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 Amiodarone's Effects In Heart Failure

September 1, 1996 - Amiodarone is often used to treat arrhythmia in heart failure patients. Small studies showed amiodarone improving heart function and ability to exercise. The U.S. Department of Veterans Affairs studied amiodarone's effects on left heart function, CHF symptoms, and hospitalizations for heart failure.
     Researchers studied 674 patients with class 2 to 4 symptoms and an ejection fraction of 40% or less. Patients took amiodarone at 300 to 400mg daily or placebo for an average of 45 months. Patients were evaluated at study start and after 6, 12, and 24 months.
     Ejection fractions increased more in amiodarone patients than in placebo patients at each follow-up (8% versus 3% at 6 months, and 9% versus 2% at 24 months). However, heart failure symptoms, need for diuretics, and number of hospitalizations were the same in both groups.
     Among the 28% of CHF patients without clogged arteries, amiodarone reduced hospitalizations and heart-related deaths. Amiodarone did not improve survival or risk of sudden cardiac death. This study shows that amiodarone improves heart function - but not survival or symptoms - in heart failure patients. However, patients with CHF not caused by clogged arteries may have better survival on amiodarone.
 
Title: Effect of amiodarone on clinical status and left ventricular function in patients with congestive heart failure
Authors: Massie BM et al
Source: Circulation 1996 Jun 15; 93:2128-2134

 How Super Are Super-Aspirins?

January 14, 1999 - A study from the University of Pennsylvania shows a downside to COX-2 inhibitors. Also called "super-aspirins," this problem wasn't noticed in previous trials. One of the drugs' actions may increase risk of heart attack and stroke.
     Trials of COX-2 inhibitors for arthritis have not shown any cardiovascular risk, said Garret FitzGerald, study author. "However, the studies were too small to detect this. The question hangs out there: Will cardiovascular risk show up as COX-2 inhibitors are taken by more and more patients?"
     Aspirin and ibuprofen are NSAIDs. They inhibit an enzyme called COX. Scientists recently found that there are 2 forms of the COX enzyme: COX-1 and COX-2.
     COX-1 protects the lining of the stomach; COX-2 causes pain and inflammation. Current NSAIDs block both, while COX-2 inhibitors only block COX-2. That means they should relieve pain and inflammation without stomach upset.
     FitzGerald found that COX-2 inhibitors also suppress prostacyclin, a hormone-like substance produced in blood vessel walls that dilates blood vessels and reduces blood clotting. Since COX-2 inhibitors interfere with prostacyclin - a natural protector against clotting - the new drugs may increase risk of heart attack or stroke..
 
Title: New Cox-2 Inhibitors May Elevate Cardiovascular Risk
Source: Proceedings of the National Academy of Science, published December 5, 1998

 Vessel Dilator and Natriuretic Peptides

October 18, 1999 - In CHFers, a hormone called "vessel dilator" acts like a diuretic - better than natriuretic peptides. Dr. David Vesely compared the diuretic and natriuretic properties (lowering blood pressure and getting rid of the body's sodium) of vessel dilator versus long-acting natriuretic peptide in 17 patients with class 3 heart failure.
     Patients received one of the 2 hormones by IV for 60 minutes. Blood and urine samples were taken 60 and 30 minutes before the infusion, during the infusion, and for 3 hours after infusion. Vessel dilator significantly increased urine output, increasing flow rate almost 5 times. Urinary flow rate remained 4 times higher than before taking the drug for 3 hours after stopping the drug infusion. There was also a 300% increase in sodium elimination.
     Long-acting natriuretic peptide only doubled urine flow. It made no difference in sodium elimination. However, in a previous study of healthy people, long-acting natriuretic peptide caused 500% increase in urine flow and up to 800% more sodium elimination. So it does not work as well in CHFers.
     According to a previous study, vessel dilator does not break down in the blood. The current study shows that long-acting natriuretic peptide "is being degraded at a rapid rate in CHFer's blood, whereas vessel dilator remains in the blood to continue its positive effects."
 
Source: Am Heart J 1999;138:625-632

 Cholesterol-Lowering Drugs

August 28, 1997 - At the European Society of Cardiology meeting, from Stockholm, results of the CURVES study are in. CURVES compared 5 statin drugs for lowering cholesterol. LDL-cholesterol was reduced

Drug Dose Reduction In LDL Cholesterol
atorvastatin (Lipitor) 10 mg 38%
simvastatin (Zocor) 10 mg 28%
pravastatin (Prevachol) 20 mg 24%
lovastatin (Mevacor) 20 mg 29%
fluvastatin (Lescol) 20 mg 17%

Source: Reuters Health

 Crestor For Cholesterol

January 15, 2001 - The new cholesterol-lowering drug Crestor (rosuvastatin) may be better than Lipitor (atorvastatin), the current "gold standard" among such drugs, according to 2 new studies.
     One trial was a phase 3 head-to-head comparison. Researchers followed 516 patients given 5 or 10mg of Crestor or 10mg Lipitor. Crestor patients saw greater reductions in LDL (bad cholesterol) and greater increases in HDL (good cholesterol) than Lipitor patients.
     Results from another study, led by Dr. Evan Stein, showed that 61% of Crestor patients achieved proper target levels versus 46% of Lipitor patients.
     Crestor's 2004 label warns about serious muscle problems associated with its use, called myopathy and rhabdomyolysis. People taking cyclosporine are at high risk. See www.fda.gov/cder/drug/advisory/crestor.htm
 
Source: ACC web site

 Growth Hormone For Heart Failure

January 5, 1999 - We studied the effects of RHGH on exercise ability and heart function in patients with ischemic cardiomyopathy.
     Seven patients with an average age of 55 years were studied, with average ejection fraction of 31%, already taking standard CHF meds. The patients were studied at baseline, after 3 months of GH treatment, and 3 months after stopping GH. Heart function was measured by exercise, right heart cath at rest and after exercise, MRI, echo, and Holter monitoring.
     At a dose of 2 IU per day, GH doubled blood levels of IGF-1 (insulin-like growth factor-I). GH improved symptoms and exercise capacity significantly. Heart class went from 2.4 to 1.4 at 3 months. Vo2max went up. Heart output went up, while heart size went down after rhGH treatment. There was no significant increase in EF. The improvements were partially reversed 3 months after stopping GH but heart size was still improved 3 months after stopping treatment.
 
Title: Recombinant growth hormone therapy in patients with ischemic cardiomyopathy : effects on hemodynamics, left ventricular function, and cardiopulmonary exercise capacity
Authors: Genth-Zotz S, Zotz R, Geil S, Voigtlander T, Meyer J, Darius H
Source: Circulation 1999 Jan 5-12;99(1):18-21
PMID: 9884373, UI: 99104098

 Growth Hormone Improves Heart Function

August 20, 1999 - GH (growth hormone) is involved in many bodily processes, directly or through its mediator, IGF-1. GH may help regulate heart structure and function. In fact, giving extra GH causes the heart to contract more strongly in healthy people. RHGH given for 3 months in patients with idiopathic DCM and heart failure, improves blood flow.
     The patients Twelve male patients all had stable CHF, an average EF of 21%, and already taking digoxin, diuretics, and vasodilators. They had an average Vo2max of 10 mL/kg/minute and no arrhythmias. We did not include patients taking Coreg or other beta-blockers.
     The first 24 hours after right heart cath were the control period. During the following 24 hours, all the patients took constant IV infusion of 0.1 IU/kg/24 hours of RHGH. Standard CHF meds were continued unchanged. Meals were standardized for each patient and no extra calories were allowed.
     The measurements Heart size, left ventricular thickness, and heart function were measured by echo. A bicycle exercise test (Vo2max) was done. Right heart cath was done on the first study day, in the morning. PAP, PCWP, cardiac output, and blood pressure were measured. All these were also measured 30 minutes after right heart cath, at the end of the control period, and every 4 hours during GH infusion. Blood was drawn at study start and at 2 and 4 hours after the infusion began, then every 4 hours until the end of infusion. The same amount of RHGH was given to all patients.

With 24-hour GH infusion, average cardiac index went up 50%. After infusion, pulmonary pressures went down (a good thing), as did PCWP. We found no differences in heart rate, but did see a drop in blood pressure in all patients.
     Discussion Short-term (24-hour) continuous IV RHGH can dramatically improve both left and right heart function, raising cardiac index by 50% and lowering pulmonary artery pressure by 25% in patients with severe CHF.
     GH's effects were seen 4 to 8 hours after beginning the infusion and continued to improve heart function throughout the study. How GH increases the heart's beating strength is unknown. Patients with low blood IGF-1 levels and high GH levels got less benefit. If low blood levels of IGF-1 predict a weak response to GH, maybe the patients who would get the most benefit could be identified and treated.
 
Title: Endocrine Predictors of Acute Hemodynamic Effects of Growth Hormone in CHF
From: Am Heart J 137(6):1035-1043, 1999

 Is This Old Drug Still Any Good?

1996 - Digoxin is effective in patients with heart failure and a-fib. However, its value in CHFers with normal heart rhythm is questioned.
     In the 1980s, some large trials showed that digoxin - with or without other drugs - reduced heart failure symptoms and improved exercise ability. This was mainly seen in patients with more advanced heart failure and more enlarged hearts. The drug's effectiveness in milder heart failure was less obvious. In the last few years, digoxin has been shown to have value in mild heart failure, alone or with other drugs.
     Low doses of digoxin may be just as effective as higher doses, and cause less side effects. The recent knowledge that using digoxin too soon after a heart attack may be harmful has changed digoxin's role in CHF treatment. However, a recent large survival trial (DIG) showed that although digoxin has no effect on over-all death rate, it reduces the number of hospitalizations and deaths due to worsening heart failure; definitely a drug still worth using in heart failure treatment.
 
Title: Value of Digoxin in Heart Failure and Sinus Rhythm: New Features of an Old Drug?
Authors: Dirk J. van Veldhuisen, MD, PhD, FACC, Pieter A. de Graeff, MD, PhD, Willem J. Remme, MD, PhD, FACC, K. I. Lie, MD, PhD Groningen, The Netherlands
From: J Am Coll Cardiol 1996;28:813-9

 CHF Management - 1998

November, 1998 An "expert" panel met at the 47th Annual Scientific Session of the American College of Cardiology to discuss heart failure therapies. Here are some of their findings:

Digoxin The results of the DIG trial showed that digoxin reduces both hospitalizations and death.
Diuretics Recent studies show that using 2 different diuretics together - such as Lasix and zaroxolyn - is more effective than using one diuretic at higher dose. Patient symptoms - especially shortness of breath on exertion - usually dictate dose changes. Taking diuretics more than once during the day is a good idea since one dose only lasts 6 to 7 hours.
     The loss of electrolytes including potassium, magnesium and calcium caused by diuretics is a problem. Some of this may be offset with the use of ACE inhibitors, which cause CHFers to retain electrolytes. Potassium, magnesium and calcium supplements may also be needed.
Aldactone (spironolactone) Spironolactone inhibits aldosterone. In theory, aldosterone causes heart fibrosis, which worsens heart failure.
Ace Inhibitors Surprisingly, only 40% of CHFers are taking ACE inhibitors. Many of these take doses much lower than suggested doses from trials. Some doctors believe that lower doses of ACE inhibitors are as effective and are safer than higher doses. This is not true. The ATLAS trial studied low-dose (2.5 to 5mg daily) and high-dose (32.5 to 35mg daily) ACE inhibitor use. The trial included 3000 patients with class 2, 3, and 4 heart failure. At the end of 4 years, the higher-dose group had 8% lower risk of death and 12% less all-cause mortality and hospitalization. Higher doses were tolerated just as well as lower doses.
ACE Receptor Blockers ARBs give benefits like ACE inhibitors and may be better tolerated because they cause less coughing. However, ACE inhibitors are still considered the best heart failure therapy at this time.
Beta-Blockers Beta-blockers are well tolerated by most CHFers if the dose is raised very carefully. Little data exist regarding their use in patients with class 4 CHF, though. Beta-blockers may prevent heart remodeling in heart failure and increase ejection fraction.
Conclusions According to current expert opinion, digoxin reduces hospitalization and death in heart failure patients. ACE inhibitors are underused and many patients are taking too-low doses. Combination diuretic therapy is better than single diuretic therapy. Finally, ARBs give results similar to those of ACE inhibitors and may be better tolerated.
 
Title: Drug Therapy for Congestive Heart Failure
Speaker: Milton Packer, MD, Columbia College of Physicians and Surgeons, New York, NY
Reviewer: Ken Grauer, MD

 Aldactone Lowers Risk In Severe CHF

August, 1999 - The RALES trial tested whether 25mg of spironolactone a day would reduce risk of death or hospitalization in CHF patients already on standard meds. The trial began in March of 1995 and was stopped early on August 24, 1998, so doctors could start using the results of the study to treat their patients.
     Patients were in class 3 or 4 heart failure at time of enrollment. All patients were already taking an ACE inhibitor and a loop diuretic, and all had an ejection fraction less than 35%. Treatment with digoxin and vasodilators was allowed. Patients were randomly assigned to take either 25mg of spironolactone once a day or placebo. If hyperkalemia developed, the dose was lowered to 25mg every other day.
     1663 patients from 195 medical centers in 15 countries participated. Eight hundred forty-one patients took placebo and 822 took spironolactone. During the study, 433 patients (200 in the placebo group and 214 in the drug group) stopped treatment for some reason. After 2 years of follow-up, the average daily drug dose was 31mg in the placebo group and 26mg in the drug group.
     46% of placebo patients died during the study versus 35% of spironolactone patients - a 30% relative reduction in risk of all-cause death. Thirty-seven percent of placebo patients and 27% of spironolactone patients' deaths were heart-related. Reduced risk of death was studied with respect to sex, heart class, starting potassium level, use of potassium supplements, and use of beta-blockers. Benefit was the same regardless.
     There were 753 heart-related hospitalizations in the placebo group and 515 in the spironolactone group - a 30% relative reduction in hospitalization for heart-related reasons. Serious hyperkalemia only occurred in one percent of placebo patients and 2% of spironolactone patients. Breast pain was reported by 10% of the men in the spironolactone group. The use of a selective aldosterone blocker like eplerenone (Inspra) may reduce this side effect.

Changes In Heart Class
Placebo patients Aldactone patients
33% improved 41% improved
18% didn't change 21% didn't change
48% worsened or died 38% worsened or died

Spironolactone reduced risk of death from all causes and from heart-related causes. It also reduced heart-related hospitalizations in patients with severe heart failure. It improved heart failure symptoms. These reductions in risk of death and hospitalization were seen after 2 to 3 months of treatment and lasted throughout the study.
     Patients in this study were in worse heart class and at higher risk than those in studies of bisoprolol, digoxin, amlodipine, or Coreg. However, these patients were at less risk than those in a study of enalapril.
     Aldosterone is the hormone that Aldactone "blocks." It makes the body retain sodium, causing heart failure patients to retain fluid. Research shows that aldosterone also causes heart and blood vessel fibrosis, other blood vessel damage, blood pressure variations, and prevents the heart from properly using norepinephrine.
     We don't know why spironolactone lowered risk of death and hospitalization. It is not from the drug's diuretic effect or from its effect on potassium. The reduction in risk of death was the same in CHFers taking a beta-blocker and those who were not.
 
Source: Press release; to be released in the September 2, 1999 New England Journal Of Medicine

 Aldactone (spironolactone) - 2001

December, 2000 - Before spironolactone is started, patients taking ACE inhibitors should have their ACE inhibitor doses raised to target doses if possible. Target doses are: 150mg per day for captopril, 20mg per day for enalapril, and 20mg per day for lisinopril.
     Spironolactone should not be taken by patients with blood levels of creatinine over 2.5 mg/dL or with a history of high potassium (over 5 mEq/L). Patients should be aware of other "potassium-sparing" drugs they take. Such drugs can increase blood potassium levels. If the patient takes potassium pills, this should be re-evaluated by their doctor.
     Patients taking spironolactone and ACE inhibitors should have frequent blood potassium testing: at least once or twice a month when starting spironolactone or if the patient starts feeling worse. If the patient's blood potassium remains stable, it can be then checked less often.
     Adverse effects are relatively mild and rare except for gynecomastia - breast pain and even permanent breast swelling - which was much greater in men than women. Ten percent of men suffered this side effect.
 
Title: Spironolactone in the Management of Congestive Heart Failure
Author: Steven Kayser
Source: Prog Cardiovasc Nurs 15(4):145-148, 2000

 Aldactone Plus ACE Inhibitors Effective

January 22, 2001 - When given with ACE inhibitors after a heart attack, aldosterone inhibitors like Aldactone reduce collagen buildup. This drug combination may also reduce heart enlargement.
     Dr. Maria Modena studied 46 patients who had angioplasty after a first heart attack. When leaving the hospital, patients were randomly selected to take either an aldosterone inhibitor called potassium canrenoate, or placebo each day. All patients were also taking ACE inhibitors. (Jon's Note: potassium canrenoate is chemically similar to Aldactone. It is a by-product of Aldactone use in humans)
     At 3, 6, and 12 months of follow-up, collagen production was much higher in the placebo group. After 6 and 12 months, heart size was also reduced in the treated group. The team believes that extra collagen production is part of the heart's attempts to repair itself and that too much collagen caused by this "repair" process actually makes heart enlargement worse.
     These findings agree with the RALES results, said Dr. Gary Francis. "These drugs appear to be more than weak diuretics," he continues. "They may be potent anti-remodeling agents."
 
Source: Am Heart J 2001;141:1-2,41-46

 Pharmacists Needed For CHF Care

September 13, 1999 - The role of a pharmacist as part of the team treating CHFers has not been studied. Almost 200 heart failure patients with an EF less than 45% were randomized to a treatment group or a control group.
     Patients in the treatment group were evaluated by a clinical pharmacist, who gave drug suggestions to the doctor and provided patient education with follow-up monitoring by telephone. The control group got standard care. Primary end point was all-cause mortality plus heart failure events.
     Average follow-up was 6 months. All-cause mortality and heart failure events were significantly lower in the intervention group (4 events) compared to the control group (16 events). Patients in the intervention group received higher ACE inhibitor doses. Use of other vasodilators in patients who did not tolerate ACE inhibitors was higher in the intervention group (75% versus 26%).
 
Title: Reduction in heart failure events by the addition of a clinical pharmacist to the heart failure management team: results of the Pharmacist in Heart Failure Assessment Recommendation and Monitoring (PHARM) Study
Authors: Gattis WA, Hasselblad V, Whellan DJ, O'Connor CM
Source: Arch Intern Med 1999 Sep 13;159(16):1939-45
PMID: 10493325, UI: 99421068

 Tolvaptan Helps Hospitalized CHFers

June 3, 2003 - 254 patients were included in this trial. Sixty-three took placebo, 64 took 30mg tolvaptan, 64 took 45mg tolvaptan, and 63 took 60mg tolvaptan once daily for 25 days. Patients could drink as much fluid as they wanted and took consistent Lasix doses.
     At day one, body weight went down in all 3 tolvaptan groups but went up in placebo patients. This reduced body weight was maintained during the study, but no further reduction was seen after day one. Urine output also was greater in the tolvaptan patients at all doses. Edema went down and patients with low blood sodium levels had a return to normal levels in tolvaptan patients, but not in the placebo group. No changes in heart rate, blood pressure, blood potassium, or kidney function were seen.
 
Title: Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial.
Authors: Gheorghiade M, Niazi I, Ouyang J, Czerwiec F, Kambayashi J, Zampino M, Orlandi C; Tolvaptan Investigators.
Source: Circulation. 2003 Jun 3;107(21):2690-6. Epub 2003 May 12.
PMID: 12742979

All information on this site is opinion only. All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor. Use the reference information at the end of each article to search MedLine for more complete and accurate information. All original copyrights apply. No information on this page should be used by any person to affect their medical, legal, educational, social, or psychological treatment in any way. I am not a doctor. This web site and all its pages, graphics, and content copyright © 1997, 1998, 1999, 2000, 2001, 2002, 2003, 2004 Jon C.

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