Heartbytes New CHF Drugs IV Drugs Coreg & beta-blockers Surgeries ICDs & More Archived articles here Updated

May 22, 2005

Ace Inhibitors benazepril - Lotensin by Novartis captopril - Capoten by Bristol-Myers Squibb enalapril - Vasotec by Merck fosinopril - Monopril by Bristol-Myers Squibb imidapril - Not approved for human use in the USA - approved in Japan lisinopril - Prinivil by Merck or Zestril by Astra-Zeneca moexipril - Univasc by Schwarz Pharma quinapril - Accupril by Pfizer perindopril erbumine - Aceon by Rhone-Polenc Rorer ramipril - Altace by Hoechst Marion Roussel, King Pharmaceuticals trandolapril - Mavik by Knoll Pharmaceutical (BASF) ARBS - Angiotension II Receptor Blockers candesartan cilexetil - Atacand by Astra Merck eprosartan - Teveten irbesartan - Avapro by Sanofi losartan - Cozaar by Merck olmesartan medoxomil - Benicar by Sankyo Pharma telmisartan - Micardis valsartan - Diovan by Novartis

Angiotensin II - The Problem
We are talking about the chemical messengers in the body called neurohormones. For those of us with heart failure, the neurohormone called angiotensin II is not a good thing. Angiotensin II helps controls the cardiovascular system. It causes blood vessels to shrink (vasoconstriction), which raises blood pressure. Angiotensin II also causes the body to release aldosterone - a substance that causes our kidneys to retain sodium and fluid, causing edema. Angiotensin II also causes the body to release a substance called vasopressin or ADH, which causes us to retain fluid even more. Angiotensin II is a real bug-a-boo for us CHFers.

ACE Inhibitors - Why They Work
We all have angiotensin one in our systems. Angiotensin one is converted into angiotensin II by an enzyme in your body called ACE (Angiotensin Converting Enzyme). ACE is what we block with ACE inhibitors - blocking it prevents angiotensin I from converting into angiotensin II. Reducing angiotensin II lets our blood vessels relax and expand. This lowers blood pressure, which makes the heart's job a lot easier. Think of it this way: If you pump the same amount of water at the same speed through a little pipe as through a big pipe, there's higher pressure in the small one. The fluid shoots out of the small pipe, but calmly flows out of the big one, even though they are both moving the same amount of water. The pump pushing the water through that skinny pipe has to work a lot harder than the pump glushing it through the big pipe. The same principle applies to our blood vessels. If our arteries relax, they get bigger (vasodilation) and the pump has an easier job - less pressure. That's called reducing "afterload." ACE inhibitors do this for us. "Super" ACE inhibitors called vasopeptidase inhibitors were also tested for CHF but carry higher risk for side effects. ACE also helps control the amount of blood in your body - your blood "volume." Blocking ACE reduces the overall amount of blood in your body. This means your tired old heart has less blood to pump, which makes its job easier. ACE inhibitors increase the level of potassium in your blood, so they partly offset potassium loss caused by diuretics like Lasix and Demadex. Finally, ACE inhibitors help us live longer and feel better. The articles below show that ACE inhibitors reduce our risk of death by 20% to 40%. The other two types of drugs that do this are beta-blockers and Aldactone (spironolactone). ACE inhibitors slow heart remodeling, preventing our hearts from getting even weaker over time. It can take several months for the full effect of ACE inhibitors to show up, and improve our quality of life. Hang in there, because ACE inhibitors do work and all CHFers should be on them if possible. It's even in the official heart failure treatment guidelines. Unfortunately, many doctors don't offer us ACE inhibitors if we have any kidney problems or if our blood pressure is low. This is unwise - see this article. Monopril (fosinopril) is processed by the liver as well as the kidneys, so CHFers with kidney problems can usually take it okay. People with low blood pressure, surprisingly enough, often tolerate ACE inhibitors quite well (although not always).

it can't affect us. only 55% left the hospital with ACE inhibitors.ACE Inhibitors ACE Inhibitors Should Be Standard Treatment For CHF Aspirin. ACE Inhibitors. If angiotensin II can't connect to cell receptors.which can happen. In Conclusion..Telmisartan can significantly raise blood digoxin levels. but not in those taking all 3 drugs. 2004 .. So ACE inhibitors can't completely stop angiotensin II from affecting you. Note . an ARB will often do the job. only about one in eight filled a prescription within 30 . it seems like a good idea to block the stuff at other places too.especially on captopril. ACE inhibitor use may reduce your zinc level so you might want to take a zinc supplement.And Keep Taking . Of this group. The most important receptor is called the AT-1 receptor (there is also an AT-2 receptor)." a good CHF specialist will keep you on an ACE inhibitor for life. Eighty-one percent of these patients filled an ACE inhibitor prescription within 30 days. In patients who did not receive ACE inhibitors when leaving the hospital. Double-check your doc on this to be sure you are getting a high enough dose! Even if you improve to normal heart function and consider yourself "cured. More CHFers need to leave the hospital already on ACE inhibitors and also need more help refilling their prescriptions once they get home.. The question is: Do ARBs help CHFers already taking an ACE inhibitor? This has not been completely decided yet. Only 67% of patients with reduced EF were sent home with ACE inhibitors.Many CHFers either do not start taking ACE inhibitors or stop taking them just one month after they go home from the hospital. and Mortality ACE Inhibitors Slow Heart Damage Caused By CHF High Dose Better For CHF High Doses Better Once Again Higher Doses Well Tolerated In CHF Patients Losartan Eases ACE Inhibitor Cough ELITE 2 . Since ACE inhibitors can't do it all. Federal and state records allowed researchers to collect clinical information and track prescription drug purchases. Among all CHFers (including those with normal EF). Over time.Diabetic Results ARBs Slow Worsening Of Diabetic Nephropathy ACE Inhibitors & ARBs Reduce Death And Complications In CHFers ACE Inhibitors For CHFers With Low Blood Pressure Works Fine ACE Inhibitors Improve Artery "Stretchability" in CHF Patients Stomach Pain Side Effect Must Be Considered In ACE Inhibitor Patients NSAIDs (Indomethacin) & ACE Inhibitors Don't Mix NSAIDs Interfere With ACE Inhibitors Valsartan Better than Coreg Regarding Sexual Ability In Men ACE Inhibitors Help Patients With Extra Problems Even More ACE Inhibitors Help Prevent CHF In High-Risk Patients The CHARM trials for ARBs In Heart Failure ARB Plus ACE Inhibitor FDA-Approved For Heart Failure NEW CHFers Need To Keep Taking ACE Inhibitors June 2. your angiotensin II level rises again. ACE Inhibitor & ARB Links Med Line Plus On ACE Inhibitors Post Grad Med On ARBs Ace Inhibitors For Chronic CHF This Page More CHFers Need To Take . ARBs block angiotensin II receptors on cell walls.ARBs Angiotensin II Receptor Blockers Angiotensin II is also made at other places in the body. All were enrolled in both the Medicare and the Tennessee Medicaid program when they entered the hospital. from these other places in the body. ARBs do have some excellent uses we are sure about. High doses are better than low doses but doctors don't usually prescribe them . It may stop you from getting CHF again down the road . Why taking all 3 drugs gave worse results is unknown.due to simple ignorance. After a year. In patients who don't tolerate an ACE inhibitor for some other reason. In patients who develop a bad cough from using an ACE inhibitor. The RESOLVD study compared an ARB alone to using an ACE inhibitor alone to using both an ACE inhibitor and an ARB. 77% filled a prescription within 30 days and only 63% were still filling prescriptions a year later. there is a period where angiotensin II is almost completely stopped. Data was studied on 219 CHFers with reduced EF and 960 heart failure patients in general. and that's smart.Losartan Versus Captopril In Elderly Losartan Improves Heart Size Blood Levels Of Angiotensin II Point To Prognosis HOPE Trial Results HOPE Trial . Complications and mortality improved most in CHFers taking the ARB with either an ACE inhibitor or a beta-blocker. Your sense of taste could possibly go goofy on you after starting an starting ACE inhibitor too . After starting an ACE inhibitor. an ARB can often be used without the cough. Using both worked better to improve heart enlargement and EF. The ValHeft trial added an ARB to standard CHF therapy. ARBs do help CHF. only 66% of these patients were still filling their prescriptions.

Reicher-Reiss H. Source: June 2. In the CHF patients. Of these patients. Limacher M. ACE Inhibitors Should Be Standard Therapy November 3. Authors: Javed Butler.5 to 35mg per day during the trial.100 patients with class 2 to class 4 CHF and an EF of 30% or less. Researchers studied how many patients stopped treatment (seeing if they tolerated the drug) within a year of starting it for the first time.days. and Mortality 1999 . and other drugs being taken such as beta-blockers. 1999 . compared with doses of 325 to 350mg in other trials .487 patients taking enalapril (Vasotec) at the start of a medical trial. Quinones MA. The data suggest that use of low-dose aspirin (250mg or less) with ACE inhibitors is safe and may benefit CAD patients. 2004. Mason's group concludes that "doctors' perceptions of the risks of ACE inhibitors for CHF patients are exaggerated. The enalapril group had a lot less progressive damage to their hearts than the placebo group. They also measured the cost of treatment.Dr. Patrick Arbogast." High dose patients did have more side effects such as dizziness. Koilpillai C. "that patients taking high doses did not see any more improvement in heart class than those who took low doses. there was no difference in the rate of side effects leading to dose reduction or withdrawal between the ACE inhibitor and placebo groups. The 301 patients in our study had echos and were then given either enalapril or placebo.aspirin safety and effectiveness may depend on taking a lower dose. high potassium levels and kidney problems. A relatively low aspirin dose of 250mg was used in the study. but rather "lack of resources and expertise. Heart size increased in placebo patients and decreased in enalapril-treated patients.321:1113-1116." said researchers. Patients took either low or high doses of lisinopril for up to 5 years. Marie Griffin. These findings contradict a theory that aspirin might reduce ACE inhibitor benefit in heart failure patients.5 to 5mg per day and high lisinopril doses of 32. Dr. only 8% of patients reported side effects.Chronic heart failure patients should be kept on high doses of ACE inhibitors instead of low doses. They compared 579 patients taking ACE inhibitors only (the control group) to 618 patients taking both ACE inhibitors and aspirin. After a 5 year follow-up. 1999." In an editorial. Title: Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Milton Packer studied more than 3. This study shows that enalapril slows progressive heart enlargement in CHF patients. 2% of those patients stopped taking the drug because of their side effects. Mason's group notes that the costs of identifying and treating these patients is small "and do not affect the costeffectiveness of ACE inhibitors for CHF. They had echos again after 4 and 12 months of therapy. During the test dose part of the trial.569 had CHF.The SOLVD trial showed that enalapril (Vasotec) greatly improves quality of life for patients with left ventricular dysfunction." Source: BMJ 2000. the authors found that mortality was higher in patients taking only ACE inhibitors (27%) than in patients taking both ACE inhibitors and aspirin (19%). James Daugherty. heart class . low blood pressure." Based on these findings. Title: Outpatient utilization of angiotensin-converting enzyme inhibitors among heart failure patients after hospital discharge. John Cleland says that fear of side effects is not what prevents doctors from effectively treating CHF patients. Dr.1095-1096 Aspirin. "It is noteworthy.91(10):2504-7 PMID: 7743619. 2. 2000 .575 CAD patients who were screened for a heart attack prevention trial. mortality was lower in the 221 taking both aspirin and ACE inhibitor (24%) than among 243 taking only an ACE inhibitor (35%). Risk of death remained lower in aspirin users after adjusting for factors such as age. The protective effect of aspirin when used with ACE inhibitors was even more pronounced in patients with congestive heart failure. Volume 43. Shindler D.33:1920-1925 Ace Inhibitors Slow Heart Remodeling May. However. . 1995 . digoxin and diuretics. Patients with moderate to severe CHF had 12% lower risk of death or hospitalization for any reason.. Results of the SOLVD echocardiography substudy. Wayne Ray. Issue 11 Pages 2036-2043. This lack of difference suggests that changes in symptoms cannot be used as a guide in selecting ACE inhibitor dose. Greenberg B. et al Source: J Am Coll Cardiol. Dr. "Overall. Dr.Taking aspirin may improve survival in patients with CAD (coronary artery disease) who are also taking ACE inhibitors especially in CHF patients. James Mason collected data on 7. diabetes. Goldbourt U. Title: Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors: a cohort study of 11. because a higher dose may reduce risk of death and hospitalization even if there is no improvement in symptoms. In this sub-study we examined changes in heart structure and heart function in SOLVD patients to see if enalapril slowed remodeling.575 patients with coronary artery disease Authors: Leor J. Manoj Jain. Shelton B Source: Circulation 1995 May 15.91(10):2573-2581 Comment in: Circulation 1995 May 15. The study used low lisinopril doses of 2. coughing occurred less often in the high-dose group. if placed on a high dose of ACE inhibitor compared to a low dose. sex." the authors write. Benedict C. Researchers studied mortality data on 11. with or without CHF. ACE Inhibitors. UI: 95262234 High Dose Better For CHF November 15. high blood pressure.

Losartan (an ARB) is a good alternative to ACE inhibitors for heart failure patients. The dose of enalapril (Vasotec) at study start was either 5mg BID (16 patients).5 to 15mg daily for 2 to 4 weeks. ATLAS included 3. patients were mostly men with an average age of 72 years. In ELITE. At 48 weeks. Heart failure patients benefit from higher doses of ACE inhibitors. MD. Per Omvik studied the long-term effects of losartan in 28 patients with high blood pressure. Maly. Title: ELITE II . irritating cough from ACE inhibitor use. F. 1999 Higher Doses Well Tolerated January 22. Candinas. At study start. exercise capacity was poor and neurohormone levels were high. ELITE 2 was done to study this. Some groups are thought to be at higher risk for side effects from high-dose ACE inhibitor use. Patients took 50mg to 100mg . All patients were stabilized at 12. There were no changes in heart class. Kiowski. About the same number of patients withdrew from each group (high-dose and lowdose) due to side effects. One group took a low dose of 2. Captopril was started at 6. heart-related death.5 to 5mg daily while the other group took a high dose of 32. In both groups. angiotensin II receptors in the body may become more sensitive. Title: Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study. heart failure deaths. all-cause hospitalizations. Higher ACE inhibitor dose improves daily functioning and lowers blood levels of harmful hormones in CHF patients. Follath Source: Am Heart J 138(4):654-662. W.Evaluation of Losartan in The Elderly Study.Long-term losartan use reduces blood pressure and may improve heart function. and heart attack . sudden cardiac death. No differences were seen in all-cause mortality. shortness of breath when lying down. High dose ACE inhibitor improves not only CHF symptoms and exercise ability. hospitalization for CHF. Brunner-La Rocca. 1997 . including people with low blood pressure. About 25% in each group were taking a beta-blocker and 50% were on digoxin (Lanoxin). Average EF was 31% in both groups. These groups were closely watched.5 to 35mg daily. but also reduces chemicals that worsen CHF. R.About 10% of heart failure patients develop a chronic.The original ELITE trial showed 46% reduction in all-cause death and 64% reduction in SCD with losartan compared to captopril. There were 3. 10mg BID (18 patients).The ATLAS study showed that higher doses of Prinivil/Zestril are better than lower doses for reducing death and hospitalizations in CHFers.either fatal or nonfatal. poor kidney function.578 took 50mg losartan per day. E. Massie's group. Losartan was started at 12. so they not cause as much coughing. Vo2max increased when patients were on the highest dose . or stroke between the groups. Eighty percent had ischemic CHF.We studied 45 patients (43 men and 2 women) aged 33 to 74 years with an average EF of 28%. or edema. especially in patients who get a bad cough on ACE inhibitors.5mg and increased to 50mg per day. heart attack. 2000 . Lancet 1997 Mar 15. ELITE II did not confirm ELITE's finding that losartan is better than captopril for improving survival. resuscitated cardiac arrest. who had never taken ACE inhibitors. However. Secondary endpoints were SCD. took either the ARB Cozaar (losartan) or the ACE inhibitor Capoten (captopril). MD and Betram Pitt. then they were split into 2 groups.25mg and increased to 50mg TID. The event rate was 16% in the captopril group and 18% in the losartan group." says Dr.a good thing. These results "provide a clear message that higher ACE inhibitor doses can and should be used in most patients. Dr. patients had more CHF symptoms on low doses (10mg) than when taking higher doses. Patients had less CHF symptoms on the highest dose. The lower death rate of people taking losartan in this trial was unexpected and is unexplained. Source: Arch Intern Med 2001:161:165-171 Losartan Eases Ace Cough March 15. Cases of worsening kidney function or high potassium level were few. so lowering blood levels of it is important. Poole-Wilson. 349:747-752 Source: Journal Watch: Cardiology 28 April 1997 ELITE 2 Results December 20. This is also the first large trial studying whether low blood pressure and kidney problems happen more often on high doses. Episodes of low blood pressure happened only 5% more often in the high-dose group. All patients were treated for 4 weeks with each different dose. Three hundred and fifty-two patients took losartan and 370 took captopril.100:rt1-rt7 Higher Doses Better 1999 . ELITE) Author: Pitt B et al. ARBs block receptors for angiotensin II rather than ACE formation. ELITE 2's primary endpoint was all-cause mortality.152 patients in the trial and 1.Source: Circulation 1999. Weilenmann. Title: Within-Patient Comparison of Effects of Different Dosages of Enalapril on Functional Capacity and Neurohormone Levels in Patients With Chronic Heart Failure Authors: H. During long-term therapy. 2001 . or hospitalizations.574 took 50mg captopril 3 times a day while 1. D.164 class 2 to class 4 CHFers with ejection fractions of 30% or less. Neurohormone levels were 25% higher when patients were on the low dose. Cough occurred in 4% of captopril patients and none of the losartan patients. 1999 . Twelve percent of losartan patients versus 21% of captopril patients stopped treatment because of side effects. age of 70 years or older. Serious adverse events happened more often on lower doses. 722 patients over age 65 with class 2 to class 4 CHF. Angiotensin II causes great harm in CHF patients over time. fewer losartan patients died (5% versus 9%) and had fewer hospitalizations. Losartan Lowers BP & Improves Heart Size October 23. Losartan also reduces left ventricular size in patients with enlarged hearts. or diabetes. No difference was seen in SCD. or 20mg BID (11 patients). The Losartan Heart Failure Survival Study Presented by: Philip A.

high blood pressure.21:14-16.513 type 2 diabetic patients. 2000 . using an ARB can reduce worsening of kidney function by 70%. Levels in the remaining patients stayed in a normal range. Cardiac index and heart rate remained unchanged. The authors think that adding ARBs to ACE inhibitor therapy may benefit such patients. and regardless of current treatment for high blood sugar. and risk of heart attack were all reduced in the Ramipril group. 9% of placebo patients suffered heart-related events compared to 5% in the 300mg irbesartan group. Dr.6% to 6. High levels are linked to death or worsening heart failure.The ACE inhibitor ramipril definitely lowers risk of heart-related events and kidney disease in diabetic patients. plus another risk factor for heart disease. CHFers may have high angiotensin II levels. The RENAAL trial compared 50mg or 100mg losartan per day and placebo in 1. Barry Brenner in Boston. . Roig says. a 17% reduction in need for procedures like bypass or angioplasty. ANP. With 2-1/2 years average follow-up. and from 193/104mm Hg to 179/96mm Hg during exercise. Edmund Lewis in Chicago studied 1." Total peripheral resistance was reduced 12 to 15%. The patients were taking either 20mg or more enalapril per day. In the IRMA 2 trial. None had a low ejection fraction or heart failure. Death rates from any cause were 10% in the ramipril group and 12% in the placebo group. "Ramipril's benefit was seen regardless of whether patients had a history of heart-related events. Parving said he would start all type 2 diabetics with high blood pressure on irbesartan anyway. norepinephrine. Angiotensin II levels increased in half the patients. or placebo. There was a 32% reduction in the development of new heart failure. Lewis . stroke by 33% and heart-related death by 37% (relative risk). because these patients have a 10 to 25% higher risk of developing kidney dysfunction. or heart-related death was 25% lower in the ramipril diabetic group than in the placebo diabetic group. Ramipril reduced rates of death from heart-related causes . or 150mg captopril or more per day. Patients took 10mg of ramipril or a placebo daily.253-259 ARBs Slow Diabetic Nephropathy May 21. and a 24% reduction in nephropathy (common in diabetics) [relative risk]. Vitamin E supplements did not change risk of adverse heart-related outcomes. All had type 2 diabetes and established kidney disease. In the IDNT trial. Lewis said." Dr. or stroke. whether or not they had type one or type two diabetes. Dr. There was a 27% reduction in left ventricular size in 18 patients with enlarged hearts. "This study showed for the first time that chronic high blood levels of angiotensin II are linked to higher mortality and complications. Six hundred and fifty-one patients took 10mg ramipril once per day and the rest took placebo in the 4-1/2 year trial. Source: Eur Heart J 2000. Source: Am Heart J 2000. Also. Parving in Denmark studied 590 patients from 30 to 70 years of age who had microalbuminuria. "intra-arterial pressure was reduced from 165/102mm Hg to 145/91mm Hg at rest. None of the patients had a low ejection fraction or heart failure. Eulalia Roig measured blood levels of aldosterone. Most patients taking losartan needed to also take another drug to bring their blood pressure under 140/90 mmHg. angiotensin II. The IRMA 2. Ramipril also lowered risk of heart attack by 22%. stroke." Dr. to protect against kidney disease.only 33% as often as the placebo group and only 37% as often as the amlodipine group. compared to 10% in the 150mg irbesartan group and 5% in the 300mg irbesartan group. 2000 .577 diabetic patients aged 65 years and older. need for procedures like bypass or angioplasty. Losartan also reduced the risk of endstage kidney disease or death by 20%. Follow-up visits were at one month and then every 6 months. "Irbesartan protects the kidneys in these patients.". Brenner said. The HOPE study treated 3. IDNT and RENAAL trials combine to show that regardless of blood pressure reduction. along with 400 IU of vitamin E or placebo. or placebo. Risk of stroke. Parving said.355:246-247. Losartan reduced progression of kidney disease to end-stage kidney failure by 28%.losartan per day for 8 months. Combined outcome of heart attack. "Losartan should be a first-line drug for treating high blood pressure patients with type 2 diabetes. said Dr. 15% of placebo patients progressed to diabetic nephropathy. Patients took either 10mg ramipril or placebo once daily in the evening and 400 IU vitamin E or placebo daily.715 men and women with high blood pressure from 30 to 70 years of age. who had heart disease. peripheral vascular disease. Source: N Engl J Med 2000.140:624-630 Blood ACE Levels Predictor February 7. said Dr. At follow-up. kidney disease did not progress nearly as far in the irbesartan group. "Irbesartan should be given as soon as you detect microalbuminuria. and TNF in 70 CHFers after 6 months of ACE inhibitor use.342:145-153.Even while taking ACE inhibitors." Dr.6% in Ramipril group versus 8% in placebo group. Dr. All patients had established kidney disease and 94% had high blood pressure. Salim Yusuf studied 9. During 2 years of follow-up. Patients took either irbesartan. 2001 . the calcium channel blocker amlodipine.despite ACE inhibitor therapy .4%.201-202 HOPE Trial: Diabetic Subgroup January 22. During exercise.53-57 HOPE Trial Results January 20. and a 28% reduction in heart attack. 2000 . and were followed for 4-1/2 years. Increased angiotensin II meant higher risk for death or heart failure. or diabetes.Dr. Heart attack rates were 10% in the ramipril group and 12% in the placebo group. Dr. Patients took either 150mg or 300mg irbesartan per day.297 high-risk patients age 55 or older who had a history of coronary artery disease." the investigators say. "This may explain why . stroke. Ramipril reduced diabetic complications from 7. Blood pressure measured over 24 hours with patients moving around freely went down 10% to 13%.Results from 3 clinical trials now show that the ARBs irbesartan (Avapro) and losartan (Cozaar) slow diabetic kidney failure (nephropathy) in patients with type 2 diabetes.many CHFers still have symptoms and poor outcomes. Ramipril patients also showed a 24% reduction in overall risk of death." Dr.. Source: Lancet 2000. heart output increased 7% to 9% but was unchanged at rest.

"We believe that ACE inhibitors should be the main treatment for heart failure. artery diameters remained the same in all 3 groups. He stopped her Prinivil and her symptoms disappeared. group A continued standard treatment. The second case was a 41 year old woman who came to the emergency room with cramp-like stomach pain.Taking indomethacin and either captopril or losartan greatly reduces the heart drug's effectiveness. During surgery." Source: Reuters Health Artery Flexibility Better With ACE Inhibitor August 25. mostly involving women. with systolic blood pressures ranging from 60 to 100 mmHg. Giannattasio gave results from a study of 30 CHF patients.Heart failure patients with low blood pressure can benefit from ACE inhibitor use. researchers measured the diameter and stretchability of the radial artery (in the arm). nausea. Failure to consider this condition may lead to unnecessary surgery. which completely stopped her symptoms and led to normal bowel tests. Her gallbladder had also been removed a month earlier for similar symptoms. stretchability "significantly" increased in groups B and C.355:1568-1569. The patients either took 50mg losartan once a day or 25mg captopril twice a day." Dr.152 elderly CHF patients." In a second report. according to a report at a meeting of the International Society of Hypertension. group B took a high-dose ACE inhibitor. ACE inhibitor patients were hospitalized less for heart failure (14%) than placebo patients (19%). At study start. Source: Reuters Health ACE Inhibitor Side Effect Under-diagnosed November 28. Douglas found an inflamed. with better heart class . researchers measured the change in average 24 hour diastolic blood pressure. but low blood pressure symptoms actually got better. Dr. . Dr. All patients saw symptoms improve. sudden death rates. Stretchability (distensibility) was also unchanged in all 3 arteries in group A. The first was a 67 year old woman who came to the emergency room with severe stomach pain. Fewer patients taking losartan stopped treatment because of cough. 98mm Hg at optimum dose.Source: Reuters Health and The 16th annual meeting of the American Society of Hypertension ACE Inhibitors Reduce Complications & Mortality May 8. After 6 weeks. 45% in the carotid artery and 33% in the aortic artery. David Douglas said that a CT scan showed a swollen and thickened small bowel and ascites. Bertram Pitt compared the effects of the ARB losartan to the ACE inhibitor captopril in 3. 2000 . placebo-controlled ACE inhibitor trials in patients with reduced left ventricular function. the difference was even bigger (23% versus 29% in placebo patients). Akosah said. and they had fewer repeat heart attacks (9% versus 11%). patients showed a 99% improvement in radial artery flexibility. Low blood pressure patients have been kept out of ACE inhibitor trials for CHF. The patients were divided into 3 groups. In the first report. At 4 weeks.A report of 2 patients who suffered swelling of internal organs after taking ACE inhibitors suggests that this complication may be an under-recognized cause of stomach pain. A stomach CT scan showed thickening of the small bowel and ascites. Her gallbladder had been removed trying to fix the pain.1575-1587. which was increased to 50mg twice a day after one week. In these patients and in 30 control patients." Source: Lancet 2000. After 8 weeks of treatment. In group B. 65% in the carotid artery and 90% in the aortic artery." "We studied ACE inhibitor use in CHF patients who were denied this medication based just on the complexity of their illness. and group C continued standard therapy with an ARB added. swollen small intestine. 83% of the 18 low BP patients were tolerating 20mg of lisinopril or equivalent. 2000 . The average systolic blood pressure was 86mm Hg at start. and 107mm Hg at maximum lisinopril dose. according to researcher Dr. Overall death rates. Salim Yusuf and associates analyzed 5 long-term. The researchers stopped her Monopril. The authors conclude that "ACE inhibitors should be routinely used long-term in all eligible high-risk patients. Dr. according to two reports in the May 6th issue of The Lancet. carotid artery (in the neck) and the abdominal aorta. Three patients stayed at 20mg. 82% were taking the maximum dose of 40mg. digoxin and low-dose ACE inhibitors. and her only medication was Prinivil for high blood pressure. Dr. and vomiting. C. Dr. In the 3 post-MI trials.75:1201-1204 Indomethacin & ACE Inhibitors Don't Mix October 9. and number of hospital admissions were about the same in both groups. patients showed a 75% improvement in radial artery flexibility. 18 of whom had low BP. but there were no other real differences. The team studied 100 CHF patients. The researchers raised lisinopril doses to pre-determined "best" or "maximum" doses. Reuters Health ACE Inhibitors In CHFers With Low Blood Pressure October 26. 2000 . However. The radial artery and abdominal aorta of CHF patients were much stiffer than in healthy control patients. "Visceral angioedema should be considered in patients with unexplained stomach pain who take ACE inhibitors. In group C. The woman had a history of high blood pressure and had suffered similar pain during previous Monopril treatment. Dr. To test the effect of taking indomethacin. Kwame Akosah. and that low BP "may be the single most important reason why doctors don't prescribe ACE inhibitors. Source: Mayo Clin Proc 2000. Death rate for ACE inhibitor patients (23%) was lower than for placebo patients (27%). After a treatment period with diuretics." Such symptoms are reason to stop ACE inhibitor treatment. Eight cases of this "visceral angioedema" after ACE inhibitor treatment have been reported. She restarted Monopril 3 days before this episode. diameter of the radial and carotid artery were similar in all patients but the diameter of the abdominal aorta was higher in CHFers. 2000 . "although ARBs may be useful when ACE inhibitors are not tolerated. nausea and vomiting.In heart failure patients. artery stiffness can be reversed by ACE inhibitors. patients were also given 75mg of indomethacin per day.ACE inhibitors improve many outcome measures in heart failure patients. 2000 . Paul Conlin's team studied 281 high blood pressure patients. At 8 weeks. Akosah noted that "not only were ACE inhibitors well tolerated. Dr." the authors say.

and were then crossed over to the other drug. valsartan (Diovan) may actually improve sexual function in such men. However. "Patients over 55 years with heart disease should be considered for ramipril to lower their risk of serious events.107:1278-1284. Coreg also gave worsening results. The researchers are not sure why this ocurred but there you have it. The patients took either valsartan or Coreg. who may or may not have taken an ACE inhibitor CHARM Overall All the above trials. The patients were randomized to either placebo or indomethacin for 3 weeks. Only one man on valsartan complained of not being able to get an erection.36:461-465.Elderly patients taking an ACE inhibitor are at risk of high blood pressure if they also take NSAIDs. they got a bigger benefit than patients who usually get ACE inhibitors! The researchers say "life-saving therapy is being withheld on the basis of questionable evidence" and suggest that ACE inhibitors be given to more patients.Dr. ACE Inhibitors To Prevent CHF February. Starting candesartan dose was 4mg or 8mg once a day." Dr. Patients were not included if they had a history of heart failure.does not. or diabetes plus one other risk factor. If the patient is also taking an ACE inhibitor. In other words. Morgan points out.297 patients to take 10mg ramipril daily or placebo for 4-1/2 years. After 16 weeks.1230-1232 The CHARM Trial For ARBs In CHF September. while 15% of Coreg-treated patients reported this problem. Source: J Am Geriatr Soc 2002.13:1161-1167 ARBs and Sexual Performance February 1. 2001 . were included. 2003 . valsartan an ARB . and lowered blood levels of renin. Indomethacin significantly raised blood pressure and lowered pulse rate in patients taking Vasotec. Ramipril patients went into heart failure 23% less often and had 24% less heart-related death and heart failure. Both treatments lowered blood pressure. but not in patients taking enalapril. patients with coronary artery disease." Source: Circulation 2003. Malcolm Arnold randomly assigned 9. indomethacin "significantly reduced their effectiveness. 2000 . "The major problem is the patient who takes indomethacin or other NSAIDs off and on. CHARM had 3 subtrials in specific groups of heart failure patients: CHARM-Alternative Patients with EF less than 41% who could not tolerate ACE inhibitors CHARM-Added Patients with EF less than 41% who were also taking an ACE inhibitor chosen by their doctor CHARM-Preserved Patients with EF greater than than 40%. The lower renin level overcomes this in patients taking amlodipine. Ali Ahmed studied 295 older patients hospitalized for CHF.70-73 More Patients Need ACE Inhibitors October. high potassium levels.Ramipril may lower risk of heart failure in people at high risk for it. sexual activity rebounded and actually improved with valsartan.While both heart drugs lowered diastolic blood pressure." High blood pressure patients taking these drugs along with indomethacin need to be monitored for proper blood pressure control. that these men did not have CHF. At hospital discharge. This was a crossover study of 120 newly diagnosed men never before treated for high blood pressure. In such patients amlodipine may be a better choice than enalapril. Dr. but Coreg was linked to fewer episodes of sexual intercourse during the first month of therapy. this will cause "blood pressure to go out of control.14:27-31. or weak kidney function. Such patients were 65% less likely to get an ACE inhibitor than patients without such problems. Eighteen percent had conditions like low blood pressure.029 patients who had a heart attack during the study. This was not seen in patients taking Norvasc. These patients had a 31% reduction in absolute risk of death in the year after hospital discharge. Source: Am J Hypertens 2001. 2002 . In those with normal EF there was 22% less heart failure and 15% less hospitalizations for heart failure. Trefor Morgan studied 30 patients averaging 72 years old on Vasotec (enalapril) and 31 patients averaging 69 years old on Norvasc (amlodipine). In fact. known low ejection fraction or uncontrolled high blood pressure. 2003 . stroke. increased up to a maximum . but who still have a normal EF.50. All had high blood pressure being effectively controlled by the drug they were taking. Roberto Fogari studied the impact of valsartan and Coreg on sexual activity. peripheral artery disease. Dr." Researchers think that indomethacin causes a CHFer's body to retain sodium. Patients with such conditions who took ACE inhibitors did well despite doctors' views that such conditions prohibit ACE inhibitor use. Forty similar men took placebo. Adding indomethacin to either drug caused weight gain. combined for analyzing overall mortality Patients took either candesartan or placebo. sexual activity was measured by questionnaire. Howevere. Dr.The CHARM trials showed that the long-acting ARB candesartan reduces heart-related deaths and CHF hospital admissions. 63% of patients began taking an ACE inhibitor. Ramipril reduced the rate of heart failure by 13% in 1. compared to a 15% reduction in patients without these problems. NSAIDs Raise Blood Pressure December 28.While the beta-blocker Coreg may worsen sexual function in men treated for high blood pressure. Arnold said. guys! Please note though. Dr. Source: Hypertension 2000. Source: Am J Hypertens 2000. This was seen "on top" of standard therapy including beta-blockers and ACE inhibitors.

and kidney dysfunction (12%). or open-heart surgery in the previous 4 weeks were not included in the trial. CHARM-Overall showed that candesartan did not greatly reduce risk of heart attack. Candesartan reduced relative risk of heart-related death or CHF hospitalization 23%. there was no difference in risk of heart-related death. These results were similar in men and women. That means you need to treat 14 patients with candesartan to prevent one patient from having heart-related death or CHF hospitalization." He believes adding candesartan to other CHF meds will benefit patients. This shows that ARB patients need routine blood testing. CHARM-OVERALL Summarizing CHARM-Overall. Fifty-five percent were also taking a beta-blocker and 17% took spironolactone. Patients with kidney failure. Philip Poole-Wilson was invited by the European Cardiology Society to interpret CHARM results. Benefit was seen when added to current therapy of ACE inhibitors and beta-blockers. and combined heartrelated death or hospital admission for CHF 16%." he said. Candesartan reduced relative risk of heart-related death or CHF hospital admission 15%. there are few trials done with just these patients . Primary end point for each sub-trial was heart-related death or CHF hospitalization. Eight percent of candesartan patients stopped due to worsening kidney function versus 4% of placebo patients. reduced kidney function in 6% versus 3% of placebo patients. with only one of 39 patients with a history of it having an episode that made them quit taking candesartan. except that significantly fewer patients on the ARB stopped treatment due to side effects. but new-onset diabetes was reduced (163 cases or 6%) versus placebo (202 or 7%). ELITE II showed no real differences between an ARB (losartan) and an ACE inhibitor (captopril). What Does It Mean? Dr. Four percent of candesartan patients stopped taking the drug due to low blood pressure versus 1% of placebo patients. Three percent withdrew due to low potassium levels versus less than 1% of placebo patients. high blood pressure. CHARM-Added showed benefit in patients on target dose of an ACE inhibitor.) Dr. or standard therapy plus candesartan. relative risk of heart-related death was reduced 12%. CHARM-Added showed benefit in patients already on a beta-blocker and an ACE inhibitor. CHARM-PRESERVED CHARM-Preserved included 3. "The only problem. 2. candesartan did cause low blood pressure in 4% of CHFers versus 2% of placebo patients. heart attack. Poole-Wilson cited 4 points from CHARM that he considers important: 1.Captopril may not be the best ACE inhibitor to use in such studies. With an average 41 months followup. but fewer candesartan patients were hospitalized for CHF (402) than placebo patients (566). Poole-Wilson Dr. This means that 23 patients need to take candesartan for 3 years in order to prevent one heart-related death or CHF hospitalization. Source: Medscape Title: CHARM: Candesartan in Heart Failure ." Proper doses and drug combinations are becoming tough to figure. CHARM-Overall showed an increase in fatal cancer. Angioedema was rare in CHARM-Alternative. He said that before CHARM.601 CHFers. Primary outcome for the overall program (CHARM-Overall) was all-cause death. (Jon's Note . primary end point was reached in 42% of placebo patients and 38% of candesartan patients. 4. CHARM included 7. After an average 37 months follow-up. With candesartan. high potassium. at 6 months and then every 4 months.it's getting too expensive to afford as well!) Dr. Candesartan was well tolerated by these ACE inhibitor-intolerant patients: 22% dropped out versus 19% of placebo patients. that is 23% of patients dying versus 25% in the placebo group. In CHARM-Overall. With an average follow-up of 34 months. Author: Linda Brookes. hospital admission for CHF 21%. Poole-Wilson said the results of CHARM-Added were "reasonably convincing. Patients were being treated with standard therapy including beta-blockers. stroke. This contradicts ValHeFT. blood potassium level and kidney function need to be monitored. digoxin (Lanoxin). at close to target doses.Assessment of Reduction in Mortality and Morbidity. as patients tolerated it. There were relatively few side effects when the ARB was added to ACE inhibitor therapy.548 CHFers taking an ACE inhibitor. The most common reasons for ACE inhibitor intolerance was cough (72%). decreased kidney function (6% versus 3%). The lead researcher for this sub-trial said that although almost half of all CHFers seen in the "real world" have normal LV systolic function. 3. diuretics. and in CHFers of all ages. ARB Plus ACE Inhibitor FDA-Approved For Heart Failure . MSc. CHARM-ADDED CHARM-Added included 2. CHARM-ALTERNATIVE CHARM-Alternative included 2. 4. However. Aldactone (spironolactone).3%). Marc Pfeffer said that after an average follow-up of 38 months.diastolic heart failure. (Jon's Note . A 40% relative risk reduction was seen in development of new diabetes in candesartan patients. "is that this is the 8th drug heart failure patients are going to be taking. So angioedema on an ACE inhibitor should not prevent a CHFer from trying an ARB. This is similar to the HOPE and LIFE trials and suggests that blocking the renin-angiotensin system with ACE inhibitors or ARBs helps prevent diabetes. low blood pressure (13%). and high potassium levels (2% versus 0. stroke. Patients were seen at 2. and 6 weeks. analyzing the 3 studies showed a 9% relative reduction in all-cause death. so the ARB benefit isn't because patients were not taking a high enough dose of ACE inhibitor. 33% of candesartan patients had reached the end point versus 40% of placebo patients. but this was probably due to chance.dose of 32mg a day.028 CHFers who did not tolerate ACE inhibitors. or need for procedures like bypass or angioplasty. CHARM-Alternative found only one case of angioedema on candesartan in the 39 patients intolerant of ACE inhibitors because of angioedema.023 CHFers. Dr. This is similar to the risk reduction seen in the SOLVD ACE inhibitor trial. They got standard therapy. Ninety-six percent were at target dose. and high potassium level in 2% versus less than 1%. and sometimes ACE inhibitors. In absolute terms.

1998. and content copyright © 1997. graphics. Talk to Jon Site Index .pdf Source: Heartwire.fda. When used with an ACE inhibitor for heart failure. 2002. All original copyrights apply. 2005 for treating class 2 to class 4 CHFers.fda. trials. social. I am not a doctor. Source: www. based on another part of the CHARM trial called CHARM-Alternative.May 19. 2000. This web site and all its pages. Atacand's dose is FDA-recommended to start at 4 mg once a day and rise to a target dose of 32 mg once a day. I am not a doctor. All information on this site is opinion only. explanations. 2003. 2001. 1999. educational.Adding the ARB Atacand (candesartan cilexetil) to ACE inhibitor therapy was FDA approved May 18. and studies have been re-written in plain English and may contain errors.gov/cder/foi/label/2005/020838s022lbl. The official recommendation is for CHFers with an EF of 40% or less. legal.gov/cder/foi/appletter/2005/020838s022ltr. 2004. or psychological treatment in any way. This came from CHARM-Added trial results. 2005 Jon C. Use the reference information at the end of each article to search MedLine for more complete and accurate information. All concepts. No information on this page should be used by any person to affect their medical. 2005 .pdf Source: www. The ARB was already FDA-approved for CHFers who can't tolerate ACE inhibitors.

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