Case Study Of Unstable Angina

Case Study Of Unstable AnginaThe patient in mount is a 61 year old male, Mr. X, admitted to hospital in the late evening for a case of unstable angina. Presenting complaints include left-sided chest bformer(a) which was less(prenominal)(prenominal) severe than that of his previous doorway and localized nuisance during rest. Absent symptoms are prof enforce sweating as well as na mathematical functiona and vomiting, orthopnea and paroxysmal nocturnal dypsnoea, cough and fever. forbearings past medical history includes diabetes mellitus and hypertension diagnosed 6 years ago, ischaemic heart disease (IHD) since 3 years ago, for which the last hospital admission was 11 months ago. In the previous admission for IHD, Mr. X also suffered from pneumonia and ventricular failure, his electrocardiogram (ECG) indicated right bundle branch block, his blood serum troponin I levels were 0.3 ng/mL ( modal(prenominal) levels 0-0.1 ng/mL), and his creatinine levels were 5.0 mg/dL (normal for males 0.2-0.6 mg/dL). Mr. X is also afflicted with degenerative kidney disease, for which his baseline creatinine during his last admission was 208 mol//L. Mr. X has retired from the military and is sustainment with his wife, who monitors his medications and compliance. He used to be a chronic smoker but has stopped smoking 15 years ago. His previous medication history is as be low-tonedDrug and FormStrengthFrequencyFurosemide tabs40 mgBDOmeprazole tabs20 mgPRNAmlodipine tabs10 mgODSimvastatin tabs20 mgONPerindopril tabs4 mgODTable 1 Table showing past medications of Mr. X.Mr. X takes no non-prescription medications and has no known drug allergies.On examination he appears to be alert and comfortable on his nasal cannula for delivery of atomic number 8 3L/min. His strain pressure is 134/81 mmHg, pulse rate is 76 bpm, body temperature 37oC, SpO2 of 99%, abdomen feels soft and non-tender, and no pedal oedema was detect. A blood glucose strip test reveals that Mr. Xs glucose level s were 10.3 mmol/L. requirement ECG shows right bundle branch block and no ischaemic changes. The tentative diagnosis was unstable angina and further tests were scheduled, including a full blood count (FBC), renal profile (RP), liver function test (LFT), troponin and creatinine (CKMB) investigations, as well as a urine full examination and microscopy (UFEME). The immediate send shoot was to give Mr. X subcutaneous enoxaparin 60 mg stat and twice daily thereafter, acetylsalicylic acid 75 mg tablets erst daily, lovastatin 20 mg tablets once daily, sublingual glyceryl trinitrate when required, and to continue the 3L/min oxygen cannula.Clinical ProgressDay 1MorningPatient was well, free from chest pain, tolerating orally and suffering from no nausea or vomiting. He had minimal shortness of breath (SOB). Troponin I levels were at 0.15 ng/mL and ECG showed no acute or evolving changes. frugality plasma glucose was at 4.8 mmol/L (within normal direct). Secondary dehydration was obs erved using the skin pinch test, so patient was started on intravenous normal saline solution drip (3 x 500 mL bag per 24 hours). Patient was found to be anaemic due to pre-existing chronic renal failure.EveningPatient account mild chest pain and SOB. His troponin I levels were 0.15 ng/mL and other life-sustainings were normal. His creatinine levels were 423 mol/L.Day 2Patient felt comfortable and his vitals were normal. His creatinine levels decreased to 345 mol/L.Day 3Patients jibe was well, no chest pain was reported but he was passive experiencing some SOB in the morning, which subsided in the afternoon. Patient was put on continuous peritoneal dialysis in the late morning. Patients vitals were normal, and he was taken off enoxaparin in the evening.Day 4Patient complained of chest pain in the morning, with minimal SOB. His vitals were normal. Subcutaneous enoxaparin 60 mg was given and the IV saline was continued.Lab FindingsUrine Biochemical Analysis (Day 1)Investigation va lues principle valuesProtein++100 mg/dLGlucose prejudicialnegativeBloodnegativeLeucocytes+-10 WBC/LKetonenegativenegativeBilenegativenegativeUrobillinogennormalSpecific gravity1.0251.003 1.040pH5.54.6 8.0NitritenegativenegativeTable 2 Results of urine biochemical analysis on Day 1Lipid Panel Fasting Serum Lipidplasm add cholesterol / mmol/L4.5Desirable Borderline 5.17-6.19 naughty luck 6.20Plasma triglyceride / mmol/L1.27 Desirable Borderline 1.7-5.64High risk 5.65Plasma LDL-cholesterol / mmol/L2.91 Desirable Borderline 3.36-4.12High risk 4.13Plasma HDL-cholesterol / mmol/L1.01 Desirable 1.03High risk Total cholesterol / HDL-cholesterol4.5Desirable Borderline 3.8-5.8High risk 5.9Table 3 Results of lipoid panel (fasting serum lipid levels).Renal ProfileElectrolytesMeasured levels on Day 1-1.14amMeasured levels on Day 1-12.54amMeasured levels on Day 2-10.47amNormal rangeUrea / mmol/L22.822.421.12.8-7.2Sodium / mmol/L129128129136-146Potassium / mmol/L5.34.84.73.5-5.1Chloride / mmo l/L989410198-107Creatinine / mol/L42339834558-96Table 4 Renal profile of Mr. X showing levels of electrolytes and creatinine.Plasma troponin I 0.15 ng/mLLiver Function TestMeasured levelNormal rangePlasma total protein81 g/L66-83 g/LPlasma albumin34 g/L35-52 g/LPlasma globulin47g/L25-44 g/LA/G ratio0.70.9-1.8Plasma alkaline phosphatase119 u/L30-120 u/LPlasma aspartate transaminase19 u/LPlasma alanine transaminase43 u/L Plasma total bilirubin6 mol/L5-21 mol/LESR47mm/hour 0-20 mm/hourTable 5 Results of liver function test showing protein and liver enzyme levels in plasma.Full Blood cipher (FBC) (Beckman Coulter)Cell typeMeasured levelNormal rangeWBC9.9109/L4-10109/LRBC3.341012/L3.8-4.81012/LHaemoglobin95g/L120-150g/LHaematocrit0.273L/L0.36-0.46L/LMean cell volume81.8fl.83-101fl.Mean cell haemoglobin28.4pg.27-32pgMCH concentration347g/L315-345g/LPlatelets353109/L150-400109/LRDW19.4%Neutrophils3.32-7 x109/LLymphocytes1.741-3 x109/LMonocytes0.550.2-1.0 x109/LEosinophils0.210.02-0.5 x10 9/LBasophils0.030.02-0.1 x109/LTable 6 Full blood count of Mr. X.Vital Stats ChartDateTimeBlood impel/ mmHgTemperature / oCPulse Rate/ bpmSpO2/ %Blood Glucose levels/ mmol/LDay 011.05 pm140/80379110013.911.30 pm137/843780100Day 18.30 am130/8037704.8 (fasting)3.55 pm130/70379010.30 pm108/643781Day 28.20 am119/6937784.50 pm130/9037829.69.45 pm140/9037806.7Day 38.50 am114/773772986.6Table 7 Records of vital stats of Mr. X from Day 0 3.Disease Overview Pharmacological Basis of Drug TherapyAcute coronary syndrome (ACS) is a broad term used to classify a continuum of symptoms and events stemming from acute ischaemic episodes affecting the cardiac heftiness.1 This includes unstable angina, non-ST segment elevation myocardial infarct (NTEMI), and ST segment elevation infarction. It is usually characterised by chest pain which increases in its severity at rest or with physical exertion. The ischaemic events usually arise from the development of unstable atheromatous plaques,2 which expl ains the fact that stable angina (due to a stable coronary atheromatous plaque) is not included under this umbrella term. Rupture, ulceration or fissures of the atherosclerotic plaque often leads to formation of a thrombus, causing occlusion of coronary arteries and inadequate blood flow and, after, inadequate supply of oxygen and nutrients to the cardiac muscle. This can be precipitated by acute extend factors on the sclerotic cap usually consisting of fibrous material, which is caused by local blood flow disturbances or vasospasms3. Unstable angina usually occurs without cardiac muscle damage while myocardial infarction (MI) may occur with or without myocardium damage. The thrombus formed in unstable angina is labile and obstruction is transient, and not a full-on occlusion as would occur in MI.4 Unstable angina occurs at rest and is almost indistinguishable from a non-ST segment inflated myocardial infarction except in the severity of cardiac muscle ischaemia. Theoretical defin itions of unstable angina would include changes in usual patterns of stable angina after a stable pain-free period, or severe acute anginal pain causing almost total incapacity5, though it is difficult to define it exactly as the term is often used by medical professionals to describe a range of different conditions intermediate between stable angina and MI. The primary clinical symptoms of unstable angina are sudden occurrence of chest pain that persists for more than 20 minutes which may be felt in other areas such as the jaw, arm, shoulder, neck or back without cause (as opposed to stable angina which stems from physical exercise) shortness of breath, rapid pulse rate, and sometimes a rapid drop in blood pressure. Patients suffering from an ACS cook a senior high risk of MI and achievable even death immediate hospitalization is often required1 and word is of a more urgent nature compared to that of stable angina. It has been suggested by the National Health Service (NHS) Ho spital Episode Statistics in 1998 that green out of every million per population is affected with unstable angina, or 10 acute hospital admissions per week.6 On a more recent note, NHS has reported in 2009 that angina affects between 10-15% of women and 10-20% of men aged 65 and above in England.7 Due to the close down relationship between unstable angina and coronary events, it is worth noting that the highest averaged rates of cardiovascular events were observed in Glasgow and Belfast (UK), North Karelia and Kuopio (Finland), Newcastle (Australia), and Warsaw (Poland).8Diagnosis of an unstable angina episode, or any ACS in that matter, is found on several aspects9. Physical symptoms include anginal pain at rest that lasts for 20 minutes or more new onset angina severely limiting ability of physical activity or changes in existing angina intensity, frequency or length of attack. One or more of these symptoms are an urgent indication that the patient is suffering from an ACS atta ck. Upon admission to hospital, ECG and blood tests should be performed to confirm the type of ACS in order to initiate extendment. In unstable angina, the ST segment is not elevated and levels of cardiac enzymes are normal (especially troponin T and I). If the onset of symptoms is unclear as to indicate ACS, a measurement of serum troponin concentration should be carried out 12 hours from bear witnessation to establish the diagnosis.10 Treatment of unstable angina and NSTEMI are similar in terms of pharmacological anxiety indeed they are at presentation indistinguishable except in terms of the severity and extent of cardiac muscle ischaemia, in which the ischaemia is less severe in unstable angina and less troponin T and I are released into the bloodstream.Antiplatelet agents. Aspirin and clopidogrel are the immediate emergency drugs used in the ambulance, both being antiplatelet drugs. Aspirin is an irreversible inhibitor of arachidonate cyclooxygenase (COX) enzyme, in which co valent acetylation of the serine moiety in a hydrophobic channel in the enzyme11 reduces synthesis of thromboxane A2 in platelets and prostaglandins in the endothelium. This prevents platelet aggregation and further enlargement of the thrombus formed in the coronary artery. Clopidogrel is an inhibitor of the ADP-dependent activation of the GPIIb/IIIa receptor and prevents the formation of fibrinogen bridges between glycoprotein IIb/IIIa receptors on the surfaces of platelets11, subsequently preventing platelet activation. Glycoprotein IIB/IIIA receptor antagonists, eg, abxicimab, induct the advantage of inhibiting all pathways in the platelet activation process by inhibiting the glycoprotein IIB/IIIA receptor.Anticoagulants. Unfractionated heparin is an activator of antithrombin III, which inhibits the action of thrombin and serine proteases. The heparin also binds to thrombin the unite effect of this and the heparin-antithrombin intricate formed inhibits thrombin, which decreases the conversion of fibrinogen to fibrin and reduces platelet aggregation. In contrast, low molecular weight heparins (LMWH) have molecular sizes that are too nice to bind to thrombin but still bind to antithrombin III, which inactivates all serine proteases including Factors XIIa, IXa, and Xa11, preventing the coagulation process. Direct thrombin inhibitors such as hirudin and bivalirudin inhibit thrombin reversibly. These agents can bind to free and bound thrombin, thus have the ability to prevent and dissolve preformed clots. Synthetic pentasaccharides (fondaparinux) is a selective indirect inhibitor of Factor Xa. It binds to antithrombin III reversibly, catalyzing the inactivation of Factor Xa12 and inhibiting the coagulation cascade.Beta blockers. all beta blockers bind to beta-adrenoceptors, competitively antagonizing the action of catecholamines. These drugs block the beta-1 adrenoceptors at the heart, achieving a decreased heart rate and force of cardiac contractions, as w ell as lowering blood pressure. Atenolol is relatively specific for cardiac beta-1 adrenoceptors and exerts fewer side effects associated with beta-2 adrenoceptor blockade, for example bronchospasm in asthmatics.Nitrates. Organic nitrates mimic the actions of endogenous azotic oxide to relax vascular smooth muscle by increasing the synthesis of cGMP, leading to the dephosphorylation of myosin light chains.11 Vasodilatation of coronary arteries causes change magnitude coronary blood flow and conjugated with its effects of decreasing arterial pressure and also cardiac output, the myocardial oxygen consumption is largely reduced.Statins. Also termed HMG-CoA reductase inhibitors, these medicines inhibit the rate-limiting enzyme in the synthesis of cholesterol, in which this enzyme converts HMG-CoA to mevalonic acid. boom inhibitors are diuretics acting on the rennin-angiotensin system which inhibit the angiotensin-converting enzyme (ACE) and block the production of angiotensin II from angiotensin I. This reduces vascular resistance, increases tissue perfusion, and reduces cardiac afterload.angiotensin II receptor inhibitors also act on the same system as the ACE inhibitors, except that they block the angiotensin II receptors directly sooner of inhibiting their formation. The outcome is the same as above.Evidence for Treatment of the ConditionAntiplatelet AgentsThe SIGN guidelines advocate that aspirin and clopidogrel be given to patients with ECG ischaemic changes or increased levels of cardiac markers and aspirin is advocated for all patients suffering from ACS. A meta-analysis of 287 randomised trials proves the protective effect of aspirin on patients with unstable angina, halving the rate of cardiovascular events, including death, non-fatal MI and strokes, or also termed the first primary outcome while in those with an acute MI, it reduces the rate of coronary events by almost a third13. Long-term use of aspirin for these patients was also shown to be a ben eficial antiplatelet therapy. According to the same study, reduction of serious vascular events by clopidogrel was 10% compared to aspirin. The combined use of clopidogrel and aspirin as compared with a placebo and aspirin showed significantly higher(prenominal) success rates in reducing occurrences of first primary outcomes (9.3% compared to 11.4%, POn the flipside, although short term studies have shown that antiplatelet medications are effective for patients with renal failure in the prevention of serious vascular events13, the risks of bleeding is increased by renal disease15, posing a possible contraindication for antiplatelets to Mr. X. A clinical study found that treatment for NSTEMI ACS in patients with chronic renal disease (mild to moderate stages) was less aggressive than those with normal renal function, scorn the risk that these patients with renal disease would experience greater obstinate outcomes from insufficient treatment for ACS compared to the other patient gro up16. However the available information on adverse effects of antiplatelets on patients with varying degrees of renal disease is limited and it would appear that this would result in the reluctance of medical professionals in using this class of drugs for patients with chronic renal disease as well as ACS.It can be inferred that Mr. X would gain the maximum benefits if his medications were changed to aspirin 300 mg and clopidogrel 300 mg stat and aspirin 75 mg and clopidogrel 75 mg thereafter, in which the patient should be closely monitored for signs of bleeding.Heparins LMWHsA 2003 review of 7 studies involving 11,092 patients with non-ST elevation ACS found that low molecular weight heparins (LMWH) were more effective than unfractionated heparins in reducing MI events, requirement for revascularization procedures, and thrombocytopenia17. No difference in the mortality, recurrent angina, major and minor bleeds were observed in the two types of drugs. A meta-analysis of 12 randomi sed trials with 17,157 patients involved found that patients who have had a non-ST elevation ACS who were put on aspirin experienced no significant difference in benefits in efficacy (preventing MI or death) or safety (major and minor bleeding complications) when they were put on unfractionated heparin or LMWH17, implicating no difference in the thrombolytic effect in both classes of drugs. These results are partially similar to those of the first review. Another meta-analysis of 2 phase-3 trials comparing enoxaparin and unfractionated heparin, on the other hand, showed a significant (20%) difference in reducing death or severe cardiac ischaemic events18. From an economic point of view, authors of yet other meta-analysis on the publication stated that the cost of LMWH is 3-5 times higher than unfractionated heparin19. From these data it can be concluded that LMWHs does indeed have additional positive treatment outcomes compared to unfractionated heparins22 it does not show signifi cantly decreased side effects (bleeding).Enoxaparin has, though, an increased bleeding effect on patients with renal disease as reported by an investigation of 106 patients, in which total bleeding complications occurred in 22% of normal patients and 51% of patients with impaired renal function (pIt is still the drug of choice for patients present with non-ST elevated ACS, and this is applicable to Mr. X with unstable angina.Beta-BlockersBeta-blockers were not prescribed for Mr. X. The SIGN guidelines states that beta-blockers should be the drug of choice for first line treatment of anginal pain in patients with non-ST elevated ACS. A meta-analysis of 5 trials consisting of 4700 patients in all showed a 13% reduction in anginal pain with the use of beta blockers (initially IV then oral for a week) in patients with non-ST elevated, MI-characterised chest pain23. It was stated in the clinical progress Mr. X had chest pain on Day 1 and 4, thus the addition of a beta blocker to his medi cations would be useful in alleviating his pain. contempt the popular belief that beta-blockers are contraindicated in patients with diabetes mellitus, it is possible to treat these patients using beta-blockers as long as good glycaemic control is achieved and the patient is monitored regularly24. This would further support its use in Mr. X furthermore, several studies have shown that diabetic patients derive a significant benefit from the use of beta-blockers after an MI, in which diabetic patients had a significantly lower mortality 1 year post-discharge25, total mortality after 3 years, and deaths from cardiac events26. A multicentre randomise trial, the HINT trial, on patients with unstable angina found that metoprolol, a relatively cardioselective beta blocker, reduced occurrence of myocardial ischaemia or progress to MI within 48 hours, indicating that metoprolol has a short term beneficial effect on patients not already taking beta blockers prior to the unstable angina epis ode27. It has been suggested that beta-blockers be the first line treatment for unstable angina and if patients remain unstable, a calcium channel blocker should be added28.StatinsThe beneficial effects of statins in reducing mortality and cardiovascular events have been proven by a meta-analysis of large, randomized controlled trials (n=90,056) where coronary artery disease was present or absent29. The positive results were also proven spanning a large range of serum cholesterol levels. Investigations comparing the use of intense versus moderate doses of statins in the early stages and post-ACS showed positive results a meta-analysis of 4 large trials (n=27,548) shows a 16% reduction in cardiovascular deaths or MI, as well as a 16% reduction in cardiovascular deaths or coronary events30. This view is shared by another meta-analysis of the same subject of 13 randomised controlled trials which found a decrease in mortality and coronary events after 4 months of treatment31. These dat a support the use of statins by Mr. X.NitratesNitrates have been widely used in relieving pain from unstable angina, despite its lack of clinical evidence in supporting its role in improving natural selection and reducing the rate of MI and cardiovascular events32. ISIS-433 and GISSI-334 reports no significant difference of the use of glyceryl trinitrate post-MI in reducing the overall mortality however this may be explained by the fact that more than 50% of patients in the controlled group are also on other forms of nitrate therapy, such as intravenous glyceryl trinitrate. Despite this, nitrates will still be of use for reducing the pain in post-MI patients and those with unstable angina. The BNF advises against the use of nitrates in patients with serious anaemia (HbGlycaemic controlMr. Xs plasma glucose levels were elevated on the day he was admitted to hospital (13.9 mmol/L). Diabetes mellitus has been proven to be a strong independent risk marker for coronary heart disease pat ients with ailing controlled diabetes at hospital admission have a worse outlook on prognosis and future development of cardiovascular events35. The DIGAMI investigation reports that the use of intensive insulin therapy increased long-term prognosis (P=0.011) of patients presenting with hyperglycemia (11mmol/L) at admission compared with those on standard antidiabetic therapy36. These data support the use of insulin to control the blood glucose levels of Mr. X which were highly increased upon admission. This is also supported by the SIGN guidelines which advocate immediate control of blood glucose is carried out for MI patients with glucose levels of more than 11.0 mmol/L for at least 24 hours.ACE InhibitorsThe SIGN guidelines recommend that patients with unstable angina should be given ACE inhibitors as long-term therapy. In patients at high risk of cardiovascular events, ACE inhibitors (ramipril was investigated in a report37) have been proven to reduce overall mortality, MI, and stroke, particularly in patients with diabetes mellitus. Perindopril was found to reduce cardiovascular risk (relative risk reduction =20%, P=0.0003) in a population with stable coronary heart disease in absence of heart failure38 in a double-blinded, randomized multicentre trial involving 13,655 patients. A meta-analysis of the 2 above trials and a third one (PEACE) showed a reduction in overall mortality, cardiovascular death, non-fatal myocardial infarction, stroke, heart failure, and coronary artery bypass surgery by ACE inhibitors39. This demonstrates the benefits of ACE inhibitors in patients with atherosclerosis as patients who had an ACS event would have a higher rate of cardiovascular events, the positive outcomes of ACE inhibitors can perhaps be extrapolated to this population in order to decrease coronary events and improve prognosis. However, the BNF advises caution and close clinical monitoring if ACE inhibitors are to be used in patients with hyponatremia (Oxygen ther apyOn admission, Mr. Xs SpO2 was 99% and remained high throughout his stay in the hospital. The use of oxygen therapy is significantly beneficial only in hypoxic patients (with SpO2 Anaemia and Unstable AnginaAnaemia can disturb the balance between myocardial oxygen supply and demand a decrease in the number of red blood cells can lead to a reduction in the supply of oxygen to the myocardium. Thus even upion of the causative factor would be sensible in the treatment of unstable angina for the patient in context. Mr. X was given a combination of ferrous fumarate, vitamin B complex, and folic acid for treatment of his anaemia. From the data in Table 6, it can be seen that Mr. X has low haemoglobin concentrations (95 g/L) and a low mean cell volume (81.8 fl.). To confirm that Mr. X is indeed suffering from iron-deficiency anaemia (as suggested by his treatment medication), three parameters must be conventional namely the plasma iron, the plasma ferritin, and total iron binding capacit y. However, as very few conditions can cause abnormalities in the mean cell volume, and a decreased value is due to iron-deficiency anaemia or thalassemia42, it is safe to assume that Mr. Xs anaemic condition is due to an insufficiency of iron. Iron supplements are given to correct the iron status of the patient, in which the ferrous form given orally is found to be cheap, safe and effective in the majority of patients with iron-deficiency anaemia2. Vitamin B complex and folic acid are only indicated in patients with the respective deficiencies2 there is little evidence that they would be of any significant benefit in patients with iron-deficiency anaemia.Summary found on the evidence given, Mr. Xs aspirin dose should be changed to 300 mg stat and 75 mg thereafter, and clopidogrel should be added into his medication profile in the same doses. These changes gibe that Mr. X is obtaining sufficient antiplatelet effects from his medications to prevent another attack of unstable angina or even a myocardial infarction. Present drugs that were given for his condition that are suitable and supported by evidences include enoxaparin, lovastatin, insulin, and GTN these can be safely continued without problems. A beta-blocker (metoprolol tablets) may be given additionally in doses of 50-100 mg as evidences described above have shown that they can be safely used in diabetic patients contrary to popular belief an ACE inhibitor (perindopril as previously used by Mr. X) may be initiated coupled with regular electrolyte