Mr. G is a 50-year-old male with BMI 26.0 (height 1.7m; weight 75kg), which indicates overweight. He was admitted into the hospital for acute central chest pain associated with shortness of breath for 30 minutes.
Presenting Complaint
The chest pain was of sudden onset. The pain radiated to the left shoulder and back. Mr G described the pain as pressing type with chest tightness. The pain was not relieved by rest. Therefore, the family sent him to hospital. It took about 30 minutes from the onset of chest pain to arrival in hospital. Associated with the chest pain, there was also profuse cold sweat, nausea and shortness of breath.
History of the Present Illness
Mr. G had past presenting complaint of chest pain for the past 5 days since last discharge 1 week ago. He also complained of having reduced effort tolerance, orthopnea and paroxysmal nocturnal dyspnea. There was no history unilateral leg swelling. There was no history of trauma to the chest. He has no fever, cough, hemoptysis.
Past medical History
Mr. G has past medical history of hypertension, ischemic heart disease and hypercholesterolaemia. He had a valvular operation in 1995 and stenting in 2005. He did angiogram last month and two vessels disease were identified. He is planned for a bypass surgery next month. He has no known drug or food allergy.
Social and Occupational History
Mr. G is currently unemployed. He is married with two children. He is staying with his family. He is neither a smoker nor a drinker.
Family History
He has a strong family history of ischemic heart disease and hypertension.
Drug History
He is currently on the below medication:
Tablet Enalapril 20mg OD
Tablet Aspirin 75mg OD
Sublingual GTN 300mcg tablet, 1 tablet when necessary for chest pain
Tablet Isosorbide dinitrate 20mg BD
Tablet Atenolol 100mg OD
MR Tablet Trimethazidine 35mg BD
Tablet Artovastatin 40mg ON
Tablet Warfarin 7mg OD
Examination Details
Upon admission to the emergency department, the patient was examined by the doctor. Patient's blood pressure was 157/97 mmHg, pulse rate 67 beats per minute, body temperature 37°C and SPO2 96% under room air. He was alert and conscious. Systemic review was unremarkable. Lungs were clear with no crepitation. Cardiovascular system showed S1S2 pansystolic murmur. Prosthetic click was heard. Electrocardiogram (ECG) was carried out immediately and showed ST depression and T-wave inversion. Blood samples were then taken for the following tests:
Coagulation Profile
Liver function test
Cardiac enzymes test
Renal profile
Full blood count
Impression/Diagnosis
The impression was unstable angina with underlying hypertension, ischeamic heart disease and hypercholesterolaemia.
Management Plan
Immediate treatment was given. High flow oxygen of 3L/min was given via face mask to ensure adequate oxygenation and to maintain SPO2 at 94-98%. Two large bore cannulas were set as anticipation for IV drug administration and blood taking for investigation. And, the following drugs were given for acute treatment of this patient:
Sublingual GTN 400mcg tablet
Tablet Aspirin 300mg stat
Tablet Clopidrogel 300mg stat
Subcutaneous injection of 60mg Enoxaparin stat
Mr G was then admitted to the ward and the following plan was carried out:
Vital signs and SPO2 monitoring 4 hourly
Blood glucose monitoring TDS
To get earlier bypass surgery appointment
Continue the following medications:
Tablet Enalapril 20mg OD
Sublingual GTN 300mcg tablet, 1 tablet when necessary for chest pain
Tablet isosorbide dinitrate 20mg BD
Tablet Atenolol 100mg OD
MR Tablet Trimethazidine 35mg BD
Tablet artovastatin 40mg ON
Tablet Warfarin 7mg OD
Clinical progress
Day 2
On examination, patient was alert, conscious and well orientated. However, he still complained of chest heaviness and shortness of breath when lying down.
The vital signs were as follows:
Blood pressure: 130/68 mmHg
Pulse rate: 60 beats per minute
Respiratory rate: 20 breaths per minute
Temperature: 37°C
Patient's respiratory system was checked and showed that lungs were clear. There was no crepitation. Chest X-ray was done and showed that there was no fluid in the lung. This ruled out the possibility of pulmonary oedema.
Patient was propped up on bed and was advised to continue on his medications and inform the nurse/doctor if he experienced any chest pain.
Day 3
On examination, patient was alert, conscious and comfortable. When interviewed, he claimed that he was feeling much better at the moment. But he complained having chest pain while defecating yesterday. Doctor suspected patient might have constipation and planned to give 15mL lactulose twice daily.
The vital signs were as follows:
Blood pressure: 130/80 mmHg
Pulse rate: 72 beats per minute
Respiratory rate: 20 breaths per minute
Temperature: 37°C
Patient's blood results were reviewed. (refer investigations section)
Summary of blood results:
Coagulation Profile- High PT, INR within reference range
Cardiac enzymes within reference range - confirm diagnosis of unstable angina
Patient's blood glucose monitoring was off as it showed constant and normal readings throughout day 1 and 2.
Day 1 6.4; 6.1; 6.1
Day 2 5.5
Other medications are continued. Vital sign monitoring was carried out 4 hourly. And patient was reminded to inform the nurse if he experienced any chest pain.
Day 4
On examination, patient was alert, conscious and comfortable. He had no more chest pain and shortness of breath. He was able to mobilize.
The vital signs were as follows:
Blood pressure: 120/80 mmHg
Pulse rate: 72 beats per minute
Respiratory rate: 20 breaths per minute
Temperature: 37°C
The patient was to complete enoxaparin today and to be discharged. He was also arranged for an earlier bypass surgery appointment.
Investigations
Coagulation Profile
Components
Results: Day 1
Results: Day 3
Reference range
Prothrombin time
35.0↑
34.0↑
11.9-14.5 s
INR
3.4
3.23
2.0-4.0
APTT
82.8↑
72.6↑
29.5-42.3
APTT ratio
2.31
2.02
-
Liver function test
Components
Results
Reference Range
Total protein
65
64-83 g/L
Albumin
42
35-50 g/L
Globulin
23↓
25-39 g/L
A/G ratio
1.8
0.9-1.8
ALP
81
30-120 IU/L
ALT
47↑
0-41 IU/L
Total Bilirubin
16
< 17 µmol/L
Cardiac enzymes test
Components
Results
Reference range
Aspartate transaminase, AST
30
Up to 31 IU/L
Creatine kinase, CK
103
38-174 IU/L
Lactate dehydrogenase, LDH
475
240-480/L
Renal profile
ClCr: 84.72mL/min (normal 78-120ml/min)
Component
Results
Reference range
Urea
3.7
1.7-8.3
Sodium
140
136-145
Potassium
4.1
3.4-5
Chloride
104
98-106
Creatinine
98
62-106
Full blood count
Full Blood Count
Results
Reference range
HGB
14.2
13.5-17.5 g/L
RBC
4.9
4.5-5.9 x 1012/L
WBC
8.0
5.2-12.4 x 109/L
HCT
43
41.0-53.0%
MCV
87
80-100 fl
MCH
29
26-34pg
MCHC
33
31-37 g/L
RDW
14
11.5-14.5 %
PLT
252
130-400 x109L
MPV
12.0↑
6.8-10.8
Differential count:
Differential Count
Results
Reference range
Neutrophils
48
40-74%
Lymphocytes
37
19-48%
Monocytes
11↑
3.4-9%
Eosinophils
4
0-7%
Basophils
1
0-1.5%
Drug chart during hospitalisation
Tablet Enalapril 20mg OD
Sublingual GTN 300mcg tablet, 1 tablet when necessary for chest pain
Tablet isosorbide dinitrate 20mg BD
Tablet Atenolol 100mg OD
MR Tablet Trimethazidine 35mg BD
S/C Enoxaparin 60mg BD
Tablet artovastatin 40mg ON
Tablet Warfarin 7mg OD
Lactulose 15ml BD
Discharge Plan
He was discharged with the following medications:
Tablet Aspirin 75mg OD
Tablet Enalapril 20mg OD
Tablet isosorbide dinitrate 20mg BD
Sublingual glyceryl trinitrate 1 tablet when necessary ie chest pain
Tablet Atenolol 100mg OD
MR Tablet Trimethazidine 35mg BD
Tablet artovastatin 40mg ON
Tablet Warfarin 7mg OD
Appointments:
Patient was referred to National Heart Institute for earlier bypass surgery.
Counseling:
The nature of the disease was explained to the patient - how the therapy going to help him and how he can improve his prognosis.
Both patient and his family members were educated about healthy lifestyle modifications to cut down risk factors of future attacks.
Patient was advised to be compliant to medications which help to reduce morbidity and mortality.
Patient was advised to go to the casualty if his condition deteriorates or if similar attack occurs again.
Disease Overview
Unstable angina (UA), a clinical syndrome subset of the acute coronary syndrome (ACS), is an intermediate myocardial syndrome between stable angina and acute myocardial infarction (AMI). In United Kingdom, there are approximately 114,000 patients being admitted into the hospital with ACS annually. Also, in 2005, more than 70,000 percutaneous coronary interventions (PCIs) were undertaken. ACSs have caught much attention due to its association with a high risk of morbidity and mortality. Guidelines have been produced, updated and reviewed to ensure the best treatment for the patients.
UA can be simply defined as a chest pain or discomfort that is experienced when the heart muscle does not get enough oxygen supply. In contrast to stable angina, UA occurs mainly due to a reduction of myocardial blood flow caused by an occlusive or a partially occlusive coronary artery thrombus. It often occurs at rest and even wakes people from restful sleep. It does not produce an elevation in the ST-segment of the ECG, in the same way as NSTEMI. Therefore, at many times of initial clinical presentation, UA and NSTEMI are indistinguishable. Because they have similar conditions, their treatments are identical as well.
2.1 Pathophysiology
The underlying cause of UA can be explained by different mechanisms as described in the American College of Cardiology/American Heart Association (ACC/AHA) practice guidelines for the management of UA/NSTEMI. In general, it happens mainly due to atherosclerosis, which is the hardening of the artery due to the build-up of fatty deposits called plaques in the coronary artery. Age, male gender, family history, obesity, hypertension, smoking, diabetes mellitus and hyperlipidaemia are the major factors responsible for the development of atherosclerotic plaques. Arterial inflammation caused by either noninfectious or infectious stimuli can lead to plaque expansion, destabilization and rupture of the atherosclerotic plaque. The disruption and erosion of the atherosclerotic plaque, subsequently leads to a cascade of pathological processes. As a result of exposure of blood to the thrombogenic lipid core and endothelium, which are rich in tissue factor, the extrinsic coagulation cascade is activated. This eventually leads to the formation of a fibrin clot or a thrombus that partially occludes the artery, reducing the blood flow or oxygen supply to the myocardium.
2.2 Diagnosis
The diagnosis of UA is based on:
Patients' signs and symptoms
Patients with UA always have presented symptoms of acute central chest pain for more than 20 minutes. The pain may radiate to the shoulder, left arm, back or jaw. Patients may have associated symptoms such as nausea, shortness of breath, palpitations or sweatiness.
Electrocardiogram (ECG) changes
The guidelines recommend the performance of a 12-lead ECG within 10 minutes of patient presentation. The patterns of presenting ECG will determine the immediate treatment. Patient with UA have a characteristic ECG of ST-depression and T-wave inversion.
Blood Test (Biochemical markers levels)
The serum levels of Troponin T, Troponin I, CK-MB and cardiac enzymes define the main diagnostic of ACS. The SIGN guideline states that patient should have their biochemical markers level measured within 12 hours from the onset of symptoms for appropriate management. While NSTEMI is characterized by a typical rise in serum levels, UA is characterized by a normal serum levels.
Patients past medical history
Patients with UA often have past medical history of hypertension, ischeamic heart diease and hypercholesteraemia.
2.3 Pharmacological basis of drug therapy
In the case scenario, Mr. G was managed with the following drugs in the hospital:
Oxygen Therapy
High flow oxygen by face mask is given to the patient at the emergency department to maintain oxygen saturation at 94-98%. It also helps to improve myocardial oxygenation and function, thus reducing the pain.
Nitrate
Sublingual GTN 400mcg tablet is given every 5 minutes and up to 3 doses in the emergency department to provide rapid symptomatic relief in UA/NSTEMI patients. Nitrates are potent coronary vasodilators that provide rapid ischaemic pain relief, but their effect last only for 20 to 30 minutes. They cause venodilation, which lowers preload and myocardial oxygen demand. Besides, arterial vasodilation can lower blood pressure, thus reducing myocardial oxygen demand. All these relieve coronary artery vasospasm and improve myocardial oxygenation.
Antiplatelet
Aspirin and clopidrogel are the most commonly used antiplatelets in the acute management of UA/NSTEMI. Antiplatelet decreases platelet aggregation and thrombus formation in the arteries by inhibiting cyclooxgenase (COX) enzymes activity in platelet irreversibly. Patient presented with an UA/NSTEMI are treated with high dose aspirin or clopidogrel 300mg immediately. Combination therapy of aspirin 300mg and clopidrogel 300mg are also routinely used. The initial dose is followed by a long term treatment of low dose 75mg aspirin. This is to prevent further cardiovascular events.
Anticoagulant
Parenteral anticoagulant, either a low molecular weight heparin (LMWH) or an unfractionated heparin (UFH), is initiated to prevent blood vessels complications. It has rapid onset of action in comparison to oral anticoagulant. The main use of anticoagulant is to prevent the formation of thrombus or extension of an existing thrombus in the blood vessels. It acts by enhancing the activity of antithrombin III in the coagulation cascade, thus preventing the conversion of fibrinogen to fibrin. LMWH such as dalteparin and enoxaparin are widely used anticoagulants. They are usually preferred over UFH in preventing venous thromboembolism. LMWH/UFH is given every 12 hours usually for 2-8 days during hospital stay.
Beta-blocker
Beta-blocker has anti-ischaemic, anti-arryhthmic and anti-hypertensive properties. Intravenous or oral beta-blocker is administered within the first 24 hours, without any contraindications. Beta-blocker acts by blocking beta-adrenoceptors in the heart, thus reducing myocardial contractility and oxygen demand. It also blunts the contractibility responses of the heart to chest pain.
Angiotensin-converting enzyme (ACE) inhibitor
ACE inhibitor is optimized in patient after MI attack in order to reduce mortality, decrease reinfarction and prevent the development of heart failure. It has anti-hypertensive effect that they cause reduction in systolic, diastolic and mean arterial blood pressure by vasodilation. ACE inhibitor act by inhibiting the conversion of inactive angiotensin I to active angiotension II, which is a potent vasoconstrictor. Inhibition of synthesis of angiotensin II results in a decrease in the secretion of aldosterone.
Statin
Statin is also called lipid-lowering drugs that reduce the blood total cholesterol levels. It act by competitively inhibiting the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase in the liver, thus preventing the synthesis of cholesterol. Other mechanism action involves stabilization of the vulnerable atherosclerotic plaque. All these reduce the vascular events markedly.
Trimetazidine
Trimetazidine-1-(2,3,4 trimethoxy benzyl)-piperazine dihydrochloride is an anti-anginal drug used by the patient as a long-term treatment for angina pectoris. It is a metabolic modulator that optimizes myocardial energy metabolism. It inhibits the oxidation of fatty acids by blocking the enzyme 3-ketoacyl CoA thiolase (3-KAT), thus promoting myocardial glucose metabolism.
Evidence for treatment
According to the ACC/AHA practice guidelines for the management of UA/NSTEMI, pharmacological therapy of UA/NSTEMI includes:
Oxygen therapy
According to the guidelines, high flow oxygen by face mask should be given to patients with hypoxia (oxygen saturation less than 90%), pulmonary oedema or continuing myocardial ischaemia. This is to maintain patients' oxygen saturation at 94-98%. There has been no convincing evidence to support the benefits of oxygen administration. In fact, a controlled trial of administering oxygen to patients presented with uncomplicated MI within the 24 hours in hospital showed no improvement in mortality or number of use of nitrates. However, this does not mean that oxygen should be withheld in hypoxia patients. Oxygen administration, indeed, helps to improve myocardial oxygenation and function, thus reducing the chest pain in patients presenting with ACS.
Case summary: Mr. G was given high flow oxygen by face mask in the emergency department despite his SpO2 of 96%.
Nitrates
Nitrates are recommended by the guidelines as the first-line anti-ischaemic drug. Sublingual GTN 400mcg tablet is often given without delay at the time of presentation every 5 minutes. This is followed by IV nitroglycerin if there is no sign of symptomatic relief after three sublingual GTN tablets. Short-acting nitrates are beneficial for they provide rapid pain relief effect. Once they have been symptoms free for 24 hours, patients are switched to long-acting oral nitrates as prophylaxis.
A critical review of the randomized controlled ISSI-4 (Fourth International Study of Infarct Survival) trial reveals that the nitrates caused a significant reduction in mortality rate with p <0.001 in acute MI stage during the first 2 days of treatment. (1) This trial justifies the acute benefit of nitrates, but not the subacute benefit. In fact, oral mononitrates failed to produce any significant reduction in mortality rate over the 4-weeks trial period. Comparable observations were noticed in the GISSI-3 trial which showed no significant improvement in mortality rate in patients of whom was given a 24 hour IV GTN followed by 6 weeks of GTN transdermal patch.
Case summary: A sublingual GTN 400mcg was given to Mr. G in the emergency department. This is appropriate for rapid ischaemic pain relief as justified in ISIS-4 trial stated above. In the ward, he was continued on long-acting isosorbide dinitrate 20mg BD. Short-acting sublingual GTN tablet was also given for the patient to take only when necessary for rapid chest pain relief.
Morphine
The guidelines recommend the slow intravenous injection of diamorphine 2-5mgs or morphine 5-10mgs, along with an anti-emetic drug, metoclopramide 10mg in patients with presenting UA/NSTEMI if symptoms are not relieved by nitrates. IV morphine has potential benefits for its potent analgesic, anxiolytic and hemodynamic effects. However, there has been no prospective study available to support its efficacy in the initial management for pain relief. Furthermore, morphine use is associated with adverse effects such as hypotension, nausea, vomiting or even more severe respiratory distress. And, results from an analysis of CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines) Quality Improvement Initiative showed that morphine use, either alone or in combination with GTN, have no significant benefits but is associated with higher mortality in UA/NSTEMI patients. Therefore, more prospective, randomized clinical trials are needed to be conducted in order to assess the appropriateness and safety of morphine administration to patient with UA/NSTEMI for chest pain relief.
Case Summary: Mr. G was not given any IV morphine for his chest pain at the emergency department.
Antiplatelet
A collaborative meta-analysis of randomized controlled trials (RCTs) of antiplatelet therapy successfully demonstrated the efficacy of aspirin in preventing death and other vascular events in high risk patients. The results of the trial showed that aspirin reduced the rate of vascular events by 50% in patients with UA/NSTEMI and 30% in patients with acute MI as compared to placebo. Therefore, it is strongly recommended by the guidelines to treat patient with UA/NSTEMI immediately with high dose aspirin 300mg within 24 hours of admission. Besides its acute effects, long-term treatment of low dose aspirin has well-established benefits in preventing recurrent MI in patients with coronary heart diseases, with relative risk reduction of 37%. Therefore, patients should be maintained on long-term aspirin 75-150mg as a secondary prevention of MI after an UA/NSTEMI attack, unless contraindications such as gastrointestinal bleeding develop.
Combination antiplatelet therapy with aspirin and clopidrogel is also beneficial in patients with UA/NSTEMI. The CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial successfully demonstrated the significant efficacy of combination therapy of aspirin and clopidrogel (risk reduction by an additional 20%) compared to aspirin monotherapy in preventing major vascular events in ACS patients. The benefit was observed within 24 hours, indicating a superior acute clinical effect. Furthermore, Clopidogrel versus Aspirin in Patients at RISK of Ischemic Events (CAPRIE) trial showed the consistent benefit of clopidogrel throughout the 3-years follow up in patients with cardiovascular diseases. Therefore, the guidelines now recommend the addition of clopidogrel to the current aspirin antiplatelet therapy as both acute and subacute MI treatment.
Case summary: A combination therapy of aspirin 300mg and clopidrogel 300mg was administered to Mr. G in the emergency department, which is appropriate. This was followed by a low dose aspirin 75mg for secondary prevention. As demonstrated in the CURE trial, a dual-antiplatelet therapy will result in better outcomes. Besides, patient experienced recurrent event despite having daily 75mg aspirin as preventive previously. Therefore, a combination therapy of aspirin 75mg and clopidogrel 75mg can be considered in this patient, with careful monitoring of any signs of major bleeding.
Anticoagulant Therapy
Heparin, either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), is used as anticoagulants in the management of UA/NSTEMI. The guidelines recommend that anticoagulant either a LMWH or UFH should be initiated once an intermediate or high risk UA/NSTEMI is diagnosed. This is essential to improve disease outcomes and to lower the risk of MI and death. A meta-analysis of RCTs showed that short-term UFH or LMWH therapy reduced the risk of MI and death by 50% in aspirin-treated patients with UA/NSTEMI, with no difference in efficacy and safety. In fact, there is convincing evidence in aspirin-treated patients that LMWH is a better anticoagulant. Comparative ESSENCE (Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events) trial has demonstrated the superiority and efficacy of the LMWH over UFH as an acute regimen. In comparison with UFH, LMWH (enoxaparin) causes an additional of 20% risk reduction of vascular events in patients with UA/NSTEMI, without causing any increase in events of major hemorrhage. Enoxaparin also has more durable effects that it is often administered every 12 hours by subcutaneous injection. It has advantages over UFH for it is associated with lower risk of heparin-induced thrombocytopenia. Also, it does not require anticoagulation monitoring. All these indicate that enoxaparin is now recommended as the most preferable anticoagulant for the acute management of patients with high risk UA/NSTEMI in the ACC/AHA UA/NSTEMI 2007 practice guidelines.
Case summary: Patient was given enoxaparin 60mg subcutaneously at emergency department and continued with the same dose every 12 hours in the ward until he was discharged.
Beta-blockers
Beta-blockers are recommended as the first line anti-anginal agent in patients with UA/NSTEMI. The initiation of beta-blockers in all patients during the acute phase of MI can be reviewed by two large trials. In the ISIS-1 trial, patients presented with MI were randomly administered IV atenolol, followed by a 7-days oral therapy. The results of the trial showed that there was a significant reduction in mortality rate during the 1-week period. The beneficial effects occurred within 24 hours and sustained for 1 month. In another large trial, the Metoprolol in Myocardial Infarction (MIAMI), patients were given IV metoprolol followed by a 15-days oral therapy. The results, however, showed no significant reduction in the rate of mortality during the 15-days period.
Long-term oral beta-blockers are recommended by the guidelines for secondary prevention in all patients after an acute MI, without any contraindications. The long-term use of beta-blockers has proven to help in controlling ischaemia and preventing recurrent MI. A meta-analysis of RCTs showed that beta-blockers reduce the risk of progression to acute MI by 13% in ACS patients. Another large trial involving over 35,000 acute MI patients has even demonstrated the superiority of beta-blockers in improving survival in those recovering from an episode of acute MI. The initiation of beta-blockers in these patients successfully yields an improvement in survival rate by 20-25%. The effect of long-term beta-blockers on mortality was also demonstrated in the Beta-blocker Heart Attack Trial (BHAT), in which patients mortality was reduced by 25% during the 24-months follow-up.
Case summary: Patient is currently on atenolol 100mg daily for his angina control, which is appropriate and of great benefit.
Angiotensin-converting enzyme(ACE) inhibitor
The guidelines suggest that long term ACE inhibitor should be started in all patients with UA/NSTEMI, regardless of the presence of left ventricular dysfunction or heart failure. This long term therapy has demonstrated to have beneficial effects in high risk patients in a study named the Heart Outcomes Prevention Evaluation (HOPE) study. In this study, ramipril reduced all-cause mortality and other vascular events by 22% in over 9,000 high-risk patients. The European Trial on Reduction of Cardiac events with Perindopril in Stable Coronary Artery Disease (EUROPA) trial further supports the hypothesis that ACE inhibitors are effective and helpful agents in preventing cardiovascular events, along with aspirin, beta-blockers and statins in patients with coronary diseases. Otherwise, an angiotension receptor blocker can be considered in patients who cannot tolerate ACE inhibitor due to the side effect of persistent dry cough.
Case summary: Patient is currently on Enalapril 20mg OD. He is able to tolerate enalapril well, without any complaint of dry cough.
Statin
Statin, a lipid-lowering drug should be started in all patients after the onset of UA/NSTEMI, regardless of their baseline LDL cholesterol level. A number of clinical trials have shown that addition of statin produce significant benefits in a wide range of patients irrespective of the initial LDL cholesterol level. The benefits include a reduction in MI, UA, stroke and need for revascularization and all cause mortality in comparison to patients not treated with statin. PROVE-IT (Pravastatin or Atorvastatin Evaluation and Infection Therapy- Thrombolysis In Myocardial Infarction) trial demonstrated that initiation of high dose statin produces greater efficacy and benefits than moderate and low dose statins. Therefore, simvastatin 40mg is suggested in all guidelines as the first line therapy for secondary prevention of any cardiovascular events. If acceptable lipid levels are not achieved after 6-8 weeks, patients are switched to more potent artovastatin 40mg.
Case summary: Patient is currently on atorvastatin 40mg for his cholesterol control, which is appropriate.
Anti-anginal agent, Trimetazidine
Although trimetazidine is not licensed to be used in UK nor suggested as treatment option in most UK published guidelines, controlled study has demonstrated its superiority in increasing coronary flow, thus delaying ischaemic attack. It significantly reduces the incidence of angina attacks and also results in a reduction of nitrates use. Another significant advantage is that it does not cause any variations in heart rate. Trimetazidine is also better tolerated and more effective in treatment of angina than combination therapy of nitrates, beta-blockers and CCB as reported in some studies. It also reported to have both cardiac and extracardiac benefits. However, there is no study demonstrating its effectiveness in decreasing morbidity and mortality in patients with cardiovascular disease. Therefore, further evaluations are still needed. In general, it is a safe anti-anginal drug used in poly-medicated patients because there is, yet, no known drug interaction being reported.
Case summary: Patient is currently on modified-release Trimetazidine 35mg tablet BD. He claimed that he is well-tolerated to this drug.
Oral anticoagulant
Warfarin is an oral anticoagulant drug of choice for prevention of deep-vein thrombosis. Patients with pulmonary embolism, atrial fibrillation and mechanical heart valves should be treated with an oral anticoagulant. Those with mechanical heart valves are at higher risk of developing emboli due to the turbulence flow in the blood. Therefore, the ACC/AHA UA/NSTEMI 2007 guidelines recommend that an oral anticoagulant warfarin should be initiated indefinitely along with an antiplatelet (aspirin 75-150mg daily) in patients with mechanical prothestic heart valves. This long-term management of dual-antithrombotic therapy is supported by a meta-analysis of a number of trials which demonstrated that combination therapy of warfarin (INR target ≥ 2.0) and aspirin reduces the risk of MI by 44% in patients with ACS. Although the combination therapy shows potential benefits, it is associated with an increase risk of bleeding. Therefore, it is of utmost importance to have the patient INR monitored frequently to prevent any future bleeding complications. There are, however, insufficient prospective trials available to establish the benefits of triple-antithrombotic (aspirin, clopidogrel and warfarin) therapy. The PCI guidelines alternatively stated the importance to regulate patient INR at 2.0 to 3.0 if triple-antithrombotic therapy is to be used.
Case summary: Patient had a past medical history of valvular operation 15 years ago and is currently under anticoagulant (warfarin 7mg daily) therapy, along with an antiplatelet agent (aspirin 75mg daily).
4.0 Conclusion
The evaluation of patients presented with UA/NSTEMI at the hospital begins with the clinical signs and symptoms and medical history. This is followed by ECG testing and measurement of cardiac biomarkers particularly Troponin T levels to determine the patient's risk of recurrent events and death. The patient described in the case summary was presented with an unstable angina and cardiac biomarkers within the reference range. In the emergency department, he was initiated with oxygen therapy, sublingual GTN 400mcg tablet, aspirin 300mg, clopidogrel 300mg and enoxaparin 60mg. These are consistent with the recommended treatment regimen in the guidelines of acute management of UA/NSTEMI as discussed above. In the ward, she was continued on her old medications such as beta-blockers, ACE inhibitor, long-acting nitrates and statins, which are in relation to the recommended secondary-prevention-post-MI therapy in the guidelines. Trimetazidine, although not recommended in the guidelines, has gone through critical evaluation by few clinical trials and is believed to be beneficial to this patient in this case. Warfarin is another drug not recommended in the guidelines for UA/NSTEMI treatment. However, it is of great benefits in this patient with mechanical prothestic heart valve, along with his aspirin therapy for the prevention of thrombus formation. In conclusion, Mr G was well managed in the hospital with appropriate drug treatments as suggested in the guidelines. He should be referred to the National Heart Institute as soon as possible for his bypass surgery to avoid any MI complications.
