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May 1, 1996 - Is human growth hormone a promising treatment for idiopathic DCM? Italian researchers used RHGH (recombinant human growth hormone) in 7 patients with idiopathic DCM. These patients, averaging 46 years old, had heart failure despite standard meds. They had enlarged hearts and ejection fractions less than 40%, but were in stable condition and normal heart rhythm. None had clogged arteries, heart valve problems, hypertrophic cardiomyopathy, high blood pressure, diabetes, or alcoholism.
Injected with 4 IU of growth hormone every other day for 3 months, patients improved in all aspects of their condition. Symptoms got better, exercise time increased, and quality of life improved. Heart size went down and ejection fraction went up. Most of the changes were reduced but still there 3 months after growth hormone was stopped.
This small, uncontrolled study shows remarkable benefits from growth hormone treatment of idiopathic DCM. However, the follow-up period was only 3 months. Further study is needed.
Title: A preliminary study of growth hormone in the treatment of dilated cardiomyopathy
Authors: Fazio S et al
Source: N Engl J Med 1996 Mar 28; 334:809-814
June 3, 1997 - IV immune globulin therapy in patients with newly diagnosed dilated cardiomyopathy may be effective. At the University of Pittsburgh, 10 adults waiting for heart transplant with acute DCM were treated with IV immune globulin. Nine of the 10 patients recovered and were discharged without needing a heart transplant.
Patients was hospitalized with class 3 to 4 heart failure and an ejection fraction less than 40%. All patients had CHF symptoms for less than 6 months when enrolled in the study. They were between the ages of 19 and 55 years.
Each was treated with high-dose (2g/kg) IV immune globulin. One patient died before therapy was completed. The other 9 recovered and were discharged. "All patients showed functional improvement and at one year follow-up were class 1 or 2. None has been rehospitalized for CHF," Dr. Dennis McNamara said.
In a similar group of 72 patients waiting at their hospital for heart transplant, and given standard meds, 25% improved enough to be removed from the transplant list. At one year follow-up, 31% of these 72 patients had received transplants or were dead.
Source: Circulation 1997;95:2476-2478
February 11, 1998 - Texas Biotechnology Inc, today announced positive results that ended a phase 2 heart failure trial testing TBC11251, an ETA-blocker (endothelin-A blocker). In patients with moderate to severe heart failure, ETA-blocker patients showed improvement versus placebo in heart function and blood flow, especially pulmonary artery pressure.
This double blind, randomized, placebo-controlled trial was done with class 3 to 4 heart failure patients, using a single intravenous dose. The trial was stopped early due to its success in 24 patients. This allows the company to proceed with trials using different doses.
"This trial is the first evidence of effectiveness for an ETA-selective compound in heart failure," said Dr. Wilson S. Colucci. He added, "These results are exciting because blocking endothelin has the potential to relieve pressure on the right heart, which would be complementary to ACE inhibitors. If these early results with TBC11251 can be confirmed in larger trials, it could represent a real advance for heart failure patients." Raised endothelin levels are seen in severe heart failure.
Title: Texas Biotechnology Reports Positive Phase IIa Trial Results of Endothelin Receptor Antagonist in CHF
Source: Texas Biotechnology Corporation
2001 - In a trial of patients with moderate heart failure who were followed for up to 9 months, adding an ET blocker to standard CHF meds did not help. ENCOR trial results were given at the ACC Conference in March, 2001. Researchers say that although non-selective ET blockers don't help, perhaps a selective ET blocker might. The ENABLE trial also showed higher risk of death with bosentan, a non-selective endothelin blocker.
Endothelin is one of the body's natural vasoconstrictors. Endothelin levels are high in CHFers. Patients with severe CHF have the highest levels. Endothelin has its effect when it hooks up to 2 types of receptors - ETa and ETb. Enrasentan is a pill that blocks both ETa and ETb receptors. The ENCOR trial compared enrasentan to placebo in heart failure patients.
Patients in the trial were class 2 to 3, had an average EF of 25%, and were already taking standard CHF meds. This was a double-blind, randomized, 6-group, placebo-controlled trial.
419 patients took either placebo, high-dose ACE inhibitor, or were in one of 4 groups taking enrasentan. Dose was raised to target dose at different speeds. Treatment was for 9 months. The trial's main endpoint was whether CHF was "unchanged," "improved," or "worse."
There was no improvement seen with enrasentan versus placebo. In fact, when enrasentan-treated groups as a whole were considered, more patients in the placebo group improved than enrasentan patients, while fewer placebo patients got worse.
Hospitalizations and withdrawals from the drug due to worsening heart failure were higher in the enrasentan group. There was also higher mortality in the enrasentan group. Time to death, hospitalization for heart failure, or withdrawal due to worsening heart failure was worse in the 4 enrasentan groups combined.
Adverse events were also more common in the enrasentan group. Heart failure was 28% versus 17% in the placebo group, SOB was 23% versus 19% in the placebo group, and anemia was 16% versus 5% in the placebo group.
Title: Effects of Enrasentan, a Nonselective Endothelin Receptor Antagonist in Class II-III Heart Failure: Results of the ENCOR Trial
Presenter: William T. Abraham, MD
November 11, 1999 - - A study is out on a new drug called omapatrilat. This is one of a new class of drugs called vasopeptidase inhibitors. The study suggests that omapatrilat may reduce deaths and hospitalizations from heart failure by almost 30%, says Dr. Jean-Lucien Rouleau.
The new drug works in two ways. Like ACE inhibitors, it blocks angiotensin. Omapatrilat also neutralizes a substance called neutral endopeptidase, causing blood vessels to relax. "Omapatrilat is the first drug in this class and it may work better than ACE inhibitors," says Rouleau.
In the study, 289 patients took 40mg of omapatrilat daily and 284 patients took 20mg of the ACE inhibitor lisinopril for 24 weeks. The patients' average age was 64 years and 79% were male. All had mild to moderate CHF.
After 12 weeks, the patients' treadmill tests improved in both groups. Heart function also improved. Side effects included diarrhea and mild dizziness. Improvement was seen in death rate and hospitalization for worsening heart failure.
Only 16 patients in the omapatrilat group experienced any adverse events versus 29 in the lisinopril group. A new study of omapatrilat called OVERTURE has already started. It will enroll 4,420 patients.
Jon's note from April of 2002: This drug is off the table for now. It caused angioedema and its safety is now being questioned.
Source: The AHA 1999 Scientific Sessions
August 18, 2000 - Omapatrilat (Vanlev) is a new ACE-and-vasopeptidase inhibitor, sort of a super-ACE inhibitor. It was compared to lisinopril in heart failure patients. However, in April, Bristol-Myers Squibb temporarily withdrew its new drug application from the FDA because of a higher than expected rate of angioedema.
Dr. Jean Rouleau studied 573 patients with class 2 to class 4 heart failure. Researchers randomly assigned 289 patients to take 40mg omapatrilat daily and 284 patients to take 20mg lisinopril daily for 24 weeks. (Jon's Note: Why one drug's dose was twice as high as the other's is unexplained in the article) At 12 weeks, both groups did a treadmill exercise test.
Both drugs improved treadmill test results about the same. Both were "fairly well tolerated." There were serious heart-related events in 7% of omapatrilat patients and in 12% of lisinopril patients. Omapatrilat was slightly better at reducing death and hospitalization for heart failure. Omapatrilat improved heart class more than lisinopril in class 3 patients, but not in class 2 patients.
Diarrhea, nausea, and vomiting were twice as common in the omapatrilat group. Doctors Messerli and Nussberger suggest that some of these patients may have had gastrointestinal swelling. They continue, "Omapatrilat carries a higher risk of life-threatening angioedema than ACE inhibitors do."
Source: Lancet 2000;356:615-620,608-609
October 6, 1999 - The FDA has approved Pfizer's dofetilide (Tikosyn) for maintaining and converting to normal heart rhythm in a-fib and atrial flutter patients. Dofetilide is a selective potassium channel blocker.
More than 8500 patients participated in trials, in which the drug maintained patients in normal heart rhythm for more than a year, and also successfully converted patients back to normal rhythm. Dofetilide did not increase mortality in 1500 severely ill patients recently studied. However, it can cause dangerous arrhythmias.
March 17, 2000 - Jon's Note : Baycol has been taken off the market due to high risk for serious muscle problems called myopathy/rhabdomyolysis. See www.fda.gov/medwatch/safety/2001/Baycol2.htm.
The cholesterol-lowering drug cerivastatin (Lipobay/Baycol) improves endothelial dysfunction after 2 weeks of therapy. People with average LDL levels of 197 mg/dL were randomly assigned to take either 0.4mg cerivastatin a day or placebo. Blood flow in the forearm was used to measure endothelial function.
Two weeks of cerivastatin use in patients with high cholesterol improved vasodilation, resulting in a 200% increase in blood flow. Placebo-treated patients showed no change. Average LDL levels went down 33% in the cerivastatin group compared to no change in the placebo group.
Source: ACC 2000 Scientific Sessions, Reuters Health
February 28, 2000 - Moxonidine reduces nervous system activity in CHFers, perhaps by inhibiting certain cell receptors. in the central nervous system. Dr. Karl Swedberg randomized 97 patients with symptomatic CHF to either placebo or moxonidine at 0.1mg, 0.2mg or 0.3mg twice a day. All patients on moxonidine started on 0.1mg twice a day, and the dose was gradually increased. All patients were class 2 or 3 and had an EF less than 40%.
Moxonidine significantly reduced systolic blood pressure (the first blood pressure number) in this 12-week study. Patients' heart rates were went down at 12 weeks. Nervous system activity was reduced, based on changes in blood levels of norepinephrine. The link between moxonidine dose and norepinephrine level was significant at both 4 and 12 weeks.
Low blood pressure symptoms during the trial were managed by just lowering dose. There were no big differences between the 4 groups in adverse events. While the findings are encouraging, the actual benefit of targeting norepinephrine levels needs more study.
Source: J Am Coll Cardiol 2000;35:398-404
|The MOXCON trial showed increased mortality with moxonidine use in heart failure patients, so further study is unlikely.|
October 12, 1999 - Etomoxir has been through Phase 1 and Phase 2 trials with 200 volunteers and diabetes patients. The drug - originally designed for diabetes - showed favourable effects on the heart. A MediGene phase one study in heart failure patients showed promising results.
Etomoxir inhibits CPT1, an enzyme involved in cell fatty acid oxidation. Inhibiting CPT1 causes a shift from fatty acid oxidation to glucose oxidation, a more efficient supplier of energy in a diseased heart. Researchers say, "Our results suggest that oxidation of fatty acids is greatly increased in CHF patients. We think this drug will tackle that deregulation of heart metabolism."
|June 14, 2002 - MediGene stopped developing etomoxir for heart failure. Their last phase 2 trials did not give promising results.|
December 20, 1999 - NEP (neutral endopeptidase) inhibitors block the metabolism of atrial natriuretic factor. This type of drug may benefit heart failure patients, but studies got different results. The first study suggests that ecadotril does not give benefit. The second study suggests that candoxatril does have potential for treating CHF.
In the first trial, Dr. Christopher O'Connor added ecadotril to standard CHF meds. Researchers randomly assigned 31 patients to rising doses of 50 to 400mg ecadotril twice a day, and 19 patients to placebo. No consistent changes in neurohormone levels were seen after 10 weeks of treatment. They also report that there were "no substantial improvements with ecadotril treatment."
In the second trial, Dr. David Northridge compared candoxatril to Lasix (furosemide) in patients with mild chronic heart failure. The team randomized patients to twice-a-day therapy for 9 days with 20mg Lasix, 200mg candoxatril or 400mg candoxatril.
The authors report that candoxatril treatment "caused a slight decline in systolic blood pressure and an increase in blood and urine levels of atrial natriuretic factor." So the drug was inhibiting the body's ANP. They also found that - unlike Lasix - candoxatril had no effect on the RAS (Jon's note: RAS is what ACE inhibitors inhibit - Lasix irritates it.)
Exercise capacity was reduced by 30 seconds in the Lasix group but increased by 12 seconds in the 200mg candoxatril group and increased by 35 seconds in the 400mg candoxatril group. Researchers conclude that, "candoxatril has diuretic effects equal to 20mg Lasix twice a day without Lasix' possibly harmful activation of the RAS."
Source: Am Heart J 1999;138:1007-1008,1140-1157
March 22, 2001 - Studies of Enbrel (a TNF blocker) for heart failure stopped early. An independent monitoring board has decided that ongoing trials of Enbrel (etanercept) for chronic CHF will not meet goals.
The phase 2 Enbrel trial was actually 2 trials: RENAISSANCE in North America and RECOVER in Europe. The primary endpoint of the studies was improvement in heart class; and hospitalization for heart failure and death; and combined complications and mortality.
Source: Immunex Corporation - www.immunex.com/investor/pressreleases/pr010322c.html
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.