All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- Source: Int J Cardiol 2001 Feb;77(2-3):131-8 Title: Effects of the replacement of the angiotensin converting enzyme inhibitor enalapril by the angiotensin II receptor blocker telmisartan in patients with congestive heart failure. Author: Dunselman PH. (Jon's note: Enalapril is generic Vasotec) INTRODUCTION: We compared the effects of an ACE inhibitor (enalapril) to an ARB (telmisartan) on abilty to exercise. The study lasted 12 weeks. 378 patients took either once-daily telmisartan at 10, 20, 40, or 80mg - OR - they just continued taking 10mg enalapril twice a day. Patients were mostly men, averaging 69 years old. They all had stable class 2 (63%) to class 3 (37%) heart failure with an average EF of 26%. They were all taking enalapril and diuretics at study start. Almost half were also taking digoxin. Primary endpoint was bicycle exercise time. Secondary endpoints were changes in ejection fraction, quality of life, blood pressure, heart class, and neurohormonal changes. FINDINGS: No meaningful differences were seen in exercise time. There was a small increase in blood pressure in all groups except the 80 mg telmisartan group, compared to enalapril patients. Side effects were similar between the 2 drugs. Cough occurred in 6% of enalapril patients and in 3% of telmisartan patients. CONCLUSIONS: In patients with stable, mild to moderate CHF, enalapril was replaced by telmisartan for 12 weeks without ill effects. No differences were seen in exercise capacity between the 4 different doses of telmisartan. PMID: 11182175 ============================================================= Source: Eur J Heart Fail 2000 Dec;2(4):407-12 Title: Effect of beta 1 blockade with atenolol on progression of heart failure in patients pretreated with high-dose enalapril. Author: Sturm B, Pacher R, Strametz-Juranek J, Berger R, Frey B, Stanek B. INTRODUCTION: The impact of beta-blockers added to high dose ACE inhibitors has not been studied. We studied the effect of atenolol added to 40mg enalapril per day in CHF patients in a double-blind placebo-controlled trial. 119 class 2-3 patients and an EF less than 26%, taking 40 mg enalapril daily were studied. They took a "challenge" dose of 12.5 mg atenolol. 100 of the patients tolerated the challenge dose - 54 idiopathic, 28 ischemic, 18 other cardiomyopathy. These 100 patients took either 90 mg atenolol or placebo, in addition to their enalapril. Primary endpoint was combined worsening heart failure or death within 2 years. Secondary endpoint was hospitalization for heart related events. FINDINGS: After an average of one year, we saw a significant difference between the atenolol and placebo group. 27 patients had developed worsening heart failure - 8 in the atenolol group versus 19 in the placebo group). Thirteen patients had died - 5 in the atenolol group versus 8 in the placebo group. There were 23 hospitalizations for heart related events - 6 in the atenolol group versus 21 in the placebo group. Seventeen hospitalizations were for due to worsening heart failure - 5 in the atenolol group versus 12 in the placebo group. Ten hospitalizations were due to arrhythmias - one in the atenolol group versus 9 in the placebo group. CONCLUSIONS: In patients with weak hearts, beta-blockers can give a lot of benefits when added to high dose enalapril. PMID: 11113718 ============================================================= Source: Klin Med (Mosk) 2000;78(7):36-9 Title: Prospects of endothelial dysfunction reversion in patients with congestive heart failure Authors: Vizir VA, Berezin AE. (Jon's note: The endothelium is the very important layer of cells lining the inside of blood vessels) INTRODUCTION: We studied the effect of the ACE inhibitor enalapril and the ARB losartan on endothelial function of the shoulder artery in CHF patients. Treatment lasted 12 weeks. 96 patients averaging 47 years old with stable effort angina, class 2-3 CHF and an EF less than 35% were studied. All patients were in normal heart rhythm. Patients were split into 3 groups of 32 patients each. Group 1: took long-acting nitrates, digoxin, aspirin and Lasix. Group 2: took 10mg enalapril daily. Group 3: took 25mg losartan daily. FINDINGS: Enalapril caused more vasodilation. Enalapril and losartan both improved endothelium-dependent vasodilation caused by nitroglycerin. CONCLUSIONS: Enalapril reversed endothelial dysfunction better than losartan. PMID: 10979640 ============================================================= Source: Eur J Heart Fail 2000 Sep;2(3):299-304 Title: First-dose hypotension after angiotensin-converting enzyme (ACE) inhibitors in chronic heart failure: a comparison of enalapril and perindopril. Authors: Vitovec J, Spinar J. INTRODUCTION: First-dose hypotension is an episode of greatly reduced blood pressure after taking the first dose of a drug. We compareed the first-dose response to low-dose enalapril and perindopril in patients with stable class 2-4 heart failure. All 298 patients had an EF less than 40% and had none had taken ACE inhibitors before. This was single blind, randomised, parallel, prospective study. Patients took either a single 2.5 mg dose of enalapril or 2 mg of perindopril. Ambulatory blood pressure monitoring started 2 hours before the drug was taken and went on for at least 10 hours afterward. FINDINGS: Blood pressure dropped the most 4 hours after taking the drug in both groups, dropped more in the enalapril group. Enalapril patients experienced more low blood episodes but not more problems from low BP. No low blood pressure related symptoms requiring any action were seen. CONCLUSIONS: A low dose of perindopril is well-tolerated in CHF patients and causes less first-dose low blood pressure than a low dose of enalapril. PMID: 10938492 ============================================================= Source: Am Heart J 2000 Jul;140(1):34-42 Title: Dissociation between ACE activity and autonomic response to ACE inhibition in patients with heart failure. Authors: Binkley PF, Nunziata E, Haas GJ, Starling RC, Leier CV, Cody RJ. INTRODUCTION: Giving CHF patients ACE inhibitors increases heart rate variability. We gave 7 CHF patients a 3-hour infusion of the ACE inhibitor enalaprilat. Blood flow, heart rate, and blood pressure variability, and ACE blood levels were measured during and after the infusion. FINDINGS: Blood levels of ACE were lower during and after enalaprilat infusion. Other than a small decline in right atrial and PCWP, blood flow remained unchanged. Low-frequency heart rate variability was increased in the enalaprilat group. There was no change in blood pressure variability in either group. CONCLUSIONS: Certain measurements increased with ACE inhibitor infusion but then dropped below study start. This suggests that enzyme systems are involved that are independent from the classic angiotensin forming pathways. The lack of change in blood flow or in blood pressure variability suggests that these are not a reflex response to ACE inhibitor-caused vasodilation. PMID: 10874261 ============================================================= Source: Diabetes Care 2000 Mar;23(3):377-80 Title: Enalapril prevents clinical proteinuria in diabetic patients with low ejection fraction. Authors: Capes SE, Gerstein HC, Negassa A, Yusuf S. Jon's note: See this web page about proteinuria: http://www.niddk.nih.gov/health/kidney/pubs/proteinuria/proteinuria.htm INTRODUCTION: Proteinuria is a risk factor for both kidney disease and heart disease. The effect of ACE inhibitors in preventing proteinuria in diabetic and non-diabetic heart failure patients is not known. SOLVD data were analyzed for distribution of proteinuria and heart-related risk factors; the effect of proteinuria on risk of hospitalization for CHF and mortality; and the effect of enalapril in preventing new proteinuria. FINDINGS: 5,487 out of 6,797 SOLVD patients were tested for proteinuria at study start. 177 patients (3%) had proteinuria. These patients had higher blood pressure: Systolic - 137 versus 125 mmHg in non-proteinuria patients Diastolic - 83 versus 77 mmHg in non-proteinuria patients They were also more likely to have diabetes - 41 versus 18%, and had slightly lower ejection fractions and worse heart class. Patients with proteinuria also had higher rates of hospitalization for CHF and higher mortality. Enalapril prevented proteinuria in diabetic patients but not in nondiabetic patients without proteinuria at study start. CONCLUSIONS: Clinical proteinuria is an independent predictor of hospitalization for CHF and mortality, in diabetic and nondiabetic CHF patients. Enalapril significantly reduces the risk of proteinuria in diabetic CHF patients. PMID: 10868869 ============================================================= Source: J Am Coll Cardiol 2000 Dec;36(7):2090-5 Comment in: J Am Coll Cardiol. 2000 Dec;36(7):2096-7 Title: Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study. Authors: Nanas JN, Alexopoulos G, Anastasiou-Nana MI, Karidis K, Tirologos A, Zobolos S, Pirgakis V, Anthopoulos L, Sideris D, Stamatelopoulos SF, Moulopoulos SD. INTRODUCTION: ACE inhibitors give many benefits in CHF patients but there is still discussion about the best dose. We compared survival to "clinical" measurements in CHF patients treated with standard doses versus high doses of enalapril. 248 heart failure patients with an average age of 56 years took either a dose as high as they could tolerate of enalapril, up to 20 mg per day in Group 1 (122 patients) or up to 60 mg per day in Group 2 (126 patients). Group 1 patients were class 2, had average systolic blood pressure of 117 mm Hg, average heart rate of 85 and average ejection fraction of 20%. Group 2 patients were almost identical. FINDINGS: After a one year follow-up, 22 (18%) of 122 Group 1 patients and 23 (18%) of 126 Group 2 patients had died. Heart class was the same in both groups. Systolic blood pressure was th esame. Heart rate went down slightly (5 beats per minute) in both groups. EF went up about the same in both groups - to about 31%. Mortality went down about 13% in both groups. CONCLUSIONS: No meaningful differences were seen in survival or "clinical" measurements between patients taking standard dose and those taking high dose enalapril. PMID: 11127445 ============================================================= Source: Eur Heart J 2000 Jan;21(1):53-7 Comment in: Eur Heart J. 2000 Jan;21(1):14-6 Title: Clinical implications of increased plasma angiotensin II despite ACE inhibitor therapy in patients with congestive heart failure. Authors: Roig E, Perez-Villa F, Morales M, Jimenez W, Orus J, Heras M, Sanz G. INTRODUCTION: We tested the rate and consequences of high blood levels of angiotensin II - despite ACE inhibitor therapy - in CHF patients. We studied 70 patients with an average age of 59 years and an average EF of 24%. End-systolic heart size was 59 and end-diastolic diameter was 71 mm. Six months after they started ACE inhibitor therapy, we measured blood levels of: 1) renin activity 2) aldosterone 3) norepinephrine 4) atrial natriuretic peptide (ANP) 5) angiotensin II 6) tumour necrosis factor (TNF) 7) interleukin-6 8) interleukin-1B FINDINGS: Despite enalapril or captopril therapy, 35 patients (50%) had increased blood levels of angiotensin II (average 33 pg. ml(-1), range 17-84). levels were in the normal range for the other 35 patients (average 10 pg. ml(-1), range 5-15). Increased angiostensin II levels were associated with: 1) renin activity 2) interleukin-6 3) functional heart class 3-4 4) furosemide (Lasix) dose 5) lack of beta-blocker therapy 6) norepinephrine Analysis identified blood renin activity, norepinephrine, and interleukin-6 as independent predictors of high angiotensin II level. During an average 3 year follow-up, 9 (13%) patients died and 13 had new heart failure episodes. CONCLUSIONS: 50% of patients with heart failure had increased blood levels of angiotension II despite chronic ACE inhibitor therapy. These patients had more neurohormonal activity and poor prognosis. Increased blood levels of angiotensin II - despite ACE inhibitor therapy - predicted death or heart failure. PMID: 10610744 ============================================================= Source: Am J Cardiol 1999 Nov 1;84(9):1038-43 Title: Synergistic efficacy of enalapril and losartan on exercise performance and oxygen consumption at peak exercise in congestive heart failure. Authors: Guazzi M, Palermo P, Pontone G, Susini F, Agostoni P. INTRODUCTION: Oxygen consumption at peak exercise (peak Vo2) is a strong independent predictor of outcome in CHF. ACE inhibitors and ARBs improve peak Vo2. We studied the how and why, and whether taking both improved peak Vo2 even more. 20 CHF patients were randomized to take either: 1) placebo + placebo (P+P) 2) 20 mg per day enalapril + placebo (E+P) 3) 50 mg per day losartan + placebo (L+P) 4) enalapril + losartan (E+L) or the same drugs in the reverse order, each for 8 weeks. Pulmonary function, exercise stress test, blood levels of neurohormones, and quality of life were measuerd at the end of each phase. FINDINGS: E+P (16%) and L+P (15%) increased peak Vo2. Enalapril improved lung function. Losartan increased exercising muscle blood flow. In combination, they further increased peak Vo2, up 10% from E+P and 11% from L+P. E+P (by 70 pg/ml) and L+P (by 100 pg/ml) lowered blood levels of norepinephrine and lowered aldosterone by 1.6 ng/dl. These changes were greater when the drugs were combined - 140 pg/ml for norepinephrine and 5.6 ng/dl for aldosterone. Quality of life score did not improve much at each treatment step. CONCLUSIONS: Lorsartan and enalapril similarly increased peak Vo2 in CHF patients, but different drug targets may be synergistic when the 2 drugs are combined - for greater improvement still. PMID: 10569660 ============================================================= Source: Am Heart J 1999 Oct;138(4 Pt 1):654-62 Title: Within-patient comparison of effects of different dosages of enalapril on functional capacity and neurohormone levels in patients with chronic heart failure. Authors: Brunner-La Rocca HP, Weilenmann D, Kiowski W, Maly FE, Candinas R, Follath F. INTRODUCTION: Conflicting results exist on the dose to effect relation of ACE inhibitors. We studied 45 patients with an average age of 55 years. All had stable CHF and were taking either 5 mg enalapril twice daily (16 patients), 10 mg twice daily (18 patients), or 20 mg twice daily (11 patients). This dose was changed 3 times to treat all patients with each dose for 4 weeks each. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine, and enalaprilat trough levels were measured. FINDINGS: After raising enalapril to 40 mg daily, patients in the 10 mg group showed an increase in Vo2max and less neurohormonal stimulation. The opposite changes were seen after reducing enalapril dose to 10 mg daily in patients in the other 2 groups. Neurohormone levels were higher and exercise capacity lower while patients were taking 10 mg of enalapril per day than when they were taking 40 mg per day: ANP: 172 pg/ml at 10 mg enalapril versus 139 pg/mL at 40 mg BNP: 193 pg/ml at 10 mg enalapril versus 152 pg/mL at 40 mg norepinephrine: 4.2 nmol/L at 10mg enalapril versus 3.5 nmol/L at 40 mg mVo2: 22 mL. kg(-1). min(-1) at 10mg enalapril versus 21.3 mL. kg(-1). min(-1) at 40 mg CONCLUSIONS: High doses of enalapril improve exercise capacity and reduce neurohumoral stimulation. These measures get worse after reducing enalapril dose. Thus hear failure patients benefit from increasing dosage of ACE inhibitors. PMID: 10502210