作者：
Weinfeld, MSChertow, GMStevenson, LWHarvard Univ
Brigham & Womens Hosp Sch Med Cardiovasc DivDept Med Boston MA 02115 USA Harvard Univ
Brigham & Womens Hosp Sch Med Renal DivDept Med Boston MA 02115 USA MIT
Harvard Mit Div Hlth Sci & Technol Clin Investigator Training Program Beth Israel Deaconess Med Ctr Cambridge MA 02139 USA
Background Chronic heart failure is associated with impaired renal function, which may worsen during therapy. The incidence, predictors, and consequences of aggravated renal dysfunction (ARD) in patients undergoing in...
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Background Chronic heart failure is associated with impaired renal function, which may worsen during therapy. The incidence, predictors, and consequences of aggravated renal dysfunction (ARD) in patients undergoing intensive therapy for advanced chronic heart failure are unknown. Methods we reviewed the experience of 48 consecutive patients hospitalized for treatment of advanced chronic heart failure who underwent intravenous diuretic therapy with a weight loss of greater than or equal to 2 kg. Evaluation included baseline renal function and echocardiography in all patients and hemodynamic measurements in 38 (79%) patients. Results ARD, defined as greater than or equal to 25% increase in serum creatinine concentration greater than or equal to 2 mg/dl, developed in 10 (21%) patients. Patients with ARD developing were older (aged 58 +/- 16 years vs 51 +/- 13 years;P =.006) and had lower baseline creatinine clearance (49 +/- 21 mL/min vs 74 +/- 26 mL/min;P =.01) but had the same serum creatinine at baseline. They were more likely to have atrial fibrillation (70% vs 29%, P =.02) but did not have lower filling pressures, cardiac output, or estimated renal perfusion pressure. Length of stay was longer if ARD developed (median 17 vs 9 days, P =.02). Mortality rate after discharge was increased in the patients with ARD (relative risk 5.3, P =.002). Conclusions In patients undergoing intensive treatment for heart failure, ARD is common and clinically significant. The relation among baseline factors, ARD, and worsened outcome may reflect complex cardiorenal interactions. Better understanding of the causes and prevention of ARD during heart failure therapy may in the future lead to better outcomes.
Objective The aim of the study was to assess the effects of carvedilol, a vasodilating nonselective P-blocker, on the indexes of left ventricular remodeling after acute myocardial infarction in those with left ventric...
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Objective The aim of the study was to assess the effects of carvedilol, a vasodilating nonselective P-blocker, on the indexes of left ventricular remodeling after acute myocardial infarction in those with left ventricular dysfunction. Methods and Results Forty-nine patients with predischarge left ventricular election fraction <45% after acute myocardial infarction were evaluated in a double-blind, randomized, placebo-controlled, parallel group study (selected from the database of the Carvedilol Heart Attack Pilot Study: CHAPS). Patients received medication after thrombolysis and continued to do so for 6 months. Two-dimensional echocardiography was performed before discharge (7 to 10 days after admission) and at 3 months after acute myocardial infarction. Analysis of variance showed that wall thickness opposite the site of infarction decreased from (mean +/- SD) 12.3 +/- 2.1 mm to 11.0 +/- 2.4 mm with carvedilol compared with 11.6 +/- 1.9 mm to 12.2 +/- 1.9 mm with placebo (P = .01). left ventricular mass changed from 235 +/- 74 g to 217 +/- 64 g with carvedilol compared with 227 +/- 80 g to 252 +/- 85 g with placebo (P = .02). Carvedilol prevented alteration of sphericity index (ratio of long and short axis of left ventricle) that changed from 1.65 +/- 0.29 to 1.66 +/- 20 with carvedilol compared with 1.58 +/- 0.33 to 1.39 +/- 0.19 with placebo (P = .02);alteration was also prevented of wail thickening abnormality at infarct site, which changed from 9.2 +/- 3.1 cm(2) to 9.1 +/- 3.5 cm(2) with carvedilol compared with 10.3 +/- 3.3 cm(2) to 13.5 +/- 4.6 cm(2) with placebo (P = .002). Conclusion Carvedilol administered early after acute myocardial infarction results in attenuation of left ventricular remodeling in patients with persistent left ventricular dysfunction before discharge.
OBJECTIVES We assessed whether the intravenous administration of nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts beneficial effect-on microvascular function and functional and clinical ...
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OBJECTIVES We assessed whether the intravenous administration of nicorandil, an adenosine triphosphate (ATP)-sensitive K+ channel opener, exerts beneficial effect-on microvascular function and functional and clinical outcomes in patients with acute myocardial infarction (AMI). BACKGROUND Experimental studies documented that ATP-sensitive K+ channel opener exerts cardioprotection after prolonged ischemia. METHODS We randomly divided 81 patients with a first anterior AMI into two groups, nicorandil (n = 40) and control groups (n = 41). All patients received successful coronary angioplasty within 12 h after the symptom onset and underwent myocardial contrast echcardiography (MCE) with the intracoronary injection of sonicated microbubbles. In the nicorandil group, we injected 4 mg of nicorandil followed by the infusion at 6 mg/h for 24 h and by oral nicorandil (15 mg/day). RESULTS The improvement in regional left ventricular function, nail motion score and regional wall motion was significantly better in the nicorandil group then in the control group. Intractable congestive heart failure, malignant ventricular arrhythmia and pericardial effusion were more frequently found in the control group than in the nicorandil group (15% vs. 37%, 5% vs. 20% and 8% vs. 37%, p < 0.05, respectively). The frequency of sizable MCE no reflow phenomenon was significantly lower in the nicorandil group than in the control group (15% vs. 33%, p < 0.05). CONCLUSIONS Intravenous nicorandil in conjunction with coronary angioplasty is associated with better functional and clinical outcomes compared to angioplasty alone in patients with an anterior AMI. Myocardial contrast echocardiography findings imply that an improvement in microvascular function with nicorandil may be attributable to this better outcome. CT Am (C) 1999 by the American College of Cardiology.
Objective: To study the pharmacokinetics of cilostazol following single oral administration of 50 to 200mg in healthy young males, and after repeated oral administration of 100mg every 12 hours to patients with periph...
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Objective: To study the pharmacokinetics of cilostazol following single oral administration of 50 to 200mg in healthy young males, and after repeated oral administration of 100mg every 12 hours to patients with peripheral arterial disease (PAD). Design: The healthy male single dose study was a single-centre, randomised sequence, open-label, incomplete block, 3-period, 4-treatment, crossover design. The patient study was a single-centre, multiple dose, open-label study. Study Participants: 20 healthy nonsmoking male volunteers were enrolled and successfully completed the single dose study. 26 patients (21 males, 5 females) with intermittent claudication resulting from PAD were enrolled and completed the single/multiple dose study. Main Outcome Measures: Noncompartmental pharmacokinetic parameters, the area under the plasma concentration-time curve from zero to the time of last measurable plasma concentration, and maximum plasma concentration. Results: Peak plasma concentrations of cilostazol occurred about 3 hours after drug administration and then declined biexponentially with concentrations detectable (>20 mu g/L) in the plasma for at least 36 hours postdose. The apparent elimination half-life of cilostazol (approximately 11 hours) was similar after a single dose or after multiple doses, with steady state being reached within 4 days. Cilostazol accumulated 1.7-fold following multiple dose administration. The apparent volume of distribution (V-2/F;2.76 L/kg) suggested extensive distribution of cilostazol in the tissues. The oral clearance of cilostazol (CL/F;0.18 L/h/kg) was much lower than liver blood flow, indicating a low extraction ratio drug, and hence low probability of a significant first-pass effect. None of the administered doses were recovered in the urine as unchanged cilostazol, suggesting that metabolism, rather than urinary excretion, is the major elimination route. Following single oral doses of 50 to 200mg, the plasma concentrations of cilostazol and
OBJECTIVES The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to lest the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. BACKGROUND Reperfusi...
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OBJECTIVES The Acute Myocardial Infarction STudy of ADenosine (AMISTAD) trial was designed to lest the hypothesis that adenosine as an adjunct to thrombolysis would reduce myocardial infarct size. BACKGROUND Reperfusion therapy for acute myocardial infarction (MI) has been shown to reduce mortality, but reperfusion itself also may have deleterious effects. METHODS The AMISTAD trial was a prospective, open-label trial of thrombolysis with randomization to adenosine or placebo in 236 patients within 6 h of infarction onset. The primary end point was infarct size as determined by Tc-99 m sestamibi single-photon emission computed tomography (SPECT) imaging 6 +/- 1 days after enrollment based on multivariable regression modeling to adjust for covariates. Secondary end points were myocardial salvage index and a composite of in-hospital clinical outcomes (death, reinfarction, shock, congestive heart failure or stroke). RESULTS In all, 236 patients were enrolled. Final infarct size was assessed in 197 (83%) patients. There was a 33% relative reduction in infarct size (p = 0.03) with adenosine. There was a 67% relative reduction in infarct size in patients with anterior infarction (15% in the adenosine group vs. 45.5% in the placebo group) but no reduction in patients with infarcts located elsewhere (11.5% for both groups). Patients randomized to adenosine tended to reach the composite clinical end point more often than those assigned to placebo (22% vs. 16% odds ratio, 1.43;95% confidence interval, 0.71 to 2.89). CONCLUSIONS Many agents thought to attenuate reperfusion injury have been unsuccessful in clinical investigation. In this study, adenosine resulted in a significant reduction in infarct size. These data support the need for a large clinical outcome trial. (C) 1999 by the American College of Cardiology.
In a double-blind, randomized, 3-month multicenter study, the safety and tolerability and the antianginal and anti-ischemic efficacy of carvedilol 25 to 50 mg twice daily were assessed in comparison with metoprolol 50...
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In a double-blind, randomized, 3-month multicenter study, the safety and tolerability and the antianginal and anti-ischemic efficacy of carvedilol 25 to 50 mg twice daily were assessed in comparison with metoprolol 50 ta 100 mg twice daily in younger and elderly patients with stable angina. After a 7-day placebo run-in at the end of which a symptom-limited bicycle ergometric exercise was performed, 368 patients were randomly allocated to the parallel treatment groups. After 4 weeks of therapy with a low dose, a further exercise test was performed and patients were titrated in single-blind fashion to the higher dose if the increase in total exercise time was <1 minute, and there was no safety concern. After a further 8 weeks of treatment a third exercise test was performed. Carvedilol low dose/high dose was shown to be at least as safe and well tolerated as metoprolol low dose/high dose both in younger and elderly patients. There were no thitherto unknown adverse events and no marked change in the types of events after increase of the doses. Early adverse events after treatment initiation or uptitration were equal with both medications, indicating no particular risk associated with carvedilol's vasodilatory action. No rebound phenomena were observed. Both drugs showed good antianginal and anti-ischemic efficacy, with marked increases on uptitration including patients greater than or equal to 65 years of age. However, in the doses selected, which appeared equipment with respect to beta blockade, carvedilol's improvement of time to 1-mm ST-segment depression was statistically significantly greater than that of metoprolol. This could be due to its additional vasodilatory or antioxidative actions. Based on the safety and efficacy data of the present study, use of the higher of the 2 recommended doses of carvedilol and metoprolol appears justified in younger and elderly patients without adequate therapeutic control at lower doses. (C)1999 by Excerpta Medico, Inc.
The effects of a beta blocker (atenolol), a calcium antagonist (amlodipine), and a nitrate (isosorbide-5-mononitrate) on anginal symptoms in 10 patients with syndrome X were assessed in a crossover, double-blind, rand...
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The effects of a beta blocker (atenolol), a calcium antagonist (amlodipine), and a nitrate (isosorbide-5-mononitrate) on anginal symptoms in 10 patients with syndrome X were assessed in a crossover, double-blind, randomized trial. Only atenolol was found to significantly improve chest pain episodes, suggesting that it should be the preferred drug when starting pharmacologic treatment of patients with syndrome X.
Intravenous digoxin induces constriction of normal and stenotic coronary arteries in patients with coronary artery disease, which may lead to ischemic complications. We found that pretreatment with oral nisoldipine an...
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Intravenous digoxin induces constriction of normal and stenotic coronary arteries in patients with coronary artery disease, which may lead to ischemic complications. We found that pretreatment with oral nisoldipine and intracoronary nitroglycerin neutralizes this digoxin-induced effect.
Maximal oral vasodilator therapy resulted in long-term reduction of initially elevated pulmonary vascular resistance in 10 of 13 patients with severe heart failure who tolerated inotrope-supported uptitration of after...
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Maximal oral vasodilator therapy resulted in long-term reduction of initially elevated pulmonary vascular resistance in 10 of 13 patients with severe heart failure who tolerated inotrope-supported uptitration of afterload reduction. Eleven patients were unable to tolerate vasodilator therapy and required inotropic support for successful cardiac transplantation.
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