Effect of estrogen on exercise electrocardiograms in healthy postmenopausal women.
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Administration, Oral↗
Biomedical subjects
S M Mohiuddin
Publications and source records attributed to S M Mohiuddin.
Esmolol versus diltiazem in the treatment of postoperative atrial fibrillation/atrial flutter after open heart surgery.
BACKGROUND: Supraventricular tachyarrhythmias are common after open heart surgery. Possible causative factors for these arrhythmias include operative trauma, atrial ischemia, electrolyte imbalances, pericardial irritation, and excess catecholamines. Two agents commonly used to control ventricular rate in atrial fibrillation or atrial flutter (AF/AFL) are beta-blockers and calcium channel blockers. METHODS AND RESULTS: This randomized study was designed to compare the safety and efficacy of intravenous diltiazem versus intravenous esmolol in patients with postoperative AF/AFL after coronary bypass surgery and/or valve replacement surgery. A comparative cost analysis was also performed. Thirty patients received either esmolol (n = 15) or diltiazem (n = 15) for AF/AFL. During the first 6 hours of treatment, 66.6% of esmolol-treated patients converted to sinus rhythm compared with 13.3% of the diltiazem-treated patients (P <.05). At 24 hours, 66.6% of the diltiazem group converted to SR compared with 80% of the esmolol group (not significant). Drug-induced side effects, time to rate control (<90 beats/min), number of patients requiring cardioversion, and length of hospitalization were similar for the two groups. The drug cost/successfully treated patient for esmolol versus diltiazem was $254 versus $437 at 6 hours and $529 versus $262 at 24 hours. CONCLUSIONS: Although this is a small study, it suggests that esmolol is more effective in converting patients to normal sinus rhythm than diltiazem during the initial dosing period. No differences in conversion rates were observed between the two groups after 24 hours. Additional studies are needed to confirm whether esmolol is the initial drug of choice in patients with postoperative AF/AFL after coronary bypass surgery.
Adrenergic beta-Antagonists↗
Benzocaine-induced methemoglobinemia during an outpatient procedure.
Outpatient transesophageal echocardiography was performed in a 69-year-old man with a history of aortic valve repair. During the procedure the patient became markedly cyanotic and hypotensive. Oxygen saturation measured by pulse oximetry decreased from 97% to the mid-80s. The man's condition continued to deteriorate. On transfer to a critical care unit, blood analysis by co-oximetry showed methemoglobin saturation of 67.8%. The patient's condition improved significantly after intravenous administration of methylene blue 1 mg/kg. With increasing numbers of outpatient procedures performed under topical anesthesia, measures should be in place to deal with a potential life-threatening adverse event such as methemoglobinemia.
Aged↗
A population-based treat-to-target pharmacoeconomic analysis of HMG-CoA reductase inhibitors in hypercholesterolemia.
The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have become the drugs of choice for the treatment of patients with hypercholesterolemia. However, one of the major concerns with these drugs is cost. In an attempt to develop a cost-effective treatment strategy for patients referred to our lipid clinic, we conducted a meta-analysis to estimate the lipid-lowering efficacy of the various HMG-CoA reductase inhibitors alone or in combination with niacin or cholestyramine. Based on cholesterol-lowering efficacy estimates derived from a literature-based meta-analysis, we performed a population-based treat-to-target analysis. Fifty-six trials with 101 monotherapy cohorts and 20 trials with 31 combination-therapy cohorts (573 patients) were included in the meta-analysis. Based on reduction in low-density lipoprotein cholesterol (LDL-C), the most effective monotherapy was atorvastatin and the least effective monotherapy was fluvastatin. Combination therapy was more effective in reducing LDL-C than monotherapy with the respective HMG-CoA reductase inhibitor. However, on the basis of dollars spent per percentage of LDL-C reduction, combination therapy was frequently less cost-effective than monotherapy. In addition, combination therapy was associated with a higher rate of noncompliance and a greater risk of drug-drug interactions. As a result, we based our treat-to-target analysis on the use of monotherapy as first-line treatment, with combination therapy reserved for patients failing to achieve the target LDL-C levels of the US National Cholesterol Education Program Adult Treatment Panel II (NCEP ATP-II) with monotherapy. In the population-based treat-to-target analysis, atorvastatin was the most cost-effective drug for high-risk patients (those with coronary heart disease [CHD]), whereas fluvastatin was the most cost-effective agent for low-risk patients (<2 risk factors for CHD) and moderate-risk patients (> or =2 risk factors for CHD). If 1 drug is chosen to treat all patients (i.e., in cases of formulary restriction), atorvastatin would be the most cost-effective agent. In adapting the findings on cholesterol-lowering efficacy from this analysis to our lipid clinic, we concluded that the most cost-effective treatment approach is to individualize the selection of an HMG-CoA reductase inhibitor based on both coronary risk and the LDL-C reduction required to achieve NCEP ATP-II goals. Based on our results, 2 agents--atorvastatin and fluvastatin--should be available on the formulary.
Cholesterol↗
Fixed-dose combination vs monotherapy in hypertension: a meta-analysis evaluation.
Fixed-dose combination antihypertensive therapy has received interest since the publication of the JNC-VI report. Relatively few head-to-head comparative studies between fixed-dose combinations and first-line monotherapies for hypertension have been published. The objective of this study was to conduct a meta-analysis of various first-line monotherapies and the fixed-dose combination of amlodipine/benazepril. The results of the meta-analysis were used to compare the efficacy and safety of the first-line monotherapies with amlodipine/benazepril. The meta-analysis included 82 studies that included 110 treatment groups (cohorts). The study compared nine different monotherapies and one combination therapy (amlodipine/benazepril). Of the 82 studies, 22 were placebo-controlled and 60 were active treatment controlled. The mean absolute decrease in supine diastolic blood pressure (BP) ranged from 9.7 to 13.3 mm Hg with verapamil showing the greatest effect and captopril the least (13.3 +/- 3.0 mm Hg; 9.7 +/- 2.9 mm Hg, respectively). When studies were weighted by sample size, atenolol, verapamil, lisinopril and amlodipine/benazepril showed the greatest BP effect. When studies were weighted by variance, amlodipine/benazepril and atenolol showed the greatest BP effect. The percentage of patients controlled on therapy ranged from 54% to 79%. Lisinopril and amlodipine/benazepril showed the greatest percent controlled. The overall incidence of adverse effects ranged from 12.1% to 41.8% with lisinopril having the lowest and nifedipine having the highest incidence. The overall incidence of adverse effects resulting in drug discontinuance ranged from 1.3% to 10.7%, with amlodipine/benazepril having the lowest and nifedipine having the highest incidence. The results of the meta-analysis indicate that amlodipine/benazepril produces above average reductions in BP with a lower than average incidence of overall side effects and the lowest incidence of adverse effects resulting in drug discontinuance. The fixed-dose combination of amlodipine/benazepril achieves its goal of effective BP lowering with a minimum of significant side effects.
Amlodipine↗
Treatment of asymptomatic myocardial ischemia.
BACKGROUND: Asymptomatic myocardial ischemia is commonly observed in patients with coronary artery disease. Numerous studies have shown that patients with asymptomatic ischemia are at higher risk for adverse outcome than those without ischemia. Several recent studies have investigated the therapeutic options available in the management of patients with asymptomatic myocardial ischemia. METHODS: Recently published randomized controlled trials investigating the treatment of asymptomatic myocardial ischemia were reviewed. RESULTS: The controlled trials suggest that (1) asymptomatic ischemia can be suppressed to various degrees using pharmacologic therapy or revascularization, (2) beta-blockers are in general superior to calcium channel blockers or nitrates in relieving asymptomatic ischemia, and (3) revascularization is superior to pharmacologic therapy. CONCLUSIONS: A growing body of evidence suggests that in patients with coronary artery disease, treatment of asymptomatic ischemia may result in improved outcome. However, because of significant limitations in the published studies, additional studies with large sample sizes and broader inclusion criteria are needed.
Adrenergic beta-Antagonists↗
Efficacy and safety of clonazepam in refractory neurally mediated syncope.
Neurally mediated syncope is a complex syndrome that is often difficult to manage using currently available treatment strategies. The efficacy and safety of clonazepam was evaluated in 35 patients with refractory neurally mediated syncope. All patients had syncope (n = 33) or disabling presyncope (n = 2) and a positive head-up tilt table test (HUTT) despite treatment with one or more of the following therapies: beta-blocker, high-salt diet, fludrocortisone, elastic compression stockings, and disopyramide. Clonazepam was initiated at 0.5 mg/day and titrated in 0.25-0.5 mg/day increments for symptom control. Early (first 8 weeks) symptomatic response was achieved in 31 of 35 (89%) patients. Early HUTT reverted to negative in 29 of 35 (83%) patients. Two patients discontinued clonazepam during early follow-up due to side effects. Thirty-three patients received long-term clonazepam therapy. Twenty-five patients had late HUTT with 21 remaining negative. Of the eight patients who did not have late HUTT, one patient discontinued clonazepam prior to HUTT due to side effects. Seven patients refused late HUTT. All seven patients achieved symptomatic control on clonazepam with two requiring dose titration. Of the 21 patients with a negative late HUTT, 18 achieved symptomatic control with two of these patients requiring dose titration. Two patients who had only partial symptom control despite dose titration achieved total symptomatic control with the addition of disopyramide and beta-blockers. Two patients with a negative late HUTT discontinued clonazepam due to side effects. One patient had been symptomatically controlled while the other had recurrent symptoms with dose limiting side effects occurring after clonazepam dose titration. In the 4 patients with a positive late HUTT, 2 patients were symptomatically controlled, 1 patients required combination therapy with a beta-blocker to achieve symptomatic control, and 1 patient discontinued therapy due to side effects. Overall, 29 of 35 (83%) patients continue to receive clonazepam with symptom control. Based on intention-to-treat HUTT results, 21 of 35 (60%) patients were responders. Four patients required clonazepam dose titration and three required combination therapy with clonazepam plus disopyramide and/or a beta-blocker to achieve control. Clonazepam was discontinued in 6 patients, 5 for side effects and 1 following a transient ischemic attack. Clonazepam appears to be an effective therapeutic alternative in patients with refractory neurally mediated syncope. Based on our preliminary findings, a placebo controlled evaluation of clonazepam in neurally mediated syncope is warranted.
Adrenergic beta-Antagonists↗
Comparison of 24-hour ambulatory blood pressure data in hypertensive patients switched from nifedipine-GITS to nifedipine-CC.
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.
Adult↗
Anticoagulation and elective surgery.
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Anticoagulants↗
Cost-minimization analysis of intravenous adenosine and dipyridamole in thallous chloride TI 201 SPECT myocardial perfusion imaging.
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.
Adenosine↗
Further elucidation of pharmacokinetic interaction between diltiazem and warfarin.
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.
Adult↗
Stress testing with closed-loop arbutamine as an alternative to exercise. The International Arbutamine Study Group.
OBJECTIVES: This study compared exercise and pharmacologic stress testing using arbutamine delivered by a closed-loop device for the detection of coronary artery disease. BACKGROUND: Arbutamine, an agent designed to simulate exercise, has been developed in conjunction with a closed-loop delivery device that modulates the rate of administration on the basis of physiologic feedback. METHODS: Two hundred ten patients (180 men, 30 women) with symptoms and angiographic evidence of coronary artery disease were studied. Ischemia was categorized in three ways: 1) the presence of angina; 2) the occurrence of > or = 0.1-mV horizontal or downsloping ST segment depression or elevation at 60 ms after the J point; or 3) the presence of either condition 1 or 2. RESULTS: In the 210 patients, the mean increase in heart rate and systolic blood pressure evoked by arbutamine and exercise was 51 and 53 beats/min (p = NS) and 36 and 44 mm Hg (p < 0.0001), respectively. Arbutamine detected ischemia more often than exercise with each of the three ischemic end points. Sensitivity for detecting ischemia by either angina or ST segment change was 84% (95% confidence interval ¿ change was 84% (95% confidence interval [CI] 79% to 89%) for arbutamine and 75% (95% CI 69% to 81%) for exercise testing (p = 0.014). For angina alone, sensitivity was 73% (95% CI 67% to 79%) for arbutamine and 64% (95% CI 57% to 71%) for exercise (p = 0.026). For ST segment change alone, sensitivity was 47% (95% CI 40% to 54%) for arbutamine and 44% (95% CI 37% to 51%) for exercise (p = 0.426). Cardiac events occurred in five patients (1.8%) within 24 h of the arbutamine test. CONCLUSIONS: In detecting documented coronary artery disease, the sensitivity of arbutamine testing was equal to that of exercise for the electrocardiographic end point of ST segment change alone. Arbutamine testing was significantly superior to exercise testing for either ST change or angina or for angina alone.
Aged↗
Using transesophageal echocardiography to manage critically ill patients. What role in hemodynamic instability, MI, embolic disease, trauma?
When transthoracic echocardiographic images are suboptimal, transesophageal echocardiography offers a new window for visualization of the heart and thoracic aorta. It can be performed at bedside in 15 to 20 minutes. Complications (emesis, hypoxemia, hypotension) are rare and easily reversed or averted by administration of naloxone or flumazenil. Indications include evaluation of hemodynamic instability, ventricular function, mitral regurgitation, ventricular septal defects, aneurysm, endocarditis, intracardiac sources of embolus, valve pathology, aortic dissection, intra-aortic debris, and trauma. Results can be analyzed immediately and used to guide further evaluation, medical therapy, or surgery.
Cardiovascular Diseases↗
Comparison of fixed-dose transdermal nicotine, tapered-dose transdermal nicotine, and buspirone in smoking cessation.
The authors compared the outcome of 208 smokers treated with fixed-dose transdermal nicotine (n = 69), tapered-dose transdermal nicotine (n = 71), or buspirone (n = 68). At baseline, there were no significant differences among the three treatment groups with regard to age, gender, educational level, duration of smoking, number of cigarettes smoked per day, concomitant disease states or drug use, or Fagerstrom score. All smokers participated in a behavior modification program. Fixed-dose transdermal nicotine was given at a dose of 21 or 22 mg/day for 6 weeks. Tapered-dose transdermal nicotine was given at a dose of 21 or 22 mg/day for 4 weeks, 14 mg/day for 4 weeks and 7 mg/day for 4 weeks. Both transdermal nicotine regimens were initiated on the evening before the attempted quit date. Buspirone was started 21 days before the quit attempt and continued for 7 days after the quit attempt. Buspirone was initiated at 5 mg TID for 7 days and then 10 mg TID for 21 days. Smoking cessation was assessed by patient diaries and random plasma thiocyanate determinations. Dropouts for any reason were considered treatment failures. Quit rates were as shown in the Table I. Discontinuation of treatment for perceived side effects and dropouts for all reasons were not significantly different among the treatment groups. The authors conclude that fixed-dose transdermal nicotine, tapered-dose transdermal nicotine, and buspirone are associated with similar efficacy and safety when combined with behavior modification in smoking cessation.
Administration, Cutaneous↗
Inversion of the left atrial appendage: clinical and echocardiographic correlates.
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Adult↗
Safety of esmolol in patients with acute myocardial infarction treated with thrombolytic therapy who had relative contraindications to beta-blocker therapy.
OBJECTIVE: This study was conducted to evaluate the safety of esmolol in 114 patients treated with thrombolytic therapy for acute myocardial infarction who also had relative contraindications to beta-blockade, and the predictive value of patient tolerance to esmolol and subsequent patient tolerance of oral beta-blocker therapy. PATIENTS: One hundred and fourteen patients with myocardial infarction documented by enzyme concentrations and electrocardiographic changes who also had relative contraindications to beta-blockade. METHODS: Esmolol was initiated during acute myocardial infarction for myocardial ischemia (n = 88), hypertension (n = 13), or supraventricular tachycardia (n = 13). Relative contraindications to beta-blocker therapy included either active signs/symptoms of left ventricular dysfunction or a history of congestive heart failure (n = 40), a history of chronic obstructive pulmonary disease or asthma (n = 31), bradycardia (HR < 60 beats/min; n = 18), peripheral vascular disease (n = 15), or hypotension (systolic BP < 100 mm Hg; n = 14). RESULTS: During initial esmolol dose titration, 69 patients tolerated 300 micrograms/kg/min, 12 patients tolerated 200 micrograms/kg/min, 17 patients tolerated 100 micrograms/kg/min, and 16 patients tolerated 50 micrograms/kg/min. Twenty-eight patients (25 percent) developed dose-limiting adverse effects during esmolol maintenance infusions. Sixteen patients required esmolol dose reduction and 12 required esmolol discontinuation. Adverse effects reversed within 30-45 minutes following dose reduction or discontinuation. The 86 patients who tolerated esmolol infusions without dose reduction or drug discontinuation were subsequently treated with oral beta-blockers. Eleven of these patients (13 percent) developed adverse effects requiring oral beta-blocker discontinuation. Nine of these patients had tolerated only 50 micrograms/kg/min of esmolol, and the other 2 patients had tolerated only 100 micrograms/kg/min. CONCLUSIONS: Esmolol can be used safely in most patients treated with thrombolytic therapy for acute myocardial infarction who have relative contraindications to beta-blockers. Tolerance to higher maintenance doses of esmolol is a good predictor of subsequent outcome with oral beta-blocker therapy.
Adrenergic beta-Antagonists↗
Nonsteroidal antiinflammatory drug use in patients receiving warfarin: emphasis on nabumetone.
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.
Anti-Inflammatory Agents, Non-Steroidal↗
Loss of efficacy during long-term cifenline therapy: development of antiarrhythmic resistance?
OBJECTIVE: To describe the possible development of antiarrhythmic resistance to cifenline, an investigational Class I agent. METHODS: Forty patients with chronic ventricular premature depolarizations (VPDs) underwent dose-ranging studies with cifenline, an investigational Class I antiarrhythmic agent. Patients had a minimum of 30 VPDs/h detected by ambulatory electrocardiographic (ECG) monitoring over a 48-hour baseline placebo lead-in period. Twenty-two patients (55 percent) who initially responded received long-term cifenline therapy. Ambulatory ECG monitoring over 24 hours was repeated during active cifenline therapy at three-month intervals and during placebo reintroduction at six-month intervals. RESULTS: After an average follow-up of 28 months, VPD frequency during cifenline therapy was similar to that during initial baseline placebo therapy in 8 of the 22 patients (36 percent) who initially responded. Placebo reintroduction following cifenline failure showed a VPD frequency similar to that with active therapy. All patients had further cifenline dosage increases without success. Plasma cifenline concentrations increased in all patients and were in the high therapeutic range. All 8 patients were switched to other Class I antiarrhythmic agents with successful VPD suppression during treatment with the first alternative drug. CONCLUSIONS: We conclude that antiarrhythmic resistance occurred with cifenline in these patients as (1) initial efficacy was established for a minimum of two years, (2) VPD frequency was similar during cifenline therapy and placebo reintroduction, (3) cifenline therapy failure continued despite further dosage titration, and (4) alternative Class I antiarrhythmic therapy was successful in all patients. Repeat intermittent ambulatory ECG monitoring is necessary not only to assess the continued need for antiarrhythmic drug therapy, but also to establish continued long-term efficacy.
Adult↗