EVIDENCE-BASED CASE REPORT

Group A3:
Alfi Fajar Almasyhur (0806358041)
Fidini Hayati (0806357921)
Jackson Kamaruddin (0806357985)
Prinindita Artiara Dewi (0706302726)
Syifa Fauziah Fadhly (0706302732)

Supervisor:
dr. Nani Cahyani, SpKO

COMMUNITY MEDICINE CLINICAL PRACTICE MODULE

FACULTY OF MEDICINE, UNIVERSITAS INDONESIA
MARCH 2014
 STATEMENT OF APPROVAL

This report,

Title : “In patients with metabolic syndrome, does long term administration of acetylsalicylic
acid prevent the incidence of cardiovascular complications?”
Authors: Group A3 which consists of:
1. Alfi Fajar Almasyhur (0806358041)
2. Fidini Hayati (0806357921)
3. Jackson Kamaruddin (0806357985)
4. Prinindita Artiara Dewi (0706302726)
5. Syifa Fauziah Fadhly (0706302732)

Has been approved and accepted as a task for the Community Medicine Clinical Practice
Module, Faculty of Medicine Universitas Indonesia.

Supervisor:

dr. Nani Cahyani, SpKO

 STATEMENT OF ORIGINALITY

We, the undersigned below, hereby state that this paper was produced with no act of plagiarism
according to the rules applied by Universitas Indonesia.

If in the future we would be proven to commit plagiarism, we will take full responsibility and
accept any penalties assigned by Universitas Indonesia.

Jakarta, March 2014

Alfi Fajar Almasyhur (0806358041)

Fidini Hayati (0806357921)

Jackson Kamaruddin (0806357985)

Prinindita Artiara Dewi (0706302726)

Syifa Fauziah Fadhly (0706302732)

EVIDENCE BASE CASE REPORT

In patients with metabolic syndrome without previous cardiovascular event, does long
term administration of acetylsalicylic acid prevent the incidence of cardiovascular
complications?
Almasyhur AFa, Dewi PAa, Fadhly SFa, Hayati F a, Kamaruddin Ja, Cahyani Nb
a
Faculty of Medicine, Universitas Indonesia, bDepartment of Sports Medicine, Cipto
Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia

Abstract

Introduction:
Patients with metabolic syndrome are at high risk to experience cardiovascular disease (CVD).
Acetylsalicylic acid is a drug known to prevent the occurrence of cardiovascular
complications. The mechanism of action of acetylsalicylic acid is by inhibiting synthesis of
prostaglandin by COX and inhibiting platelet aggregation. The use of acetylsalicylic acid for
secondary prevention in patients with previous myocardial infarction, stroke or transient
cerebral ischemia is proven to be effective. However, use of this drug for patients without
previous cardiovascular complications remains inconclusive. This report aimed to investigate
the administration of acetylsalicylic acid as a primary prevention of CVD complications.
Methods: A literature search was conducted to find articles which

Results:

Conclusion:
CASE ILLUSTRATION

A female patient 58 years old came for a routine control for her health problems. Since 8 years
before current visit to the clinic, patient had a chief complaint of frequent urination. She
frequently woke up at midnight for micturition as many as 6 times. Patient also mentioned that
she frequently felt thirsty and had a snacking habit. There was no decrease in appetite nor her
weight. Patient then consulted a doctor and was said that she suffered from diabetes mellitus. She
admitted that the highest fasting blood glucose ever experienced was 176. Patient was then given
Metformin and Glimepirid which were consumed routinely thrice daily and once daily,
respectively. Complaints were said to decrease and subside. Since 5 years before current visit,
patient admitted that she was diagnosed having hypertension with highest blood pressure ever
measured was 150/90 mmHg. Patient was then given Captopril which was consumed twice daily.
Simultaneously, patient was also diagnosed of having high cholesterol level, with triglyceride
level 266. Then she was given Simvastatin to be consumed once daily. Besides those drugs,
patient was also given Thrombo Aspilet which was consumed once daily. Since 3 years before
current visit, patient complained of tingling and decreased sensation in both her hands and feet.
However, it was said that it happened occasionally. Her eyes were said to be blurry however
there was no floating objects following her eye movement. She never had stroke nor chest pain
before. Patient mentioned that her urinated a lot daily, clear in color, and painless upon urination.
There was no history of asthma, allergy, heart problems, lungs and kidney problems in patient
and her family. Patient’s father had a history of liver disease and her younger sister also had
diabetes mellitus.
Upon physical examination, the patient appeared in mild pain. Her blood pressure was 130/70
mmHg, radial pulse 75 bpm, respiratory rate 16 times/minute, and axillary temperature 36.3 oC.
Her pupils were isochoric, conjungtiva were not pale, sclera not icteric. Her pharynx was not
hyperemic, tonsils T1/T1. Her lungs were symmetrical in static and dynamic condition, chest
expansion normal, fremitus were equal on both lung fields, sonor upon percussion, and, upon
auscultation, her lung sounds were vesicular on both long fields with no ronchi or wheezing. Her
heart borders were normal, heart sounds were regular, no murmur or gallop. Her abdomen was
flat, with no tenderness and no palpable liver or spleen, shifting dullness sign was negative and
her bowel sounds were normal. Her extremities were warm with no edema. There were no

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swollen or tender joints, however there was crepitation on both knees. Her neurological
examination was unremarkable with +2 score on both sides for biceps, triceps and patellar
reflexes and no pathological reflexes.

Doctors discovered there was an issue on the use of acetylsalicylic acid (Thrombo Aspilet) on
patients with metabolic syndrome without previous cardiovascular event. It was thought that its
use might prevent cardiovascular events in the future.

INTRODUCTION

Cardiovascular diseases (CVD) are currently number one cause of death which occurs all over
the world. It contributed to 30% of deaths in the world, which causes 17.3 million of deaths in
year 20081. About 7.3 million of these deaths were because of coronary heart disease and the 6.2
million were caused by stroke2. The number of deaths will increase to 23.3 million in year
20301,3.

Cardiovascular diseases can be defined as disorders which involves the heart and blood vessels.
It consists of coronary heart disease, cerebrovascular disease, peripheral arterial disease,
rheumatic heart disease, congenital heart disease, and deep vein thrombosis4.

CVD can be affected by several risk factors. The risk factors are unhealthy diet, physical
inactivity, use of tobacco, and alcohol consumption 1. These risk factors may present as increased
blood pressure, blood glucose, lipids, overweight and obesity. The avoidance of these risk factors
may decrease the risk of having CVD.

According to International Diabetes Federation (2006) 1, metabolic syndrome or also known as

syndrome X is defined as a cluster of syndrome which criteria are consists of a person with
central obesity (increased waist circumference, for South Asians: ≥ 90 cm for male and ≥ 80 cm
for female) combined with the presence of at least 2 of the followings:

- Increased blood pressure: systolic blood pressure ≥ 130 mmHg or diastolic blood
pressure ≥ 85 mmHg, or treatment of previously diagnosed hypertension;
- Elevated serum triglycerides: ≥ 150 mg/dL (≥ 1.7 mmol/L), or treatment for lipid
abnormality;
2
 - Decreased HDL cholesterol level: < 40 mg/dL (men) or < 50 mg/dL (women) or
treatment for lipid abnormality;
- Impaired fasting glucose: ≥ 100 mg/dL (5.6 mmol/L), or previously diagnoses type 2
diabetes

Each of these conditions is a potential risk factor of CVD which makes a person with metabolic
syndrome has a high risk of developing CVD. Therefore, an aggressive management is necessary
to control each of the conditions thus may prevent the occurrence of CVD. Acetylsalicylic acid is
a drug known to prevent the occurrence of CVD. The mechanism of action of acetylsalicylic acid
is by inhibiting synthesis of prostaglandin by COX and inhibiting platelet aggregation. The use
of acetylsalicylic acid for secondary prevention in patients with previous myocardial infarction,
stroke or transient cerebral ischemia is proven to be effective 6. Aside from the advantage, this
drug has serious complication which is bleeding. The data about primary prevention of CVD
events of this drug remain inconclusive. Therefore this report aims to investigate the
administration of acetylsalicylic acid as a primary prevention of CVD complications.

CLINICAL QUESTION
“In patients with metabolic syndrome without previous CVD event, does long term
administration of acetylsalicylic acid prevent the incidence of cardiovascular complications?”

Table 1 – Formulation of Clinical Question

Patient/Problem Intervention Comparison Outcome
Patients with Acetylsalicylic acid Placebo Incidence of
metabolic cardiovascular
syndrome without complication
previous CVD
event
Type of Question Intervention /Treatment
Study design Meta-analysis, systematic review, randomized controlled trials (from
highest to lowest level of evidence)

METHODS

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Search Strategy
Search was conducted using databases Pubmed and Cochrane from 18-22th March 2014.
Keywords used were “acetylsalicylic acid”, “cardiovascular event”, “metabolic syndrome”.
Searching was conducted by using synonyms and related terms with keywords. Filters activated
were systematic reviews, randomized controlled trial, meta-analysis and clinical trial.

Table 2 – Search Strategy

Engines Search Terms Hits
Pubmed 38

Ovid (aspirin or acetylsalicylic acid) and "cardiovascular event*"

Cochrane

Selection Criteria

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Metabolic Syndrome AND Aspirin AND Cardiovascular AND Prevention

Pubmed Cochrane

71 17

Check for duplication

76
Inclusion criteria

Clinical trial
Systematic review
Meta analysis Screening for titles and
abstract

Exclusion criteria
1
Etiology studies
Children < 18 years
Non English article
Figure 1 - Search
FullStrategy Flow Chart
text availability

Full text reading

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RESULTS
After reading full texts, only one journal was found to meet our criteria. This randomized
controlled trial is a double blind study conducted by Xiu Ren Gao et al in China. The subjects
were 121 patients with metabolic syndrome who were randomized into three groups. The first
group received 100 mg/day of aspirin, the second group received 300 mg/day of aspirin and the
third group received placebo. The intervention lasted for two weeks.

Validity
The PICO question of this review is “In patients with metabolic syndrome without previous
CVD event, does long term administration of acetylsalicylic acid prevent the incidence of
cardiovascular complications?”. In this study, the incidence of cardiovascular complications
were measured by the inflammatory markers hs-CRP, TNF-α, IL-6, TXB2 and 6-keto-PGF1-α.
In terms of randomization, all patients in this study were randomly divided into three groups
during the period from September 2005 to March 2007. The technique used was double blind
because it is stated that the doctors told all participants to take either aspirin or placebo in a
double-blind way. Moreover, all patients who were randomized completed the study. At the start
of the trial, these groups were similar because it is stated that no statistical differences in all
parameters. During the study, all groups were treated equally.

Importance
Results show a decrease in blood levels of hs-CRP, TNF-α, IL-6 and TXB2 in patients who
received 300 mg/day of aspirin for 2 weeks. Statistically significant results were shown for
inflammatory mediators (hs-CRP, TNF-α, IL-6) and TXB2 with p values of 0.0009, 0.0005,
0.0267, and 0.0012, respectively. Furthermore, there was also a decrease in blood levels of hs-
CRP, TNF-α, IL-6 and TXB2 in patients who received 100 mg/day of aspirin for 2 weeks.
However, statistically significant results were only shown for inflammatory mediator hs-CRP
and TXB2 with p values of 0.0201 and 0.0001, respectively. In the placebo group, no effect was
observed because all inflammatory markers showed no statistical difference between
pretreatment and post-treatment.

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Applicability
Our patient is a 58-year-old female with metabolic syndrome and has no history of previous
cardiovascular event. She was given aspirin as a primary prevention. In this study, the subjects
had metabolic syndrome and aged between 43 to 61 years old. Approximately half of the
patients were female and Asian ethnic. Therefore, our patient is similar to those in the study. The
treatment is feasible in our setting because the administration of 100 mg/day or 300 mg/day for
aspirin is possible. It is believed that the standard for aspirin administration is only 80 mg/day,
but the recommended administration to provide benefits for decreasing inflammatory markers
which may contribute to cardiovascular complication in patients with metabolic syndrome
according to the study is 100 mg/day or 300 mg/day.

DISCUSSION

CONCLUSION AND SUGGESTIONS

REFERENCES
1. WHO. Global Status Report on Noncommunicable Diseases 2010. Geneva: 2011
2. WHO. Global Atlas on Cardiovascular Disease Prevention and Control. Geneva: 2011
3. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002
to 2030. PLoS Med, 2006, 3(11):e442
4. WHO. Cardiovascular Diseases (CVDs). 2013 [cited 2014 16 March ]; Available from:
http://www.who.int/mediacentre/factsheets/fs317/en/
5. International Diabetes Federation. The IDF consensus worldwide definition of the
Metabolic Syndrome.2006 [cited 2014, 16th of March]: Available from:
http://www.idf.org/metabolic-syndrome.
6. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens
C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A. Antithrombotic
Trialists' (ATT) Collaboration. Aspirin in the primary and secondary prevention of
vascular disease: collaborative meta-analysis of individual participant data from
randomised trials. Lancet2009;373:1849–1860.

7.

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