Abstract
Background:
Medically managed individuals represent a high-risk group among patients with non–ST-elevation acute myocardial infarction (NSTE-AMI). We hypothesized that prognosis in this group is heterogeneous, depending on whether medical management was decided with or without coronary angiography (CAG).
Methods:
Using data from the French Registry of Acute ST-Elevation or Non–ST-Elevation Myocardial Infarction (FAST-MI), we analysed data from 798 patients with NSTE-AMI who were medically managed (i.e. without revascularization during the index hospitalization). Patients were categorized according to the performance of CAG and, if performed, to the extent of coronary artery disease (CAD).
Results:
There were marked differences in baseline demographics, according to whether CAG was performed and to the extent of CAD. While the overall mortality rate at five years was high (56.2%), it differed greatly between groups, with patients who did not undergo CAG having a higher mortality rate (77.4%) than patients who underwent CAG (36.7%, p<0.001), and a higher mortality rate even than patients with multivessel CAD (54.2%, p<0.001). By multivariable analysis, non-performance of CAG was an independent predictor of all-cause mortality among medically managed NSTE-AMI patients (adjusted hazard ratios (95% confidence intervals) 3.19 (1.79–5.67) at 30 days, 2.28 (1.60–3.26) at one year, and 1.63 (1.28–2.07) at five years; all p<0.001).
Conclusion:
Medically managed patients with NSTE-AMI are a heterogeneous group in terms of baseline characteristics and outcomes. The highest risk patients are those who do not undergo CAG. Non-performance of CAG is a strong predictor of death. (FAST-MI, NCT00673036).
Keywords
Introduction
Early coronary angiography (CAG) with intent for myocardial revascularization has become the standard of care for patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS) at moderate to high risk.1,2 However, a sizeable proportion of patients with NSTE-ACS do not undergo CAG.3–8 This is not related solely to a lack of access to CAG or to patient refusal, but is due to a variety of reasons. Some patients may not undergo CAG because they are considered at too low risk of recurrent cardiovascular events to warrant an invasive strategy. Conversely, other patients are deemed ‘too sick’ to undergo CAG because of advanced age or severe comorbidities. Even among patients with NSTE-ACS who did undergo CAG, up to one-third of the patients with significant coronary artery disease (CAD) did not undergo revascularization in recent randomized trials,6,9,10 due to either a low risk of recurrent coronary events or a high risk of periprocedural complications related to an unfavourable coronary anatomy, severe left ventricular dysfunction or advanced comorbidities.9,10
Medically managed patients (i.e. who do not undergo myocardial revascularization) have a worse outcome than patients who undergo intervention.3, 9–11 This finding has stimulated an assessment of the efficacy of novel antithrombotic agents in this group of patients, albeit with mixed results.6,7,12,13 We hypothesized that medically managed patients with NSTE-ACS are a heterogeneous group in terms of their baseline characteristics and outcomes, and specifically that the mere decision to perform CAG, as well as the extent of CAD, would have strong associations with long-term outcomes. To test these hypotheses, we analysed data from the French Registry of Acute ST-Elevation or Non–ST-Elevation Myocardial Infarction (FAST-MI) with the aims of studying the impact of the non-performance of CAG and of the extent of CAD on five-year mortality.
Methods
Patients
The methods and results of FAST-MI have been published.14,15 Briefly, FAST-MI is a nationwide observational registry of patients with an initial diagnosis of acute myocardial infarction (AMI) recruited consecutively in 223 French centres over a period of one month (over two months for diabetic patients) starting on 1 October 2005. All patients aged ⩾18 years were included in the registry if they had elevated troponin or creatine kinase-MB levels, and recent (⩽48 h) symptoms compatible with an AMI, new pathological (⩾40 ms) Q waves on at least two contiguous leads, or persistent ST-segment elevation or depression ⩾0.1 mV. The study complied with the Declaration of Helsinki, the protocol was approved by the Committee for the Protection of Human Subjects in Biomedical Research of Saint-Antoine University Hospital, and patients gave informed consent for participation in the registry.
For the purpose of the present analysis, we focused on medically managed patients with non–ST-segment elevation AMI (NSTE-AMI), we excluded those with ST-segment elevation AMI (STE-AMI) – defined as persistent ST-segment elevation or presumably new left bundle branch block on the initial diagnostic electrocardiogram – as well as patients treated with either percutaneous or surgical revascularization during the index hospital stay. Patients were then categorized according to whether they underwent CAG during the index hospital stay; and, for those who did undergo CAG, according to the extent of CAD (i.e. no or minimal, single-vessel, or multivessel CAD). Significant CAD was defined as the presence of at least one luminal diameter stenosis of ⩾50% by visual estimation. Patients with a history of coronary artery bypass graft surgery (CABG) who underwent CAG were categorized as having multivessel CAD.
Outcomes
The primary clinical outcome was all-cause mortality at five years after admission. Secondary clinical outcomes were all-cause mortality at 30 days and at one year after admission; and cardiovascular and non-cardiovascular mortality at five years after admission. Cardiovascular mortality was defined as death related to myocardial infarction, stroke, or aortic/peripheral artery disease. The primary analysis was a comparison of clinical outcomes between patients who underwent CAG versus patients who did not undergo CAG. The secondary analysis investigated whether the extent of CAD had an effect on clinical outcomes.
Statistical analysis
Comparisons of baseline characteristics between groups were performed using Pearson’s chi-squared test or Fisher’s exact test for categorical variables, and Student’s t test, the Mann-Whitney U test, or the Kruskal-Wallis test for continuous variables, as appropriate.
Total numbers and Kaplan–Meier estimated rates of mortality at 30 days, one year, and five years after the index event–along with hazard ratios (HRs) and 95% confidence intervals (CIs), and p values from unadjusted Cox proportional hazards regression models–are presented according to performance of CAG (primary analysis) and extent of CAD (secondary analysis). The group of patients who underwent CAG was used as the reference in the primary analysis and the group with no or minimal CAD was used as the reference in the secondary analysis.
A multivariable Cox regression model was used to examine the association between performance of CAG and mortality, and the association between the extent of CAD and mortality, at 30 days, one year, and five years. To better define whether mortality risk difference according to performance of CAG varied over time, we performed an additional landmark analysis of all-cause mortality from hospital admission to 30 days, 30 days to one year, and 1–5 years.
Variables used in this adjusted model included the admission Global Registry of Acute Coronary Events (GRACE) 2.0 score, baseline clinical characteristics, and medications received in the first 48 h. In the survival landmark analysis, we added statin treatment at hospital discharge for the period from 30 days to one year, and statin treatment at one year for the period from 1–5 years.
For the primary analysis comparing patients who did or did not undergo CAG, two sensitivity analyses were performed: (a) excluding patients who died during the index hospitalization, and (b) excluding patients who died during the index hospitalization and survivors who underwent revascularization during the five-year follow-up. These analyses allowed for additional adjustment on medical treatment and left ventricular ejection fraction at discharge. Since CAG is likely to be performed more frequently in hospitals with a cardiac catheterization laboratory available on site versus those without, and mortality might have been influenced by hospital type, two additional sensitivity analysis were performed in which five-year all-cause mortality was analysed by hospital type and after adding hospital type as a covariable in the Cox model.
All p values are two-sided. A p value of 0.05 was considered significant. All analyses were performed using the IBM-SPSS 20.1 software.
Results
A total of 3670 patients were enrolled in FAST-MI (1872 with STE-AMI and 1798 with NSTE-AMI). The population for this analysis comprised 798 patients with NSTE-AMI who were managed medically, of whom 418 (52.4%) underwent CAG and 380 (47.6%) did not undergo CAG during the index hospitalization (Figure 1). Among the medically managed patients who underwent CAG, 123 (29.4%) had no or minimal CAD, 98 (23.4%) had single-vessel CAD, and 197 (47.1%) had multivessel CAD.
Flow chart of the French Registry of Acute ST-Elevation or Non–ST-Elevation Myocardial Infarction (FAST-MI) study population. Patients included in this analysis are indicated by a grey frame. Patients with a history of coronary artery bypass graft surgery who underwent coronary angiography (CAG) were categorized as having multivessel coronary artery disease (CAD). NSTE-AMI: non–ST-elevation acute myocardial infarction; STE-AMI: ST-elevation acute myocardial infarction.
Baseline characteristics
The study population consisted predominantly (56.6%) of men; mean±standard deviation (SD) age was 74±13 years. There were marked differences in baseline characteristics according to whether CAG was performed and according to the presence and extent of CAD (Table 1). Patients who did not undergo CAG were older and more frequently women, and had a higher prevalence of hypertension but a lower prevalence of family history of premature CAD, dyslipidaemia, and smoking. They also had a more frequent history of myocardial infarction, chronic heart failure, stroke or transient ischaemic attack, and peripheral artery disease; a higher prevalence of chronic kidney disease; and higher Killip class and mean GRACE risk score on admission.
Patient baseline characteristics and prescribed therapies during index hospitalization.
ACE: angiotensin-converting enzyme; ARB: angiotensin II receptor blockers; CABG: coronary artery bypass graft surgery; CAD: coronary artery disease; CAG: coronary angiography; COPD: chronic obstructive pulmonary disease; GRACE: Global Registry of Acute Coronary Events; NSTE-AMI: non–ST-elevation acute myocardial infarction; TIA: transient ischaemic attack.
Values are numbers (%) or means±standard deviation (SD). Percentages were calculated after excluding missing data.
Value of p for CAG performed versus CAG not performed; bglobal p value for multiple comparisons between patients who underwent CAG according to extent of CAD; cdefined as serum creatinine levels ⩾2 mg/dl, or history of kidney transplantation or haemodialysis; dpercentages are calculated for patients who were discharged alive after index hospitalization (overall, n=713; CAG not performed, n=315; CAG performed, n=398; no or minimal CAD, n=121; single-vessel CAD, n=95; multivessel CAD, n=182).
Important differences in baseline characteristics were also found between patients who underwent CAG according to the extent of CAD, where a greater extent of CAD was associated with higher risk baseline characteristics, including: older age; predominantly male sex; higher prevalence of diabetes mellitus, hypertension, dyslipidaemia, chronic kidney disease, prior myocardial revascularization or AMI, and chronic heart failure; more frequent history of stroke or transient ischaemic attack, and peripheral artery disease; and higher Killip class and mean GRACE risk score.
Outcomes
Overall, 10.2% of medically managed patients with NSTE-AMI had died at 30 days, 26.9% at one year, and 56.2% at five years. All-cause mortality rates were consistently higher in patients who did not undergo CAG versus those who did, at 30 days (16.8% vs 4.1%, p<0.001), at one year (42.9% vs 12.4%, p<0.001), and at five years (77.4% vs 36.7%, p<0.001) (Table 2 and Figure 2(a)).
Relationships between performance of coronary angiography (CAG) during the index hospitalization, severity of coronary artery disease (CAD), and all-cause death: unadjusted and adjusted analysis.
CABG: coronary artery bypass graft; CI: confidence interval; HR: hazard ratio; KM : Kaplan–Meier; Ref: reference group.
Values are numbers and Kaplan–Meier rates or HRs and 95% CIs.
Adjusted for the admission Global Registry of Acute Coronary Events (GRACE) score, baseline clinical characteristics, and medications received in the first 48 h.
Kaplan–Meier survival curves up to five years according to the performance of coronary angiography (CAG) during the index hospitalization and the extent of coronary artery disease (CAD).
In the group who underwent CAG, all-cause mortality increased with the extent of CAD, due to consistently higher all-cause mortality rates in patients with multivessel CAD versus patients with no or minimal CAD (Table 2 and Figure 2(b)). At five years, all-cause mortality rates were 19.3% in patients with no or minimal CAD, 23.7% in patients with single-vessel CAD, and 54.2% in patients with multivessel CAD (p<0.001 for the comparison between the three subgroups). All-cause mortality at five years was lower in these three subgroups, even in patients with multivessel CAD, than among patients who did not undergo CAG (all p<0.001).
By multivariable analysis, non-performance of CAG during the index hospitalization was an independent predictor of all-cause mortality among medically managed patients with NSTE-AMI (Table 2). This finding was consistent at 30 days, one year and five years (all p<0.001). Among patients who underwent CAG, the presence of multivessel CAD was an independent predictor of all-cause mortality at one year (p=0.01) and at five years (p=0.001) (Table 2). Non-performance of CAG and multivessel CAD were also independent predictors of both cardiovascular mortality and non-cardiovascular mortality at five years (see Supplementary Material, Table).
In addition, the results from a landmark analysis (see Supplementary Material, Figure) suggested that the difference in all-cause mortality between patients who did or did not undergo CAG increased steadily during the 30 days after the index event (16.8% vs 4.1%; adjusted HR 3.19 (95% CI 1.79–5.67); p=0.001), from 30 days to one year (31.3% vs. 8.8%; adjusted HR 2.03 (95% CI 1.27–3.24); p=0.001), and also from 1–5 years (39.8% vs. 27.4%; adjusted HR 1.44 (95% CI 1.05–1.98); p=0.01).
In a sensitivity analysis excluding 75 patients (9.4% of medically managed patients) who died during the index hospitalization, adjusted HR for all-cause mortality was 1.82 (95% CI 1.39–2.37) at five years in patients who did not undergo CAG versus patients who underwent CAG during the index hospitalization (p<0.001). Similar results were found in a second sensitivity analysis excluding the 75 patients who died during the index hospitalization and 68 patients (9.4% of hospital survivors) who underwent myocardial revascularization over the five-year follow-up (adjusted HR for five-year all-cause mortality was 1.77 (95% CI 1.35–2.33); p<0.001). In two additional sensitivity analyses, adjusted HR for all-cause mortality at five years in patients who did not undergo CAG during the index hospitalization versus patients who did, were not different whether they were admitted in hospitals with (adjusted HR 1.69 (95% CI 1.14–2.52); 61% of patients underwent CAG) or without (adjusted HR 1.63 (95% CI 1.20–2.22); 39% of patients underwent CAG) a cardiac catheterization laboratory available on-site, or whether the on-site availability of a cardiac catheterization laboratory was added as a covariable in the Cox model (adjusted HR unchanged).
Discussion
The main finding of this analysis from the FAST-MI registry is that the non-performance of CAG is an independent predictor of all-cause mortality at five years in medically managed patients with NSTE-AMI. The presence of multivessel CAD in medically managed patients who did undergo CAG was also an independent predictor of all-cause mortality at five years; however, even in patients with multivessel CAD, mortality remained lower than in patients who did not undergo CAG.
Medically managed patients with NSTE-ACS
Current guidelines advocate early invasive management in NSTE-ACS, particularly for patients who are at moderate to high risk of death or recurrent myocardial infarction.1,2 Such an invasive approach, on a background of optimal medical therapy, has led to dramatic improvements in the prognosis of patients with NSTE-ACS, including higher survival rates.5,16 However, 9–27% of patients with NSTE-ACS enrolled in recent clinical trials not requiring planned invasive management,6–8 and as many as 26–39% of NSTE-ACS registry patients,3–5 did not undergo CAG. Furthermore, in patients with NSTE-ACS who underwent CAG, approximately 10% had no significant CAD, while 12–32% of those with significant CAD eventually did not undergo revascularization.6,9,10 Hence, revascularization rates barely exceed 60% in most contemporary clinical trials of NSTE-ACS,6,7 and 50% in NSTE-ACS registries.3–5 The increased mortality of medically managed patients with NSTE-ACS has been consistently reported in both retrospective analyses of randomized clinical trials9,10 and in registries.3,11 It thus appears that medically managed patients with NSTE-ACS represent a sizable group of individuals with poor outcomes despite recent advances in medical therapies.
Study strengths
Our results add to the characterization of this group in several ways. First, medically managed patients with NSTE-AMI display very high mortality rates at five years (56%). Prior reports of long-term follow-up of patients with NSTE-AMI in the GRACE UK-Belgian 17 and Duke 18 registries found mortality rates of 22% at five years and 45% at four years, respectively. However, the majority of these patients were managed invasively. Lower mortality rates (8–12%) were recently reported in medically managed patients recruited in randomized clinical trials, but these patients were at lower risk and the duration of follow-up was shorter (12–30 months).9,10,13
Second, patients who did not undergo CAG during the index hospitalization (48% of the study population) displayed the poorest prognosis among medically managed patients with NSTE-AMI, with a five-year all-cause death rate of 77.4% versus 36.7% in patients who underwent CAG. In an earlier report from this registry, 15 as well as in the Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines (CRUSADE) registry, 11 higher short-term and long-term mortality rates were found in patients with NSTE-AMI who did not undergo early CAG versus patients who were treated with an early invasive approach (regardless of whether CAG was followed by revascularization). Since in both studies the lower death rates of revascularized patients may contribute to some extent to the better prognosis of invasively managed patients, we restricted the present analysis to non-revascularized patients to better define the prognostic impact of not performing CAG in medically managed patients. The strikingly high mortality rate of patients who did not undergo CAG in the present report is unlikely to be causally linked to non-performance of CAG per se, as suggested by the observation that not only cardiovascular mortality, but also non-cardiovascular mortality, were higher in these patients versus patients who underwent CAG. Rather, it points to the previously reported paradox according to which, in a real-life setting, an invasive strategy is used less frequently in NSTE-ACS patients at highest risk of recurrent ischaemic events, who would derive more benefit from revascularization than their lower risk counterparts. 19 In fact, we observed that patients who did not undergo CAG had higher Killip class and GRACE risk score. Both a higher baseline risk and more severe long-term outcomes were also reported in medically managed NSTE-ACS patients who did not undergo CAG in recent retrospective analyses of the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) and Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) randomized trials.6,20 Interestingly, the mortality rates of medically managed patients who did not undergo CAG were much higher in FAST-MI than in TRILOGY ACS (77.4% at five years vs 9.6% at 30 months), due to the remarkably higher risk profile of the FAST-MI patients (mean age of 80 years versus 63 years, female sex in 51% vs 38%, Killip class ⩾2 in 55% vs 12%, and mean GRACE risk score of 178 vs 117, respectively). The landmark analysis indicated that the survival curves of patients who did or did not undergo CAG separated early and diverged steadily over the five-year follow-up, suggesting that the higher risk burden of patients who did not undergo CAG is durable. Along the same lines, the fact that the availability of an on-site cardiac catheterization laboratory did not influence five-year mortality (even though it was associated with more frequent performance of CAG) reflects on the major impact of baseline risk, rather than of the hospital type, on long-term mortality of medically managed NSTE-AMI patients.
Third, the absence of revascularization did not reflect a ‘lenient’ policy regarding invasive management of NSTE-AMI in the FAST-MI registry. Indeed, 52.4% of medically managed patients did undergo CAG during the index hospitalization. Among these patients, 29.4% had no or minimal CAD, a figure similar to that reported in the medically managed patients in the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial (26.4%). 12 In contrast, 51.8% of medically managed patients who underwent CAG had no significant CAD in the TRACER trial, a study in which significance of CAD was set at ⩾70% stenosis (vs ⩾50% in the present registry) and patients without troponin elevation could be included, hence favouring the inclusion of more patients without angiographic CAD. 6 Conversely, only 17% of the patients included in the TRILOGY ACS trial, which recruited exclusively patients selected for management without revascularization, had no significant CAD, 20 the difference with our results being explained by the exclusion of patients without at least one stenosis >30% in TRILOGY ACS. In our study, as well as in the TRACER 6 and TRILOGY ACS 20 trials and the CRUSADE registry, 21 the demographic characteristics of patients with no or minimal CAD indicated both a lower baseline risk – reflected by a lower GRACE risk score – and a better prognosis than patients with significant CAD.
Fourth, there was a gradual increase in risk profile and five-year mortality with the number of diseased coronary arteries. Compared to patients with no or minimal CAD, patients with one-vessel CAD and, more markedly, patients with multivessel CAD (including those with a history of CABG), were older and more often men, had a higher atherosclerotic burden, and presented with higher GRACE risk scores and Killip classes. All-cause mortality also increased with the extent of CAD, with the lowest five-year mortality in patients with no or minimal CAD (19.3%) and the highest mortality in patients with multivessel CAD (54.2%). Similar trends of higher mortality with increasing burden of coronary atherosclerosis have been reported previously in medically managed NSTE-ACS patients recruited in the ACUITY trial, albeit with a shorter follow-up (one year) and an overall mortality risk that was considerably lower than in the FAST-MI cohort. 12 There is no doubt that the decision not to proceed to revascularization in patients with the most extensive forms of coronary atherosclerosis stemmed from an appropriate evaluation of both patient characteristics and coronary anatomy. However, the prognosis of these medically managed NSTE-ACS patients with multivessel CAD remains alarmingly poor.
Finally, we found that patients who did not undergo CAG stood at the extreme end of the spectrum of medically managed patients with NSTE-ACS in terms of risk profile and outcomes, even when compared to patients with the most extensive forms of CAD, a reminder of the prior observation that those patients who cannot perform a non-invasive test to detect myocardial ischaemia, due a higher risk profile or a multiplicity of comorbidities, have a worse prognosis than those who underwent the test irrespective of its result. 22
Perspectives for improvement of care
The poor prognosis of medically managed patients with NSTE-AMI is a matter of concern and several approaches might be considered to improve their outcomes. Whether a more aggressive use of invasive procedures is needed, either acutely or at a later stage, warrants further study. Also, better care should be taken to provide optimal medical therapy to these patients. Indeed, the decisions not to perform early CAG in the CRUSADE registry, 23 or not to proceed to revascularization in the GRACE 24 and in the Kaiser Permanente Northern California 25 registries, have been associated with suboptimal concomitant use of guideline-directed drug treatments. Recently, more potent inhibitors of the P2Y12 receptor have been compared with clopidogrel in medically managed patients with NSTE-ACS on aspirin. In the TRILOGY ACS trial, 20 prasugrel did not demonstrate a clear advantage over clopidogrel in the overall population. However, in an exploratory subgroup analysis comparing patients who had a CAG before enrolment (43% of the total population) and those who had not, the primary endpoint of cardiovascular death, myocardial infarction, or stroke was reduced (by 23%) only in patients who underwent CAG and had significant CAD. 20 Similarly, in a retrospective analysis of the NSTE-ACS patients recruited in the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor reduced the same primary endpoint (by about 15%), as well as all-cause mortality (by about 25%), in both revascularized and medically managed patients. 7 Further studies specifically dedicated to medically managed patients with NSTE-ACS are clearly warranted.
Study limitations
First, patients were recruited in FAST-MI in 2005 over a two-month period. Standards of care used for these patients may not fully apply to more contemporary cohorts, and sample size is by design smaller than other ACS registries that recruited patients over many years.3–5,11,25,26 However, all of these other ACS registries were started between 1999–2007, their longest reported follow-up is at five years, 17 and they have thus far provided little information with respect to long-term outcomes in medically managed patients. FAST-MI is therefore the most contemporary registry of acute coronary syndromes providing five-year outcomes in medically managed NSTE-AMI patients. Second, by design this is a post-hoc, subgroup analysis of medically managed patients with NSTE-AMI in a large prospective AMI registry. Even though multivariable adjustment was used to compare outcomes between these groups, residual confounding cannot be ruled out. Third, the reasons not to perform CAG were left to the discretion of the treating physicians and were not captured. Hence, it is possible that in some cases CAG was not performed for reasons unrelated to baseline risk (e.g. technical issues or patient refusal). Fourth, our results may have been influenced by the definition of the medically managed status, which included patients who died during the index hospitalization (before CAG could be considered), as well as patients who were not revascularized initially but underwent myocardial revascularization during follow-up, thus introducing potential biases favouring survival in the group who underwent CAG; however, even after excluding these patients in two sensitivity analyses, the mortality rates of patients who did not undergo CAG remained higher. Finally, as the mean age of the study population was 74 years, our results may not apply to younger patients, such as those encountered in emerging countries.
Conclusions
Medically managed patients with NSTE-AMI are a heterogeneous group in terms of baseline characteristics and outcomes. The non-performance of CAG is a powerful marker of risk. Patients who did not undergo CAG had the highest five-year mortality, even higher than that of patients with the most extensive forms of coronary atherosclerosis who did not undergo revascularization. At the other end of the spectrum, patients with no or minimal CAD fared well. Clinical trials aimed at improving the dire prognosis of medically managed patients with NSTE-ACS are warranted and should take into account this heterogeneity to better define optimal care in such patients.
Footnotes
Acknowledgements
The authors are indebted to all participating physicians; to Nadine Roumier, from International Clinical Trials Association (Fontaine-lès-Dijon, France); to the personnel of Unité de Recherche Clinique Paris Est (URC-EST) under the leadership of Elodie Drouet and of INSERM unit 1027 (Toulouse); to Vincent Bataille, for his careful data management; to Benoît Pace (Société Française de Cardiologie) for designing the electronic case report form; and to Geneviève Mulak, Frédérique Fortin and the registry committee of the Société Française de Cardiologie. Editorial support was provided by Sophie Rushton-Smith of MedLink Healthcare Communications Limited.
Conflict of interest
L Feldman has received research grants from Sanofi and Bristol-Myers Squibb. PG Steg has received research grant (to INSERM U1148) from NYU School of Medicine, Sanofi, and Servier; speaking or consulting fees from Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Medtronic, Novartis, Pfizer, Roche, Sanofi, Servier, The Medicines Company; and owns stocks from Aterovax. J Ferrières has received research grants from Amgen, CNIEL and Merck; and lecture fees from Amgen, AstraZeneca, Merck and Sanofi; T Simon has received research grants from Pfizer and Servier for the FAST-MI registry; speaking fees from Sanofi and Eli Lilly; and has served as a board member for Bayer. N Danchin has received research grants from AstraZeneca, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, MSD, Novartis, Sanofi-Aventis, Servier, and The Medicines Company; and has served on advisory panels or received lecture fees from Amgen, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli-Lilly, Menarini, Merck-Serono, Novo-Nordisk, Roche, Servier, and Sanofi-Aventis. All other authors have reported that they have no relationship relevant to the contents of this paper to disclose.
Funding
This work was supported by unrestricted grants from Pfizer and Servier to the French Society of Cardiology and an additional grant from the Caisse Nationale d’Assurance-Maladie-Travailleurs Salariés. The sponsors had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the manuscript.