Multiple-dose efficacy and safety of an extended-release form of niacin in the management of hyperlipidemia.

This multicenter trial evaluated the safety and efficacy of escalating doses of Niaspan (niacin extended-release tablets) and placebo (administered once-a-day at bedtime) in patients with primary hyperlipidemia on the percent change from baseline in levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B. Extended-release niacin was initiated at a dose of 375 mg/day, raised to 500 mg/day, and further increased in 500-mg increments at 4-week intervals to a maximum of 3,000 mg/day. A total of 131 patients (n = 87, extended-release niacin; n = 44, placebo) were treated for 25 weeks with study medication after a 6-week diet lead-in/drug washout phase and 2-week baseline LDL cholesterol stability phase. Significant decreases from baseline in levels of LDL cholesterol and apolipoprotein B became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or =0. 05), reaching 21% and 20%, respectively, at the 3,000-mg/day dose. Significant increases from baseline in levels of high-density lipoprotein cholesterol became apparent with the 500-mg/day dose and were consistent at all subsequent doses (p < or = 0.05), reaching 30% at the 3,000-mg dose. Significant decreases from baseline in triglycerides and lipoprotein(a) occurred at the 1,000-mg dose and were apparent at all subsequent doses (p < or =0.05), reaching 44% and 26%, respectively, at the 3,000-mg dose. The most common adverse events were flushing and gastrointestinal disturbance. Transaminase increases were relatively small, and the proportion of patients who developed liver function abnormalities on extended-release niacin was not significantly different from placebo. Thus, extended-release niacin was generally well tolerated and demonstrated a dose-related ability to alter favorably most elements of the lipid profile.

Equivalent efficacy of a time-release form of niacin (Niaspan) given once-a-night versus plain niacin in the management of hyperlipidemia.

This study compared the efficacy and safety of a once-a-night, time-release niacin formulation, Niaspan (Kos Pharmaceuticals, Miami Lakes, FL), with plain niacin and placebo for the treatment of primary hypercholesterolemia. The study was conducted in nine academic lipid research clinics in a randomized, double-blind design. Niaspan 1.5 g at bedtime was compared with plain niacin 1.5 g/d after 8 weeks and 3.0 g/d after 16 weeks in divided doses and with placebo. A total of 223 hypercholesterolemic adult men and women participated. Compared with placebo at 8 weeks, Niaspan versus plain niacin at 1.5 g/d showed comparable efficacy, comparably lowering total cholesterol (C) (8%/8%), triglycerides (16%/18%), low-density lipoprotein (LDL)-C (12%/12%), apolipoprotein (apo B) (12%/12%), apo E (9%/7%), and lipoprotein(a) [Lp(a)] (15%/11%), and raising high-density lipoprotein (HDL)-C (20%/17%), HDL2-C (37%/33%), HDL3-C (17%/16%), and apo A-I (8%/6%) (P < or = .05 in all instances). After 16 weeks, the Niaspan effect on LDL-C and triglyceride was unchanged while the plain niacin effect approximately doubled. At equal doses of 1.5 g/d of Niapan versus plain niacin, respectively, AST increased 5.0% versus 4.8% (difference not significant [NS]), fasting plasma glucose increased 4.8% versus 4.5% (NS), and uric acid concentrations increased less, 6% versus 16% (P=.0001). Flushing events were more frequent with plain niacin versus Niaspan (1,905 v 576, P < .001). Flushing severity was slightly greater with Niaspan, but still well tolerated. In conclusion, Niaspan 1.5 g hour of sleep (hs) has comparable efficacy, a lower incidence of flushing, a lesser uric acid rise, and an equivalent hepatic enzyme effect than 500 mg thrice-daily plain niacin in hyperlipidemic subjects. Niaspan may be an equivalent or better alternative to plain niacin at moderate doses in the management of hyperlipidemia.

Advances in pacing for the patient with sick sinus syndrome.

Sick sinus syndrome, the significant clinical manifestation of progressive sinus node dysfunction, is the most frequent indication for the implantation of permanent pacing systems in the United States. Revolutionary advances in pacemaker hardware and programmability now allow a careful tailoring of device, mode, and program for the individual patient and underlying electrophysiologic abnormalities. Evidence indicates that appropriate mode selection in this group of patients not only ameliorates symptoms but may decrease the incidence of complications and help maintain an acceptable quality of life. Most available data is retrospective and uncontrolled, therefore controversy remains regarding mode recommendations. More conclusive data may be produced by clinical trials currently in progress. This article reviews the latest innovations and recommendations regarding permanent pacing for sick sinus syndrome.

New indications for permanent cardiac pacing.

Data are slowly accumulating regarding the possible benefits and appropriate uses of permanent cardiac pacing in a variety of pathophysiologic states or syndromes other than the broad categories and indications of sinus node dysfunction and atrioventricular block. The subjective and physiologic indications for pacing in these disorders are not symptomatic bradycardia or fulfillment of previously accepted criteria for antibradycardia pacing, and pacing is not the first or only therapy used. Therefore, individual patient evaluation, often including documentation of the response to temporary pacing therapy prior to implantation of a permanent device, is helpful and may be necessary. Controversy regarding the data available, and expanding clinical use of permanent cardiac pacing in a number of these conditions or syndromes, remains.

Prehospital actions by health-care providers and physicians.

Extensive worldwide experience and literature exist on the benefits of early intervention in patients with an acute myocardial infarction. To make these benefits available to as much of the population as possible a number of goals have to be accomplished. Patients and bystanders must be taught to recognize the significance of symptoms and call immediately for assistance. Local emergency medical service has to dispatch appropriate personnel and equipment to the scene expeditiously. Transport without unacceptable delays must occur to appropriate facilities along with rapid initiation of treatment. A program to achieve these goals would be expected to substantially reduce morbidity and mortality. Attention is directed to prehospital actions by health-care providers including dispatch of personnel and equipment to the scene, stabilization and treatment in the field, and triage and transport of the patient to the most appropriate medical facility.

Early management of acute myocardial ischemic events. Recommendations. Quality of Patient Care Committee, Florida Chapter, American College of Cardiology.

A Consensus Development Conference conducted by the Quality of Patient Care Committee, Florida Chapter, American College of Cardiology, for the Early Management of Acute Myocardial Ischemic Events in Florida was held August 26-28, 1994, at St. Joseph's Heart Institute, Tampa. Twenty recommendations were proposed to improve the management of patients with these conditions and to reduce mortality and long-term morbidity from coronary heart disease.

Regional distribution of 2-deoxy-2[18F]-fluoro-D-glucose for metabolic imaging using positron emission tomography.

Radiopharmaceutical availability is one of the reasons dissemination and growth of clinical PET imaging remains problematic. A 'regional' cyclotron-radiopharmacy facility for the production of the positron emitting radionuclide 2-deoxy-2[18F]-fluoro-D-glucose (FDG), has been operational for over 2 years and supplies this radiopharmaceutical to five camera facilities, four distant and one on-site. The RDS 11 MeV cyclotron is capable of dual bombardment of targets yielding 60 GBq (1600 mCi) of F-18 in a 90 minute period. F-18 labelled FDG is produced by an automated synthesis module yielding 22.2 GBq (600 mCi) FDG. The PET radiopharmacy is required to perform extensive quality assurance activities including a number of tests to insure final product and safety. [18F]FDG is shipped in unit dose vials, 6 ml, two per shielded container, meeting Department of Transportation (DOT) specifications (43 x 43 cm cubes, styrofoam packing, 22 lb. lead shield). This adheres to regulations requiring no more than 200 millirem per hour (mR/Hr) exposure at the container surface, and 10 mR/hr at a distance of 1 meter. Total transport time, utilizing private air and ground couriers, to distant facilities is approximately 100-120 minutes. Based on patient scheduling and protocol used, allowing 45-60 minutes between dose administrations, and availability of 22.2 GBq (600 mCi), 20-22 unit doses can be supplied, divided and shipped in a number of ways. The regional-commercial distribution of PET radiopharmaceuticals, specifically [18F]FDG, is feasible. This provides availability of metabolic imaging at sites distant to radiopharmaceutical production.

Late follow-up of dual-chamber rate-adaptive pacing.

Dual-chamber pacing systems with sensor-based rate-adaptive capability (DDDR pacemakers) provide paced patients with the potential benefits of both a reliable chronotropic response and maintenance of atrioventricular (AV) synchrony. However, there is concern that clinical and programming complexities may necessitate frequent reprogramming of pacemakers from the DDDR mode to less physiologic pacing modes (in particular VVI or VVIR). Consequently, this study assessed the stability of pacing-mode programming, and the factors affecting pacing-mode selection in patients with a DDDR-capable pacing system. Clinical status during follow-up (18.2 +/- 6.7 months) was assessed in 75 patients. Principal diagnoses providing an indication for pacing were: (1) AV block alone, 18 of 75 patients (24%); (2) sick sinus syndrome alone, 41 (55%); and (3) combined AV block and sick sinus syndrome, 16 (21%). Twenty-three patients had history of atrial tachyarrhythmias. At implantation, 66 devices (88%) were programmed to DDDR mode, 7 (9%) to DDD, and 2 (3%) to DVIR. At last follow-up, the respective distribution of programmed modes was 83% DDDR, 10% DDD, 4% DVIR and 3% VVIR. During the study, the initial pacing mode remained unchanged in 54 patients (72%) and needed modification in 21 (28%). Of the latter 21 patients, atrial tachycardia was the basis for a programming change in 11 (52%), of whom 8 had history of atrial tachycardias. In general, postimplant atrial arrhythmia occurrences proved controllable, and ultimately return to a rate-adaptive dual-chamber pacing mode (DDDR, DDD or DVIR) was achieved in most cases. The remaining reprogrammings were primarily to optimize hemodynamic benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Positron emission tomography in clinical practice.

Positron emission tomography (PET) has been considered a research tool; however, advances in hardware and software, along with availability of small medical cyclotrons, make clinical metabolic imaging feasible. There is accumulating data, especially in the areas of neurology and cardiology, to support its use in the appropriate clinical setting and patient population.

Rate augmentation and atrial arrhythmias in DDDR pacing.

Dual chamber, rate-modulated pacemakers provide the capability of augmenting the heart rate of patients with chronotropic incompetence but also may cause atrial arrhythmias because of high rate, competitive atrial pacing. We studied ten patients with two consecutive 24-hour Holter monitors during which they were alternately programmed to either DDD or DDDR pacing in random order. Maximum heart rates (max HR) were measured at every 15-minute interval during each 24-hour period. DDDR pacing showed rate augmentation, 80 +/- 7 average max HR when compared with DDD pacing, average max HR 76 +/- 5. These results were even more striking when waking hours (7 am to 10 pm) were compared: average max HR 86 +/- 7 DDDR versus 78 +/- 4 average max HR DDD. Several patients showed marked rate augmentation. Seven of ten patients preferred DDDR pacing over DDD pacing. In the entire population, DDDR pacing did not result in an increased number of atrial arrhythmias (1.25 atrial events/24 hour) when compared to DDD pacing (1.75 atrial events/24 hour). We conclude that DDDR pacing provides heart rate augmentation during daily life in a clinical population while not resulting in a significant increase in atrial arrhythmias.