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Biomedical subjects

V Kinhal

Publications and source records attributed to V Kinhal.

12 recordsLinked to original sources

Safety and efficacy of carvedilol in severe heart failure. The U.S. Carvedilol Heart Failure Study Group.

BACKGROUND: Many patients remain markedly symptomatic despite optimal current therapy for heart failure. Beta-blockers have often been viewed as contraindicated in this group because of their potential adverse short-term effects on cardiac function. METHODS AND RESULTS: One hundred thirty-one patients with severe congestive heart failure were enrolled into a double-blind, placebo-controlled study of the vasodilating beta-blocker carvedilol. All patients had symptomatic, advanced heart failure while on standard triple therapy, as evidenced by a mean ejection fraction of 0.22, marked reduction in distance traveled in a 6-minute corridor walk test, and severe impairment in quality of life measured by the Minnesota Living With Heart Failure Questionnaire. After a 2-week, open-label test of 6.25 mg twice daily carvedilol, 105 patients were randomized (2:1) to receive either carvedilol (up to 25 mg twice daily, n = 70) or matching placebo (n = 35) for 6 months while background therapy with digoxin, diuretics, and an angiotensin-converting enzyme inhibitor remained constant. Ten patients (8%) did not complete the open-label period because of adverse events and 11.4% in both the carvedilol and placebo groups dropped out in the double-blind phase. The study was terminated early by the Data Safety and Monitoring Board and follow-up evaluation was therefore aborted before the projected number of patients and follow-up time was achieved. Quality of life, which was the primary endpoint, improved similarly in the carvedilol and placebo groups, whereas the global assessment by the physicians and the patient exhibited a better response to carvedilol (P < .05). Hospitalization and mortality rate were too low to evaluate a difference, and exercise time and New York Heart Association classification did not change significantly in response to the drug. Left ventricular ejection fraction rose significantly (+0.09) in the carvedilol group compared with the placebo group (+0.02, P = .004). CONCLUSION: The beta-blocker carvedilol can be safely employed in patients with severe heart failure. Improved left ventricular function with a trend for some improvement in symptoms combined with the experience with the drug in the larger population of less severe patients in this multicenter trial suggests that carvedilol may have a favorable long-term effect in heart failure of diverse severity.

Adrenergic beta-Antagonists↗

Double-blind, placebo-controlled study of the effects of carvedilol in patients with moderate to severe heart failure. The PRECISE Trial. Prospective Randomized Evaluation of Carvedilol on Symptoms and Exercise.

BACKGROUND: Carvedilol has improved the symptomatic status of patients with moderate to severe heart failure in single-center studies, but its clinical effects have not been evaluated in large, multicenter trials. METHODS AND RESULTS: We enrolled 278 patients with moderate to severe heart failure (6-minute walk distance, 150 to 450 m) and a left ventricular ejection fraction < or = 0.35 at 31 centers. After an open-label, run-in period, each patient was randomly assigned (double-blind) to either placebo (n = 145) or carvedilol (n = 133; target dose, 25 to 50 mg BID) for 6 months, while background therapy with digoxin, diuretics, and an ACE inhibitor remained constant. Compared with placebo, patients in the carvedilol group had a greater frequency of symptomatic improvement and lower risk of clinical deterioration, as evaluated by changes in the NYHA functional class (P = .014) or by a global assessment of progress judged either by the patient (P = .002) or by the physician (P < .001). In addition, treatment with carvedilol was associated with a significant increase in ejection fraction (P < .001) and a significant decrease in the combined risk of morbidity and mortality (P = .029). In contrast, carvedilol therapy had little effect on indirect measures of patient benefit, including changes in exercise tolerance or quality-of-life scores. The effects of the drug were similar in patients with ischemic heart disease or idiopathic dilated cardiomyopathy as the cause of heart failure. CONCLUSIONS: These findings indicate that, in addition to its favorable effects on survival, carvedilol produces important clinical benefits in patients with moderate to severe heart failure treated with digoxin, diuretics, and an ACE inhibitor.

Adrenergic beta-Antagonists↗

Hemodynamic effects of dilevalol in patients with systemic hypertension and left ventricular dysfunction.

Hemodynamic and left ventricular function parameters were measured in patients with mild to moderate hypertension and compromised left ventricular function who were given dilevalol, an antihypertensive agent with selective beta 2-agonism and nonselective beta-antagonist activity. After a 2- to 3-week placebo washout period, 9 patients were given dilevalol titrated upward from 100 to 600 mg twice daily over a 7-week period to achieve a supine diastolic blood pressure of less than 90 mm Hg with a decrease of greater than or equal to 10 mm Hg from baseline. Multigated radionuclide ventriculography and systolic and diastolic time intervals were performed after the pretreatment placebo washout, at the end of 2 weeks' maintenance dosing, and after a 7- to 10-day post-treatment discontinuation and placebo washout period. At an average daily dose of dilevalol, 444 mg, heart rate at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. Systolic and diastolic blood pressures at rest decreased significantly (p less than 0.01) during treatment and increased during post-treatment placebo. At maximal exercise, changes in blood pressure and heart rate were significantly blunted (p less than 0.05) during treatment. Ejection fraction at rest increased significantly (p less than 0.01) during treatment, with no significant change occurring during exercise, and decreased during post-treatment placebo. Preejection period decreased significantly during treatment (p less than 0.005) and increased during post-treatment placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

The efficacy and safety of dilevalol in patients with chronic stable angina pectoris.

This is the first reported large clinical trial of the antianginal and acute ischemic effectiveness and safety of dilevalol (the R, R-isomer of labetalol) in patients with chronic stable angina pectoris. This was a multicenter double blind fixed-dose parallel group placebo controlled trial. Patients with chronic stable angina and positive and reproducible exercise tests (+/- 20%) were included. If randomized, patients entered one of four fixed dose groups (twice a day placebo, 100 mgm, 200 mgm and 400 mgm bid for 2 weeks). Exercise testing was performed at 2 hours (peak) and 12 hours (trough) postdosing. This was followed by a 2-week once-a-day dosing regimen in which patients received the same total daily dose as the prior 2 weeks, with the full dose in the morning and a matched placebo in the evening. Exercise testing was performed at 2 hours (peak) and 24 hours (trough) postdosing. Anginal frequency and NTG consumption were significantly reduced, and equally so, by qd and bid regimens. The time of exercise to the onset of angina increased and the proportion of patients terminating exercise because of moderate angina decreased in a dose response fashion for both peak and trough tests and for both qd and bid regimens. There was also a dose related decrease in exercise induced ST segment depression and an increase in time to 1 mm ST depression. In 15 patients, 24-hour ambulatory monitoring also revealed a decrease in episodes of silent ischemia. No significant side effects related to the study drug occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Achieving therapeutic goals in insulin-using diabetic patients with non-insulin-dependent diabetes mellitus. A weight reduction-exercise-oral agent approach.

Non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes in the civilized world. Its consequences include microvascular and macrovascular disease, both of which appear to evolve from a common background of obesity and physical inactivity. The current study was undertaken in obese patients with NIDDM to see whether improvements could be made in glycemic control as well as in many cardiovascular risk factors (obesity, hypertension, lipid abnormalities, and physical inactivity) that are typical of this condition. Fifteen obese insulin-using patients with NIDDM (average body mass index, 34.0) were treated with a 500-calorie formula diet for eight to 12 weeks. Administration of insulin and diuretics was discontinued at the onset of the study. A eucaloric diet was begun at eight to 12 weeks and maintained until Week 24. A behaviorally oriented nutrition-exercise program was instituted at the beginning of the study. Glipizide or placebo was added (randomized) at Week 15 if the fasting plasma glucose level in patients exceeded 115 mg/dl. Patients lost an average of 22 pounds over the course of 24 weeks. Frequency and duration of physical activity increased significantly from baseline, as did the maximal oxygen consumption rate. Glycemic control by 15 weeks (without insulin) was similar to baseline (with insulin). With the addition of glipizide at Week 15, both fasting plasma glucose and glucose tolerance improved significantly. This improvement was not observed with placebo. In addition, both systolic and diastolic blood pressure decreased by about 10 mm Hg. There were no significant changes in the levels of serum lipids or glycosylated hemoglobin. In conclusion, a multifaceted intervention program, employing weight reduction, exercise, diet, and glipizide therapy, can be instituted in insulin-using patients with NIDDM, with improvement in glycemic control and in certain risk factors (hypertension, obesity, physical inactivity) for cardiovascular disease.

Adult↗

The therapeutic implications of diastolic time changes in systemic hypertension.

Twenty-five patients with chronic systemic hypertension were studied. Systolic time intervals and diastolic time were determined at baseline and after 12 weeks of therapy with nadolol, with or without bendroflumethiazide (treatment phase I), then after 12 weeks of therapy with hydralazine, bendroflumethiazide, or both (treatment phase II). Systolic, diastolic, and mean blood pressures were equally controlled after either treatment regimen. Heart rate was significantly slower after treatment phase I compared to baseline or after treatment phase II (p less than 0.001). Systolic time per minute was significantly shorter and diastolic time per beat and per minute were significantly longer after treatment phase I compared to baseline or after treatment phase II (p less than 0.001). Double and triple products decreased after either mode of therapy; however, these parameters were significantly lower after treatment phase I compared to treatment phase II (p less than 0.01). These changes in systolic and diastolic time and double and triple products may be of clinical significance during therapy of chronic systemic hypertension and may help explain the regression of left ventricular hypertrophy in patients with hypertension treated with sympathetic blocking agents.

Adult↗

Common cardiac arrhythmias: recognition and treatment.

Cardiac arrhythmias are commonly seen in the everyday practice of medicine by the physician. Although certain arrhythmias may be suspected clinically, precise diagnosis is made by electrocardiographic recording of the abnormal rhythm. Once the arrhythmia has been recorded, the next steps are proper electrocardiographic diagnosis and selection of proper treatment. The specific mode of therapy and the speed with which it is delivered will depend not only on the type of arrhythmia, but also on the hemodynamic consequences of the rhythm abnormality on the patient's cardiovascular system. The purpose of this paper is to discuss the electrocardiographic criteria of common cardiac arrhythmias as well as current concepts regarding therapy.

Arrhythmias, Cardiac↗