to demonstrate objective evidence of ischemia; however, myocardial perfusion SPECT was not a prerequisite for enrollment, thereby accounting for the small size of the substudy. Joshi notes an important potential interrelationship between regional perfusion ischemia and left ventricular function. COURAGE nuclear patients had an average ejection fraction of 57%, with few patients having marked systolic dysfunction. Additional stratification by left ventricular function and ischemia within the current cohort results in patient subsets that are too limited in size. Thus, further investigation as to the value of both parameters in larger, adequately powered cohorts will provide important clues as to how to further improve secondary prevention of stable angina patients.
Archives Des Maladies Du Coeur Et Des Vaisseaux Pratique, 1996
The American Heart Journal, Feb 1, 1996
In the Studies of Left Ventricular Dysfunction (LVD), enalapril or placebo was administered in a ... more In the Studies of Left Ventricular Dysfunction (LVD), enalapril or placebo was administered in a double-blind fashion to 6797 participants with ejection fraction-<0.35. During 40 months' average follow-up, 28.1% of participants randomized to enalapril reported side effects compared with 16.0% in the placebo group (p < 0.0001). Enalapril use was associated with a higher rate of symptoms related to hypotension (14.8% vs 7.1%, p<0.0001), azotemia (3.8% vs 1.6%, p < 0.0001), cough (5.0% vs 2.0%, p < 0.0001), fatigue (5.8% vs 3.5%, p < 0.0001), hyperkalemia (1.2% vs 0.4%, p = 0.0002), and angioedema (0.4% vs 0.1%, p<0.05). Side effects resulted in discontinuation of blinded therapy in 15.2% of the enalapril group compared with 8.6% in the placebo group (p < 0.0001). Thus enalapril is well tolerated by patients with LVD; however, hypotension, azotemia, cough, fatigue, and other side effects result in discontinuation of therapy in a significant minority of patients. (AM HEART J 1996;131:350-5.) In patients with left ventricular dysfunction (LVD), angiotensin-converting enzyme (ACE) inhibitors have been shown to improve hemodynamic function, relieve symptoms, reduce the need for hospitaliza-From the
Revista Espanola De Cardiologia, 2011
Se referió para una coronarografía a un varó n de 73 añ os que acudió a urgencias por una angina ... more Se referió para una coronarografía a un varó n de 73 añ os que acudió a urgencias por una angina de novo. El procedimiento se realizó vía arteria radial derecha con un introductor de 6 Fr. Se administraron 10 mg de verapamilo y 5.000 U de heparina por vía intraarterial. Al retirar el introductor se observó una estructura tubular en el lugar de punció n. Ante la sospecha de que pudiera ser el endotelio, se realizó una ligadura y se resecó. El estudio Doppler demostró que el flujo radial era patente y el paciente fue dado de alta. En el seguimiento al mes, el pulso radial apenas era perceptible, pero el paciente permanecía asintomá tico. En el estudio anatomopatoló gico, se observó una estructura de 2 Â 29 mm (fig. 1). El examen microscó pico determinó que se trataba de una arteria muscular. Sorprendentemente, las tres capas del vaso estaban presentes. La adventicia se situaba entre la media y la íntima, por lo que se había producido una eversió n parcial de la arteria (figs. 2 y 3). En el caso presentado, el pulso radial era patente tras la avulsió n de la arteria, lo que podría explicarse si el fragmento de arteria fuera una rama menor que emergiera de la arteria radial o si no se hubiera extraído parte de la adventicia dejando un canal permeable. La extracció n total de la arteria radial es una complicació n infrecuente que, aunque parezca grave, no difiere de la trombosis de la arteria radial y rara vez se acompañ a de síntomas de isquemia.
Circulation, Nov 26, 2013
Archives Des Maladies Du Coeur Et Des Vaisseaux Pratique, 1997
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Papers by Gilbert Gosselin