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Statins: The Magic vs The Reality

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WHAT IS ACUTE CORONARY SYNDROME

Acute coronary syndrome (ACS) refers to a spectrum of clinical symptoms ranging from heart attack with specific changes in ECG called ST-segment elevation myocardial infarction (STEMI) to non–ST-segment elevation myocardial infarction (NSTEMI) or unstable angina. 

 

ACS is almost always associated with rupture of an atherosclerotic plaque and consequently a partial or complete blockage of a coronary artery.

 

In some instances, however, stable coronary artery disease (CAD) may result in ACS
in the absence of plaque rupture and thrombosis, when physiologic stress such as trauma,
blood loss, anemia, infection, arrhythmia increases demands on the heart.

The diagnosis of acute myocardial infarction (heart attack) in this setting requires a finding of the typical rise and fall of biochemical markers of myocardial necrosis in addition to at least 1 of the following:

  • Ischemic symptoms

  • Development of pathologic Q waves on ECG

  • Ischemic ST-segment changes on ECG or during a coronary intervention

 

In the absence of clinical coronary artery disease, after emotional or physical stress a syndrome called takotsubo may occur. Takotsubo (the name comes from the Japanese word Octopus Pot) consists of chest pain, ischemic ST-segment and T-wave changes on ECG, elevated levels of biomarkers of cardiac cells injury, and transient left ventricular apical ballooning (the heart looks like an octopus pot). The etiology of this syndrome is not well understood but it is probably related to a surge of catecholamine stress hormones and/or high sensitivity to those hormones.

 

SIGNS AND SYMPTOMS

The most common complaints reported by patients with ACS include the following:

  • Pain, which is usually described as pressure, squeezing, or a burning sensation in the chest which may radiate to the neck, shoulder, jaw, arm, back or upper abdomen

  • Shortness of breath during physical activity which resolves with rest

  • Palpitations 

  • Nausea 

  • Limited tolerance of physical activity

 

There are also physical signs of ACS such as:

  • Very low blood pressure (hypotension) which indicates dysfunction of large or small heart chambers (ventricles or atrias) due to myocardial ischemia or heart attack

  • Very high blood pressure (hypertension) which may reflect raised catecholamine levels eg. due to anxiety 

  • Pulmonary edema and other signs of left heart failure

  • Cool, clammy skin

  • Changes in heart sounds - a doctor will hear a third heart sound (S3) and, frequently, a fourth heart sound (S4), a systolic murmur related to dynamic obstruction of the left ventricular outflow tract

 

DIAGNOSIS

Electrocardiography (ECG) is the most important diagnostic test for angina. ECG changes that may be seen during anginal episodes include the following:

  • Transient ST-segment elevations

  • Dynamic T-wave changes: Inversions, normalizations, or hyperacute changes

  • ST depressions: These may be junctional, downsloping, or horizontal

 

Laboratory studies include the following:

  • Creatine kinase isoenzyme MB (CK-MB) levels

  • Cardiac troponin levels

  • Myoglobin levels

  • Complete blood count

  • Basic metabolic panel

 

Diagnostic imaging modalities include the following:

  • Chest X-ray

  • Echocardiography

  • Myocardial perfusion imaging

  • Cardiac angiography

  • Computed tomography, including CT coronary angiography and CT coronary artery calcium scoring

 

DIFFERENTIAL DIAGNOSIS

  • Cardiovascular: ST-segment elevation infarction, acute pericarditis, myocarditis, aortic stenosis, aortic dissection, pulmonary embolism.

  • Respiratory: pneumonia, pneumothorax.

  • Gastrointestinal: oesophageal spasm, oesophagitis, gastro-oesophageal reflux, acute gastritis, cholecystitis, pancreatitis.

  • Musculoskeletal chest pain.

 

 

MANAGEMENT

Initial therapy focuses on the following:

  • Stabilizing the patient’s condition

  • Relieving ischemic pain

  • Providing antithrombotic therapy

Immediate management of a suspected ACS:

  • Arrange urgent hospital admission (phone 999)

  • Resuscitation as required

  • Pain relief: GTN and/or an intravenous opioid (antiemetic with opioids)

  • Single loading dose of 300 mg aspirin unless the person is allergic

  • A resting 12-lead ECG

  • Oxygen saturation using pulse oximetry before hospital admission if possible. Oxygen supply if oxygen saturation (SpO2) is less than 94% with no risk of hypercapnic respiratory failure; aim for SpO2 of 94-98% (aim for 88-92% for people with chronic obstructive pulmonary disease)

 

Antiplatelet and anticoagulant therapy

Aspirin: single 300-mg loading dose to all patients, unless contra-indicated, and continue indefinitely. Clopidogrel monotherapy for patients with aspirin hypersensitivity.

 

Clopidogrel:

300-mg loading dose for patients with a predicted 6-month mortality of more than 1.5% and no contra indications (such as increased bleeding risk).

300-mg loading dose for all patients with no contra indications who may undergo primary coronary intervention (PCI) within 24 hours of admission.

Continuing standard dose for 12 months.

Clopidogrel should be stopped 5 days before CABG in patients with low risk. For patients at intermediate or higher risk, whether to continue clopidogrel before CABG depends on the balance of ischaemic and bleeding risk.

 

Prasugrel in combination with aspirin is recommended as an option for preventing atherothrombotic events in people with ACS having percutaneous coronary intervention, only when immediate primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction is necessary; or stent thrombosis has occurred during clopidogrel treatment; or the patient has diabetes 

 

Ticagrelor in combination with low-dose aspirin is recommended for up to 12 months as a treatment option in adults with ACS with STEMI that cardiologists intend to treat with PCI; or NSTEMI; or admitted to hospital with unstable angina.

 

Glycoprotein IIb/IIIa inhibitors:

Eptifibatide or tirofiban for patients at intermediate or higher risk if angiography is scheduled within 96 hours of admission.

Abciximab as an adjunct to PCI for patients at intermediate or higher risk who are not already receiving a glycoprotein inhibitor (GPI).

 

Antithrombin therapy: anticoagulants are used in the treatment of NSTE-ACS to inhibit thrombin generation and/or activity, thereby reducing thrombus related events.

 

Fondaparinux for patients without a high bleeding risk unless angiography is planned within 24 hours of admission. Unfractionated heparin as an alternative to fondaparinux if angiography is likely within 24 hours of admission. In patients with a high bleeding risk the choice and dose of antithrombin should be considered carefully.

 

Unfractionated heparin, with dose adjusted to clotting function, for patients with creatinine above 265 μmol/L. Systemic unfractionated heparin (50-100 units/kg) in the cardiac catheter laboratory for patients on fondaparinux who are undergoing PCI.

 

As an alternative to the combination of a heparin plus a GPI, bivalirudin should be considered for patients :
1. Who are at intermediate or higher risk, and are not already receiving a GPI or fondaparinux and are scheduled for angiography within 24 hours of admission.

2. Undergoing PCI who are at intermediate or higher risk and are not already on a GPI or fondaparinux.

Revascularisation:

Patients with NSTE-ACS should be assessed for risk (using GRACE scoring system, as above) of cardiovascular event. If they are medium to high risk they should undergo early in-hospital coronary angiography, possibly with GPIIb/IIIa inhibitor.

If the patient is low-risk but symptoms are recurring, they should also undergo coronary angiography.


The proportion of patients with NSTE-ACS undergoing CABG (coronary artery bypass surgery) during initial hospitalisation is about 10%. The benefit from bypass surgery is greatest when patients can be operated on after several days of medical stabilisation, depending on the individual risk.

 

Other treatment:

Nitrates (sublingual, oral or intravenous): for ongoing pain whilst waiting for more definitive procedures, and may overcome superimposed coronary artery spasm.

 

Beta-blockers improve outcome and can reduce the severity and frequency of attacks.

 

Calcium antagonists (eg, diltiazem, verapamil) are used for patients who cannot tolerate beta-blockers, or are used in addition to beta-blockers. Verapamil should not be combined with a beta-blocker.

 

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality and should be started when the patient is an in-patient unless contra-indicated.

 

Hyperglycaemia:

Hyperglycaemia in patients admitted to hospital for an ACS should be managed by keeping blood glucose levels below 11.0 mmol/L while avoiding hypoglycaemia. A dose-adjusted insulin infusion with regular monitoring of blood glucose levels should be considered.

 

All patients with hyperglycaemia after ACS and without known diabetes should be tested for HbA1c levels before discharge and fasting blood glucose levels no earlier than 4 days after the onset of ACS.

 

PROGNOSIS

People with non-ST-segment elevation ACS have a high incidence of recurrent myocardial ischaemia, a similar long-term outcome to those with STEMI, and a worse outcome than people with unstable angina.

 

In-hospital death and re-infarction affect 5-10%. Despite optimal treatment with anti-ischaemic and antithrombotic drugs, death and recurrent myocardial infarction occur in another 5-10% of patients in the month after an acute episode.

Factors associated with a poorer prognosis include:

  • Advancing age

  • Presence and severity of ECG changes of ischaemia

  • Magnitude of rise in biomarkers of myocardial injury (eg. serum troponin)

  • Left ventricular dysfunction, cardiogenic shock

  • Increased heart rate, arrhythmias (ventricular fibrillation, atrial fibrillation)

  • Renal impairment

  • Diabetes mellitus

  • Anaemia

  • Cerebrovascular disease

  • Peripheral vascular disease

 

Six-month mortality rates in the Global Registry of Acute Coronary Events (GRACE) were 13% for patients with NSTEMI ACS and 8% for those with unstable angina. An elevated level of troponin (a type of regulatory protein found in skeletal and cardiac muscle) permits risk stratification of patients with ACS and identifies patients at high risk for adverse cardiac events (ie. myocardial infarction, death) up to 6 months after the index event.

 

COMPLICATIONS

  • Acute myocardial infarction

  • Cardiogenic shock

  • Ischaemic mitral regurgitation

  • Supraventricular arrhythmias: rare complication of ischaemia but may precipitate ischaemic events

  • Ventricular arrhythmias: simple and complex premature ventricular contractions and nonsustained ventricular tachycardia

  • Atrioventricular nodal blockade: usually transient in setting of reversible ischaemia (treatment is guided by location of block and haemodynamic stability)

 

PRIMARY PREVENTION

Study has shown that 4 of 5 heart attacks can be prevented by implementing healthy habits:

  • Smoking cessation. The risk of recurrent coronary events decreases 50% at 1 year after smoking cessation. Bupropion increases the likelihood of successful smoking cessation

  • Healthy dietary habits - the benefits of a low-cholesterol, low-salt diet

  • Healthy exercise habits - the benefits of regular exercises at least 3 times per week

  • Blood pressure, hyperlipidaemia and diabetes control

  • Compliance with medications, particularly aspirin and clopidogrel

SECONDARY PREVENTION
After stabilisation, secondary risk reduction measures should be implemented. These include:

  • Healthy lifestyle habits

  • Continued aspirin therapy 

  • Management of hypertension

  • Statins

  • ACE inhibitors and beta-blockers

  • Treadmill exercise testing

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The Silver-lined Heart is a registered charity in England and Wales (1155244). Registered company in England and Wales (08196579). Registered address:  24 Holborn Viaduct, London, EC1A 2BN