REVIEW ON ISCHEMIC HEART DISEASES AND ITS MEDICATION

 

MANAGEMENT: [Ohman, EM. ,March 2016]
The treatment of chronic ischaemic heart disease has two major goals:
(i) to prevent myocardial infarction (MI) and death, thereby improving life expectancy.
(ii) to reduce symptoms of angina and the occurrence of ischaemia, which should improve quality of life.

Medical therapy with aggressive cardiovascular risk factor modification is the cornerstone of therapy for chronic ischaemic heart disease. This holds true for patients being treated either medically or with coronary revascularization. The treatment strategies for chronic stable angina is separated into two important divisions:
(1) anti-anginal therapy and
(2) education and risk factor modification.

Anti-anginal therapy
Conditions that exacerbate and provoke angina should be considered; these include medications such as vasodilators, excessive thyroid replacement therapy, and vasoconstrictors. Medical problems such as profound anaemia, uncontrolled hypertension, hyperthyroidism, and hypoxemia should also be considered. Primary cardiac disorders such as tachy-and brady-arrhythmias, valvular heart disease (especially aortic stenosis), and hypertrophic cardiomyopathy may also exacerbate angina pectoris and should be excluded. Careful attention to history, thorough physical examination, and selection of appropriate laboratory and other diagnostic studies can help identify these clinical conditions.

β-blockers
β-blockers decrease heart rate, contractility and arterial pressure, resulting in decreased myocardial oxygen demand. In patients with chronic stable exertional angina, β-blockers decrease heart rate and blood pressure during exercise, and the onset of angina (ischaemic threshold) is delayed or avoided. Various types of β- blockers are available for the treatment of hypertension and angina (Table 1). All β-blockers appear to be equally effective in reducing angina pectoris. In the treatment of stable angina, it is conventional to adjust the dose of these drugs to reduce the resting heart rate to 50-60 beats per minute.

Table 1: Properties of β-blockers in clinical use

Drugs

Selectivity

Partial agonist activity

Usual dose for angina

Propranolol

None

No

20-80 mg bid

Metoprolol

β1

No

50-200 mg bid

Atenolol

β1

No

50-200 mg bid

Nadolol

None

No

40-80 mg qd

Timolol

None

No

10 mg bid

Acebutolol

β1

Yes

200-600 mg bid

Betaxolol

β1

No

10-20 mg qd

Bisoprolol

β1

No

10 mg qd

Esmolol (intravenous)

β1

No

50-300 mg/kg/min

Labetalol*

None

No

200-600 mg bid

Carvedilol*

None

No

12.5-50 mg bid

* combined α- and β-blocker. bid- twice a day ; qd – every day; tid – three times a day

The absolute cardiac contraindications for the use of β-blockers are severe bradycardia, pre-existing high degree atrioventricular block, sick sinus syndrome, and severe decompensated left ventricular failure (β-blockers have now been shown to reduce total mortality in patients with compensated heart failure). β- blockers should also be avoided in patients with pure vasospastic angina (Prinzmetal angina) because these agents may induce coronary vasospasm from unopposed α-receptor activity. Asthma and bronchospastic disease, severe depression, and severe peripheral vascular disease are relative contraindications. Most diabetic patients tolerate β-blockers, although these agents should be used cautiously in patients who require insulin. In the absence of contraindications, β- blockers are preferred as initial therapy. The evidence for this approach is strongest in patients with a history of prior MI, for which this class of drugs has been shown to reduce mortality.

Calcium antagonists
Calcium antagonists effectively treat hypertension and angina pectoris. These agents are commonly divided into the dihydropyridine and nondihydropyridine classes (Table 2). Calcium antagonists decrease coronary vascular resistance and increase coronary blood flow. All of these agents cause dilatation of the epicardial coronary vessels and the microcirculation arteriolar resistance vessels. Dilatation of the epicardial coronary arteries is the principal mechanism that allows calcium antagonists to relieve vasospastic angina. Calcium antagonists also concurrently decrease myocardial oxygen demand, primarily by reduction of systemic vascular resistance and reduction in arterial pressure. In addition, certain calcium antagonists (verapamil and diltiazem) reduce myocardial oxygen demand by decreasing heart rate and contractility.

Table 2: Properties of calcium antagonists in clinical use

Drugs

Usual dose

Duration of action

Side effects

Dihydropyridines

     

Nifedipine

Immediate release: 30-90 mg daily orally

Slow release: 30-180 mg orally

Short

Hypotension, dizziness, flushing, nausea, constipation, edema

Amlodipine

5-10 mg qd

Long

Headache, edema

Felodipine

5-10 mg qd

Long

Headache, edema

Isradipine

2.5-10 mg bid

Medium

Headache, fatigue

Nicardipine

20-40 mg tid

Short

Headache, dizziness, flushing, edema

Non-dihydropyridines

     

Bepridil

200-400 mg qd

Long

Arrhythmias, dizziness, nausea

Diltiazem

Immediate release: 30-80 mg 4 times daily

Short

Hypotension, dizziness, flushing, bradycardia, edema

 

Slow release: 120-320 mg qd

Long

 

Verapamil

Immediate release: 80-160 mg tid

Slow release: 120-480 mg qd

Short

Long

Hypotension, myocardial depression, heart failure, edema,

bid – twice a day; qd – every day; tid - three times a day

Short-acting dihydropyridine calcium antagonists have the potential to enhance the risk of adverse cardiac events and should be avoided. Long-acting calcium antagonists of the dihydro-and nondihydropyridine class relieve angina and are appropriate initial therapy in patients with contraindications to β-blockers. They can also be substituted for β-blockers in patients who develop unacceptable side effects or can be used in combination with β-blockers when initial β-blockers therapy is unsuccessful.

Nitrates
Nitrates dilate epicardial coronary arteries and arterioles and reduce cardiac preload. They also relieve coronary spasm and dynamic stenoses, especially at epicardial sites. Their use is associated with reflex tachycardia, an effect that may increase myocardial oxygen demand. This response may be blunted by the concomitant administration of β-blockers or calcium antagonists, such as diltiazem or verapamil, which slow conduction.

Nitrates are available in multiple preparations exhibiting wide duration in clinical effect (Table 3). Short-acting nitrates, which are most often administered as sublingual tablets or buccal mucosal spray, are commonly used to treat acute episodes of angina. Unless contraindications exist, all patients with chronic stable angina should be given a short-acting nitrate and should be properly instucted in its use. The efficacy and action of long-acting nitrates depend on the dosing, bioavailability, and half-life of the various preparations. The most important aspect of long-term nitrate therapy is to ensure an adequate nitrate-free interval (typically night time), which will prevent nitrate tolerance.

Table 3: Properties of nitrates in clinical use

Compound

Route

Dose

Duration of effect

Nitroglycerin

 

Sublingual tablets

0.3-0.6 mg up to 1.5 mg

Short 2-3 minutes

Spray

0.4 mg as needed

Short 2-3 minutes

Ointment

2% 6 X 6 in., 15 X 15 cm

7.5-40 mg

Effect up to 7 h

Transdermal

0.2—0.8 mg/h every 12 h

8-12 h during intermittent therapy

Oral sustained release

2.5-13 mg

4-8 h

Buccal

1-3 mg 3 times daily

3-5 h

Intravenous

5-200 μg/min.

Tolerance in 7-8 h

Isosorbide dinitrate

 

Sublingual

2.5-15 mg

Up to 60 min.

Oral

5-80 mg, 2-3 times daily

Up to 8h

Spray

1.25 mg on tongue as needed

2-3 min.

Chewable

5 mg

2-2.5 h

Oral slow release

40 mg 1-2 times daily

Up to 8 h

Intravenous

1.25-5.0 mg/h

Tolerance in 7-8 h

Ointment

100 mg/24 h

Not effective

Isosorbide-5- mononitrate

 

Oral

 

20 mg twice daily / 60-240 mg once daily

12-24 h

 

In patients with exertional stable angina, nitrates improve exercise tolerance, increase the time to onset of angina, and decrease ST-segment depression during treadmill exercise testing. Combined with β-blockers or calcium antagonists, nitrates produce greater anti-anginal and anti-ischaemic effects in patients with stable angina.

Revascularization
CABG versus medical therapy
Evidence from randomized clinical trials has demonstrated that coronary artery bypass grafts (CABG) improves mortality when compared to medical therapy for patients with significant left main disease, three vessel disease with left ventricular ejection fraction (LVEF) of less than 50%, or multi-vessel disease with involvement of the proximal left anterior descending artery (LAD). Although these trials were performed in an era prior to the availability of percutaneous coronary intervention (PCI) and the routine use of aspirin, β-blockers, and lipid lowering therapy, these surgical indications remain currently valid.

CABG versus PCI
PCI may be considered in patients with multi-vessel CAD (including the proximal LAD), who have anatomy suitable for catheter-based technique, do not have diabetes, and have normal left ventricular function. CABG or PCI may be considered in appropriate patients with single or multi-vessel CAD who have not been treated successfully by medical therapy and can undergo revascularization with acceptable risk.

PCI versus medical therapy   (Nitroglycerin Sublingual ,.2017)
Many trials illustrate that low-risk patients with chronic stable angina pectoris and normal left ventricular function can be treated safely with medical therapy. Because of the risk of procedure-related complications, clinicians must carefully balance this excess hazard with the need for greater symptomatic improvement when selecting patients for PCI.

Antiplatelet agents
Aspirin (75-150 mg) exerts its antithrombotic effect by inhibiting cyclo-oxygenase and synthesis of platelet thromboxane A2. It is effective in preventing first heart attacks, improving mortality in acute coronary syndromes, and reducing adverse cardiovascular events in patients with stable angina pectoris. Aspirin should therefore be considered as first line therapy in all patients with chronic ischaemic heart disease. In patients with absolute aspirin contraindications alternative antiplatelet regimes such as dipyridamole (Persantine), ticlopidine (Ticlid), glycoprotein 11b/111a receptor antagonists may be considered, although the clinical data supporting their use in angina pectoris is less established.

Lipid lowering therapy
Of the classes of antihyperlipidemic drugs, the hydroxy-methylglutanyl coenzyme A reductase inhibitors or statins are the most potent agents available in lowering total and low density lipoprotein (LDL) and atherogenic cholesterol and are the only lipid-lowering agents shown to improve overall mortality in clinical trials. Furthermore, statins also exhibit anti-inflammatory properties, which may positively modify the artherosclerotic process.

Therefore, statins should be considered in all patients with established CAD and LDL cholesterol ≥ 130 mg/dL, targeting the on-therapy LDL cholesterol to less than 100 mg/dL. In general, modification of diet and exercise are less effective than statins in achieving the target levels of LDL cholesterol; thus, lipid lowering pharmacotherapy is usually required in patients with angina and should be considered as first-line therapy in disease modification.

A high density lipoprotein (HDL), antiatherogenic cholesterol level of less than 35 mg/dL is an independent risk factor for adverse cardiovascular events. Hygienic measures such as weight loss, exercise, alcohol consumption, diabetes control, and smoking cessation may provide modest increases in HDL cholesterol. Recently, a randomized trial comparing the fibrate gemfibrozil to placebo demonstrated reduced cardiovascular mortality in patients with CAD and an isolated HDL cholesterol of less than 35 mg/dL.

Education and Risk Factor Reduction   (Walker C, et al.,2009)
Identification and treatment of coronary disease risk factors in patients with angina is necessary for optimal secondary prevention of chronic ischaemic heart disease. Established and modifiable coronary disease risk factors, such as cigarette smoking, hypertension, diabetes mellitus, and hyperlipidemia, are common in patients with chronic ischaemic heart disease. These risk factors are readily amenable to modification, and their treatment can affect clinical outcome favourably.

Studies show that the risk of death from CAD is inversely proportional to education. It is therefore important for the physician to assess the patient’s baseline understanding of his or her condition and to appropriately educate the patient and his or her family on the pathology and pathophysiology of the disease, prognosis of condition, and treatment and risk factor reduction options.

Obesity
Obesity is a common condition associated with an increased risk for coronary artery disease and mortality. Obesity is also associated with and contributes to other coronary risk factors, including high blood pressure, glucose intolerance, low levels of HDL cholesterol, and elevated triglycerides. Thus, much of the increased CAD risk associated with obesity is mediated by these factors. Weight reduction in obese patients with coronary disease can likely reduce the risk of future events because weight reduction will reduce other modifiable risk factors and reduce the increased myocardial oxygen demand imposed by obesity. Weight reduction is therefore recommended in all obese patients with ischaemic heart disease. Strategies to improve weight reduction include:
a. lowering total caloric intake,
b. eating foods low in cholesterol and saturated fat and high in fibre and unsaturated fat, and
c. exercise training.

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