Research Orientation by Dr.Iram

2. DR. IRAM ASLAM
PG Resident - MD Cardiology
Under Supervision of
PROFESSOR DR. BILAL S. MOHYDIN
HEAD OF CARDIOLOGY DEPARTMENT
KEMU/Mayo Hospital, Lahore
RESEARCH TITLE
COMPARISON OF CLINICAL OUTCOME OF 20mg AND 40mg ROSUVASTATIN
IN PATIENTS WITH ST ELEVATION ACUTE MYOCARDIAL INFARCTION (STEMI)
AFTER PERCUTANEOUS CORONARY INTERVENTION (PCI) OVER 2 MONTHS

3. INTRODUCTION
31.8% of all deaths worldwide out of which half were due to ischemic
heart disease (1)
Percutaneous coronary intervention as a reperfusion strategy
Peri-procedural myocardial injury (PMI) (5)
The treatment of the ACS patient does not end with revascularization
Lipid lowering measures
AHA guideline: lower LDL-C to <70 mg/dL or achieve a 50% decrease from
baseline
ESC guideline : < 55 mg/dL LDL-C (7)

4.  Pleiotropic effects like anti-inflammatory effects, improve endothelial
function, decrease oxidative stress, plaque stabilization and inhibit
thrombogenic responses
 Intensity of statin therapy
High ≥50%
Moderate 30-49%
Low <30%
 High-intensity statins significantly reduced major vascular events by
15% with no significant reduction in coronary deaths as compared with
moderate-intensity statin therapy and lowers risk of all-cause mortality in
patients presenting with ventricular tachyarrhythmias (8)

5.  High intensity rosuvastatin administered before PCI significantly (9-12)
Improves microvascular myocardial perfusion
Reduce ischemia-reperfusion injury
Effectively reduce MACE
Reduce peri-procedural myocardial injury and infarction
Significantly improves long-term clinical outcomes
 Extreme high-intensity rosuvastatin therapy (40 mg) is well tolerated
and safe in Indian ACS patients (13)

6. A RECENT STUDY DONE BY WEIFENG HE , MAOLIN CAO,
ZHIFENG LI, PUBLISHED IN WILEY IN FEB,2020
REPORTED(14)
20mg Rosuvastatin 40mg Rosuvastatin
mean CK-MB 24hrs Post PCI 59.77± 17.31 39.54± 13.25
mean ALT 24hrs Post PCI 28.54± 6.98 24.15± 10.25
mean TnI 24hrs Post PCI 1.85± 0.59 1.16±0.72
mean Cumulative MACE 15 3
p-value < 0.05
Clinical data on the benefit of 20mg versus 40mg rosuvastatin for
reducing PMI and post PCI MACE regarding Pakistani patients and
patients with ST elevation MI is limited.

7. HYPOTHESIS
40mg rosuvastatin shows improved clinical outcome in patients with
ST elevation acute myocardial infarction (STEMI) after percutaneous
coronary intervention (PCI) as compared to 20mg rosuvastatin over 2
months.

8. OBJECTIVE
 Primary objective
Reducing major adverse cardiovascular events
Secondary objectives
1. Cardiac biomarker levels
2. New onset diabetes
3. Safety and tolerability profile
Through this study if we will find better outcome of 40mg rosuvastatin
then in future it can be used effectively and safely in our patients with
STEMI who are tolerant or have no contraindication for high intensity
statin therapy.

9. OPERATIONAL DEFINITION
ST elevation acute myocardial infarction (STEMI) :
Electrocardiography (ECG)
In a clinical setting of either:
Characteristic symptoms of myocardial ischemia
or
A rise in biomarkers of myocardial necrosis (15)

10. MATERIALS AND METHODS
Study design: Randomized controlled trial
Settings: Department of Cardiology Mayo Hospital, Lahore
Duration of Study: 6 months
Sampling Technique: Non-Probability convenient sampling
Treatment allocation: Randomized to 20mg or 40mg
rosuvastatin using computer generated random number table.

11.  SAMPLE SIZE:
66 patients (33 patients in each group)
Estimated by using 5% level of significance, 90% power of test with
expected mean value rosuvastatin 20mg on 28.54 ± 6.98 and
rosuvastatin 40mg on 24.15 ± 10.25.(14)
Here
σ2= Variance
Z1- α= Confidence level 95% = 1.96
Z1-β = Power of test 90%
µ1 = Population mean I = 28.54
µ2 = Population mean II = 24.15

12.  SELECTION CRITERIA
INCLUSION CRITERIA:
1. All the patients with >18 years of age
2. Diagnosed with STEMI
3. Within 24 hours of ischemic symptoms onset

13. Exclusion Criteria:
1. Patients younger than 18 years of age
2. Patients with NSTE-ACS
3. Patients with >24hrs time passed since onset of ischemic symptoms
4. Patients who had contraindications of coronary angiography or PCI
5. Patients in whom study drug is contraindicated
6. Patients with previous MI
7. Patients who are currently taking statins
8. Presence of significant non-cardiac conditions
9. Non-cardiac comorbidity with a life expectation < 1 year
10. Participation in any investigational drug or cardiac/ non-cardiac device study within
30 days prior to study entry
11. Clinically significant heart disease requiring CABG (high syntax score), cardiac
transplantation, surgical repair and/or replacement during the course of the study.
12. Patients with psychiatric illness

14. OUTCOME
MACE (Major cardiovascular events) including arrhythmias, cardiac death, re-
hospitalization, surgical or percutaneous intervention, recurrence of angina and stroke
will be measured at 6th week and 2 months after treatment
Plasma levels of Creatine Kinase-MB, Alanine transaminase and Troponin I
measured pre-PCI and at 24 hours and 1 week after PCI
 HbA1c (glycosylated haemoglobin) and Lipid profile
measured pr-PCI and 6 weeks after PCI
 Tolerability
history of myalgia/myopathy according to Statin-Associated Muscle Symptom Clinical
Index (SAMS-CI)(16) with increased creatine phosphokinase (CPK) enzyme level
The follow-up will last for 2 months preferably by direct visit or if patient is reluctant to
travel due to current pandemic era on phone call consultation will be done.

15. DATA COLLECTION PROCEDURE
AND METHODOLOGY
66 cases
Fulfilling the inclusion/exclusion criteria
Written informed consent
Baseline clinical assessment, plasma CKMB, TnI, ALT, HbA1c and an
echocardiographic Doppler evaluation
Randomized to group-A (20mg Rosuvstatin) or group-B (40mg Rosuvstatin)
All patients will receive successful PCI (residual stenosis <20% and TIMI flow III)
and the guideline directed medical therapy
Reevaluated clinically after 24hrs, 1 week ,6 weeks and 2 months after PCI
 All data will be recorded by researcher herself

16. STATISTICAL ANALYSIS
All data will be entered and analysed using SPSS version 26
Qualitative data like gender , diabetic or non-diabetic ,MACE will be
presented in form of frequency (%)
 The quantitative data like age, height, weight, BMI, plasma levels of
CK-MB , ALT, TnI and HbA1c will be presented in the form of mean ±
S.D.
 Comparison between 20mg Rosuvastatin and 40mg Rosuvastatin
applies paired t test.
P-value ≤ 0.05 will be considered as significant

17. REFERENCES
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Ioacara S, Popescu AC, Tenenbaum J, Dimulescu DR, Popescu MR, Sirbu A, et al. Acute myocardial infarction mortality rates and
trends in Romania between 1994 and 2017. Int J Environ Res Public Health. 2019;17(1):285.
Khan MA, Hashim MJ, Mustafa H, Baniyas MY, Al Suwaidi SKBM, AlKatheeri R, et al. Global epidemiology of ischemic heart disease:
Results from the Global Burden of disease study. Cureus. 2020;12(7):e9349.
Lewis B. Percutaneous coronary intervention in patients with acute coronary syndrome: focus on bivalirudin. Vasc Health Risk
Manag. 2008;4(3):493–505.
Sun Y, Qi G, Gao Y, Zhang H, Pang X, Zhao W, et al. Effect of different loading doses of atorvastatin on percutaneous coronary
intervention for acute coronary syndromes. Can J Cardiol. 2010;26(9):481–5.
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guidelines and the society for cardiovascular angiography and interventions. J Am CollCardiol. 2011;58(24):e44-122.
Gencer B, Giugliano RP. Management of LDL-cholesterol after an acute coronary syndrome: Key comparisons of the American and
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Rusnak J, Behnes M, Schupp T, Lang S, Reiser L, Taton G, et al. Statin therapy is associated with improved survival in patients with
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Kim JW, Yun KH, Kim EK, Kim YC, Joe D-Y, Ko JS, et al. Effect of high dose rosuvastatin loading before primary percutaneous
coronary intervention on infarct size in patients with ST-segment elevation Myocardial Infarction. Korean Circ J. 2014;44(2):76–81.

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Jiang F, Yang J, Zhang L, Li R, Zhuo L, Sun L, et al. Rosuvastatin reduces ischemia-reperfusion injury in patients with acute
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intervention: a meta-analysis of fourteen randomized controlled trials. Lipids Health Dis. 2015;14(1):97.
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Shah CP, Shah BP, Dani SI, Channa BB, Lakshmanan SS, Krishnamani NC, et al. Efficacy and safety of the intensive dose of
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He W, Cao M, Li Z. Effects of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST-
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accuracy-of-ldl-c-estimation

19. Exclusion Criteria
● Patients who had contraindications of
coronary angiography or PCI □Yes □No
● Patients with previous MI □Yes □No
● Patients in whom study drug is contraindicated □Yes □No
● Presence of significant non-cardiac conditions □Yes □No
● Patients with stage III renal failure □Yes □No
● Active liver disease(ALT level >3x UNL) □Yes □No
● Patients who are currently on stains □Yes □No
● Known allergy/intolerance to study drug □Yes □No
● Non-cardiac comorbidity with a life
expectation< 1 year □Yes □No
● Known familial hypercholesterolemia □Yes □No
● Secondary causes of hyperlipoproteinemia □Yes □No
● Known skeletal muscle disease □Yes □No
● Participation in any investigational drug or
cardiac/non-cardiacdevice study within
30 days prior to study entry □Yes □No
● Clinically significant heart disease requiring CABG,
cardiac transplantation, surgical repair and/or
replacement during the course of the study □Yes □No
● Patients with psychiatric illness □Yes □No
FOLLOW-UP:
 Done at 1 week □Yes □No
 Done at 6 weeks □Yes □No
 Done at 2 months □Yes □No
 Compliance to medication □Yes □No
 Any adverse effect of drug observed □Yes □No
6.11 ANNEXURE AND CONSENTS
PROFORMA
Study group □ Group-A □ Group-B S. NO:
Hospital Record No. --------------------------------- Date: -------------------------------------
Personal Data:
Name------------------------------------- S/o,D/o,W/o -----------------------------------------------
Age-------------- Gender---------------
Height-------------------------------
Weight------------------------------
BMI---------------------------------
□ Diabetic □ Non-diabetic □ Pre-diabetes
Inclusion Criteria
● Age >18 years □Yes □No
● Diagnosed with STEMI □Yes □No
● Time since onset of ischemic symptoms is <24 hrs □Yes □No

20. Baseline AT 24 hrs At 1st week
CK-MB
TnI
ALT
Baseline At 6th week
HbA1c (%)
LDL
(mg/dL)
□ Direct
□ Estimated
by Eq 2
HDL(mg/dL)
Triglyceride
(mg/dL)
Total
Cholesterol (mg/dL)
At 6th Week At 2nd Month
Arrythmias
Cardiac death
Rehospitalization
Recurrence of angina
Surgical or
Percutaneous
intervention
Stroke
Tolerability
By Equation 2 LDL-C (17)
LDL-C(mg/dL) = TC/0.948 – HDL-C/0.971 – (TG/8.56 + (TG x Non HDL-C)/2140 –
TG2/16100) – 9.44
OUTCOME :

21. PARAMETER SCORE
Distribution of symptoms
Symmetric, hip flexors or thigh
Symmetric, calves
Symmetric, upper proximal extremities
Not specific to any area, asymmetric or intermittent
3
2
2
1
Timing of symptom onset
<4 weeks
>4-12 weeks
>12 weeks
3
2
1
Timing of muscle symptom improvement after statin withdrawal (dechallenge)
<2 weeks
2-4 weeks
No improvement >4 weeks
2
1
0
Rechallenge with a statin
Same symptoms recur in <4 weeks
Same symptoms recur in 4-12 weeks
Same symptoms recur in >12 weeks or do not recur
3
1
0
Likelihood that patient's muscle symptoms are due to statin use
Probable 9-11 Possible 7-8 Unlikely<7
STATIN-ASSOCIATED MUSCLE SYMPTOMS CLINICAL INDEX (SAMS-CI) TO DETERMINE THE
LIKELIHOOD OF STATIN INVOLVEMENT IN MYALGIAS

22. PATIENT INFORMED CONSENT FORM
I agree to participate in this study:
“COMPARISON OF CLINICAL OUTCOME OF 20mg AND 40mg ROSUVASTATIN IN PATIENTS WITH ST ELEVATION ACUTE
MYOCARDIAL INFARCTION (STEMI) AFTER PERCUTANEOUS CORONARY INTERVENTION (PCI) OVER 2 MONTHS”
The doctor has informed me that I am suffering from heart attack( ST elevation acute MI) which will be treated by stenting
followed by different doses of lipid lowering drug(tablet rosuvastatin 20mg or 40mg).
I have also been informed in detail about possible benefits and side effects of the study. I understand that I am free to
withdraw from the study whenever I want to. I have been told that my doctor will continue to give me all possible care even after my
discontinuation of the study.
I allow my doctor or any other person authorized by my doctor to contact me at my home or at an address given by me
for treatment and follow up. I have been assured that the information provided by me will be kept confidential and will be used for
research purpose only.
Investigator’s signature:
Date: