Major adverse cardiac effect

Over the last decade, several studies in tens of thousands of patients have revealed that lowering cholesterol, specifically lowering LDL cholesterol with statins, is effective for both primary and secondary prevention of IHD-related events. Statins shown to decrease morbidity and mortality associated with IHD include lovastatin, simvastatin, pravastatin, and atorvas-tatin.22,23 A recent meta-analysis showed that the risk of major adverse cardiac events is reduced by 21% with the use of statins in patients at high risk for IHD-related events.23... 

In 1997, Condado et al. was the first to investigate the effectiveness of ICB after PTCA in human coronary arteries. Twenty-one patients who underwent PTCA for unstable angina received ICB (gamma radiation) for prevention of restenosis, Immediate and six-month follow-up revealed improved freedom from major adverse cardiac event (MACE) defined as death, myocardial infarction or target lesion revascularization compared with several previously completed balloon angioplasty trials (20), More importantly, this trial demonstrated that ICB was a feasible technique for the prevention of restenosis without any unexpected acute complications in humans. 

The major adverse medical effects of cannabis include increased heart rate, orthostatic hypotension, and respiratory irritation (from smoked caimabis). Thus, medical screening should include evaluation of the cardiovascular and respiratory systems. Individuals with a past or current condition that makes them less tolerant of increased heart rate (e.g., a cardiac arrhythmia, coronary artery disease), decreased Wood pressure (e.g., history of syncope), or respiratory irritation (e.g., asthma, hronchitis) should be excluded. 

Several serious toxicities have been observed, with a fatahty rate of 5% in the initial studies. The major adverse effect is severe hypotension in as many as 85% of patients, which may lead to myocardial infarctions, pulmonary edema, and strokes. This hypotension is thought to be due to a capillary leak syndrome resulting from extravasation of plasma proteins and fluid into ex-travascular space and a loss of vascular tone. Patients with significant cardiac, pulmonary, renal, hepatic, or CNS conditions should not receive therapy with aldesleukin. Other adverse reactions include nausea and vomiting, diarrhea, stomatitis, anorexia, altered mental status, fevers, and fatigue. 

The adverse effects of most serious concern relate to the cardiovascular system and seizure threshold. Actions on the adrenergic and cholinergic systems probably contribute to both hypotensive and direct cardiac effects, including alterations in heart rate, quinidine-like delays in conduction, and reduced myocardial contractility. The seizure threshold is lowered, increasing the frequency of epileptic seizures. All of these adverse effects can occur at therapeutic dosages in susceptible populations, such as elderly people, children, and people with cardiac problems or epilepsy, but are also a major cause of morbidity and mortality in accidental or intentional overdosage. Doses in excess of 500 mg can be seriously toxic, and death is fairly common when doses of 2 g or more are taken. 

Although adenosine and ATP very commonly cause adverse effects, they are generally mild and usually transient, because adenosine is rapidly eliminated from the blood (with a half-life of less than 10 seconds). Adverse effects have been reported in 81% of patients given adenosine and 94% of patients given ATP (5). Exercise reduces the noncardiac adverse effects and the incidence of major dysrhythmias (6). Reducing the duration of adenosine infusion from 6 to 4 minutes reduced the incidence of chest discomfort and ischemic ST segment changes, but had no impact on non-cardiac effects (7). 

Antidysrhythmic dmgs can themselves cause cardiac dysrhythmias, their major adverse effect. The risk of antidysrhythmic-induced cardiac dysrhythmias (prodys-rhythmic effects) has been estimated at about 11-13% in non-invasive studies (18,19) and at up to 20% in invasive electrophysiological studies. However, the risk varies from dmg to drug and is particularly low with class III drugs. In one study the quoted risks of dysrhythmias were flecainide 30%, quinidine 18%, propafenone 7%, sotalol 6%, and amiodar-one 0% (20). However, amiodarone does cause dysrhythmias, especially when the QT interval is over 600 ms. 

The incidence of major adverse reactions to dipyridamole was determined in a multicenter retrospective study, involving 73 806 patients who underwent intravenous dipjridamole stress imaging in 59 hospitals and 19 countries (4). The main conclusion was that the risk of serious dipjridamole-induced adverse effects is very low, a conclusion that is in line with other reports (5), and comparable to that reported for exercise testing in a similar patient population. Combined major adverse events among the entire patient population included 7 cardiac deaths (0.95 per 10000), 13 non-fatal myocardial infarctions (1.76 per 10000), 6 non-fatal sustained ventricular dysrhythmias (0.81 per 10000) (ventricular tachycardia in 2 and ventricular fibrillation in 4), 9 transient cerebral ischemic attacks (1.22 per 10000), 1 stroke, and 9 severe cases of bronch-ospasm (1.22 per 10000). Minor non-cardiac adverse effects were less frequent among the elderly and more frequent in women and patients taking maintenance aspirin. 

The pharmacokinetics and safety of the 5% lidocaine patches have been studied in 20 healthy volunteers, who applied four patches to the skin either every 24 hours or every 12 hours for 3 days (67). Mean steady-state plasma concentrations were 186 and 225 ng/ml respectively, well below those required for an antidysrhythmic effect (1500 ng/ml) or a risk of toxicity (5000 ng/ml). The patches were well tolerated, with no major cutaneous adverse effects. This is in line with data from postmarketing surveillance studies, which have shown that since the availability of lidocaine patches in 1999, no adverse cardiac or other serious adverse events have been reported (68). 

Olprinone is an inhibitor of phosphodiesterase type III, and has a positive inotropic effect. It is given intravenously and is mostly eliminated by the kidneys. Its pharmacological effects have been reviewed (1). Its major adverse effects are cardiac dysrhythmias and thrombocytopenia, the latter with a reported incidence of 0.43%. 

Reduction in adverse side effects one of the major advantages of clonidine is its minimal effect on respiratory drive. Additionally, the bradycardia and decrease in sympathetic outflow can be protective in patients with cardiac disease. 

Depression is common, is frequently unrecognized or underestimated, and may be deadly. For example, 50% of completed suicides are associated with a major depressive episode. Furthermore, depression can adversely affect life activities in a variety of ways. Medical disorders such as cardiovascular disease are also affected by depression, often predicting future cardiac events and hastening death, which is unfortunate, given that there is a very specific set of diagnostic criteria and that there is a variety of effective pharmacologic and somatic therapies (see Chapter 7.) (8). 

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