\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{Temporal Trends in Prognosis of Patients with Acute Coronary Syndrome
Complicated by Ventricular Tachyarrhythmia}



\author[1]{Ella Yahud}%
\author[1]{Avishag Laish Farkash}%
\author[1]{Nir Shlomo}%
\author[1]{Noam Fink}%
\author[2]{Ilan Goldenberg}%
\author[3]{Eli I. Lev}%
\author[4]{Elad Asher}%
\affil[1]{Affiliation not available}%
\affil[2]{University of Rochester}%
\affil[3]{Assuta Ashdod Hospital}%
\affil[4]{Shaare Zedek Medical Center}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Objectives: To evaluate clinical characteristics and prognosis of
patients presented with ventricular tachyarrhythmia (VTA) during the
course of acute coronary syndrome (ACS) and to analyze it according to
period of presentation. Background: VTA is an infrequent yet serious
complication of ACS. There is limited data regarding the incidence and
prognostic implications of VTA in the last decade as compared with the
previous decade. Methods: We evaluated clinical characteristics, major
adverse cardiovascular events, short and long- term mortality of
patients hospitalized with ACS who were enrolled in the Acute Coronary
Syndrome Israeli Survey (ACSIS) during the years 2000-2016. Patients
were classified into three groups: no VTA, early VTA ([?]48h of onset) and
late VTA (\textgreater{}48h of onset). Data were analyzed according to
decades of presentation (current decade vs. previous decade). Results:
The study population comprised 15,200 patients. VTA occurred in 487
(3.2\%) of patients. Early VTA presented in 373/487 (77\%) patients and
late VTA in 114/487 (23\%) patients. VTA's, occurring in ACS patients
were associated with increased risk of in-hospital, 30-days, 1-year and
5-year mortality rates during both early and late periods in compared
with no VTA. Moreover, late VTA was associated with the highest
mortality rate with up to 65\% in 5-year follow up (p\textless{}0.001).
Nevertheless, late VTA was associated with lower mortality rate in the
current decade (2008-2016) compared with last decade (2000-2006).
Conclusions: Any VTA following ACS was associated with high short and
long-term mortality rate. However, over the past decade there has been a
significant improvement in survival rates, especially in patients with
late VTA. This may be attributed to early and invasive reperfusion
therapy, implantable cardioverter defibrillator implantation and better
medical treatment.%
\end{abstract}%



\sloppy


\textbf{Temporal Trends in Prognosis of Patients with Acute Coronary
Syndrome Complicated by Ventricular Tachyarrhythmia}

Ella Yahud MD\selectlanguage{ngerman}¹, Avishag Laish-Farkash MD, PhD¹, Nir Shlomo MSc², Noam
Fink MD², Ilan Goldenberg MD\textsuperscript{3}, Eli Lev MD¹, Elad Asher
MD, MHA\textsuperscript{4}

¹\emph{Cardiology Division, Assuta Ashdod University Hospital, Israel}

² \emph{Leviev Heart Center, Sheba Medical Center, Tel Hashomer, Israel}

\textsuperscript{3} \emph{University of Rochester Medical Center,
Rochester, NY, USA}

\emph{\textsuperscript{4} Heart Institute, Shaare Zedek Medical Center,
Hebrew University, Jerusalem, Israel}

\textbf{Corresponding Author:}

Ella Yahud, MD

Assuta Ashdod University Hospital

7747629 Ha-Refua St 7, Ashdod, Israel

Tel: +972523935075

Fax: +972737436226

Email: ellaya@assuta.co.il

No conflict of interest and no relationship with industry exists

\textbf{Abstract:}

Objectives: To evaluate clinical characteristics and prognosis of
patients presented with ventricular tachyarrhythmia (VTA) during the
course of acute coronary syndrome (ACS) and to analyze it according to
period of presentation.

Background: VTA is an infrequent yet serious complication of ACS. There
is limited data regarding the incidence and prognostic implications of
VTA in the last decade as compared with the previous decade.

Methods: We evaluated clinical characteristics, major adverse
cardiovascular events, short and long- term mortality of patients
hospitalized with ACS who were enrolled in the Acute Coronary Syndrome
Israeli Survey (ACSIS) during the years 2000-2016. Patients were
classified into three groups: no VTA, early VTA (\selectlanguage{english}[?]48h of onset) and late
VTA (\textgreater{}48h of onset). Data were analyzed according to
decades of presentation (current decade vs. previous decade).

Results: The study population comprised 15,200 patients\textbf{.} VTA
occurred in 487 (3.2\%) of patients. Early VTA presented in 373/487
(77\%) patients and late VTA in 114/487 (23\%) patients. VTA's,
occurring in ACS patients were associated with increased risk of
in-hospital, 30-days, 1-year and 5-year mortality rates during both
early and late periods in compared with no VTA. Moreover, late VTA was
associated with the highest mortality rate with up to 65\% in 5-year
follow up (p\textless{}0.001). Nevertheless, late VTA was associated
with lower mortality rate in the current decade (2008-2016) compared
with last decade (2000-2006).

Conclusions: Any VTA following ACS was associated with high short and
long-term mortality rate. However, over the past decade there has been a
significant improvement in survival rates, especially in patients with
late VTA. This may be attributed to early and invasive reperfusion
therapy, implantable cardioverter defibrillator implantation and better
medical treatment.

Key words: Ventricular tachyarrhythmia, all-cause mortality, acute
coronary syndrome, NSTEMI, STEMI, risk-factors.

What is already known about this tt does this article add?

\emph{What is known about this topic?}

VTA is rare yet serious complication of acute coronary syndrome (ACS)
and has adverse implications on in-hospital and long-term mortality
based on older trials. VTA associated with acute myocardial infarction
(AMI) are classified as early (within the first 48 hours) which are the
most frequent cause of AMI-related death and late (after 48 hours),
usually associated with ventricular dysfunction. Limited data exists
regarding the association between VTA observed during AMI
hospitalization and short and long-term mortality.

\emph{What does this study contribute to the literature?}

In the current study, majority of VTA occurred during the first 48 hours
of ACS. The incidence of both early and late VTA did not change
significantly during the years 2000-2016, suggesting it was not related
to medical treatment. The overall prognosis of ACS patients improved in
the last decade and the most prominent improvement was seen in those who
had late VTA.

\textbf{Introduction}

Ventricular tachyarrhythmia (VTA) especially sustained ventricular
tachycardia and ventricular fibrillation, is an infrequent yet serious
complication of acute coronary syndrome (ACS). Prior studies reported
that VTA complicates 2-8\% of ACS cases and has adverse implications on
in-hospital and long-term mortality (1, 2). Early VTAs occur in the
first 48 hours of acute myocardial infarction (AMI) and are the most
frequent cause of AMI-related death (3). Late VTAs i.e. \textgreater{}
48 hours of AMI onset are usually associated with ventricular
dysfunction (4). Over the past decade, major advances in the treatment
of patients with AMI have occurred and led to improved survival (5).
Currently, however, there is limited data regarding the incidence and
temporal trends over recent years in the outcomes of patients presenting
with VTA complicating ACS. Moreover, limited information exists
regarding the association between VTA observed during ACS
hospitalization to short and long-term mortality. This is despite
overall enhanced therapy and improved survival among ACS patients.
Therefore, the purpose of the current study was to evaluated temporal
trends of clinical characteristics and outcomes over the last two
decades (2000-2016) among ACS patients presenting with and without VTA
who were enrolled in the Acute Coronary Syndrome Israeli Survey (ACSIS)
survey.

\section*{Methods}

{\label{methods}}

\subsubsection*{Study population}

{\label{study-population}}

The present study is a cohort data analysis of patients who were
enrolled prospectively in the ACSIS from 2000 to 2016. Details of ACSIS
have been previously reported (6). In brief, this survey is conducted
biennially over a 2-month period among ACS patients admitted to coronary
care units and cardiology wards in all 27 public hospitals in Israel.

Patient management was at the discretion of the attending physicians.
The diagnosis of AMI and ST-segment elevation MI (STEMI) or non-
ST-segment elevation MI (NSTEMI), was made by the attending cardiologist
according to pre-specified survey criteria based on accepted guidelines.
In total 15,200 patients were enrolled in our study. The patients were
grouped according to the occurrence of ventricular arrhythmias during
the course of index AMI. Data included baseline demographics, medical
history, hospital course, procedures, complications, and outcome based
on hospital's charts. Additional data regarding health status, adverse
events and medication adherence were collected from the patients via
follow-up calls and from outpatients' medical records one month after
hospital discharge. Mortality rates were determined for all patients
from hospital and out-patient charts and by matching their
identification numbers with the Israeli National Population Register.
In- hospital, one year, and five-year all-cause mortality was assessed
for the absence of VTA, early VTA and late VTA according to the periods
of presentation.

\subsubsection*{Definitions and
endpoints}

{\label{definitions-and-endpoints}}

The diagnosis of VTA, sustained ventricular tachycardia or ventricular
fibrillation was based on electrocardiogram (ECG) or continuous monitor
strips. Sustained ventricular tachycardia was defined as a series of
abnormally shaped QRS complexes longer than 120 milliseconds, with a
rate 100-250 beats/minute, lasting longer than 30 seconds or requiring
electrical cardioversion due to hemodynamic collapse. Ventricular
fibrillation was defined as rapid, very irregular rhythm with
indiscernible P waves or QRS. Patients were classified into three
groups: no VTA; early VTA (\selectlanguage{english}[?]48h of onset) and late VTA
(\textgreater{}48h of onset). Survey periods were divided to early
decade (2000-2006) vs. late decade (2008-2016). Primary endpoints were
30-day, 1-year and 5-year mortality rate. Secondary endpoints included
30-day major adverse cardiac events (MACE) (all-cause mortality rate,
re-infarction, stent thrombosis and urgent revascularization). Left
ventricular ejection fraction (LVEF) was graded according to
echocardiography performed at admission in each center.

\subsubsection*{Statistical methods}

{\label{statistical-methods}}

Demographic, clinical features and the use of in-hospital therapies were
reported for all study participants. Multiple logistic regression
adjustments for age, gender, diabetes mellitus, chronic renal failure
and heart failure and for survey periods was performed to assess the
adjusted odds ratio (OR) and 95\% confidence interval (CI) of in and out
of hospital complications and 30-day, 1 and 5-year mortality rate
associated with VTA at any time during and after the admission for ACS.
The cumulative probability of all-cause mortality rate was graphically
displayed using the Kaplan--Meier method and compared using the log-rank
test. In order to evaluate the independent association of VTA with the
5-year all-cause mortality rate outcome, a Cox proportional hazards
model was constructed adjusting for survey period. We employed an
interaction-term analysis to examine whether the risk of 5-year
mortality rate associated with VTA was different in the early period as
compared with the late period. Statistical significance was accepted for
a 2-sided p\textless{}0.05. Statistical analysis was performed using the
R Statistical Package (R Foundation for Statistical Computing, Vienna,
Austria).

\textbf{Results}

Baseline characteristics

The study population comprised of 15,200 patients with ACS. Of them
11682 (77\%) were males, 5383 (35\%) suffered from diabetes mellitus
8894 (59\%) had a history of arterial hypertension, 9757 (64\%) had
dyslipidemia and 6931 (46\%) presented with STEMI. Patient's baseline
characteristics are presented in Table 1.

Ventricular tachyarrhythmia characteristics

Four hundred eighty-seven patients (3.2 \%) had VTA during their
hospitalization. Among those patients, 373/487 (77\%) had early VTA and
114/487 (23\%) had late VTA. The incidence of both types of VTA's
remained the same in the past 15 years as shown in Figure 1. Patients
with late VTA were older (65+-14 vs. 64+-13, p\textless{}0.001) and had
significantly higher incidence of co-morbidities and coronary risk
factors such as diabetes mellitus, arterial hypertension, as well as
known coronary artery disease, and chronic renal failure as shown in
Table 1.

Outcome

Rate of MACE was higher in late VTA then in early and non-VTA (49\% vs.
23\% vs. 8\%, respectively, p\textless{}0.001). As shown with logistic
regression model the presence of late VTA was associated with three
folds' higher ratios for 30 days MACE (p\textless{}0.001), Figure 2. In-
hospital and 1-year mortality rate were also higher in the presence of
late VTA as compared with no VTA {[}HR 27.44 (95\% CI 17.56- 42.49) and
9.78 (95\% CI 6.57- 11.18), respectively, p\textless{}0.001{]}. Even
after multivariate logistic regression for confounders the presence of
early VTA and late VTA, were independently associated with increased
risk of in-hospital mortality rate {[}OR 9.65 (95\% CI 7.0-13.13) and
27.64 (95\% CI 17.56-42.49), respectively, p\textless{}0.001{]}, and
early post- discharge mortality rate {[}OR 8.75 (95\% CI 5.98-12.24) and
22.6 (95\% CI 14.5-35.62), respectively, p\textless{}0.001{]}. Moreover,
multivariable Cox proportional hazard analysis including baseline
potential confounders confirmed that 5-year mortality rate was also
higher in late VTA then in early and non-VTA (HR 8.27 vs. 2.65, for late
and early VTA, respectively 95\% CI 2.05-3.42).

Late vs. Early period

The 1 and 5-year all-cause mortality rate was lower during the late
period as compared with the early period for patients with no VTA, early
VTA and late VTA (8\% vs 10\%, 20\% vs 25\% and 37\% vs 65\%, all
log-rank p \textless{}0.001, respectively for 1 year) and (20\% vs 23\%,
26\% vs 29\% and 45\% vs 75\%, all log-rank p \textless{}0.001,
respectively for 5 years) as shown in Figure 3 and 4. Moreover, the late
period was associated with lower all-cause mortality rates for
in-hospital, 1 year and 5 years mortality rate (OR 0.56, 0.66 and 0.82,
p\textless{}0.001, respectively).

In the early period ICD was implanted during hospitalization in 15
(0.2\%) patients with no VTA, 3 (1.4\%) patients with early VTA and 5
(8\%) with late VTA (p\textless{}0.001). In the late period in hospital
implantation of ICD was performed in 25 (0.4\%), 8 (5\%) and 0 patients,
respectively (p\textless{}0.001).

In our study during early period chronic treatment with beta blockers
was administered to 34\%, 24\% and 42.5\% of patients with no VTA, early
VTA and late VTA respectively, p= 0.018; beta blockers at discharge were
prescribed to 78\%, 72\% and 51\% of patients respectively,
p\textless{}0.001

During the late period 38.5\%, 35\% and 42\% of patients with no VTA,
early VTA and late VTA, respectively, used beta blockers chronically,
p=0.6 and 80.5\%, 81.5\%, 73\% of patients, respectively, were
discharged with beta blockers, p=0.4 Chronic
angiotensin-converting-enzyme inhibitor (ACEI) treatment in early period
was used in 26\%, 31\% and 22\% of patients with no VTA, early VTA and
late VTA p=0.8; ACEI after discharge were prescribed to 61\%, 61.5\% and
57\%, respectively, p=0.9

During the late period chronic ACEI treatment was administered to 32\%,
32\%, 24\% of patients with no VTA, early VTA and late VTA respectively,
p=0.08; ACEI in discharge were prescribed to 67\%, 66\%, 47\% of
patients respectively, p=0.018

\textbf{Discussion}

In the current study, VTA occurred in roughly 3\% of ACS patients
admitted to the hospital with the majority (77\%) of those arrhythmias
occurred during the first 48 hours of ACS. Moreover, the incidence of
both early and late VTA did not change significantly during the years
2000-2016, suggesting it was not related to medical treatment.

Previous data on prognostic significance of VTA is controversial. In the
HORIZONS-AMI Trial (7) there was no significant difference in MACE and
3-year mortality rate in patients with or without VTA that occurred
after primary percutaneous coronary intervention (PCI). Another recent
study, found that in patients with STEMI that survived out of hospital
cardiac arrest due to VTA and underwent primary PCI, the 1-year
mortality was equal to those without out of hospital cardiac arrest (8).
On the other hand, in the MILIS study (9) the in hospital mortality rate
was significantly increased by VTA, especially late VTA, causing cardiac
arrest during ACS hospitalization, although there was no difference in
mortality rate in the 32-month follow up as compared with patients with
no VTA. In APEX AMI trial (10), pre and post primary PCI VTA were also
shown to be associated with significantly increased 90 days mortality.
Piccini et al. (11) studied a large population of 9000 patients with
STEMI and NSTEMI undergoing PCI. In their study, the rate of early VTA
was 5.2\% and it was also related to increase mortality risk by 4.4
folds as compared with no VTA. Our data is in accord to the
aforementioned trials suggesting that VTA occurrence during the course
of ACS is not benign. Short and long-term mortality rate was increased
dramatically by the presence of early and especially late VTA as
compared with no VTA. This was consistent even after adjustment for
multiple confounders. In the logistic regression analysis model the
presence of late VTA was associated with 27 folds' increase of in
hospital mortality, 10 folds increased one-year mortality and 8 folds
increased 5 years mortality rate. The proposed reason why late VTA
carries an increased risk of death might be its association with pump
failure and hemodynamic deterioration rather than arrhythmic death (12,
13).

Interestingly, although the overall prognosis of ACS patients improved
in the last decade (14) as well as in our study, the most prominent
improvement in our study was seen in those who had late VTA, as shown in
Figures 3 and 4. Wider use of ACE inhibitors and beta blockers at
discharge in the late VTA group, early reperfusion strategy, (15, 16),
as well as wider use of implantable and wearable cardioverter
defibrillators could explain our findings.

\textbf{Limitations}

Due to its observational non-randomized design, the current study is
subject to limitations as described in detail previously (17). Thus,
despite efforts to control for confounding factors by applying
multivariate analysis, we cannot exclude unmeasured factors, which could
have biased the results. Moreover, data regarding 5 years survival rate
is limited in the late period with no long term data since the year
2016. Nevertheless, in spite of these limitations, the study in a
multicenter nationwide survey with large study population and long term
outcomes.

\textbf{Conclusions}

In summary, in this national, multicenter, contemporary ``real life''
setting, we did not observe any change in the rate of VTA. Nevertheless,
any VTA following AMI was associated with high short and long-term
mortality rate. However, over the past decade there has been a
significant improvement in survival rates, especially in patients with
late VTA that may be attributed to early and invasive reperfusion
therapy, implantable cardioverter defibrillator implantation and better
medical treatment.

This statement is to certify that all authors have seen and approved the
manuscript

being submitted, have contributed significantly to the work, attest to
the validity and legitimacy of the data and its interpretation, and
agree to its submission to the \emph{International Journal of Clinical
Practice.}

The article is the Authors' original work, has not received prior
publication and is not under consideration for publication elsewhere.

All the authors report no relationships that could be construed as a
conflict of interest.

References:

1. Metha RH, Starr AZ, Lopes RD, et al. Incidence of and outcomes
associated with ventricular tachycardia or fibrillation in patients
undergoing primary percutaneous coronary intervention, JAMA 2009,
vol.301 (pg.1779-1789).

2. Al-Khatib SM, Granger CB, Huang Y, et al. Sustained ventricular
arrhythmias among patients with acute coronary syndromes with no
ST-segment elevation: incidence, predictors, and outcomes, Circulation
2002, vol. 106 (pg.309-312)

3. Liang JJ, Hodge DO, Metha RA, Russo AM, Prasad A, Cha YM. Outcomes in
patients with sustained ventricular tachyarrhythmias occurring within
48h of acute myocardial infarction: when is ICD appropriate? Europace
2014; 16:1759-66

4. Volpi A, Cavalli A, Santoro E, Tognoni G. Incidence and prognosis of
secondary ventricular fibrillation in acute myocardial infarction.
Evidence for a protective effect of thrombolytic therapy. GISSI
Investigators. Circulation 1990; 82:1279-88

5. Yeh RW, Sidney S, Chandra M, Sorel M, Selby JV, Go AS. Population
trends in the incidence and outcomes of acute myocardial infarction. N
Engl J Med 2010; 362: 2155-2165.

6. Asher E, Abu-Much A, Goldenberg I, et al. Platelets and Thrombosis in
Sheba-PLATIS Study Group. Incidence and Clinical Features of Early Stent
Thrombosis in the Era of New P2y12 Inhibitors (PLATIS-2). PLoS One
2016;11(6):e0157437

7. Metha RH, Yu J, Piccini JP, et al. Prognostic significance of
postprocedual sustained ventricular tachycardia or fibrillation in
patients undergoing primary percutaneous coronary intervention (from the
HORIZONS-AMI Trial). Am J Cardiol 2012;109(6):805-12

8. Demirel F, Rasoulm S, Elvan A, et al. Impact of out-of-hospital
cardiac arrest due to ventricular fibrillation in patients with ST-
elevation myocardial infarction admitted for primary percutaneous
coronary intervention: Impact of ventricular fibrillation in STEMI
patients. Eur Heart J Acute Cardiovasc Care 2015;4(1):16-23.

9. Tofler GH, Stone PH, Muller JE, et al. Prognosis after cardiac arrest
due to ventricular tachycardia or ventricular fibrillation associated
with acute myocardial infarction (MILIS Study). Multicenter
investigation of the limitation of infarct size. Am J Cardiol 1987;
60(10):755-61

10. Metha RH, Starr AZ, Lopes RD, et al. Incidence of and outcomes
associated with ventricular tachycardia or fibrillation in patients
undergoing primary percutaneous coronary intervention. JAMA 2009;
301(17):1779-89.

11. Piccini JP, Berger JS, Brown DL. Early sustained ventricular
arrhythmias complicating acute myocardial infarction. Am J Med 2008;
121(9):797-804.

12. Newby KH, Thompson T, Stebbins A, Topol EJ, Califf RM, Natale A.
Sustained ventricular

arrhythmias in patients receiving thrombolytic therapy: incidence and
outcome. The GUSTO investigators. Circulation 1998; 98(23):2567--73.

13. Bulent Gorenek, Carina Blomstrom Lundqvist, Josep Brugada
Terradellas, et al. ESC Scientific Document Group. Cardiac arrhythmias
in acute coronary syndromes: position paper from the joint EHRA, ACCA,
and EAPCI task force.

EP Europace 2014; 16(11):1655--1673.

14. Moran AE, Forouzanfar MH, Roth GA, et al. Temporal trends in
ischemic heart disease mortality in 21 world regions, 1980 to 2010: the
Global Burden of Disease 2010 study. Circulation 2014;129(14):1483-92.

15. Asher E, Tal S, Mazin I, et al. Effect of Chewing vs Swallowing
Ticagrelor on Platelet Inhibition in Patients With ST-Segment Elevation
Myocardial Infarction: A Randomized Clinical Trial. JAMA Cardiol
2017;2(12):1380-1384.

16. Asher E, Frydman S, Katz M, et al. Chewing versus Swallowing
Ticagrelor to Accelerate Platelet Inhibition in Acute Coronary Syndrome
- the CHEERS study. For The PLATIS (Platelets and Thrombosis in Sheba)
Study Group. Thromb Haemost 2017;117(4):727-733

17. Asher E, Fefer P, Sabbag A, et al. Prior chronic clopidogrel therapy
is associated with increased adverse events and early stent thrombosis.
Thromb Haemost 2016; 115 (2):433--8.

Table 1: Baseline characteristics by VTA presence\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{No VTA} \textbf{N=14713}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Early VTA} \textbf{N=373}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Late VTA} \textbf{N=114}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{p-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Age(\selectlanguage{ngerman}±SD), years\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
64\selectlanguage{ngerman}±13\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
60\selectlanguage{ngerman}±12\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
65\selectlanguage{ngerman}±14\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Male gender, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11287 (77)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
308(83)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
87(76)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.030\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Weight (kg), (\selectlanguage{ngerman}±SD)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
79\selectlanguage{ngerman}±15\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
80\selectlanguage{ngerman}±17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
83\selectlanguage{ngerman}±17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.162\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Diabetes Mellitus, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5256(36)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
89(24)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
38(33)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Hypertension, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8652(59)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
171(46)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
71(62)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Dyslipidemia, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
9505(65)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
195(53)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
57(51)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Past stroke/TIA, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1186(8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
31(8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5(4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.355\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Prior Chronic Renal Failure, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11612(11)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
20(5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
120(17)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Prior COPD, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
697(6)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
23(7.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3(4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.455\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Prior MI, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4481(31)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
102(28)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
38(33)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.360\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Prior AP in 24 hours,\%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5168(35)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
77(21)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
41(36)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Prior CABG, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1481(10)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15(4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
8(7.1)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
History of PCI, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4058(28)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
77(21)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
28(25)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.009\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Heart failure, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1144(8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29(8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15(13)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.106\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Family history of CAD,\%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3466(25)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
74(21)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
31(29)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.214\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Clinical Presentation}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
STEMI, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6564(45)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
289(78)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
78(68)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Heart Rate (mean\selectlanguage{ngerman}±SD), bpm\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
80\selectlanguage{ngerman}±20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
87\selectlanguage{ngerman}±29\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
89\selectlanguage{ngerman}±24\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Treatments}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Primary Reperfusion, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4458(30)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
249(67)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
53(47)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Coronary angiography (till hospital discharge),\%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
9513(86)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
224(89)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
69(81)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.215\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
PCI, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5862(40)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
89(24)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
40(35)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Emergency CABG,\%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
700(5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11(3)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6(5)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.250\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Beta Blockers chronic, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4664(36)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
90(30)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
38(42)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.029\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Beta Blockers at discharge, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
11347(79)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
258(76)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
55(62)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\emph{Outcome}\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
MACE in 30 days, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1173(8)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
84(23)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
56(49)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
All-cause mortality 30 days, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
625(4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
69(19)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
49(43)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
All-cause mortality 1 year, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1208(9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
76(23)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
55(53)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
All-cause mortality 2 years, \%\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1596(13)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
83(26)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
60(59)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

VTA- Ventricular tachyarrhythmia, SD- standard deviation, PCI -
percutaneous coronary intervention, CABG - coronary artery bypass
grafting, STEMI -ST elevation myocardial infarction, CAD- coronary
artery disease, MACE- major adverse cardiac events, TIA - transient
ischemic attack, PAD- peripheral artery disease, COPD- chronic
obstructive pulmonary artery

disease.

Figure 1. Trends in VTA during the years 2000-2016\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Early VTA

Late VTA

\par\null

Figure 2. Major adverse cardiac events (MACE) at 30 days for early and
late VTA\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

*MACE- all-cause mortality rate, re-infarction, stent thrombosis and
urgent revascularization

CI= confidence interval, OR= odds ratio

Figure 3. One-year survival rate according to period of presentation\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

Figure 4. Five-year survival according to period of presentation\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image4/image4}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

