Literature Review 7 pages

Journal of Cardiology 68 (2016) 498–503

Original article

Treatment and outcomes of patients with recurrent myocardial infarction: A prospective observational cohort study§

Dragana Radovanovic (MD)a,*, Lea Maurer (BMed)a, Osmund Bertel (MD)b, Fabienne Witassek (MSc)a, Philip Urban (MD)c, Jean-Christophe Stauffer (MD)d, Giovanni Pedrazzini (MD)e, Paul Erne (MD)f

a AMIS Plus Data Center, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland b Cardiology Center, Klinik im Park, Zurich, Switzerland c Cardiovascular Department, La Tour Hospital, Geneva, Switzerland d Service de Cardiologie, Hôpital Cantonal, Fribourg, Switzerland e Division of Cardiology, Cardiocentro Ticino, Lugano, Switzerland f AMIS Plus, Zurich, Switzerland

A R T I C L E I N F O

Article history:

Received 28 September 2015

Received in revised form 24 November 2015

Accepted 28 November 2015

Available online 6 January 2016

Keywords:

Acute myocardial infarction

STEMI

Recurrent myocardial infarction

Treatment

Outcome

A B S T R A C T

Background: Little is known about differences in therapies and outcomes of patients with first

myocardial infarction (MI) or recurrent MI (reMI). This study aimed to evaluate the impact of prior MI on

therapies and outcomes in patients who presented with ST-elevation MI (STEMI).

Methods: All STEMI patients enrolled from 2002 to 2014 in the AMIS Plus registry were included.

Outcome was analyzed using logistic multivariate regression.

Results: From 19,665 STEMI patients, 2845 (14%) had reMI. These patients were older (69.5y vs. 64.2y;

p < 0.001), more frequently male, with more risk factors (hypertension, dyslipidemia), and more

comorbidities. Patients with reMI presented 25 min earlier than those with first MI, were more

frequently in Killip class 3/4 (12% vs. 7%; p < 0.001), and were less likely to receive guideline-

recommended drug therapy: aspirin (93% vs. 97%; p < 0.001), P2Y12 inhibitors (76% vs. 83%; p < 0.001),

or statins (73% vs. 77%; p < 0.001), or undergo primary percutaneous coronary intervention (77% vs. 87%;

p < 0.001). These patients developed more frequently cardiogenic shock (7% vs. 5%; p < 0.001) and

reinfarction (2% vs. 1%; p < 0.001) during hospitalization, and had higher crude mortality (10% vs. 5%;

p < 0.001) than patients without prior MI. Prior MI was an independent predictor of in-hospital mortality

in STEMI patients (OR 1.27; 95% CI 1.05–1.53; p < 0.001).

A subgroup (n = 4486) was followed 1 year after discharge (3893 with first MI and 593 with reMI at

initial hospitalization). Crude mortality was 2.9% for patients with first MI vs. 6.7% for those with reMI

(OR 1.68, 95% CI 1.14–2.47; p = 0.008).

Conclusions: Although patients with reMI are high-risk patients, they were less likely to receive

evidence-based treatment and had worse in-hospital and 1-year outcomes compared to patients with

first MI. Short- and long-term management of patients with recurring MI should be improved.

� 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Contents lists available at ScienceDirect

Journal of Cardiology

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / j j c c

Introduction

Survivors of acute myocardial infarction (AMI) have a substan- tial risk of recurrent infarction after discharge. In the HORIZONS AMI Trial, a prospective study of patients with ST-elevation

§ ClinicalTrials.gov Identifier: NCT01305785.

* Corresponding author at: AMIS Plus Data Center, Epidemiology, Biostatistics

and Prevention Institute (EBPI), University of Zurich, Hirschengraben 84,

8001 Zurich, Switzerland. Tel.: +41 44 634 48 34; fax: +41 44 634 49 86.

E-mail address: [email protected] (D. Radovanovic).

http://dx.doi.org/10.1016/j.jjcc.2015.11.013

0914-5087/� 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights

myocardial infarction (STEMI) who were all treated with primary percutaneous coronary intervention (PCI), the 3 year incidence of recurrent myocardial infarction (MI) was 6.9% [1]. Many studies that investigated various factors which could be associated with a reduced risk of recurrent MI such as drugs, risk factors, or comorbidities, emphasize the importance of secondary prevention after the first coronary event [2–7].

However, little is known about pretreatment, presentation patterns, in-hospital treatment, and outcome of patients with reinfarction who are not enrolled in studies of highly selected subgroups of STEMI patients.

reserved.

D. Radovanovic et al. / Journal of Cardiology 68 (2016) 498–503 499

We need to find out what the patients or doctors in charge of the patients have learnt from their experiences of a first MI.

We therefore present data from a nationwide infarction registry on patients who were admitted with STEMI with or without history of prior MI comparing their presentations, in-hospital treatments, outcomes, and 1-year follow-up.

Methods

The AMIS Plus project is an ongoing nationwide prospective cohort of patients admitted with acute coronary syndromes (ACS) to hospitals in Switzerland. It was founded by the Swiss Societies of Cardiology, Internal Medicine, and Intensive Care Medicine in 1997 with the goal to understand the transfer, use, and practicability of knowledge gained from randomized trials in the real world of daily clinical practice. Details have been previously published [8–16].

Among 106 hospitals treating ACS in Switzerland, 83 hospitals temporarily or continuously enrolled patients in AMIS Plus. Participating centers, ranging from community institutions to large tertiary facilities, provided blinded data for each patient through standardized internet- or paper-based questionnaires. All data were checked for completeness, plausibility, and consistency by the AMIS Plus Data Center in the Epidemiology, Biostatistics and Prevention Institute at the University of Zurich, and treating physicians or study nurses were queried when necessary. External monitoring has been carried out regularly since 2010 in randomly selected hospitals using randomly selected cases. The registry was approved by the Supra-Regional Ethics Committee for Clinical Studies, the Swiss Board for Data Security, and all Cantonal Ethics Commissions. Data collection is conducted in accordance with the EU Note for Guidance on Good Clinical Practice CPMP/ECH/135/95 and the Declaration of Helsinki.

The case report form comprised items addressing medical history, comorbidities, known cardiovascular risk factors, clinical presentation, out-of-hospital management, early in-hospital man- agement, reperfusion therapy, hospital course, used or planned diagnostic tests, length of stay, drugs taken regularly before admission, discharge medication, and discharge destination. Patients were enrolled on the basis of their final discharge diagnosis.

Information on known risk factors was obtained from the patient’s medical history. Patients were stated as having dyslipi- demia, arterial hypertension, and diabetes if they had been previously treated for such a condition and/or diagnosed by a physician. Patients were defined as obese if the body mass index was �30 kg/m2 and as smokers if they smoked at the time of the cardiovascular event. Patient comorbidities were assessed using the Charlson Index [17,18]. Immediate drug therapy was defined if administered within 24 hours after admission. Bleeding complica- tions were recorded if deemed clinically relevant by the individual physician in charge of the patient, without the use of a classification system when data collection started. Reinfarction was defined as clinical signs or symptoms of ischemia with electrocardiographic changes indicative of new ischemia [new ST- changes or new left bundle branch block (LBBB)] and a re-rise of biomarkers following the initial infarction. A stroke was defined as any event due to ischemic, thrombotic, or hemorrhagic distur- bances confirmed by a neurologist or imaging modality.

The primary outcome measure was in-hospital mortality. Secondary outcome measures were the rates of in-hospital major adverse cardiac or cerebrovascular events (MACCE) defined as a composite endpoint of mortality, reinfarction, and cerebrovascular events. An additional outcome measure in a subgroup of patients was 1-year mortality.

Patient selection

The present analysis included all STEMI patients enrolled in AMIS Plus between 2002 and 2014. STEMI was defined by characteristic symptoms, ST-segment elevation or new LBBB on the initial electrocardiogram and cardiac marker elevation (creatine kinase MB fraction at least twice the upper limit of normal, or troponin I, troponin T, or high-sensitive troponin above individual hospital cut-off levels for AMI).

In addition, patients were divided into two groups according to medical history of previous MI and compared in terms of presentations, treatments, and outcomes.

Subgroup analyses of 1-year mortality after discharge were performed using patients enrolled from 2006 to 2014, who had signed an informed consent form for follow-up participation.

Statistical analysis

The results are presented as percentages for categorical variables and analyzed using the non-parametric Pearson chi- square test or Fisher’s exact test as appropriate. Continuous normally distributed variables are expressed as means � 1 standard deviation (SD) and compared using the Student’s two-tailed unpaired t-test. Continuous non-normally distributed variables are expressed as median and interquartile ranges and analyzed using the Mann– Whitney U test. The differences in clinical signs at presentation, risk factors, comorbidities, and therapies between the groups were additionally adjusted for age and gender.

A univariate analysis was carried out using all available variables and only calculated for patients with no missing variables. To determine which patient characteristics were independent predictors of in-hospital mortality a multivariate logistic regression model was first performed using the following variables: past history of MI, age, sex, Killip class >2, the risk factors dyslipidemia and hypertension, and the comorbidities diabetes, renal disease, cardiovascular disease, cancer, gastric, and chronic lung diseases. Comorbidities were also expressed as a Charlson comorbidity weighted index >1 [17,18]. To assess the impact of time, the time period of the event was also included in the regression model. To determine all independent predictors of in-hospital mortality, the guideline-recommended reperfusion and drug therapies [19] were additionally included in the regression model. The results of logistic regression analysis are reported as an odds ratio (OR) with a 95% confidence interval (95% CI). A probability value of p less than 0.05 was considered significant. The IBM SPSS Statistics Version 22 (Armonk, NY, USA: IBM Corp.) was used for statistical analyses.

Results

Between 2002 and 2014, a total of 20,551 patients with STEMI were enrolled in the AMIS Plus cohort and 19,665 (95.7%) had valid data on past history of MI and were included in this study (Fig. 1).

Of the patients, 2845 (5%) had prior MI. Table 1 shows the baseline characteristics of these patients compared to the 16,820 patients with first STEMI. Patients admitted with recurrent MI were 4 years older in mean age, more often male, presented frequently with less pain and more dyspnea, more atrial fibrillation, and were more often in Killip class 3 or 4 at admission. They more frequently had hypertension, dyslipidemia, and more comorbidities. Patients with recurrent MI suffered their prior MI, a median of 49 months (IQR 21–96 months) previously. The first medical contact median was 25 minutes earlier than patients with a first MI and their infarction was smaller, based on the peak CK blood levels (Table 1).

Fig. 1. Flow chart of the patients included in the study. ACS, acute coronary syndromes; STEMI, ST-elevation myocardial infarction; NSTEMI, non-ST-elevation

myocardial infarction; UA, unstable angina; MI, myocardial infarction.

Table 1 Baseline characteristics of STEMI patients with or without prior MI.

With prior MI

Number of patientsa 2845 Sex, female (%) 632 (22.2)

Age in years, mean (SD) 69.5 (12.9)

Delay (symptom onset to FMC), median (IQR) in min 80 (30, 222)

Delay (symptom onset to admission), median (IQR) in min 165 (90, 375)

Resuscitation prior admission (%) 147/2829 (5.2)

Symptoms at admission

Pain (%) 2358/2746 (85.9)

Dyspnea (%) 886/2530 (35.0))

Killip classes >2 (%) 328/2845 (11.5)

Atrial fibrillation (%) 206/2836 (7.3)

Systolic blood pressure (mmHg, mean) (SD) 130 (28)

Heart rate (beat/min, mean) (SD) 79 (23)

Risk factors

Hypertension (%) 2018/2726 (74.0)

Dyslipidemia (%) 2040/2601 (78.4)

Obesity (BMI > 30)(%) 479/2362 (20.3)

Smoking (%) 794/2546 (31.2)

Comorbidities Diabetes (%) 759/2753 (27.6)

Cerebrovascular disease (%) 273/2845 (9.6)

Peripheral vascular disease (%) 269/2845 (9.5)

Renal disease (%) 340/2845 (12.0)

Chronic lung disease (%) 231/2845 (8.1)

Gastric disease (%) 106/2845 (3.7)

Cancer disease (%) 199/2845 (7.0)

Regular medication Aspirin (%) 2173/2741 (79.3)

Oral anticoagulant (%) 306/2671 (11.5)

Laboratory CK, max (IU/l), median (IQR) 665 (233, 1572)

Glycemia (mmol/l), 7.8 (6.4, 10.2)

Creatinine (mmol/l), median (IQR) 91 (77, 116)

STEMI, ST-elevation myocardial infarction; MI, myocardial infarction; FMC, first med a In cases with missing data N = number of patients with available data and n/N = nu

D. Radovanovic et al. / Journal of Cardiology 68 (2016) 498–503500

Immediate therapies are presented in Table 2. Patients with recurrent MI less frequently received guideline-recommended drug therapy, such as aspirin, P2Y12 inhibitors, and statins and were less likely to undergo PCI, even after adjustment for age, gender, risk factors, comorbidities, and year of MI (OR 0.75; 95% CI 0.66–0.86; p < 0.001). Although these patients arrived at hospital with shorter time delays, if they received PCI it was performed later [median 70 min (IQR 29 min, 180 min)] compared to patients with first MI [58 min (IQR 22 min, 121 min; p < 0.001)].

In-hospital complications and outcomes are shown in Fig. 2. Patients admitted for STEMI with recurrent MI developed cardiogenic shock and reinfarction during hospitalization more frequently than patients presenting with their first MI. Bleeding rates and cerebrovascular events were similar between these two groups of patients.

Crude in-hospital mortality was high in patients with recurrent MI (9.7%) compared to patients with first MI (5.4%; p < 0.001).

Results of multivariate regression analysis showed that besides Killip class >2 at admission and known comorbidities, recurrent MI was an independent predictor of in-hospital mortality (OR 1.27; 95% CI 1.05–1.53) (Fig. 3). After adding the guideline-recom- mended therapies for STEMI (PCI and drugs) to this regression model, recurrent MI remained a significant predictor of in-hospital mortality (OR 1.17; 95% CI 0.96–1.43). The rate of the composite endpoint of MACCE, which included reinfarction, stroke, or death in hospital, was higher in patients with a prior MI, 12.0% vs. 6.6% in patients with first STEMI (p < 0.001) (OR adjusted for age and gender 1.52; 95% CI 1.33–1.74; OR adjusted for all variables 1.41; 95% CI 1.19–1.67).

Without prior MI p-value OR adjusted for age

and gender (95% CI)

p-value

16,820 4512 (26.8) <0.001

64.2 (13.4) <0.001

105 (45, 300) <0.001

190 (104, 450) <0.001

980/16,743 (5.9) 0.18 0.96 (0.80–1.15) 0.65

14,495/16,354 (88.6) <0.001 0.87 (0.77–0.98) 0.025

4090/15,078 (27.1) <0.001 1.30 (1.19–1.43) <0.001

1121/16,820 (6.7) <0.001 1.60 (1.40–1.83) <0.001

648/16,758 (3.9) <0.001 1.42 (1.20–1.68) <0.001

134 (28) <0.001

78 (19) 0.008

8495/15,912 (53.4) <0.001 2.15 (1.95–2.36) <0.001

7339/14,747 (49.8) <0.001 3.81 (3.45–4.22) <0.001

2861/14,455 (19.8) 0.58 1.14 (1.02–1.27) 0.020

6792/15,393 (44.1) <0.001 0.79 (0.72–0.88) <0.001

2715/16,143 (16.8) <0.001 1.72 (1.56–1.89) <0.001

703/16,820 (4.2) <0.001 2.03 (1.76–2.33) <0.001

550/16,820 (3.3) <0.001 2.48 (2.12–2.89) <0.001

796/16,820 (4.7) <0.001 2.03 (1.76–2.33) <0.001

715/16,820 (4.3) <0.001 1.66 (1.42–1.94) <0.001

261/16,820 (1.6) <0.001 2.09 (1.65–2.64) <0.001

801/16,820 (4.8) <0.001 1.19 (1.01–1.40 0.041

3686/15,545 (23.7) <0.001 11.5 (10.4–12.7) <0.001

563/15,413 (3.7) <0.001 2.70 (2.32–3.13)) <0.001

1200 (447, 2572) <0.001

7.5 (6.4, 9.5) <0.001

82 (70, 97) <0.001

ical contact; BMI, body mass index; CK, creatine kinase.

mber of patients with characteristics/number of patients with available data.

Table 2 Immediate therapies of STEMI patients with or without prior MI.

With prior MI Without prior MI p-value OR adjusted for age

and gender (95% CI)

p-value

Number of patients 2845 16,820 Aspirin (%) 2629/2834 (92.8) 1625/16,777 (96.9) <0.001 0.49 (0.41–0.58) <0.001

P2Y12 inhibitors (%) 2143/2829 (75.8) 13,926/16,756 (83.1) <0.001 0.49 (0.41–0.58) <0.001

GP IIb/IIIa antagonist (%) 798/2797 (28.5) 5544/16,582 (33.4) <0.001 0.91 (0.83–0.99)) 0.035

Heparins (%) 2413/2827 (85.4) 14,932/16,754 (89.1) <0.001 0.76 (0.67–0.85) <0.001

Beta blocker (%) 1789/2810 (63.7) 10,453/16,670 (62.7) 0.33 1.11 (1.02–1.21) 0.013

ACEI/ARB antagonist 1575/2816 (55.9) 9041/16,677 (54.2) 0.094 1.07 (0.99–1.17) 0.088

Nitrates (%) 1523/2803 (54.3) 8831/16,585 (53.2) 0.29 1.03 (0.95–1.12) 0.41

Statin (%) 2041/2816 (72.5) 12,806/16,685 (76.8) <0.001 0.89 (0.81–0.98) 0.014

Vasopressors (%) 241/2177 (11.1) 1220/13,077 (9.3) 0.011 1.16 (1.00–1.35) 0.045

Intervention PCI (%) 2126/2769 (76.8) 14,389/16,570 (86.8) <0.001 0.67 (0.60–0.74) <0.001

Door-to-balloon time,

median in minutes (IQR)

70

(29, 180)

58

(22, 121)

<0.001

Multivessels treated (%) 237/1578 (15.0) 1331/11,386 (11.7) <0.001 1.25 (1.10–1.45) 0.004

STEMI, ST-elevation myocardial infarction; MI, myocardial infarction; ACEI/ARB, angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist; P2Y12 inhibitors, clopidogrel, prasugrel, or ticagrelor; PCI, percutaneous coronary intervention.

D. Radovanovic et al. / Journal of Cardiology 68 (2016) 498–503 501

A subgroup of 4486 patients who were followed 1 year after discharge showed that those with a past history of MI at initial hospitalization had worse outcomes. From 593 patients with recurrent MI, 6.9% suffered another MI within 1 year after discharge compared to 2.6% of 3893 patients with first MI. Crude mortality was also higher with 6.7% vs. 2.9% (adjusted OR 1.68, 95% CI 1.14–2.47; p = 0.008) (Fig. 4).

Fig. 3. Independent predictors of in-hospital mortality (N = 16,965). OR, odds ratio; CI, confidence interval; MI, myocardial infarction; CV, cardiovascular.

Fig. 2. In-hospital complications and outcomes of ST-elevation myocardial infarction (STEMI) in patients with and without prior myocardial infarction (MI)

(N = 19,665).

Discussion

Our study has several key findings with implications for further improvements in medical care. First, patients with recurrent MI seek help for their discomfort faster although they have less typical symptoms and according to their biomarker levels they also experience a smaller recurrent MI. Second, unexpectedly and in sharp contrast to their poor prognosis, management of patients with reinfarction was less active compared to patients with a first infarction. Despite presenting with shorter delays, they received treatment later and less aggressively with less frequent primary PCI and less intensive medical treatment. The initial treatment in the emergency room of patients with prior MI, however, could possibly be due to the differences in the clinical manifestations between first MI and multiple MI patients.

Independent of the risk factors included in commonly used prognostic scores, reinfarction had a profound impact on short- and long-term mortality as well as other adverse events.

The present study confirms the adverse impact of recurrent STEMI on morbidity and mortality compared with a first AMI. A previous study showed that in high-risk patients with depressed left ventricular function prior infarction, a recurrent MI increased mortality fourfold compared to the index infarctions [20]. A further study of patients with ACS, which included only 20% of STEMI patients, a prior MI was indicative of a worse outcome after 6 months with a twofold higher mortality and a further infarction [21]. Several reasons may explain these observations: recurrent MI

Fig. 4. Outcome 1 year after discharge of patients with ST-segment elevation myocardial infarction (STEMI) (N = 4486). Any intervention, any coronary

intervention; Rehospitalization, due to any cardiovascular problem, diagnostic

procedures, monitoring or/and intervention; MI, myocardial infarction.

D. Radovanovic et al. / Journal of Cardiology 68 (2016) 498–503502

may result in a reduced left ventricular ejection fraction and heart failure and may indicate a more severe and generalized form of coronary artery disease [22]. It has been demonstrated that the plasma level of vascular endothelial growth factor is elevated from day 5 to day 7 in patients with AMI and this positively correlated with left ventricular volume [23]. Thus, in our study, the Killip class was significantly higher in patients with recurrent infarction and risk factors such as diabetes, hypertension, and dyslipidemia were more prevalent. However, even after correction for these factors, reinfarction remained an independent prognostic marker. There- fore, the commonly used risk scores for acute MI may not fully indicate the high risk of these patients. This may in part explain why, in our study, a certain undertreatment was observed in patients with recurrent MI who received less and later invasive and drug treatments despite shorter delays to admission. Moreover, these patients presented more often with dyspnea and not ischemic pain, which may contribute to these shortcomings as seen in other subgroups of female and aged infarction patients. Thus, the well-known ‘‘risk treatment paradox’’ was also present in the recurrent MI patients. This paradox might also apply to the fact that patients with recurrent MI complied insufficiently with secondary prophylaxis as recommended by guidelines at the time of readmission. Given the shorter presentation delays this cannot be due to an ‘‘attenuated’’ patient awareness. Therefore, our data suggest that insufficient secondary prevention at admission combined with suboptimal in-hospital treatment may contribute to the dismal outcome. The use of new cardioprotective strategies, such as n-3 polyunsaturated fatty acids, may reduce plaque burden and stabilize plaque components leading to a reduced rate of complications [24].

It has been reported that the symptoms of recurrent infarction were not similar to those of the first infarction [25]. Data from the Augsburg Coronary Event Registry showed a mismatch of presenting symptoms at first and recurrent AMI and this was highest for dyspnea [26]. The results of our study are in line with these findings.

However, to the best of our knowledge there are scarce data on possible differences in treatment between patients with first and those with recurrent MI. With this study we intended to draw attention to the patients who presented with STEMI and a prior MI. The time period of recurrent MI could be very broad, from just a couple of days or months to decades. This observation should be investigated and the time components need to be analyzed more precisely [27]. It is known that the occurrence of recurrent MI in the first year after STEMI is associated with subsequent mortality [2].

Patients with past history of MI who presented with STEMI are at higher risk than those admitted for a first STEMI. Prior MI is an independent predictor of in-hospital mortality even after adjust- ment for age, additional comorbidities, and worse admission heart function. These patients deserve improved care in hospital and close observation during the post-discharge period.

Limitations

Our study should be interpreted in the context of the following limitations. First, the weaknesses of AMIS Plus are common to all observational studies. Participation is voluntary; the number of participating hospitals varied and might therefore not be entirely representative of all-comers to all hospitals in the country despite the permanent involvement of more than 70% of all hospitals treating MI. Second, this study is not a case-control study and unrecognized biases could occur. Third, the choice of drugs and interventions in patients was at the discretion of the treating physicians, which hence reflects common practice in Switzerland. Although the multivariable model used included a number of

factors, it is likely that other parameters may explain some of the differences between patients with first vs. those with recurrent MI. There were no angiographic data available to evaluate if the involved ischemia region of the recurrent MI was the same as at the first MI or if this was based on in-stent thrombosis. Another limitation is unknown indication/contraindication of the drugs and that we were not able to assess adherence to regularly taken evidence-based therapies in patients who suffered recurrent MI.

However, this study arises from the AMIS Plus cohort with a large number of patients and continuous data collection, which allows a contemporary view of this insufficiently investigated topic.

Conclusions

Patients admitted with STEMI who had prior MI are at high risk. They contact health givers faster, with less typical pain and more often dyspnea and have smaller sizes of MI. They were less likely to receive evidence-based treatment and had worse in-hospital and 1-year outcomes compared to patients with a first MI. Therefore, the conclusions of our study as to improvement in care after a first MI are straightforward: compliance with established secondary prevention measures must be improved by regular follow-up controls and correct prescription of drugs. For the in-hospital setting, physicians must be sensitized to this high-risk group of infarction patients in order to provide them with the complete spectrum of modern infarction management, which has already profoundly changed morbidity and mortality over the last years.

Funding

The AMIS Plus registry is funded by unrestricted grants from the Swiss Heart Foundation and from Abbot AG, Amgen AG, AstraZeneca AG, Bayer AG, B. Braun Medical AG, Biotronik AG, Daiichi-Sankyo/Lilly AG, Johnson & Johnson AG–Cordis Division, A Menarini AG, Mepha Pharma AG, Merck Sharp & Dohme-Chibret AG, Novartis Pharma AG, Pfizer AG, Servier AG, SIS Medical AG, St. Jude Medical, Takeda Pharma AG, Vascular Medical AG, all in Switzerland. The sponsors did not play any role in the design, data collection, analysis, or interpretation of the results.

Competing interests

The authors declare that there is no conflict of interest.

Authors’ contributions

DR: conception and design, analysis and interpretation of data, drafting of the article. LM: analysis of data, critical revision of manuscript for intellectual content. OB: substantial contributions to conception and design, acquisition of data, interpretation of data, critical revision of manuscript for intellectual content. FW: analysis of data, critical revision of manuscript for intellectual content. PU: acquisition of data, interpretation of data, critical revision of manuscript for intellectual content. JCS: acquisition of data, critical revision of manuscript for intellectual content. GP: acquisition of data, critical revision of manuscript for intellectual content. PE: conception and design, acquisition of data, interpre- tation of data, critical revision of manuscript for intellectual content. All authors read and approved the final manuscript.

Acknowledgments

This work has been presented at the ESC 2015 in London.

D. Radovanovic et al. / Journal of Cardiology 68 (2016) 498–503 503

We would like to gratefully thank our sponsors for their financial support. We also thank Jenny Piket for proofreading this manuscript.

AMIS Plus Participants 2002–2014

The authors would like to express their gratitude to the teams of the following hospitals (listed in alphabetical order with the names of the local principal investigators): Aarau, Kantonsspital (P Lessing); Affoltern am Albis, Spital (F Hess); Altdorf, Kantons- spital Uri (R Simon); Altstätten, Spital (PJ Hangartner); Baden, Kantonsspital (U Hufschmid); Basel, St. Claraspital (B Hornig); Basel, Universitätsspital (R Jeger); Bern, Beau-Site Klinik (S Trummler); Bern, Inselspital (S Windecker); Bern, Hirslanden Salem-Spital (T Rueff); Bern, Tiefenauspital (P Loretan); Biel, Spitalzentrum (C Roethlisberger); Bülach, Spital (G Mang); Burgdorf, Regionalspital Emmental (D Ryser), Davos, Spital (W Kistler); Dornach, Spital (A. Droll); Einsiedeln, Regionalspital (S Stäuble); Flawil, Spital (G Freiwald); Frauenfeld Kantonsspital (HP Schmid); Fribourg, Hôpital cantonal (JC Stauffer/S Cook); Frutigen, Spital (K Bietenhard); Genève, Hôpitaux universitaires (M Roffi); Grenchen, Spital (R Schönenberger); Herisau, Kantonales Spital (M Schmidli); Horgen, See Spital (B Federspiel); Interlaken, Spital (EM Weiss); Kreuzlingen, Herzzentrum Bodensee (K Weber); La Chaux-de-Fonds, Hôpital (H Zender); Lachen, Regionalspital (I Poepping); Langnau im Emmental, Regionalspital (A Hugi); Laufenburg, Gesundheitszentrum Fricktal (E Koltai); Lausanne, Centre hospitalier universitaire vaudois (JF Iglesias); Lugano, Cardiocentro Ticino (G Pedrazzini); Luzern, Hirslanden Klinik St. Anna (P Erne); Luzern, Luzerner Kantonsspital (1997–2013 P Erne, since 2014 F Cuculi); Männedorf, Kreisspital (T Heimes); Mendrisio, Ospedale regionale (A Pagnamenta); Meyrin, Hôpital de la Tour (P Urban); Moutier, Hôpital du Jura bernois (C Stettler); Münsingen, Spital (F Repond); Münsterlingen, Kantonsspital (F Widmer); Muri, Kreisspital für das Freiamt (C Heimgartner); Nyon, Group. Hosp. Ouest lémanique (R Polikar); Olten, Kantons- spital (S Bassetti); Rheinfelden, Gesundheitszentrum Fricktal (HU Iselin); Rorschach, Spital (M Giger); Samedan, Spital Oberengadin (P Egger); Sarnen, Kantonsspital Obwalden (T Kaeslin); Schaff- hausen, Kantonsspital (A Fischer); Schlieren, Spital Limmattal (T Herren); Scuol, Ospidal d’Engiadina Bassa (C Neumeier/G Flury); Sion, Hôpital du Valais (G Girod); Solothurn, Bürgerspital (R Vogel); Stans, Kantonsspital Nidwalden (B Niggli); St. Gallen, Kantonsspital (H Rickli); Sursee, Luzerner Kantonsspital (-2013 S Yoon, since 2014J Nossen); Thun, Spital (U Stoller); Uster, Spital (E Bächli); Walenstadt, Kantonales Spital (D Schmidt/J Hellermann); Wetzikon, GZO Spital (U Eriksson); Winterthur, Kantonsspital (T Fischer); Wolhusen, Luzener Kantonsspital (M Peter); Zofingen, Spital (S Gasser); Zollikerberg, Spital (R Fatio); Zürich, Hirslanden Klinik im Park (O Bertel); Zürich, Universitätsspital (M Maggior- ini); Zürich, Stadtspital Triemli (F Eberli); Zürich, Stadtspital Waid (S Christen).

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