RESUMEN

This randomized, controlled trial evaluated the impact of personalized follow-up on compliance rates in high-risk patients receiving combination lipid-lowering therapy over 2 years. A random sample of 30 patients 7-30 days after cardiac surgery had baseline fasting low-density lipoprotein levels higher than 130 mg/dl. All patients received lovastatin 20 mg/day and colestipol 5 g twice/day. Weekly telephone contact was made with each patient for 12 weeks. Short- and long-term compliance was assessed by pill and packet counts and refill records. Compliance and lipid profile results were significantly better in the intervention group (p<0.05) up to 2 years after the start of therapy than in the control group for all parameters except high-density lipoprotein. However, this effect was not apparent during the first 12 weeks of therapy. Short-term telephone follow-up favorably affected compliance and lipid profile results up to 2 years after start of therapy.

Asunto(s)

RESUMEN

STUDY OBJECTIVE: To evaluate 24-hour blood pressure control and frequency of adverse effects in patients with mild to moderate hypertension switched from nifedipine gastrointestinal therapeutic system (Nif-GITS) to nifedipine coat core (Nif-CC). DESIGN: Open-label, prospective, switch study SETTING: University-affiliated outpatient cardiology clinic. SUBJECTS: Twenty patients with mild to moderate essential hypertension, who were taking Nif-GITS 30, 60, or 90 mg/day for 8 weeks or longer. INTERVENTIONS: Patients stabilized with Nif-GITS 30, 60, or 90 mg were monitored over 24 hours with an ambulatory blood pressure monitor and were then switched to an equivalent dosage of Nif-CC. After 8 weeks+/-1 week taking Nif-CC, they were again monitored with a 24-hour blood pressure monitor. The 24-hour blood pressure load (percentage of values > 135/85 mm Hg for 24 hrs), daytime blood pressure load (percentage of values > 140/90 mm Hg from 7:00 A.M.-10:00 P.M.), nighttime blood pressure load (percentage of values > 120/80 mm Hg from 10:00 P.M.-7:00 A.M.), diurnal blood pressure variation, average 24-hour blood pressure, daytime blood pressure, nighttime blood pressure, mean blood pressure for the first 4 hours, and last 8 hours of the dosing interval were measured. Adverse effects such as headache, dizziness, and edema were also reported. MEASUREMENTS AND MAIN RESULTS: No differences in average 24 hour-blood pressure readings were observed but significant differences in blood pressure control during the first 4 and last 8 hours of the dosing interval were seen. Systolic and diastolic blood pressures were higher after approximately 16 hours in patients switched from Nif-GITS to Nif-CC. Although Nif-CC caused a greater initial response, it was less effective than Nif-GITS after 16 hours. This could explain the lack of differences in average 24-hour blood pressure values between formulations. Of the 20 patients, 20% experienced increased headaches, 20% showed signs of increased peripheral edema, and 10% reported occasional dizziness after switching agents. Three patients discontinued Nif-CC, two as ordered by their primary care physician and one on his own due to headache. CONCLUSION: This study suggests that patients switched from Nif-GITS to Nif-CC could experience increased blood pressure during the night or toward the end of the dosing interval. They could also experience adverse effects such as headache, edema, and dizziness, which could result in more physician visits and put patients with other disease states such as coronary heart disease at increased risk.

Asunto(s)

RESUMEN

STUDY OBJECTIVE: To evaluate the effect of cimetidine, famotidine, ranitidine, and placebo on left ventricular systolic function, aerobic metabolic performance, and exercise capacity in patients with chronic, stable heart failure. DESIGN: Double-blind, randomized, placebo-controlled, four-way crossover study. SETTING: Outpatient, university-affiliated cardiology clinic. PATIENTS: Twelve men with stable New York Heart Association class II or III heart failure secondary to ischemic heart disease or hypertension. INTERVENTIONS: Patients received in random sequence cimetidine 400 mg twice/day, famotidine 40 mg/day, ranitidine 150 mg twice/day, and placebo. Each treatment was administered for 7 days, and the periods were separated by a 1-week washout. MEASUREMENTS AND MAIN RESULTS: Before and after each treatment, patients underwent a bicycle stress echocardiogram with aerobic metabolic assessment. Left ventricular function was evaluated by calculating ejection phase indexes from Doppler echocardiographic measurements. All 12 patients successfully completed the study. No patient reported any adverse effect attributed to study drugs. None of the treatments was associated with significant changes in any measure of left ventricular systolic function, aerobic metabolic performance, or exercise capacity, nor were placebo-subtracted differences for the agents significantly different for any of the three measures. CONCLUSION: The three H2-receptor antagonists administered for 7 days at clinical dosages have no significant effect on left ventricular systolic function, aerobic metabolic performance, or exercise capacity in men with class II or III stable heart failure.

Asunto(s)

RESUMEN

STUDY OBJECTIVE: To evaluate the efficacy and safety of atropine in preventing vasovagal reactions (VVRs) during removal of femoral arterial sheaths after diagnostic left heart catheterization. DESIGN: Prospective, double-blind, randomized, placebo-controlled study. SETTING: University-affiliated, 450-bed teaching hospital. PATIENTS: One hundred sixty-five patients undergoing left heart catheterization. INTERVENTIONS: Eighty-eight patients were assigned to receive atropine 0.5 mg intravenously and 77 received placebo 5 minutes before sheath removal. MEASUREMENTS AND MAIN RESULTS: The frequency of VVRs was significantly reduced in the atropine group compared with the placebo group, 2.3% and 10.4%, respectively (overall relative risk in the atropine group 0.22, 95% CI 0.12-0.41, p=0.03). Significant decreases in systolic (35.2 +/- 5.8 mm Hg, p<0.001) and diastolic blood pressures (12.6 +/- 12.6 mm Hg, p=0.002) occurred in the 10 patients with VVRs compared with those without VVR. No cardiac arrhythmias occurred after atropine administration. Dry mouth was the only side effect reported with atropine (8/88, 9%). CONCLUSION: Atropine significantly reduced the frequency of VVRs associated with removal of femoral arterial sheaths after diagnostic left heart catheterization. The drug should be studied in a larger series of patients to assess its ability to decrease the morbidity and costs associated with VVR.

Asunto(s)

RESUMEN

OBJECTIVE: To conduct a cost-minimization analysis of intravenous adenosine and intravenous dipyridamole in thallous chloride TI 201 single-photon emission computed tomography (SPECT) myocardial perfusion imaging. DESIGN: A retrospective, open-label, cost-minimization analysis. SETTING: University hospital, outpatient nuclear medicine department. PATIENTS: Eighty-three patients undergoing dipyridamole TI 201 SPECT and 166 patients undergoing adenosine TI 201 SPECT. MAIN OUTCOME MEASURES: A cost-minimization analysis was conducted using a direct cost accounting approach estimating institutional costs. For the purpose of this study, sensitivity and specificity between adenosine SPECT and dipyridamole SPECT were assumed to be identical. Key costs evaluated included acquisition, administration, monitoring, treatment of adverse effects, follow-up care, and repeat tests. RESULTS: Adenosine increased heart rate and lowered blood pressure to a significantly greater extent than dipyridamole. The frequency of adverse reactions was not significantly different (p = 0.103) between adenosine (1.64 +/- 1.32 per patient) and dipyridamole (1.36 +/- 1.23 per patient). The frequency of prolonged and late-onset adverse effects was significantly greater for dipyridamole than for adenosine (p < 0.001). The frequency of adverse events requiring medical intervention was statistically greater for dipyridamole (24%) compared with adenosine (5%) (p < 0.00001). Total cost was significantly less for adenosine ($378.50 +/- $128.20 per patient) compared with dipyridamole ($485.60 +/- $230.40). Although adenosine had a significantly greater acquisition cost than dipyridamole (p < 0.0001), administration, monitoring, and adverse reaction costs were significantly less for adenosine than for dipyridamole. CONCLUSIONS: The cost of using dipyridamole is significantly greater than the cost of using adenosine despite adenosine's high acquisition cost. Adenosine is less expensive to use because of lower administration costs, monitoring costs, and adverse effect costs. Adenosine should be the agent of choice for pharmacologic vasodilation in the setting of myocardial perfusion imaging.

Asunto(s)

Asunto(s)

RESUMEN

The objective of this study was to compare the cost of intravenous adenosine and intravenous dipyridamole in positron emission tomography (PET) in patients with coronary artery disease. A retrospective, open-label, case-control, cost-effectiveness analysis was performed in the out-patient nuclear medicine department of a university hospital. Thirty-six patients underwent dipyridamole PET, and 72 matched patients underwent adenosine PET. A cost-effectiveness analysis was conducted using a direct cost accounting approach to estimate institutional costs. Key costs evaluated included acquisition cost, administration cost, monitoring cost, cost of management of side effects, and cost of follow-up care. The total cost of adenosine PET and dipyridamole PET was divided by their respective predictive accuracies to provide a total cost adjusted for efficacy. Adenosine increased heart rate and lowered systolic blood pressure to a significantly greater extent than dipyridamole. The number of patients experiencing adverse drug reactions was significantly greater for adenosine (82%) than for dipyridamole (67%), but the frequency of prolonged (> 5 minutes) and late-onset side effects was significantly greater for dipyridamole than for adenosine. The frequency of side effects requiring medical intervention was also significantly greater for dipyridamole (53%) than for adenosine (6%). Although adenosine had a significantly greater acquisition cost than dipyridamole, costs of monitoring, management of side effects, and follow-up care were significantly less for adenosine than for dipyridamole. As a result, the total cost of using dipyridamole is significantly greater ($928.00 per patient) than the total cost of using adenosine ($672.00 per patient). Based on these results, adenosine may be the drug of choice for pharmacologic vasodilation for PET.

Asunto(s)

RESUMEN

Histamine2 (H2)-receptor antagonists are widely prescribed for a variety of acid-mediated gastrointestinal disorders. The objective of the present study was to quantify the frequency of inappropriate H2-receptor antagonist use and its economic impact in patients who were admitted to a critical care bed at our hospital and followed as outpatients for 1 year. Eighty-eight (72%) of 123 patients admitted to the coronary care unit (CCU) or the intensive care unit over a 14-day period received H2-receptor antagonists. Forty-five (51%) of the 88 patients did not have a documented indication for H2-receptor antagonist therapy. Most of the patients without indications were admitted to the CCU for cardiac diagnoses. Thirty-eight patients (43%) were discharged on oral H2-receptor antagonist therapy. Twenty (53%) of the 38 patients had no documented indication for therapy; 17 of these patients continued H2-receptor antagonist therapy for 1 year, whereas the remaining 3 patients received therapy for 1, 2, and 3 months, respectively. The cost of therapy for the 45 patients receiving inappropriate therapy during hospitalization was $5,084.31. Outpatients costs for the 20 patients remaining on inappropriate therapy was $8,619.75. The total cost of inappropriate therapy was $13,704.06. If data collected during this 2-week period were extrapolated to 1 year, the projected annual cost of inappropriate therapy would be $356,305.56. The economic impact of inappropriate H2-receptor antagonist therapy at our institution is great. Programs designed to reduce such inappropriate use must be implemented and evaluated for their ability to decrease the associated costs.

Asunto(s)

RESUMEN

STUDY OBJECTIVE: To determine if the diagnostic accuracy and safety of intravenous adenosine myocardial perfusion imaging is significantly different in men compared with women. DESIGN: Prospective, comparative, open-label clinical trial. SETTING: Nuclear medicine laboratory in a university-affiliated hospital. PATIENTS: Consecutive patients who were referred for evaluation of known or suspected coronary artery disease. Patients were judged not to be able to exercise adequately. INTERVENTIONS: Coronary angiography was conducted within 6 weeks of an adenosine thallium-201 myocardial perfusion imaging study. MEASUREMENTS AND MAIN RESULTS: Diagnostic accuracy is shown in the table. [table: see text] Overall, side effects from adenosine were not different between men and women. The frequencies of ST depression and chest pain were significantly greater in women than men, although their etiologies are unknown. The frequency of severe side effects such as heart block and hypotension was not different between men and women. CONCLUSIONS: The diagnostic accuracy and safety of adenosine thallium-201 myocardial perfusion imaging are generally similar in women and men.

Asunto(s)

RESUMEN

Diltiazem and warfarin are both highly protein-bound providing the opportunity for a protein-binding displacement interaction to occur. Additionally, diltiazem has demonstrated the ability to inhibit the metabolic clearance of hepatically cleared drugs (e.g. warfarin). We evaluated these pharmacokinetic mechanisms for a potential interaction. A single warfarin 25 mg oral dose was given with and without oral diltiazem 30 mg 3 times daily to 20 healthy male volunteers in a randomized crossover design with a washout period of at least 6 days. Serial blood samples for INRs and free and total warfarin concentrations were obtained over 144 hours after each warfarin dose. Free fraction was extracted by equilibrium dialysis and free and total warfarin concentrations were analyzed by HPLC. Anticoagulation was assessed using AUC0-6,INR (days). Diltiazem was found not to potentiate anticoagulation by warfarin. Furthermore, warfarin protein binding displacement did not occur. Diltiazem inhibited both free and total warfarin clearance, though not statistically significant. Although slightly inhibiting metabolism of warfarin, based on warfarin clearance, diltiazem did not increase warfarin's anticoagulant effect making it an acceptable addition to therapy if required.

Asunto(s)

Asunto(s)

RESUMEN

The excretion of terfenadine into breast milk has not been reported previously. Disposition of terfenadine was prospectively studied in four healthy lactating mothers (age, 33 +/- 4 years). Subjects received 60 mg terfenadine every 12 hours over a period of 48 hours to achieve steady-state milk and plasma concentrations. Milk and plasma samples were collected at 1/2, 1, 1 1/2, 2, 3, 4, 6, 8, 12, 24, and 30 hours after the last dose. Terfenadine and its active metabolite milk and plasma concentrations were quantitated by HPLC. Terfenadine was not detected in milk or plasma. Mean +/- SD active metabolite data for milk and plasma are as follows: Cmax (ng/ml), 41.0 +/- 16.4 for milk, 309.0 +/- 120.5 for plasma; tmax (hours), 4.3 +/- 2.4 for milk, 3.9 +/- 3.0 for plasma; t1/2 beta (hours), 14.2 +/- 5.4 for milk, 11.7 +/- 6.4 for plasma; AUC(0-12) (ng.hr/ml) 320.4 +/- 99.8 for milk, 1590.0 +/- 300.4 for plasma. Metabolite milk/plasmaAUC(0-12) ratios ranged from 0.12 to 0.28 (mean, 0.21 +/- 0.07). Newborn dosage estimates based on the highest measured concentration of terfenadine metabolite in milk suggests the maximum level of newborn exposure would not exceed 0.45% of the recommended maternal weight-corrected dose. Estimated amounts consumed by the neonate after the mother is given the recommended dose of the drug are not likely to result in plasma levels producing untoward effects.

Asunto(s)

RESUMEN

In addition to efficacy and safety, the cost of therapy has become an increasingly important factor to consider when selecting drugs to treat patients with mild-to-moderate hypertension. However, acquisition prices alone do not determine the total cost of therapy. To better assess total costs, we conducted a systematic, retrospective, cost-minimization analysis of drugs used to treat 673 patients with newly diagnosed, mild-to-moderate (> 95 to < 110 mmHg) diastolic hypertension between the years 1985 and 1992. Patients included in the study had started antihypertensive monotherapy, and a minimum of one dose titration was required before adding another antihypertensive agent to the regimen. A patient had to have a diastolic blood pressure of < or = 90 mmHg while undergoing therapy to be included in the analysis. Drug classes included diuretics, beta-adrenergic blockers, centrally acting alpha 2-agonists, alpha 1-adrenergic blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors. Costs, adjusted to 1992 price levels, were analyzed for 32 individual agents for each of the following five cost variables: initial drug acquisition, supplemental drug acquisition, laboratory monitoring, clinic visits, and treatment of side effects. Mean total costs per patient for all five variables by drug class were $895 for beta-blockers, $1043 for diuretics, $1165 for centrally acting alpha 2-agonists, $1243 for ACE inhibitors, $1288 for alpha 1-blockers, and $1425 for calcium channel blockers. However, costs within each class varied considerably. Acquisition cost was often a poor predictor of the total cost of treatment. Therefore, acquisition cost must be considered in conjunction with a number of outcome variables to assess the true cost of antihypertensive therapy.

Asunto(s)

RESUMEN

We evaluated 110 patients with mild-to-moderate hypertension (diastolic blood pressure 95 to 110 mmHg) whose blood pressure was initially controlled on monotherapy with once-daily sustained-release calcium entry blockers; these patients were then switched to their respective immediate-release formulations TID. The study group consisted of 35 patients on diltiazem controlled delivery (CD) switched to immediate-release diltiazem, 41 patients on nifedipine gastrointestinal therapeutic system (GITS) switched to immediate-release nifedipine, and 34 patients on verapamil sustained-release (SR) switched to immediate-release verapamil. Outcome evaluation included a pair-wise comparison of the following during treatment with both formulations: blood pressure control, need for additional hypertensive agents, side effects, compliance, and cost of therapy. Blood pressure was controlled in 94% of patients switched from diltiazem CD to immediate-release diltiazem; 6% of patients required additional antihypertensive agents. Side effects and compliance were not significantly different between groups. Blood pressure was controlled in 78% of patients switched from nifedipine GITS to immediate-release nifedipine; 22% of patients required additional antihypertensive agents. Side effects, compliance, and cost of therapy were significantly different between groups. Side effects increased from 32% on nifedipine GITS to 58% on immediate-release nifedipine; and compliance decreased from 93% on nifedipine GITS to 76% on immediate-release nifedipine (P < 0.05). Blood pressure was controlled in 91% of patients switched from verapamil SR to verapamil immediate release; 9% of patients required additional antihypertensive agents. Side effects and compliance were not significantly different between groups, but immediate-release verapamil was significantly less expensive than verapamil SR.(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

RESUMEN

OBJECTIVE: To determine the efficacy and safety of clonidine versus placebo in smoking cessation. DESIGN: Single-center, randomized, double-blind, parallel-design comparison of transdermal clonidine with behavior modification, transdermal clonidine without behavior modification, placebo with behavior modification, and placebo without behavior modification. SETTING: Outpatient, university-based ambulatory care facility. PATIENTS: One hundred fifty generally healthy, highly nicotine-dependent cigarette smokers. INTERVENTION: Clonidine was given as the transdermal patch initiated 72 hours prior to smoking-cessation attempts and continued for six weeks thereafter. Clonidine was given at a dose of 0.2 mg/d for patients weighing more than 150 pounds (> 67.5 kg) and at a dose of 0.1 mg/d for patients weighing less than 150 pounds (< 67.5 kg). Behavior modification consisted of a total of 12 one-hour structured group training sessions. Patients not receiving behavior modification received printed material, which included the "Help Quit Kit" and the "I Quit Kit" from the American Cancer Society. MAIN OUTCOME MEASURES: Smoking-cessation rates were assessed at 6, 12, 24, and 52 weeks of follow-up. In addition, adverse reactions to clonidine or placebo were evaluated. RESULTS: Clonidine with behavior modification was statistically superior to the other three treatment groups but only at 6 weeks of follow-up. There were no differences in smoking-cessation rates among any of the treatment groups at any other follow-up intervals. Patients receiving behavior modification, regardless of whether they received clonidine, had better quit rates than patients not receiving behavior modification at all follow-up times except 52 weeks. Women receiving clonidine had significantly better quit rates than men receiving clonidine at all follow-up visits. Clonidine was associated with a significantly higher incidence of adverse effects than placebo (52 vs. 11 percent). However, the number of smokers withdrawing from the study was not greater with clonidine compared with placebo (9 vs. 7 percent, respectively). CONCLUSIONS: Clonidine is probably not effective as a pharmacologic adjunct to behavior modification in smoking cessation. It may have a potential role in women smokers who do not respond to or cannot tolerate more traditional smoking-cessation therapies.

Asunto(s)

RESUMEN

Phenylbutazone has been clearly demonstrated to interact pharmacokinetically and clinically with warfarin, although several other nonsteroidal antiinflammatory drugs (NSAIDs) also have the potential to interact with warfarin to cause alterations in prothrombin time. Aspirin is known to inhibit platelet aggregation irreversibly, whereas nonaspirin NSAIDs are thought to inhibit platelet aggregation reversibly. In contrast, nabumetone was not shown to cause significant inhibition of platelet aggregation, which may be related to the fact that nabumetone preferentially inhibits the prostaglandin synthase-2 isozyme instead of the prostaglandin synthase-1 isozyme. Furthermore, in studies in patients and normal volunteers stabilized on warfarin, nabumetone did not cause alterations in the prothrombin time or international normalized ratio. Based on data evaluating the concomitant use of nabumetone and warfarin, the relative lack of platelet inhibition, and the relatively lower risk of nabumetone-induced gastrointestinal mucosal damage as assessed by radiolabeled chromium-51 fecal blood loss studies and endoscopic evaluations, nabumetone may be preferred if concomitant therapy with warfarin is indicated.

Asunto(s)

Asunto(s)

RESUMEN

Armour found its workers' compensation costs to be disproportionately high. In response, it set up a "Focal Physician" program, which dealt successfully with the problem.

Asunto(s)

Asunto(s)