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CARDIOLOGY CASEBOOK |
Reprint requests: Louis Lemberg, MD, University of Miami Miller School of Medicine, Division of Cardiology (D-39), P.O. Box 0169690, Miami, FL 33101.
Aging is a physiological process that influences the life span when associated with risk factors such as diabetes mellitus, coronary disease, systemic hypertension, and congestive heart failure. The chronology inherent in aging should not preclude the use of effective therapy in appropriate settings. In the elderly (defined as "of or pertaining to persons in later life" by the Random House Dictionary, unabridged version), the reductions in mortality from pharmacological or therapeutic interventions are often similar. Studies have demonstrated low complication rates and high rates of successful outcomes in elderly persons undergoing percutaneous transluminal coronary angioplasty and coronary artery bypass graft surgery.1
The success of pharmacological therapy in treating chronic diseases is firmly established. However, elderly persons consume an inordinate quantity of medications compared with younger persons, and as a result are exposed to a higher risk of medication-related reactions. The average 65-year-old patient usually consumes 2 to 6 prescribed medications daily, in addition to 1 to 3 nonprescription drugs.2,3 The rate of adverse drug reactions (ADRs) typically doubles after age 70 as the number and severity of medical conditions increase and organ function deteriorates. Medication discrepancies are often the root of the problem; however, the patient’s age and the number of medications prescribed are reliable predictors. Several areas of medication non-compliance and discrepancy were found in a study in which half of the patients were taking medications that had not been documented, one third were not taking the prescribed medication, and several were taking improper doses of medications.2
QUESTIONS
ANSWERS
1. b. predictable, common
d. idiosyncratic, least common
The World Health Organization defines an ADR as any noxious, unintended, and undesired effect of a drug that occurs at doses used in therapy, prophylaxis, or diagnosis. This definition does not include therapeutic failures, intentional or accidental poisoning, or abuse.
There are 2 types of ADR: type A and type B. The majority are type A or dose related and are more frequent in the elderly. Type A ADRs are predictable and common, thus they are avoidable. Examples of drugs associated with type A ADRs include anticoagulants, antibiotics, digoxin, diuretics, hypoglycemics, nonsteroidal anti-inflammatory agents (NSAIDs), and agents with a low therapeutic ratio (ie, ratio between the average therapeutic dose and the toxic dose). Type B ADRs are idiosyncratic or allergic in nature and are less common. In the elderly, the possible side effects on renal or hepatic function often are not adequately considered when the dose of medication is selected. This may lead to complications that may affect cardiac and central nervous system function. ADRs, such as the thalidomide tragedy of the 1960s, have long been a concern, and, as a result, public policy now mandates that pharmaceutical companies provide ADR information to consumers.4
2. d. any of the above
The growing prevalence of ADRs ranks these reactions as the 4th to 6th leading cause of death in the United States; they are a common cause of hospitalization.4 In a 1988 report,4 ADRs were one of the leading causes of hospitalization, accounting for more than 2 million serious events and more than 100 000 fatalities in 1 year. Cardiovascular agents and anticoagulants frequently have been associated with ADRs that require prolonged hospitalizations. The high incidence of ADRs in the elderly is primarily a result of multiple drug use rather than advanced age.5 Many ADRs in the elderly are predictable, and so periodic review of medications and maintaining communication between provider and patient and between providers are essential for reducing the frequency of ADRs.
Debate continues about whether advanced age or specific age-related changes in physiology or function are the basis for predicting adverse or beneficial responses to drug therapy. Several potential factors for adverse drug effects in the elderly have been identified: (1) Cumulative physiological and metabolic effects of multiple drug use. The toxicities of drug combinations are often synergistic and usually greater than the sum of the toxic risks of the individual agents (eg, the combined use of NSAIDs and steroids increased the risk of peptic ulcer by 15% compared to a fourfold increase in risk when either is used alone). Combined therapy of NSAIDs and anticoagulants increases the risks of hemorrhagic peptic ulcer by a factor of 12 compared to 2 to 3.3 with the use of a single agent.2 Despite this strong evidence, these combinations continue to be prescribed. (2) Physiological effects of an individual agent (cardioactive agents that have vasodilator properties). (3) Physiological intolerance to a specific agent. (4) Associated comorbidities that compound the risk of age and predispose to additional pharmacological con-traindications (heparin, aspirin, ß-blockers, glycoprotein IIb/IIIa inhibitors). Elderly persons are often sicker with diseases that are progressive and greater in severity (eg, coronary disease, advanced congestive heart failure, insulin-dependent diabetes mellitus). (5) In current medical practice, polypharmacy is obligatory and often necessary; nevertheless, there is an indiscriminately and often unnecessary use of polypharmacy, especially observed in developing countries.2 Studies have shown a high rate of ADRs when an average of 7.8 medications are prescribed in contrast to low or no ADR when 3.3 or fewer medications were prescribed.
3. a. intolerance and sensitivity to vasodilating agents
Chronic stable (effort) angina is a major problem in the United States. Almost 50% of individuals with known coronary disease have angina, and most are elderly. As the aged population continues to increase, so does the incidence of angina and other conditions related to aging and chronic illness. The treatment of effort angina is multifaceted and typically includes lifestyle modification and the use of medication. The success of pharmacological management of effort angina in the elderly is often limited because of the high propensity of these patients to ADR. Often, intolerable side effects, along with forgetfulness and cost, place significant limits on compliance.
In the treatment of angina, where much of the therapy encompasses vasodilator agents, the tolerance to medication is often variable. Altered pharmacokinetics in elderly patients, combined with reduced tolerance to hemodynamic shifts (eg, preload reduction)—especially in the presence of orthostasis, diastolic dysfunction, or postprandial hypotension—make elderly persons more intolerant to these agents. Compliance is also lower in elderly cardiac patients who live alone and in those with impaired cognitive function, as well as when more than 4 medications are prescribed.3 In one study,3 almost 50% of patients undergoing cardiac procedures admitted that they were not consistent in taking their cardiac and lipid-lowering medications. Invasive or interventional procedures are suitable options in the elderly.3 The higher procedural risks in older patients are outweighed by the benefits accrued through longer years of survival.
4. a. effective use of medications with high therapeutic ratios
b. avoiding multiple drug combinations with additive or synergistic toxicities
c. clinical observation and therapeutic monitoring of plasma concentrations to prevent toxicity
The reduction or elimination of ADRs is emphasized in current practice. To overcome this ubiquitous problem, certain practice guidelines have been suggested: (1) Use effective medications that have high therapeutic ratios. (2) Avoid multiple drug combinations when agents have known additive or synergistic toxicities. (3) Use slow dose titration. (4) Use clinical observation and therapeutic monitoring of plasma concentrations to prevent toxicity. (5) Minimize the total number of prescribed medications and limit the number of prescribing health-care professionals (eg, physicians, nurses, nurse practitioners, physician assistants, pharmacists). (6) Continue and support professional development pertaining to pharmacological principles (kinetics and response) and their effects on the elderly. (7) Develop a pharmacological database for individual medication histories and events (eg, allergy, sensitivity, idiosyncrasy) and availability for tracking and reference. (8) Create new and safer pharmacological agents with emphasis on reducing or eliminating drug interactions and adverse effects of drug combinations.
Nurses and nurse practitioners are positioned to reduce or eliminate ADRs. Their regular home health-care visits ensure a professional assessment of their patient’s level of alertness and of the appropriate use of prescribed medications.
SUMMARY
Although the title of this Cardiology Casebook ("Pitfalls in the Management of Angina in the Elderly") is specific by necessity, the discussion is generous and is not limited to angina. The complexities of the newer pharmaceuticals and the geometric complication rates from the use of multiple drug prescriptions in the elderly significantly increase the risk of drug-related ADR. This report attempts to address this therapeutic problem in the elderly without limiting the discussion to angina pectoris.
ACKNOWLEDGMENT
Supported in part by a grant from the Applebaum Foundation, in loving memory of Joseph Applebaum.
REFERENCES
Bates DW. Drugs and adverse drug reactions: how worried should we be? JAMA. 1998;279:1216–1217.
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