Search

To the Editor. —The Air Force Coronary Atherosclerosis Prevention Study (AFCAPS) is an ongoing randomized, double-blind, placebo-controlled primary prevention trial to determine whether treatment with the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase inhibitor, lovastatin, will prevent coronary heart disease in persons with mild to moderate elevations of total and low-density lipoprotein cholesterol and low high-density lipoprotein cholesterol levels. A total of 6605 participants without clinical evidence of coronary heart disease are enrolled, including men aged 45 to 73 years and women aged 55 to 73 years. Participants will be followed annually for total coronary heart disease events during a minimum of 5 years. A trial of this size and duration provides an opportunity to evaluate the long-term impact of cholesterol-lowering drug treatment on patient quality of life (QoL). In fact, it may be argued that it is imperative to assess the impact of long-term pharmacologic therapy on QoL in asymptomatic

Objective. —To assess changes in concurrent use of products containing terfenadine and contraindicated macrolide antibiotics (erythromycin, clarithromycin, troleandomycin) and imidazole antifungals (ketoconazole, itraconazole) following reports of serious drug-drug interactions and changes in product labeling. Design. —Retrospective review of computerized pharmacy claims. Setting. —A large health insurer in New England. Patients. —Health plan members with 1 or more paid pharmacy claims for products containing terfenadine between January 1990 and June 1994. Main Outcome Measures. —Among persons with paid claims for terfenadine in any given month, percentage with a prescription for any contraindicated drug that alternatively was dispensed on the same day as ("same-day dispensing") or had therapy days that overlapped those of ("overlapping use") a prescription for terfenadine. Results. —Concurrent use of terfenadine and contraindicated drugs declined over the study period. The rate of same-day dispensing declined by 84%, from an average of 2.5 per 100 persons receiving terfenadine in 1990 to 0.4 per 100 persons during the first 6 months of 1994, while the rate of overlapping use declined by 57% (from 5.4 to 2.3 per 100 persons). Most cases involved erythromycin. Conclusions. —Despite substantial declines following reports of serious drug-drug interactions and changes in product labeling, concurrent use of terfenadine and contraindicated macrolide antibiotics and imidazole antifungals continues to occur. ( JAMA . 1996;275:1339-1341)

Background: The 1988 US National Cholesterol Education Program Expert Panel Report recommended initial treatment with niacin or bile acid sequestrants, followed by other agents if needed, to lower low-density lipoprotein cholesterol (LDL-C) levels in hypercholesterolemic patients who require drug therapy. It is unknown how the effectiveness and costs of such an approach ("stepped care") compare in typical clinical practice to those of initial therapy with lovastatin. Patients and Methods: We randomly assigned 612 patients, aged 20 to 70 years, who met 1988 National Cholesterol Education Program guidelines for drug treatment of elevated LDL-C level and had not previously used cholesterol-lowering medication, to either a steppedcare regimen or initial therapy with lovastatin (both n=306). The study, conducted at Southern California Kaiser Permanente, was designed to approximate typical practice: provider compliance with treatment plans was encouraged but not enforced, and patients paid for medication as they customarily would. Results: At 1 year, the decline in mean LDL-C level was significantly greater among patients assigned to initial treatment with lovastatin (22% vs 15% for stepped care; P P P P P P Conclusions: A stepped-care regimen beginning with niacin is less costly than initial therapy with lovastatin, but also less effective in lowering LDL-C level. While it is more effective in increasing high-density lipoprotein cholesterol levels, the tolerability of such a regimen may be a problem. (Arch Intern Med. 1996;156:731-739)

Background: Enoxaparin sodium, a low-molecular-weight heparin, was recently approved for use in the United States to prevent deep-vein thrombosis after total hip replacement surgery. Its cost-effectiveness relative to prophylaxis with low-dose warfarin sodium is unknown. Methods: A decision-analytic model was developed to compare two strategies of prophylaxis for deep-vein thrombosis with a strategy of not using prophylaxis in a hypothetical cohort of 10 000 patients undergoing total hip replacement surgery. For each of these strategies, we estimated the expected number of cases of confirmed deep-vein thrombosis or pulmonary embolism, the expected number of thromboembolic deaths, and the expected costs of venous thromboembolic care, including prophylaxis, diagnosis, and treatment. Data were drawn primarily from the published literature. Results: Compared with no prophylaxis, the use of low-dose warfarin would be expected to reduce the number of cases of confirmed deep-vein thrombosis from about 1000 (per 10 000 patients) to 420 and the number of thromboembolic deaths from about 250 to 110. Expected costs of care related to deep-vein thrombosis also would be reduced from approximately $530 to $330 per patient. Prophylaxis with enoxaparin would be expected to reduce further the number of cases of confirmed deep-vein thrombosis and the number of thromboembolic deaths (to 250 and 70, respectively) but increase costs of care by approximately $50 per patient. The cost-effectiveness of enoxaparin (relative to low-dose warfarin) is estimated to be approximately $12 000 per death averted. Conclusion: Although enoxaparin is more costly than low-dose warfarin, its cost-effectiveness in total hip replacement compares favorably with that of other generally accepted medical interventions. (Arch Intern Med. 1995;155:757-764)

Cigarette smoking is the most important preventable cause of death in the United States. Surveys of patients, however, suggest that many physicians do not routinely counsel smokers to quit. Because physicians may not consider counseling against smoking to be as worthwhile as other medical practices, we examined its cost-effectiveness. We based our estimates of the effectiveness of physician counseling on published reports of randomized trials and our estimates of its cost on average charges for physician office visits. Our results indicate that the cost-effectiveness of brief advice during routine office visits ranges from $705 to $988 per year of life saved for men and from $1204 to $2058 for women. Follow-up visits about smoking appear to be similarly cost-effective. Physician counseling against smoking, therefore, is at least as cost-effective as several other preventive medical practices and should be a routine part of health care for patients who smoke. (JAMA1989;261:75-79)

A number of methods of prophylaxis can reduce the likelihood of postoperative deep-vein thrombosis in patients undergoing major orthopedic surgery. Using techniques of decision analysis, we examine the cost-effectiveness of several of these—warfarin sodium, low-dose subcutaneous heparin sodium, graduated compression stockings, intermittent pneumatic compression, heparin plus dihydroergotamine mesylate, and heparin plus stockings—compared with clinical diagnosis and treatment only. Our results show that 153 deaths per 10 000 patients occur when no prophylaxis is used; with most prophylaxes, this number is at least halved, and the most effective methods may reduce the number of deaths by three fourths. In addition, all of the prophylaxes considered are cost saving: average costs of care (including prophylaxis costs) are reduced by $19.40 to $181.60 per patient. Prophylaxis against deep-vein thrombosis in major orthopedic surgery therefore saves both lives and health care dollars. ( JAMA 1987;257:203-208)

In Reply. —We are sorry to learn of Lotke and Day's distress about our recent study of the cost-effectiveness of prophylaxis against DVT in orthopedic surgery, in which we reported that such measures can save both lives and health care dollars. They raise a number of issues that we address in turn below. Was our analysis based only on information concerning the effectiveness of prophylaxis against calf-vein thrombi? As reported, we based our analysis on all reports of randomized, controlled trials of DVT prophylaxis in orthopedic surgery that were published between January 1976 and June 1984. We are unaware of any data that should have been included in our analysis but were not. In these trials, separate rates for proximal- and distal-vein thrombi usually are not reported. Trials that do report both rates, however, indicate comparable reductions in both calf and femoral DVT among patients receiving prophylaxis. 1 Are calf-vein

Using cholestyramine as a model, we considered the cost-effectiveness of antihyperlipemic therapy in the primary prevention of coronary heart disease among men between 35 and 74 years of age with elevated levels of total plasma cholesterol. Our findings indicate that the cost-effectiveness of treatment varies substantially, ranging from about $36 000 to over $1 million per year of life saved. Cost-effectiveness was highest for younger patients, for those with additional coronary risk factors (eg, smoking or hypertension), and for those whose course of therapy is of less-than-lifelong duration. Conversely, it is lowest for older patients, for those with no additional coronary risk factors, and for those who are treated for a lifetime. Our results suggest that pharmacologic therapy may not be cost-effective for all patients with elevated cholesterol levels, especially those over 65 years of age. For many younger patients, however—those with additional coronary risk factors and more severe elevations in cholesterol levels—the cost-effectiveness of therapy may be comparable with other accepted medical practices. (JAMA1987;258:2381-2387)

In Reply.— In response to Dr Emory, we acknowledge our oversight in including the same 25 patients from two independent reports of the efficacy of HDHE. We note that these 25 patients experienced a rate of DVT (16%) that was higher than the overall rate of DVT (12.4%) that we calculated for this prophylaxis. Thus, inclusion of these patients slightly increased the rate of DVT for HDHE, and thereby reduced its cost-effectiveness. The protocol for administration of HDHE that we used for costing was taken from the minimum regimen that we specified for inclusion of trial reports. We note that one trial indeed used this minimum regimen. Finally, as Dr Emory notes, HDHE has not been approved by the Food and Drug Administration for DVT prophylaxis in orthopedic surgery. Physicians, however, may prescribe licensed drugs for nonapproved indications, and many drugs are frequently used in this manner. 1

A nicotine chewing gum has recently become available for use as an aid in giving up cigarette smoking. Although its efficacy has been demonstrated in clinic-based smoking cessation programs, its value in a primary care setting is uncertain. We examined the cost-effectiveness of nicotine gum as an adjunct to physician's advice and counseling against smoking during routine office visits. Our findings indicate that the cost per year of life saved with this intervention ranges from $4113 to $6465 for men and from $6880 to $9473 for women, depending on age. This compares favorably with other widely accepted medical practices, eg, treatment of hypertension or hyperlipidemia. Our study, therefore, suggests that nicotine gum is a cost-effective adjunct to physician's advice against cigarette smoking in a primary care setting. (JAMA1986;256:1315-1318)