The annual scientific session of the American Heart Association (AHA) was held in Orlando on November 14-18 2009. It felt like a ghost town. I ran into Ira Schulman, my medicine resident at Bellevue when I was a third year medical student; we looked at one another and simultaneously blurted out “where is everybody?” Well Ira remains my role model and hero and it goes to show that although attendance at major medical meetings may wax and wane, the impact of a great resident and a great teacher lasts pretty much forever – a good lesson for current house staff to bear in mind.
There are probably numerous reasons for plummeting attendance at AHA. The economy, the on-line publication of trial results prior to presentation, the ubiquity of conference calls, e-mail strings and yes blogs that keep one in regular contact with colleagues throughout the country and the world without the need for face-to-face encounters are just some of the obvious causes.
The scaling back of industry support may be another major factor at play here. Certainly there are fewer exhibitors and the exhibits are far less lavish. As Muhamed Saric pointed out when I met him on the floor of the exhibit hall there were no Siemens or Philips exhibits, and in fact I could not find any cath lab manufacturers presenting their products at the AHA. The need to diminish the influence of industry on the medical profession and the need to avoid conflicts of interest were brought up at many of the presentations at the session by leaders of the AHA and other thought leaders in academic medicine, but one unintended consequence of this well-intentioned effort seems to be less financial support for the meeting itself. As shown in the table attendance at AHA has been diminishing for years. Particularly noteworthy has been the 40% drop in the number of exhibitors in attendance between 2006 and 2008.
|2006 Chicago||2007 Orlando||2008 New Orleans|
|Total Professional Attendance||18,817||18,391||17,422|
|Exhibitors in Attendance||6,411||5, 885||3,810|
The final numbers for 2009 are not available yet, but the only question will be how much the decline in attendance has accelerated. There seemed to be very few fellows in the audience, and in fact only one brave NYU cardiology fellow flew down to the meeting. That’s a shame, because there were actually a number of interesting and important presentations and even a bit of controversy to liven things up and I expect that next year in Chicago the usual boisterous and opinionated contingent of NYU cardiology fellows will show up and help select the presentations worthy of mention in Clinical Correlations.
A brief description of all 32 late-breaking clinical trials is attached. No single trial dominated the news. A number of presentations related to novel anti-platelet and anti-coagulant drugs were encouraging and reflect progress in achieving clinically meaningful improvements in anti-thrombotic therapies with the use of both old and new drugs. There were also important presentations in the fields of heart failure and electrophysiology and there was a controversial study in the field of prevention – ARBITER 6-HALTS that made headlines.
First the platelet story. The Plato STEMI trial compared clopidogrel (300 mg loading dose + 75 mg daily) to the novel oral reversible platelet P2Y12 receptor blocker ticagrelor (180 mg + 90 mg BID) in 8430 patients undergoing primary percutaneous coronary intervention (PCI) for st elevation myocardial infarction (STEMI). Ticagrelor is a cyclo-pentyl-triazolo-pyrimidine and unlike the thienopyridines clopidogrel and prasugrel it is not a pro-drug and thus has a faster onset of action and more predictable effect. Furthermore it is reversible with a short half-life so is likely to cause less bleeding and is especially beneficial compared to the thienopyridines when given to patients who require urgent coronary artery bypass grafting (CABG). In addition, there is a great deal of interest in potentially beneficial “off target” effects of ticagrelor due to adenosine release. The PLATO acute coronary syndrome (ACS) data showing better survival with ticagrelor compared to clopidogrel was presented at the European Society of Cardiology meetings in September and published recently in the New England Journal of Medicine. As seen in the table, there were similar findings in the STEMI cohort. Interestingly, there was no benefit with ticagrelor observed in the North American cohort with STEMI (just as there was no benefit observed in the 1800 North Americans in total enrolled in the 18,000 patient PLATO trials). It is always hazardous to speculate about the findings in subgroups – they could be due to chance alone – but some observers noted that most North American patients in PLATO were treated with the 600 mg clopidogrel loading dose that is commonly used here and that results in more rapid and complete inhibition of platelet function than seen with the 300 mg dose.
|End point||Ticagrelor (%)||Clopidogrel (%)||Hazard ratio for ticagrelor||p|
|Primary end point: death from vascular causes, MI, or stroke||9.3||11.0||0.85||0.02|
|Secondary end points|
|Definite stent thrombosis||1.6||2.5||0.61||0.01|
|Primary safety event: major bleeding||9.0||9.3||0.96||0.63|
The PLATO STEMI findings were not unexpected, but the results of the Champion trials which compared another novel platelet P2Y12 receptor blocker, cangrelor to clopidogrel were disappointing. Cangrelor is an intravenous drug with rapid onset of action, a plasma half-life of 3-6 minutes and complete recovery of platelet function within 60 minutes. Over 14,000 patients were enrolled in the 2 champion trials Champion-PCI and Champion-Platform which compared cangrelor to clopidogrel in a high-risk cohort of patients undergoing PCI. The studies differed only in the timing of the clopidogrel treatment (before PCI in the PCI trial and after PCI in the Platform trial). Both studies were stopped early for futility when they failed to show a difference in outcome between cangrelor and clopidogrel. In retrospect it is becoming clear why the trials failed. First of all, the comparator was clopidogrel with a 600 mg loading dose – an extremely efficacious and safe drug given at an appropriate dose. Secondly, the IV infusion of cangrelor was probably stopped too soon exposing patients who had just received stents to the risk of minimal platelet inhibition before the orally administered clopidogrel took effect. Finally, the end point was seriously flawed. The composite endpoint included myocardial infarction (MI), but patients were enrolled so early (mean of 6.3 hours after admission) that many of the troponin elevations detected and counted as events reflected myocardial injury due to the initial ACS rather than recurrent infarction due to a post PCI failure of platelet inhibition. There clearly is a need for a safe and effective IV platelet P2Y12 receptor blocker and cangrelor seems to be such a drug. Undoubtedly there will be better designed trials with this compound in the near future and cangrelor will likely become an important part of our armamentarium in treating acute coronary artery disease.
The newer anti-platelet drugs look promising, but they are expensive and not yet widely available. The role that platelet function testing will play in determining which patients are being effectively treated with aspirin and Plavix and which patients need a either a higher dose or a newer agent remains unsettled. There are a large number of platelet function tests either on the market or about to be released, but they have not yet been fully clinically validated and their use has not yet been convincingly shown to improve outcomes in patients with coronary artery disease. The POPULAR study (Do Platelet Function Assays Predict Clinical Outcomes in clopidogrel pretreated patients undergoing elective PCI) compared 8 different assays in 1609 patients undergoing elective coronary stenting to determine which test best predict clinical events. Among these tests was the research gold standard light transmittance aggregometry (LTA) using 5 and 20 micromol/L ADP and the commercially available Accumetrics Verify Now P2Y12 analyzer. These 3 assays are available at NYU, but LTA is very time consuming, requires meticulous collection of a large volume of blood and is not practical to use in most clinical settings. The primary endpoint of the study was the composite of death, MI, stent thrombosis and stroke at 1 year. The primary safety endpoint was TIMI major or minor bleeding. Unfortunately, none of the 8 assays could predict which patients would bleed. Only LTA and the Verify Now P2Y12 assay significantly correlated with events. Whether and how these findings affect management is still unclear. The GRAVITAS trial using the Verify Now assay to compare tailored clopidogrel therapy to standard dose clopidogrel in patients with “Plavix resistance” is rapidly nearing completion and should be presented in the near future. I am eagerly awaiting those findings before deciding to buy P2Y12 cartridges with your taxpayer dollars for the Accumetrics platelet analyzer in the VA cath lab.
There were no new heart failure drugs featured at the AHA, but there were presentations on optimal dosing strategies for existing drugs, advances in mechanical support devices, and insights into the role of anemia and iron deficiency.
The HEAAL (Heart Failure End Point Evaluation of Angiotensin II Antagonist Losartan) study compared high dose (150-mg/day) versus low dose (50-mg/day) losartan in patients with symptomatic heart failure and reduced left ventricular ejection fraction (LVEF) unable to tolerate ace inhibitors (ACEI). The study enrolled 3846 patients in 30 countries with NYHA class 2-4 heart failure, an LVEF <40%, and intolerance of ACEI. The high-dose was titrated from 50 mg/day over three weeks. ACEI intolerance was due to cough in 86% of cases. As shown in the table the high dose was superior to the low dose in preventing hospitalization for heart failure, although there was no effect on mortality. There was a slightly higher incidence of hyperkalemia and worsening kidney function in the high dose cohort, but this did not translate into worse outcomes. These findings are strikingly similar to those of the ATLAS study which compared high dose to low dose lisinopril in heart failure and also found less hospitalization but no effect on survival with high dose lisinopril. The lesson of these 2 trials taken together is that clinicians treating heart failure with an ACEI or ARB should titrate up the dose to the levels used in clinical trials in order to achieve optimal benefit.
|End point (per 100 patient years)||50 mg||150 mg||HR (95% CI)||p|
|Death or heart-failure hospitalization*||12.4||11.1||0.90 (0.82-0.99)||0.027|
|All-cause death||8.2||7.6||0.94 (0.84-1.04)||0.24|
|Heart-failure hospitalization||7||6||0.87 (0.76-0.98)||0.025|
|CV hospitalization||12.9||11.5||0.89 (0.81-0.98)||0.023|
There was good news in the field of destination left ventricular assist devise (LVAD) therapy. The HeartMate II study enrolled 200 patients with severe heart failure not eligible for transplant in a multi-center, prospective, randomized trial comparing treatment with the currently approved pulsatile flow device versus a continuous flow -LVAD. The actuarial survival rates at two years were 58% for the continuous flow HeartMate II and 24% for the older pulsatile flow HeartMate XVE ((p=0.008). Of the 134 patients randomized to HeartMate II, 62 survived at least two years without suffering a stroke or requiring their device to be repaired or replaced. Only seven of the 66 patients randomized to the HeartMate XVE survived two years without a repeat operation or stroke (hazard ratio 0.38, p<0.001). About 80% of patients on HeartMate II improved to NYHA class 1 or 2, with a doubling of the mean six-minute-walk distance and similar improvements in other quality-of-life measures. To put matters in perspective, this was an incredibly sick population, most hospitalized on IV inotropes, with a dismal short term prognosis and no realistic expectation of two year survival.
Much lower tech than LVAD was the FAIR heart failure trial which randomized 459 heart-failure patients in NYHA class 2 with an LVEF <40% or NYHA class 3 with an LVEF <45%, who had an initial hemoglobin level of 9.5 g/L to 13.5 g/L, depressed serum ferritin levels, and no hepatic or renal dysfunction. They were assigned in a 2:1 ratio to receive either ferric carboxymaltose (an IV iron supplement not available in the United States) or placebo. The patients were treated weekly for eight to 12 weeks (depending on the patient’s calculated iron deficit) and then every four weeks, for a total of 26 weeks of treatment. There were significant improvements in self-assessed quality of life and in the 6 minute walk test. These improvements were seen in patients with and without anemia, suggesting that it was the iron deficiency and not anemia that was responsible for the patients’ symptoms. Back when Ira Schulman was my resident, Michael Freedman was my attending. In those days, Michael not yet a geriatrician was a hematologist with great expertise in disorders of iron metabolism. He always emphasized that iron plays a crucial role in mitochondrial function and that depletion of iron stores results in muscle weakness, fatigue and symptoms indistinguishable from heart failure. I guess another lesson to take home is that when your attending is a master clinician scientist like Michael Freedman you should pay attention to his insights and his teaching.
Further support for the idea that iron deficiency and not anemia might be the most appropriate target for therapy (comes from the negative findings of the TREAT study. Treat (The Trial to Reduce cardiovascular Events with Aranesp Therapy) was not a heart failure study but rather targeted the high risk cohort of patients with diabetes, CKD and anemia. (This was a randomized double-blind placebo-controlled trial to test the hypothesis that use of darbepoetin alfa to increase hemoglobin levels to 13 g/dL would reduce the likelihood of experiencing either death or cardiovascular morbidity (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) or the composite of death or need for long-term renal replacement therapy in patients with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate of 20 to 60 mL/min/1.73m2) and anemia (hemoglobin ≤ than 11g/dL). Not only did treatment fail to reduce clinical events, but in addition, almost twice as many patients randomized to the darbepoetin had a stroke (5 percent versus 2.6 percent). Well anemia may be an appropriate target for therapy, but the evidence is accumulating that erythropoietin may not be the right therapy.
Two studies in the field of electrophysiology worth mention are PACE and REPLACE. They sound similar but are in fact very different. PACE (The Pacing to Avoid Cardiac Enlargement) trial was a prospective, multicenter, randomized, double blinded, parallel, controlled study, aiming to determine if biventricular (BiV) pacing is better than RVA pacing to preserve LV function and prevent LV remodeling. This study randomized 177 patients with normal LV function to either standard RV or BiV pacing. There were significant decreases in LVEF (7%) with standard RV pacing that were not seen with BiV pacing. Nobody is yet rushing to put in BiV pacemakers in all patients who need pacing, but this study points out the need for strategies to ensure as much native conduction as possible in patients who are paced. One reason not to put in extra leads comes from the REPLACE study. This prospective multicenter registry was undertaken to estimate the procedure complication rates for patients undergoing a pacemaker, implantable cardioverter defibrillator (ICD) or cardiac resynchronization (CRT) generator replacement with or without planned lead addition. As shown in the table, there is no free lunch in the universe, lead additions/replacements were associated with a substantial complication rate.
|Procedure||Patients with complication||Rate (%)|
|LV lead addition or revision (n=434)a||81||18.7|
|RA/RV lead addition or revision (n=234)b||26||11.1|
|No lead addition or revision (n=45)||2||4.4|
Finally, a few words about the headlines and the controversy over the Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6: HDL and LDL Treatment Strategies in Atherosclerosis (ARBITER 6 -HALTS). This study, enrolled 363 patients with known cardiovascular disease or CHD equivalent on statin therapy with LDL < 100 mg/dL and low HDL (<50 mg/dL for men and < 55 mg/dL for women) . Patients were randomized to either additional long acting niacin (Niaspan titrated up to 2 grams daily) or ezetimibe. The endpoint was regression of carotid intima-media thickness (IMT). At baseline, the mean LDL-cholesterol level was 84 mg/dL and 81 mg/dL in the niacin- and ezetimibe-treatment arms, respectively. After 14 months of treatment, mean HDL-cholesterol levels among the niacin-treated patients increased 18.4% to 50 mg/dL. In the ezetimibe arm, LDL-cholesterol levels further declined 19.2% to 66 mg/dL. Compared with ezetimibe, treatment with niacin resulted in significantly larger changes in the mean and maximal carotid IMT over 14 months. From baseline, niacin resulted in a significant regression of mean and maximal carotid IMT when measured at eight months and 14 months, whereas there was no significant change in mean or maximal IMT among those treated with ezetimibe. Although not powered for clinical outcomes, there were more major cardiovascular events in the ezetimibe arm compared with those in the niacin arm (nine events vs. two events, respectively; p=0.04). Well most clinicians believe that Niaspan is superior to ezetimibe, but this small trial with clinically insignificant differences in IMT does not provide definitive proof. The controversy arose in large part over the fact that this trial was stopped early by the data safety monitoring board, especially since there are large ongoing trials involving both Niaspan and ezetimibe. IMPROVE-IT is a large clinical-outcomes study with ezetimibe and SHARP is a study of ezetimibe in patients with renal failure. The major outcome studies for Niaspan are the NIH sponsored AIM-HIGH, due out in 2011, and the English HPS2-THRIVE, which is expected to be completed in 2013. Stay tuned.
Late Breaking Clinical Trials AHA 2009
Saturday, Nov. 14
Trans-Catheter Aortic Valve Implantation (TAVI) in France: Early results of the French Multicenter Registry – Designed to evaluate the safety and effectiveness of TAVI with the Edwards SAPIEN (Edwards Lifesciences LLC, Irvine, US) and the CoreValve (Medtronic, US) transcatheter heart valves in symptomatic adults with severe degenerative AS at high risk for AVR. 244 patient (mean age 82) enrolled. There was no overall difference in survival between the 2 valves with 1 month survival 13%.
Raptor – Designed to evaluate the feasibility of switching from femoral access to radial access as a routine strategy for cardiac catheterization with regard to safety, comfort and resources. 421 patients were randomized by 5 experienced interventional cardiologists at a single center to femoral versus radial access. Procedure times were slightly longer with radial procedures, but nursing time was dramatically shorted from over an hour to 30 minutes for PCI.
PEPCAD III – Compared drug-coated balloon (paclitaxel) in combination with a bare metal stent as an alternative to drug-eluting stents (Cypher) in the treatment of de-novo coronary lesions. There was significantly more restenosis and more stent thrombosis in the balloon arm. The drug coated balloon and bare metal stent is not an alternative to drug coated stents.
EXPIRA – Single-center, prospective randomized study to evaluate the safety and efficacy of thrombectomy in STEMI patients undergoing to primary angioplasty. The long term f/u presented showed less cardiac mortality and less MACE at 2 years with thrombectomy versus control.
Sunday, Nov. 15
POPULAR - Prospective trial to assess which platelet function test is best to predict atherothrombotic events in patients treated with aspirin and clopidogrel undergoing PCI with stent implantation. The study compared 8 assays and showed that only standard light transmittance aggregometry (LTA) using 5 and 20 micromol/L ADP and the Accumetrics Verify Now P2Y12 analyzer could predict the composite of death, MI, stent thrombosis and stroke.
CHAMPION PCI This trial compared the efficacy and safety of cangrelor versus pretreatment with a 600 mg loading dose of clopidogrel. No advantage could be demonstrated for cangrelor.
CHAMPION PLATFORM This trial compared the efficacy and safety of cangrelor versus a 600 mg loading dose of clopidogrel given immediately after the procedure. No advantage could be demonstrated for cangrelor.
PLATO trial tested whether ticagrelor is superior to clopidogrel in preventing vascular events in patients with either non-ST-elevation ACS or ST-elevation ACS with planned primary percutaneous coronary intervention (PCI). There was better survival with ticagrelor.
RELY - In the prospective randomized international multicentre RELY trial, the efficacy and safety of two blinded doses of the novel direct thrombin inhibitor dabigatran, 110 mg b.d. and 150 mg b.d., were evaluated versus open label warfarin for stroke prevention in AF and at least one risk factor for stroke. Dabigatran 150 BID was superior to warfarin for stroke prevention.
REPLACE – This prospective multicenter registry was undertaken to estimate the procedure complication rates for patients undergoing a pacemaker, implantable cardioverter defibrillator (ICD) or cardiac resynchronization (CRT) generator replacement without (Cohort 1) or with planned lead addition (Cohort 2). Lead additions/replacements were associated with a substantial complication rate.
PACE -The Pacing to Avoid Cardiac Enlargement (PACE) trial is a prospective, multicenter, randomized, double blinded, parallel, controlled study, aiming to determine if biventricular (BiV) pacing is better than RVA pacing to preserve LV function and prevent LV remodeling. There were significant decreases in LVEF with standard RV pacing that were not seen with BiV pacing.
RecordAF study is the first worldwide, prospective, observational survey of real-life management of atrial fibrillation (AF) in recently diagnosed patients. This analysis evaluated clinical outcomes of rhythm- and rate-control strategies in patients with paroxysmal or persistent AF. Successful rhythm control did not prevent clinical events.
Monday, Nov. 16
Outcomes Following Primary Percutaneous Coronary Intervention: A Comparison Between Hospitals With and Without Cardiac Surgery On-Site - To increase the number of ST-elevation myocardial infarction (STEMI) patients with timely access to primary percutaneous coronary intervention (PCI), the Massachusetts Department of Health approved a pilot program for primary PCI at hospitals without cardiac surgery on site (No SOS). To participate, No SOS hospitals were required to meet ACC/AHA guideline recommendations for hospital and operator volume of procedures. To determine the safety and efficacy of this strategy, outcomes at 30 days and one-year between patients undergoing primary PCI at No SOS and SOS hospitals were compared. There were similar mortalities and MACE rates at hospitals with and without SOS.
ARBITER 6-HALTS – Among patients at high cardiovascular risk already at their LDL-C goal on a statin but with low HDL-C, therapeutic options in the management of residual risk include combination therapy to raise HDL-C or further lower LDL-C. These therapeutic approaches were compared for their relative effects on carotid atherosclerosis. Beneficial effects were observed with niacin, but not with ezetimibe.
TREAT - The Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT) was initiated n 2004 as a randomized double-blind placebo-controlled trial to test the hypothesis that use of darbepoetin alfa to increase hemoglobin levels to 13 g/dL would reduce the likelihood of experiencing either death or cardiovascular morbidity (nonfatal myocardial infarction, congestive heart failure, stroke, or hospitalization for myocardial ischemia) or the composite of death or need for long-term renal replacement therapy in patients with type 2 diabetes, chronic kidney disease (estimated glomerular filtration rate of 20 to 60 mL/min/1.73m2) and anemia (hemoglobin ≤ than 11g/dL). Treatment failed to reduce the rate of the composite endpoint of death or cardiovascular events (nonfatal heart attack, congestive heart failure, stroke or hospitalization for myocardial ischemia). In addition, almost twice as many patients randomized to the darbepoetin had a stroke (5 percent versus 2.6 percent).
Impact of Transfusion Triggers on Postoperative Myocardial Infarction or Death – Showed that there was no difference in ACS events and 30-day mortality in 2013 high cardiac risk elderly patients undergoing hip-fracture repair randomized to liberal (10g/dL) or restrictive (8g/dL) transfusion triggers.
CASCADE – This was the first prospective randomized study to evaluate whether the addition of clopidogrel to aspirin reduces SVG intimal hyperplasia and improves graft patency following CABG. The primary outcome was vein graft intimal area. IVUS was performed in 90 patients and showed a 14.8% reduction in intimal area in the clopidogrel group, which did not reach statistical significance. There was no difference in SVG patency at 1 year (94.3% versus 93.2%).
Octopus Study – The Octostent trial is a multicenter randomized comparison of OPCAB versus PCI in 280 symptomatic coronary artery disease patients. At 7.5 years f/u there was comparable safety, but less re-intervention and better neurocognitive function with OPCAB as compared to stenting.
Bypassing The Blues – Depression is common following CABG surgery and associated with worse clinical outcomes. Several treatment trials for depression have been conducted in cardiac populations but most achieved less than anticipated benefits at reducing mood symptoms or cardiovascular morbidity, and none utilized the “collaborative care” (CC) approach proven effective in primary care. The NHLBI-funded Bypassing the Blues trial is the first to examine the impact of CC for treating depressed patients with cardiovascular disease. A telephone based CC approach tested in 302 patients randomized to CC or usual care significantly improved mental health quality of life post CABG.
POPE – Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed to prevent post op pericardial effusion after heart surgery although no study has assessed their efficacy. This study assessed whether the NSAID diclofenac was effective in reducing post operative PE (POPE) volume. The NSAID did not reduce the size of pericardial effusion and did not prevent tamponade in 196 patients with small pericardial effusions who were randomized post operatively.
Tuesday, Nov. 17
BARI2D – Examined the benefit of prompt coronary revascularization or insulin-sensitization therapy in type II diabetes (T2D) as treatment strategies to reduce non-fatal myocardial infarction (MI). In patients with more extensive CAD randomized to CABG and insulin sensitization there was less MI.
Quality of Life Results in the Bypass Angioplasty Revascularization Investigation 2 Diabetes - Duke Activity Status Index (DASI), a measure of daily activities performed without difficulty, and the RAND Medical Outcomes Study measures Energy, Health Distress and Self-rated Health were assessed at study entry and on an annual basis. Linear mixed models were used to evaluate the effect of randomized treatment on follow-up HRQoL adjusting for baseline level. Revascularization had beneficial long-term effects on QOL, especially in those with severe angina.
Economic Outcomes of the Bypass Angioplasty Revascularization Investigation 2 Diabetes - BARI2D trial randomized patients with type 2 diabetes and coronary disease in a 2×2 factorial design to 1) insulin sensitization vs. insulin provision, and 2) prompt revascularization vs. medical therapy. Prior to randomization, the physician declared whether CABG or PCI would be used if the patient were assigned to prompt revascularization. This study followed 2005 patients from 46 clinical sites for medical utilization and assigned costs using U.S. Medicare cost weights. Insulin sensitization and revascularization were significantly more costly at 4 years.
STICH - This report from the STICH core laboratory data analysis of LV function failed to identify a specific patient population that benefited from adding surgical ventricular restoration to CABG.
HEAAL - High dose (150-mg/day) versus low dose (50-mg/day) losartan significantly cut the risk of death or heart-failure hospitalization over almost five years in patients with symptomatic heart failure and reduced LVEF unable to tolerate ACEI.
FAIR-HF – This study evaluated the efficacy and safety of iron repletion with ferric carboxymaltose in CHF patients with iron deficiency with and without anemia. Iron therapy improved symptoms, functional status and QOL.
Japanese Chronic Heart Failure (J-CHF) – Low dose (5 mg/day), carvedilol improved morbidity compared to placebo in Japanese patients with chronic heart failure in the MUCHA trial. Previous large trials investigated the effects of higher dose of β-blockers on mortality in CHF. However, the effective and safe minimal dose of β-blockers remains unknown. Moreover, prediction of mortality and responsiveness based on genetic variation in CHF has not been established because of racial and individual differences. This 364 patient randomized trial failed to show a benefit for high dose carvedilol versus low and moderate dose carvedilol in Japanese patients with heart failure suggesting that low dose beta blockers may be optimal therapy for Asian heart failure patients. .
HeartMate II Destination Therapy - reports the outcomes of a multi-center, prospective, randomized trial comparing treatment with the currently approved pulsatile flow versus a continuous flow -LVAD in patients ineligible for transplantation. There was marked improvement in 2 year survival with the newer device.
Wednesday, Nov. 18
CT-CTAT is a randomized, multicenter study comparing the safety and efficiency of coronary computed tomographic angiography to standard of care evaluation of low-intermediate risk patients with acute chest pain. Time to diagnosis was shorter and cost of treatment was less with CT angio.
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a double-blind, randomized, hypertension treatment trial. Active follow-up of 42,418 participants ended on March 31, 2002 (Feb. 15, 2000 for doxazosin participants), with an average follow-up of 4.9 years (3.2 years for doxazosin). Post-trial, passive follow-up of participants was conducted through 2006 to compare long-term effects of antihypertensive treatment with a thiazide-type diuretic, a CCB, an ACE-inhibitor, or an α-receptor blocker, each drug used as initial treatment, with step-up drugs added as needed. At 10 years f/u there was no difference in overall survival supporting the original conclusion of the trial – the cheapest drug, chlorthalidone a thiazide should be preferred first line therapy for hypertension.
Enhanced Feedback for Effective Cardiac Treatment (EFFECT) – Public report cards on hospital performance are increasingly common, but whether they are an effective method for improving quality of care remains uncertain. A population-based cluster randomized trial, called the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study, was performed to evaluate whether public report cards could improve the quality of cardiac care delivery in Ontario, Canada. The introduction of report cards in one cluster of hospitals spurred improvements in process of care in other hospital clusters in anticipation of report cards. There were no improvements in AMI and CHF indicators of quality care in the hospital clusters that received early report cards.
RE-DEEM study is a phase II, randomized, double-blind, placebo-controlled, dose-escalation study evaluating the safety of four doses of the novel oral direct anti thrombin dabigatran etexilate: 50, 75, 110 or 150 mg twice daily in high risk patients with ACS treated with ASA and clopidogrel. There was a dose dependent increase in bleeding and a trend towards better efficacy with dabigatran in this setting.
Dr. Sedlis is Associate Professor of Medicine, and Chief, Division of Cardiology Manhattan Veterans Administration Medical Center