الفهرس 
Introduction and aim of work
Diagnosis of ACSOnly 14 pages are availabe for public view
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Abstract
Aim of the study: The aim of the present study is: 1- To compare the efficacy and safety of low-molecular weight heparin (LMWH) with those of unfractionated heparin (UFH) in patient with unstable angina/ non-Q-wave myocardial infarction. 2- To clarify the role of anti-factor Xa as a new molecular marker in monitoring the action of low-molecular weight heparin (LMWHs). Study population: This study included 50 patients with acute coronary syndrome (unstable angina / non-Q-wave myocardial infarction) admitted to coronary care unit (CCU) in the Emergency Hospital, Mansoura University. Eligible patients were (21) males and (29) females with recent onset anginal pain for at least 10 minutes, their age ranged between 33-75 years (mean 52.88 ± 10.15). The mean duration of hospital stay was 7.6 ± 1.36 days.Diagnosis of unstable angina or non-Q-wave myocardial infarction was decided within 24 hours from admission and was based on immediately available clinical information, ECG evidence of ischemia, echocardiography and serum cardiac markers.Patients were divided into two main groups: Group I: included 25 patients (10 males and 15 females with a mean age 51.24 ± 9.005) who received UFH. Group II: included 25 patients (11 males and 14 females with a mean age 24 ± 11.30) who received LMWH. Drugs were given for a minimum of 48 hours (maximum 7 days). Risk factors present included: hypertension, diabetes mellitus, dyslipidaemia, smoking and positive family history for CAD. Inclusion Criteria: 1- Clinical criteria: It included:- Prolonged chest pain > 10 minutes. - Anginal pain at rest within 24 hours of randomization, or - New onset (de novo) angina, or - Severe (class III of CCSC) angina, or - Recent destabilization of previously stable angina with at least CCS III angina characteristics (crescendo angina) 2- ECG criteria: It included:-A new ST-segment depression > 0.1 mv and / or -Temporary or persistent T-wave inversion of ≥ 0.1 mv below base-line in at least two contiguous leads 3- Elevated cardiac enzymes (CK and CK-MB): in patients with non-Q-wave myocardial infarction. Exclusion Criteria: 1-Previous or old Q-wave MI.
2- Chest pain related to evolving Q-wave MI.
3- Previous CABG or PTCA.
4- Bleeding tendencies due to:
a. Platelet dysfunction.
b. Thrombocytopenia.
c. Abnormal coagulation profile.
d. Those on oral anti-coagulants.
5- Contraindication to anticoagulation e.g.
a. Uncontrolled hypertension (systolic BP> 200 mm Hg of diastolic BP> 120 mm Hg).
b. Stroke within 3 months.
c. Proliferative diabetic retinopathy.
6- Advanced renal or hepatic insufficiency.
7- Pregnancy or lactation.
8- History of hypersensitivity to heparins (UFH and LMWH).
9- The presence of LBBB or pacemaker.
10- Secondary angina.
11- Major surgery < 2 months.
Evaluation of patients:
All patients underwent a thorough clinical evaluation and review with special attention to:
(1) History:
- History of angina pectoris, its duration and severity assessed according to CCS classification.
- Other cardiovascular symptoms e.g. congestive lung symptoms or low cardiac out-put symptoms
- Risk factors for CAD.
- History of previous MI, previous CABG or PTCA and its details.
- History of cerebro-vascular and / peripheral vascular disease.
- Current medication and drug history (beta-blockers, calcium channel blockers, nitrates, aspirin, hypolipidaemic drugs).
- History of bleeding tendencies.
- History of allergy to heparins (LMWH and UFH).
(2) Clinical examination: with special attention to:
- Vital signs: pulse, blood pressure, temperature and respiratory rate.
- Body mass index (BMI).
- Complete cardiac, chest, abdominal and CNS examination.
(3) Laboratory tests: included:
- CBC and ESR.
- Fasting and post-prandial blood sugar.
- Serum creatinine.
- Liver function tests.
- Serum lipids.
- Serum cardiac enzymes (CK and CK-MB).
- Coagulation profile (PT, PC, and APTT).
- Factor Xa assay.
- Anti-factor Xa assay.
Serial determination of cardiac enzymes, PT, PC, APPT, factor Xa and anti-factor Xa were done on admission and every 6 hours of anti-thrombin therapy for the initial 48 hours and then daily for 7 days and after any further episodes of severe anginal pain.
(4) ECG: For ST-segment depression > 0.1 mv and / or T-wave inversion > 0.1 mv.
(5) Echocardiography: for
- Ejection fraction (EF%).
- Percentage of Fractional Shortening (%FS ).
- Segmental wall motion (SWM) score index.
The ECG and echocardiography were done on admission and repeated as the clinical situation changes.
Results:
Clinical Results:
Base-line Clinical Characteristics:
- Unstable angina had occurred in 17 patients (68%) in group I Vs 18 (72%) in group II.
- On the other hand, non-Q-wave MI had occurred in 8 patients (32%) in group I Vs 7 patients (28%) in group II with no significant difference (P> 0.05).
- There were no significant differences in risk factors between both groups (P> 0.05).
Short-term Clinical out-come events:
- Controlled anginal pain observed in 15 patients (60%) in group I Vs 17 patients (68%) in group II during the first week of initial hospitalization with no significant difference (P> 0.05).
- On the other hand, severe recurrent anginal pain occurred in 10 patients (40%) in group I Vs 8 patients (32%) in group II with no significant difference (P> 0.05).
- There was no evidence of any major adverse effects in either treatment group. However, minor bleeding complications (ecchymosis at puncture site) were observed in 18 patients (72%) in group I Vs 15 patients (60%) in group II with no significant difference (P> 0.05).
ECG Data:
ST-segment depression and T-wave inversion (> 0.1 mv.) showed non-significant difference before and after anti-thrombin therapy among both treatment groups (P>0.05).
ST-segment depression and T-wave inversion (> 0.1 mv) showed significant improvement among both group after anti-thrombin therapy (P <0.05).
Echocardiographic Data:
WMA, SWM score and score index:
Non significant changes were observed in WMA, segmental wall motion score and score index among treatment groups before and after anti-thrombin therapy (P>0.05).
Significant improvement was observed in WMA, WMS and WMS index after anti-thrombin therapy among both groups (P<0.001, <0.05 and <0.05 respectively).
Ejection fraction (EF %) and percentage of fractional shortening ( % FS):
Non-significant changes were observed in EF% and % FS among treatment groups before and after anti-thrombin therapy (P>0.05).
Laboratory Data:
Lipid Profile:
Comparative analysis of lipid profile revealed non significant difference between both groups (P>0.05).
Cardiac markers:
Patients in each treatment group showed significant difference in CK and CK-MB markers 24 hours after anti-thrombin (P<0.05). however, results of cardiac markers after one week showed non-significant difference in either group (P>0.05).
Patients with elevated CK and CK-MB are at increased risk of severe recurrent anginal pain.
The association of recurrent anginal pain with ECG changes and elevated cardiac markers occurred in 32% of LMWH patients Vs 40% of UFH patients (P >0.05).
Significant difference was observed in CPK-index before Vs 24 hours after anti-thrombin therapy among patients with non-Q-wave myocardial infarction in both groups (P<0.05).
Haematologic monitoring:
Platelet count:
Non-significant difference was observed in platelet count before Vs after anti-thrombin therapy in the treatment groups (P>0.05).
Heparin-induced thrombocytopenia (HIT) has not been encountered in either treatment group.
PT and APTT:
Non-significant difference was observed in PT in group I Vs group II before and after anti-thrombin therapy and in APTT in group I Vs group II before therapy (P >0.05).
On the other hand, significant changes were observed in APTT in group I Vs group II after anti-thrombin therapy (P<0.001).
Factor-Xa and anti factor-Xa activity:
Non-significant difference was observed in factor-Xa in group I Vs group II before therapy (P>0.05). On the other hand, factor Xa was significantly lower in those who received LMWH when compared with those who received UFH (P<0.001).
Non-significant difference in anti-factor Xa in group I Vs group II before anti-thrombin therapy (P>0.05). On the other hand, anti factor Xa activity was significantly higher in LMWH group Vs UFH group after anti-thrombin therapy (P<0.001).
Conclusion:
On the basis of the reported data in the present study we can conclude that:
1- LMWH does provide clinical benefit above and beyond UFH in patients with unstable angina/non-Q-wave myocardial infarction.
2- LMWH is at least as safe as UFH.
3- Because of the efficacy and safety of LMWH (Enoxaparin), it should be considered as acceptable alternative to UFH for the acute phase management of patients with unstable angina/non-Q-wave myocardial infarction.
4- The recommended dosage of enoxaparin is 1 mg/kg subcutaneously twice daily for a minimum of 48 hours and a maximum of 8 days.
5- Efficacy and safety of LMWH might be improved by monitoring anti-Xa levels, but anticipated improvements in clinical outcomes and cost may be marginal and offset by inconvenience and expense.
6- Anti-Factor Xa assay is recommended as a new laboratory marker for superiority of the treatment effect of LMWH over UFH.
Limitation of the study:
1- The small number of patients being 50 patients (25 in each group) in comparison to the previous clinical trials.
2- Multilead ST-segment monitoring which is very useful in detecting or ruling-out ST-segment changes during recurrent episodes was not performed.
3- Cardiac troponins which are the preferred markers for both the diagnosis of myocardial necrosis and the estimation of prognosis were replaced by estimation of CK and CK-MB which are less specific with overlap between normal and abnormal values.
4- The present study did not include assessment of anti-factor Xa: anti-factor IIa ratios which enforce the superiority of LMWH over UFH.
5- Another Limitation in using LMWH is its cost. However, taking into account the cost incurred by hospitalization and frequent monitoring of anti-coagulation in patients treated with UFH, it is proved that the cost of LMWHs is the same or even less than the overall cost of UFHs.
6- In the present study we did not keep the patients on treatment (Enoxaparin or UFH) post hospital discharge, that is why long-term comparisons among patients in both groups could not be achieved.
Recommendations:
1- A long-term follow-up study is needed to verify the impact of therapy on long term clinical out-come.
2- A comparative study is needed to compare the efficacy and safety of Enoxaparin with other LMWHs preparations to recognize whether these LMWHs are truly clinically distinct or whether the superiority of the treatment effect of these agents compared with UFH are class effect and not related to their distinct pharmacological and biochemical profiles.Basically; the key point for a successful management of patients with unstable angina/non-Q-wave myocardial infarction lies in the appropriate matching between UFHs and LMWHs.