FULL LENGTH ARTICLE

Components and determinants of therapeutic

delay in patients with acute ST-elevation
myocardial infarction: A tertiary care
hospital-based study
Jahangir Rashid Beig a,⇑, Nisar A. Tramboo a, Kuldeep Kumar b, Irfan Yaqoob a,
Imran Hafeez a, Fayaz A. Rather a, Tariq R. Shah a, Hilal A. Rather a
a
Dept. of Cardiology, SKIMS, Srinagar
b
Dept. of Medicine, SKIMS, Srinagar

a,b
India

Background: Delayed reperfusion is associated with worse outcomes in ST-segment elevation myocardial infarction
(STEMI). This study was conducted to assess the components and determinants of therapeutic delay in STEMI patients
of our state.
Methods: This study included consecutive patients of STEMI admitted to the coronary care units of two tertiary
care hospitals in Srinagar, between 2012 and 2015. Various components of treatment delay including the patient’s
decision to delay, referral delay, transportation delay, prehospital delay, and door-to-needle time were calculated.
Factors associated with delayed treatment and clinico-demographic correlates of late presentation were identified.
Results: During a period of 3 years, 523 patients (mean age, 57.6 þ 10.5 years) were enrolled in this study. Thrombol-
ysis was administered to 60.2% patients, while 39.8% of patients could not be thrombolysed because of late presentation.
The median treatment delay was 250 minutes. Prehospital delay constituted about 83.8% of total treatment delay.
Patient’s decision to delay, referral delay, and transport delay constituted 59%, 16%, and 25% of prehospital delay,
respectively. Median door-to-needle time was 40 minutes. Residence in rural areas [odds ratio (OR), 2.35; 95% confidence
interval (CI), 1.60–3.46], absence of prior coronary artery disease (OR, 1.54; 95% CI, 1.00–2.39), and negative family history of
coronary artery disease (OR; 2.76; 95% CI, 1.86–4.10), were identified as independent predictors of delayed presentation
(p < 0.001). Interestingly, 44.7% of the patients presented late due to misdiagnosis by local healthcare providers.
Conclusion: The standard of STEMI management in our state is far from ideal, and calls for a lot of improvement.
Major efforts to reduce prehospital and in-hospital treatment delays are urgently needed.

Ó 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Keywords: Coronary artery disease, Late presentation, Prehospital delay, ST-elevation myocardial infarction,
Treatment delay
Disclosure: Authors have nothing to disclose with regard to commercial
support.

Received 3 March 2016; revised 30 May 2016; accepted 3 June 2016.

Available online 16 June 2016

⇑ Correspondence to: Dr. Jahangir Rashid Beig (M.D, D.M) 105, Sir
Syed Colony, Upper Soura, Buchpora, Srinagar, Jammu & Kashmir
190020, India. Tel.: +91 194 2401765; mobile: +91 9622671622.
E-mail addresses: jahangir3582@gmail.com (J.R. Beig), drnisartramboo@ P.O. Box 2925 Riyadh – 11461KSA
gmail.com (N.A. Tramboo), drkuldeepshan@gmail.com (K. Kumar), Tel: +966 1 2520088 ext 40151
irfan0913@yahoo.co.in (I. Yaqoob), imihaf@gmail.com (I. Hafeez), Fax: +966 1 2520718
ratherfayaz22@gmail.com (F.A. Rather), tariq6496@yahoo.co.in Email: sha@sha.org.sa
(T.R. Shah), eemaan3@yahoo.co.in (H.A. Rather). URL: www.sha.org.sa

1016–7315 Ó 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-
NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Peer review under responsibility of King Saud University.

URL: www.ksu.edu.sa
http://dx.doi.org/10.1016/j.jsha.2016.06.001 Production and hosting by Elsevier
 8 BEIG ET AL J Saudi Heart Assoc
ACUTE ST-ELEVATION MYOCARDIAL INFARCTION 2017;29:7–14
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Introduction Abbreviations

CAD coronary artery disease

I ndia has become the ‘‘global capital’’ of coro-

nary artery disease (CAD) contributing to
STEMI ST-elevation myocardial infarction

60% of the global burden of CAD with about 64 Kashmir, India, with Coronary Care Units (CCUs),
million deaths attributable to CAD annually [1]. namely Shri Maharaja Hari Singh Hospital and
ST-elevation myocardial infarction (STEMI) is Sher-i-Kashmir Institute of Medical Sciences,
one of the most lethal presentations of CAD. between 2012 and 2015. All consecutive patients
Myocardial damage caused by acute STEMI is a admitted in the CCUs of these hospitals during
time-dependent process. Timely reperfusion of this period with a final diagnosis of acute STEMI
ischemic myocardium using thrombolysis or pri- who fulfilled the eligibility criteria (described
mary percutaneous coronary intervention forms below) were enrolled in this study.
the cornerstone of acute management of STEMI;
reducing infarct size, preserving left ventricular Inclusion criteria
function, and improving short- and long-term out-
comes [2]. Inclusion criteria included patients who (1) had
Although primary percutaneous coronary inter- no contraindication to thrombolytic therapy
vention is currently the preferred modality of except late presentation (>12 hours); (2) developed
reperfusion in STEMI [3], thrombolysis still acute STEMI outside of the hospital; (3) had a
remains the most common reperfusion method known time of symptom onset; and (4) had not
used in our country due to logistic and financial developed spontaneous thrombolysis (resolution
constraints. Benefits from fibrinolytic therapy of chest pain and ST-segment elevation without
diminish on a minute-to-minute basis, with the pharmacological thrombolysis).
greatest effect occurring in those patients who In all the patients, a detailed medical history
receive it within the 1st 2 hours of symptom onset was taken, especially for cardiovascular disease
[4–7]. It has been estimated that for every 30 min- (angina, transient ischemic attack, stroke, and
utes of delay in reperfusion therapy, the patient’s peripheral vascular disease), hypertension, dys-
life is shortened by 1 year [8]. Despite significant lipidemia, diabetes mellitus, smoking, prior
efforts to improve the standard of care in STEMI CAD, and family history of CAD. We recorded
patients over the past few decades, it is estimated the specific time of onset of symptoms, time of
that up to one-third of eligible patients with STEMI seeking first consultation from a pharmacist or
still do not receive timely reperfusion [2]. A number healthcare professional (at district hospital, com-
of factors determine the delay in starting throm- munity health center, medical store, or private
bolytic therapy such as contacting emergency med- clinic), time of arrival at the tertiary care hospitals,
ical services (EMS), transporting the patient, and time of initiation of thrombolytic therapy (in
admitting the patient in the emergency depart- patients who received thrombolysis). We
ment, initial assessment of the patient including reviewed all the clinical records of patients from
obtaining and interpreting the electrocardiogram, the point of first medical contact, including dis-
decision making, and delay in preparing the drug. charge summaries and referral documents. The
In scientific literature, there is very limited data initial diagnostic evaluation, clinical impression
about the different components and determinants made by the local healthcare providers, and the
of treatment delay, in developing countries like treatment that was provided to each patient
India. The present study was conducted with an before referral to our hospitals was recorded. We
aim of assessing various components of the delay then calculated the various components of treat-
to thrombolytic treatment for patients with acute ment delay including: (1) patient’s decision delay
STEMI, and to determine the demographic and (time of onset of symptoms to time of seeking 1st
clinical characteristics of the patients related to medical consultation); (2) referral delay (time of
these delays. We also studied the reasons for late 1st medical consultation to time of referral to a ter-
presentation in STEMI patients who had not tiary care hospital); (3) transportation delay (time
received thrombolytic therapy. of referral to time of arrival at the tertiary care
hospital); (4) total prehospital delay (time of onset
of symptoms to time of arrival at the tertiary care
Materials and methods
hospital); (5) door-to-needle time (time of arrival
This observational study was conducted in two at the tertiary care hospital to time of administra-
tertiary care hospitals of Srinagar, Jammu, and tion of thrombolysis); and (5) total treatment delay
J Saudi Heart Assoc BEIG ET AL 9
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FULL LENGTH ARTICLE

(time of onset of symptoms to time of administra- Sher-i-Kashmir Institute of Medical Sciences
tion of thrombolysis). Hospitals were enrolled in this study.
Next, we determined the number and percent-
age of individuals who presented to the tertiary Patient characteristics
care hospitals in <6 hours, 6–12 hours, and The mean age of our patient cohort was
>12 hours of symptom onset. We then attempted 57.6 ± 10.5 years with a range of 32–80 years. Of
to identify factors associated with treatment delay the total 523 patients, 80.3% (420) were men and
in these three groups. Among late presenters only 19.7% (103) were women. Of the patients,
(>12 hours), we determined the number and per- 65.4% (342) belonged to a rural area and 34.6%
centage of individuals who sought consultation (181) to an urban area. The most common risk fac-
from a healthcare professional in <6 hours, 6– tors in our patients were hypertension (67.3%) and
12 hours, 12–24 hours, and >24 hours of symptom smoking (64.1%), followed by diabetes mellitus
onset. Further, we assessed the reasons and their (36.9%), family history of CAD (31.7%), dyslipi-
frequency resulting in late presentation of these demia (28.3%), and prior CAD (22.4%). Thrombol-
patients. ysis was administered to 60.2% (315) of patients,
while the remaining 39.8% did not receive any
Statistical analysis
thrombolytic therapy because of late presentation
Statistical analysis was performed using SPSS to tertiary care centers.
software package (version 20.0; SPSS Inc., Chi-
cago, IL, USA). All continuous variables were Components of prehospital, in-hospital, and total
expressed as mean ± standard deviation, and cat- treatment delays
egorical variables were reported as frequency
The overall median time between the onset of
and percentages. Differences in the distribution
symptoms and treatment was 250 minutes (range,
of characteristics in the patients, classified accord-
60–920 minutes). Prehospital delay (median,
ing to the extent of prehospital delay, were exam-
210 minutes) constituted 83.8% of the total treat-
ined using the Chi-square test for the categorical
ment delay. Patient’s decision delay (median,
variables, while the t test was employed for con-
100 minutes) constituted 59% of the prehospital
tinuous variables. A multivariate logistic regres-
delay, while referral delay (median, 40 minutes)
sion analysis was performed to identify the
constituted 16% and transport delay (median,
sociodemographic and clinical characteristics of
60 minutes) constituted 25% of the prehospital
the patients contributing independently to a pre-
delay. Median door-to-needle time was 40 min-
hospital delay of >6 hours. Statistical significance
utes and contributed to 16% of the total treatment
was defined as a p value of <0.05.
delay (Fig. 1).

Results Frequency and characteristics of patients with

During a period of 3 years, 523 consecutive acute STEMI according to prehospital delay
patients with acute STEMI admitted to CCUs Among all 523 patients with STEMI, 50.3% pre-
of Shri Maharaja Hari Singh Hospital and sented to tertiary care centers within 6 hours,

120
Meadian Time interval (minutes)

100

80

60

40

20

0
Paent Decicision Referral Delay Transport Delay Door-to-Needle Time
Delay
Components of Therapeuc Delay

Figure 1. Components of prehospital, in-hospital, and total treatment delays.

 10 BEIG ET AL J Saudi Heart Assoc
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9.9% between 6 hours and 12 hours, and the correlation on univariate analysis, i.e., age, resi-
remaining 39.8% were late presenters (>12 hours). dence, dyslipidemia, past history of CAD, and
On univariate correlation analysis of patient char- family history of CAD, were kept as predictors.
acteristics of these three groups, we found that The results showed that the patients who lived
older age (p = 0.001), residence in rural areas in rural areas [odds ratio (OR), 2.35; 95% confi-
(p < 0.0001), lack of prior history of CAD dence interval (CI), 1.60–3.46], had no prior CAD
(p = 0.022), absence of dyslipidemia (p = 0.010), (OR, 1.54; 95% CI, 1.00–2.39), and had a negative
and no family history of CAD (p = 0.0001) were family history of CAD (OR, 2.76; 95% CI, 1.86–
significantly associated with a prolonged prehos- 4.10), were significantly more likely to have a pro-
pital delay (Table 1). longed prehospital delay (p < 0.001).

Predictors of prolonged prehospital delay in Categorization of late presenters according to time

multivariate logistic regression analysis of first medical contact and reasons of late
Multivariate logistic regression analysis was presentation (>12 hours) to tertiary care hospital
performed to identify the sociodemographic and Among late presenters admitted to our tertiary
clinical characteristics of the patients that inde- care centers only 44.7% of the patients sought first
pendently predicted prolonged prehospital delay medical consultation within 12 hours and the
(>6 hours). Variables that showed a significant remaining 55.3% after 12 hours of symptom onset

Table 1. Frequency and characteristics of patients with acute ST-elevation myocardial infarction according to prehospital delay.
Characteristics Prehospital delay
<6 h 6–12 h >12 h p
N (%) N (%) N (%)
Age, mean ± SD (y) 56.02 ± 10.32 57.98 ± 9.74 59.64 ± 10.62 0.001
Sex
Male 218 (82.9) 40 (76.9) 162 (77.9) 0.323
Female 45 (17.1) 12 (23.1) 46 (22.1)
Residence
Rural 148 (56.3) 39 (75) 155 (74.5) 0.0001
Urban 115 (43.7) 13 (25) 53 (25.5)
Hypertension 81 (68.8) 31 (59.6) 141 (67.8) 0.429
DM 95 (36.1) 22 (42.3) 76 (36.5) 0.693
Smoking 172 (65.4) 30 (57.7) 133 (63.9) 0.571
Dyslipidemia 67 (25.5) 24 (46.2) 57 (27.4) 0.010
Family history of CAD 111 (42.2) 14 (26.9) 41 (19.7) 0.0001
Prior CAD 48 (18.2) 18 (34.6) 51 (24.5) 0.022
CAD = coronary artery disease; DM = diabetes mellitus; SD = standard deviation.

80 75 (36%)

70 68 (32.7%)

60

50 47 (22.6%)
Frequency (%)

40

30

20 18 (8.7%)

10

0
< 6 hours 6-12 hours 12-24 hours > 24 hours
Time delay in seeking first medical consultaon

Figure 2. Distribution of patients according to time delay in seeking first medical consultation.
J Saudi Heart Assoc BEIG ET AL 11
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11.10% Ignorance of symptoms by
paent
14.40% Misinterpretaon of symptoms
by pharmacist
55.30% Misdiagnosis by primary care
physician
19.20% Non-availability of Thrombolyc
therapy at peripheral hospital

Figure 3. Categorization of reasons for late presentation beyond 12 hours of symptom onset.

(Fig. 2). Late medical attention seekers did so STEMI do not receive timely reperfusion therapy
because of ignorance of symptoms by themselves [2]. As regards the mode of reperfusion, primary
and self-medication. The main reason of thera- percutaneous coronary intervention (PCI) has
peutic delay among those who presented to a established its unequivocal superiority over
healthcare provider within 12 hours was misinter- thrombolysis, both in terms of achieving rapid
pretation of their symptoms by a pharmacist or and sustained patency of the infarct-related artery
misdiagnosis by primary care physician (Fig. 3). in a lesser time-dependent fashion as well as min-
imizing bleeding complications [3,9]. However,
recent data suggest that <10% of STEMI patients
Discussion
in India are reperfused with primary PCI [10].
The main findings of our study were as follows. Limited availability of regional centers of excel-
(1) Nearly 40% of our STEMI patients were ineligi- lence, financial constraints, logistic and infrastruc-
ble for thrombolytic therapy due to late presenta- tural difficulties, poor ambulance services, traffic
tion to our hospitals. (2) Prehospital delay was the congestion, and lack of public awareness and edu-
major contributor of delayed treatment, contribut- cation are the major hurdles in routine implemen-
ing to 83.8% of the total treatment delay. Patient’s tation of this strategy in countries like India. Thus,
decision to delay constituted 59%, while transport thombolysis remains the most commonly used
and referral delays constituted 25% and 16% of the reperfusion modality for STEMI patients in our
prehospital delay, respectively. (3) Residence in country. In contrast to relative time-
rural areas, absence of prior CAD, and negative independence of primary PCI, successful reperfu-
family history of CAD were independent predic- sion with thrombolysis is highly time dependent.
tors of prolonged prehospital delay. (4) Nearly half Trials on fibrinolytic therapy have documented
(44.7%) of the patients presenting late to our hos- benefits of 65 lives, 37 lives, 26 lives, and 29 lives
pitals had in fact sought a medical consultation saved per 1000 treated patients in the 0–1-, 1–2-,
within 12 hours of symptom onset. Misinterpreta- 2–3-, and 3–6-hour intervals, respectively [11].
tion of the symptoms by local pharmacists or The greatest benefit occurred in those patients
physicians was the major reason of late presenta- treated within 1 hour of symptom onset, with a
tion in these patients. sharp drop off after 3 hours [12]. Studies on late
‘‘Time is muscle’’ is a well-established dictum in presenters have shown that thrombolysis is of no
the management of STEMI. The risk of 1-year benefit after 12 hours of symptom onset and may
mortality is increased by 7.5% for each 30-minute be potentially harmful in elderly patients, in
delay in treatment [9]. Early patient presentation, whom it increases the risk of cardiac rupture
rapid diagnosis, and early reperfusion constitute [13,14]. Thus, timeliness of reperfusion assumes
the pillars of success in STEMI management. utmost importance in the efficient management
Although the importance of prompt reperfusion of STEMI, especially when thrombolysis is chosen
in STEMI management cannot be over empha- as the mode of reperfusion. The goal of reperfus-
sized, it is appalling to know from global registries ing STEMI patients within the 1st 2–3 hours is,
that up to one-third of eligible patients with however, achieved in a minority of patients, even
 12 BEIG ET AL J Saudi Heart Assoc
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in developed countries, and there is a consider- factor burden seen in the study population, this
able gap between recommended guidelines and late attention seeking behavior looks particularly
real-world clinical practice. In recent years, con- worrisome. Thus, there seems to be an urgent
siderable attention has been given to devise need of initiating public education programs to
strategies that minimize pre- and in-hospital increase awareness about cardiovascular risks
treatment delays in STEMI patients. Expansion and improve the healthcare seeking attitude of
of EMS services, quick EMS dispatch, on-site elec- our population. The median transportation delay
trocardiogram, prehospital thrombolysis, rapid in our study was 60 minutes, which is longer
interhospital transfer, prehospital activation of a than that reported in other countries [22–24].
catheterization laboratory team, and shortening of Needless to say, the existence of congested urban
door-to-device time are some of the strategies that traffic in large cities such as Srinagar, lack of EMS
have been shown to reduce treatment delays in facilities, and the nonavailability of thrombolytic
Western countries. The situation is somewhat dif- therapy in the peripheral healthcare centers con-
ferent in developing countries. As far as India is tributed to this transportation delay. In particular,
concerned, the most comprehensive data about lack of EMS services appears to be the major hur-
contemporary trends in STEMI patients come dle in the process of delivering guideline-directed
from CREATE, a large clinical registry of acute treatment to STEMI patients in our setting [25].
coronary syndrome patients from 89 large hospi- We would therefore stress on the establishment
tals in 10 regions and cities across India [10]. We of state of art EMS services at the earliest, as an
shall discuss the findings of our study in the con- adapted response to this study. The median
text of data from this registry as well as other data door-to-needle time in our study was 40 minutes.
from various developed and developing countries. Although less than ideal (630 minutes), it was
The mean age of our patients was shorter than reported in the CREATE registry
57.6 ± 10.5 years. This is consistent with previous (50 minutes) and comparable to the Western reg-
studies, suggesting that CAD occurs a decade or istry data (32–40 minutes) [10,17–19]. One proba-
more earlier in Indians when compared with ble reason for this longer door-to-needle time
patients from developed countries [10,15]. The was the delay in shifting patients from the emer-
median prehospital delay in our study was gency department (ED) to the CCU, where throm-
210 minutes. It was considerably lower than the bolysis was administered. In a study, Mclean et al.
delay found in the CREATE registry (300 minutes), [26] demonstrated a 58-minute reduction in door-
but still significantly more than delays reported in to-needle time when fibrinolysis was started in
Western registries (128–170 minutes) [10,16–19]. the ED rather than exclusively in the CCU. Hence,
Furthermore, only 50.3% patients presented modification of hospital protocol to administer
within 6 hours of symptom onset, while 49.7% of thrombolysis in the ED is likely to further shorten
patients presented after 6 hours. In a study from this delay. Another approach that has gained pop-
Beijing, Song et al. [20] reported a delay of ularity in countries such as ours is to administer
>6 hours in 20.3% patients, while Khan et al. [21] fibrinolysis at peripheral heath centers and then
from Pakistan reported that 33.9% of STEMI rapidly transfer the patients to PCI-capable hospi-
patients arrived at the hospital beyond 6 hours tals for routine coronary angiography and PCI
of symptom onset. Additionally, 39.8% of our within 3–24 hours of thrombolysis (pharmacoinva-
STEMI patients were ineligible for thrombolysis sive approach). This approach combines the ben-
because of late presentation beyond 12 hours. This efits of establishing flow in the infarct-related
proportion of late presenters was considerably artery by early fibrinolysis and maintaining sus-
more than reported by Xavier et al. [10] in the tained patency of infarct-related artery by routine
CREATE registry (30.8%). Our study demon- early PCI, and has been demonstrated to provide
strated that prehospital delay was the major con- results equivalent to primary PCI [27].
tributor of delayed treatment, contributing to Our study revealed that patients presenting late
83.8% of the total treatment delay and patient’s to tertiary care hospitals were more likely to be
decision to delay constituted 59% of the prehospi- older and residing in rural areas. This finding is
tal delay. This scenario is similar to what is seen in consistent with previous studies [22,28]. Elderly
other developing countries, where patient’s delay patients more often have atypical symptoms of
to seek medical care is very long [22,23]. The main CAD and are more likely to attribute their symp-
reason for delay in seeking medical attention was toms to other comorbidities, leading to a delay in
patients thinking that symptoms would go away seeking medical attention. Lack of awareness,
or that they were not serious. Given the high risk nonavailability of standard treatment in remote
J Saudi Heart Assoc BEIG ET AL 13
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healthcare facilities, and transportation delay is the profile of such patients, and to compare it with
responsible for late presentation among the rural those included in the present study. Thirdly,
population. Again, establishment of EMS services although we meticulously reviewed all the clinical
with widespread coverage of both rural and urban records of patients from the point of first medical
areas, ensuring access to quality and affordable contact, including discharge summaries and refer-
healthcare seems to be the logical solution to this ral documents, our data is limited by the retro-
problem. Female sex has been identified as an spective chart review nature of data collection.
independent predictor of treatment delay in pre- Lastly, we did not study the clinical outcomes of
vious studies [29]. This was not the case in our these patients. A dedicated study with an aim of
study and could be a reflection of different cul- assessing the in-hospital and long-term outcomes
tural views over health and life, held by Kashmiri of different subgroups of such patients would pro-
men and women. Our study showed that history vide further insights into the state of STEMI care
of CAD in the patient or a family member was in our healthcare setting.
associated with significantly shorter prehospital
delay. As demonstrated in previous studies, a past
history or family history of CAD could increase Conclusion
the awareness of patients on symptoms of CAD, Our study reiterates the fact that the standard of
making them more sensitive in noticing the seri- STEMI management in our country is far from
ousness of such symptoms early after onset ideal, and calls for a lot of improvement. Major
[20,30,31]. Last, but not least, an important finding efforts to reduce treatment delay are needed,
of our study was that 44.7% of the patients pre- including increased public awareness, improve-
senting late to our hospitals had in fact sought a ment in peripheral healthcare infrastructure,
medical consultation within 12 hours of symptom training of paramedical staff, and establishment
onset. Misinterpretation of the symptoms by local of EMS services for rapid triage, and expedited
pharmacists or primary care physicians (assessed transfer of STEMI patients to the appropriate
by reviewing the medical records of the initial healthcare facilities.
diagnostic evaluation of the patients, and the
treatment they received from peripheral health-
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