© 2004 European Society of Cardiology
Clinical trials update from the American Heart Association meeting: ACORN-CSD, primary care trial of chronic disease management, PEACE, CREATE, SHIELD, A-HeFT, GEMINI, vitamin E meta-analysis, ESCAPE, CARP, and SCD-HeFT cost-effectiveness study
a Department of Cardiology, University of Hull, Castle Hill Hospital Cottingham, Kingston-upon-Hull, HU15 5JQ, UK
b Department of Primary Care and General Practice, University of Birmingham Edgbaston, Birmingham, B15 2TT, UK
* Corresponding author. Tel.: +44 1482 624086; fax: +44 1482 624085. E-mail address: a.p.coletta{at}hull.ac.uk
 |
Abstract |
|---|
 Top Abstract 1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
This article provides information and a commentary on landmark trials presented at the American Heart Association meeting held in November 2004, relevant to the pathophysiology, prevention, and treatment of heart failure. An open trial of the ACORN Cardiac Support Device (CSD) showed encouraging preliminary results in patients with severe heart failure. The PEACE (Prevention of Events with Angiotensin-Converting Enzyme inhibition) study supports data from previous studies showing that ACE inhibitors reduce vascular events in patients at increased risk. The CREATE (clinical trial of metabolic modulation in acute MI treatment evaluation) study of patients with acute myocardial infarction (MI) showed no mortality benefit of a glucose/insulin/potassium regimen, but treatment with reviparin reduced the incidence of death, MI, or stroke. Azimilide was not associated with a significant reduction in shocks, but reduced the shocks or episodes of markedly symptomatic ventricular tachycardia terminated by pacing in the SHIELD (Shock Inhibition Evaluation with Azimilide) study. The addition of isosorbide dinitrate plus hydralazine to standard therapy improved survival in black heart failure patients in the A-HeFT (African—American Heart Failure Trial) study. In an investigation of hypertensive patients with diabetes, carvedilol had fewer adverse effects on diabetic control than metoprolol. A meta-analysis of high-dose vitamin E supplementation suggested an association with increased mortality. The ESCAPE (Evaluation Study of CHF and Pulmonary Artery Catheterisation Effectiveness) study showed no benefit of pulmonary artery catheterisation over clinical management in patients with severe heart failure. Routine prophylactic coronary revascularisation for stable coronary disease prior to major vascular surgery showed no benefit in the CARP (Coronary Artery Revascularization Prophylaxis) study. Analysis of data from SCD-HeFT supports the cost-effectiveness of ICDs in heart failure, although overall cost implications may be prohibitive.
Key Words: ACORN-CSD • Primary care trial of chronic disease management • PEACE • CREATE • SHIELD • A-HeFT • GEMINI • Vitamin E meta-analysis • ESCAPE • CARP • SCD-HeFT cost-effectiveness
Received November 15, 2004; Accepted November 23, 2004
|
1. ACORN Cardiac Support Device (CSD) trial |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
The ACORN CSD is a high-technology fibre mesh that can be wrapped around the heart to provide some external elastic constraint and, therefore, myocardial support in diastole. Theoretically, this could prevent progressive left ventricular dilatation or even reverse it by reducing diastolic myocardial transmural stress [1]. Apart from the obvious risks of surgery and infection, there is a theoretical risk of producing iatrogenic pericardial restriction.
The ACORN-CSD trial enrolled 300 patients with heart failure (NYHA II–IV, 6 MWT <150 m) and LVSD (EF <35% and LVEDD >60 mm) who did not require CABG. Of these, 193 patients were scheduled for mitral valve surgery for mitral regurgitation. These patients were randomised to no additional procedure (n=102) or additional CSD (n=91). A total of 107 patients did not require mitral surgery and these were randomised to receive (n=57) or not to receive (n=50) CSD in addition to optimal medical therapy. The primary endpoint of the trial was a composite of (a) death, (b) major cardiac procedures (CABG, valve surgery, LVAD, transplant, or CRT), and (c) worsening NYHA class.
The patients enrolled had a mean age of 52 years, 55% were men, only 10% had IHD, mean LVEF was 27.4% (but many had severe mitral regurgitation), and LVEDD was 72 mm. Over the following year, the ACORN-CSD reduced LV diastolic volume by about 25 ml more than control (p<0.01), with some evidence of increasing effect over time. Trends to improvement in LVEF (3% v 1%) were not significant. Quality of life scores (Minnesota and SF36) both improved (p<0.05 and p=0.015, respectively) but NYHA class did not. However, the trial was unblinded and therefore subjective measurements should be treated with caution. Rehospitalisation and mortality were unaffected, but major cardiac procedures were reduced and therefore the primary endpoint was achieved (Table 1). Patients undergoing mitral surgery improved markedly even without CSD, although trends to greater benefits were observed in those who received the device. In patients who did not undergo mitral surgery, the benefits of CSD compared to control appeared greater.
|
In summary, this trial suggests that CSD can reduce LV volumes and the need for other major cardiac procedures in a highly selected group of patients with severe heart failure. This is a very encouraging preliminary result, although it needs to be viewed with caution since the trial was unblinded. The possibility of the development of long-term problems such as pericardial constriction or compression of bypass grafts needs to be excluded. Faced with a patient who has end-stage heart failure, there is now a range of options extending from expert manipulation of pharmacological therapy to CRT, erythropoietin, external counterpulsation, and LVADs. A lot more convincing data are required before this device will be used for patients who do not require surgery for another reason. On the other hand, provided long-term safety and efficacy data can be provided, the threshold to using CSD could be low as part of the routine management of patients with heart failure and major LV dilatation who require valve surgery or CABG.
|
2. Primary care-based trial of chronic disease management |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
The management of heart failure is becoming increasingly complex. In order for treatments to be delivered safely and effectively, it seems logical to provide an organised system of expert care [2–5]. The investigators in the present study attempted to contact over 40,000 Medicare patients in South Texas who had been coded for heart failure. From this population, 1069 patients with heart failure and either LVSD (LVEF <49%) or diastolic dysfunction (LVH or Doppler criteria) agreed to participate in a trial comparing usual care versus a nurse-based disease management program. Primary care physicians made all the medical decisions about the patients. The results have recently been published [25].
The mean age of the patients was 71 years, 29% were women, 62% had IHD, 39% had had a myocardial infarction (MI), 28% had diabetes mellitus, and 72% had hypertension. Seventy percent had LVSD (LVEF 35%: systolic BP, 138 mm Hg) and 30% had LVDD (LVEF 62%: systolic BP, 155 mm Hg). Fifty-seven percent were in NYHA II and 24% were in NYHA III/IV.
Overall, the disease management program reduced mortality (p=0.037) but not event-free survival. There was no effect on bed days or costs. In patients with LVSD, mortality was reduced (p=0.012) and event-free survival increased (p=0.017). Patients with LVSD randomised to the intervention lived an average of an additional 81 days. For comparison, meta-analysis of trials of CABG suggests that revascularisation of triple-vessel disease increases average survival by about the same amount over 5 years [6]. There was no effect on LVDD.
In summary, the trial shows a small benefit from a primary care-based chronic disease management program amongst patients with predominantly mild heart failure at low risk of events. Beta-blocker use was high at entry to the study. It may be that the care received in the control and intervention groups was rather similar. Other studies have suggested that specialist care might have increased benefits further. The data are consistent with other studies that have shown either a reduction in mortality or in rehospitalisation, or both [2,3]. The lack of effect in patients with LVDD may reflect the better prognosis of (and lack of effective therapies for) this group of patients.
|
3. PEACE: Prevention of Events with Angiotensin-Converting Enzyme inhibition |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
The results of PEACE have already been reported [7]. Briefly, the study recruited 8290 patients aged >50 years with proven stable coronary disease in whom a LVEF <40% or serum creatinine >177 µmol/l had been excluded, and who had tolerated 2 mg of trandolapril for 2 weeks. Patients were then randomised to double-blind placebo or trandolapril 4 mg/day. The initial intention was to randomise >14,000 patients with a primary endpoint of death or MI. Due to poor recruitment, the primary endpoint was expanded to include coronary revascularisation, and this increase in event rate allowed a reduction in study size to 8100 patients. The mean follow-up was 4.8 years.
The mean age of the patients was 64 years, 54% had had a MI, and 17% had diabetes. Ninety percent were receiving aspirin, 70% lipid-lowering drugs, and 60% beta-blockers. Seventy-two percent had undergone revascularisation prior to entry and a further 19% underwent first or repeat revascularisation during the course of the study.
Trandolapril did not reduce any of the primary or preplanned secondary outcomes. Overall, there were only six fewer cardiovascular deaths on trandolapril compared to placebo. The trial appears resoundingly neutral—but is it really different from HOPE and EUROPA, trials in which the ACE inhibitors ramipril and perindopril were shown to reduce cardiovascular events? The answer is probably not. The confidence intervals surrounding the modest effects of ACE inhibitor on the same endpoint in all three trials overlap. Indeed, for the most robust outcome, all-cause mortality, the relative benefits in PEACE (11%), EUROPA (11%), and HOPE (16%) are very similar. Absolute benefits were also similar but small (0.9%, 0.8%, and 1.8%, respectively). The HOPE trial did observe a reduction in revascularisation, where intervention was predominantly CABG (p=0.002), an outcome that showed a strong positive trend in PEACE. On the other hand, revascularisation was not reduced in EUROPA and revascularisation in this trial was probably predominantly by PCI, an outcome on which trandolapril had no effect in PEACE. Had coronary revascularisation been added to the primary endpoint of EUROPA, the effects of perindopril would have been attenuated or lost. Unfortunately, the PEACE trial has insufficient power to show an effect on outcomes such as CVS death, MI, or stroke because it included fewer patients than either EUROPA or HOPE, and also had a lower annual event rate compared to HOPE (about 2% compared to about 3%).
In HOPE, for every 1000 patients treated for 5 years, between 20 and 60 patients would have CVS death, MI, or stroke prevented. In EUROPA, it would be between 15 and 40, and in PEACE, up to about 20. Of course, this means that over 90% of patients in each of the trials obtained no demonstrable benefit. The PEACE study should make us reconsider the medical philosophy of treating large numbers of patients for small benefits. Accurate targeting of highly effective therapy to the individual patient's needs should be the goal of modern medicine. PEACE may mark the beginning of the end of the era of the megatrial. Although large studies may provide tight confidence intervals around their result, the clinical relevance of any intervention that requires a large long-term study to show a statistical effect must be questioned. In other words, large studies are only really useful when they are neutral or when they are stopped early.
However, it is possible that the trials had genuinely different results. Trandolapril reduced mortality in the TRACE study and cannot be considered ineffective, but important differences between ACE inhibitors are possible. It may be that higher doses are required in the patient group recruited to PEACE, although the dose of ramipril was only 10 mg/day in HOPE. On the other hand, differences in treatment or patients may be important. Diabetes was more common in HOPE, but no benefit in this subgroup was observed in PEACE. Most of the benefits in HOPE were confined to the 25% of patients who were not taking aspirin (Fig. 1). High aspirin use may have accounted for the trend to lesser benefit observed in EUROPA and PEACE. However, the rate of death or MI on active treatment in EUROPA and PEACE was similar despite a much higher rate of revascularisation in the latter trial. Could it be that the benefits of revascularisation and ACE inhibitors are also similar but not additive?
|
New-onset diabetes mellitus was common in PEACE (one in eight patients) and almost twice as common as in HOPE, which can only be partially accounted for by the higher baseline prevalence of diabetes in HOPE. The high rate may reflect changing criteria or improved surveillance for diabetes. The small reduction in the number of patients developing diabetes on trandolapril in PEACE is a consistent feature of trials of ACE inhibitors as well as ARBs. It is not clear whether this reflects a direct effect on cellular function or an indirect effect mediated through changes in weight and body composition.
The PEACE study reported that about one in every 25 patients had heart failure as the primary cause of death or hospitalisation. Extrapolating from epidemiological data and from the HOPE study, this finding suggests that about three times as many patients may have exhibited new-onset heart failure in other ways than was reported, making it potentially the most common serious CVS event in PEACE. Again, the consistency between the trials is remarkable.
There has been much controversy as to whether the results from these trials, particularly HOPE, simply reflected blood pressure reduction, or represented a specific ACE inhibitor effect. There is some evidence to suggest that the blood pressure effect may have been more profound than widely known in HOPE [8], and, in PEACE, there seems to have been little difference in blood pressure between the treated and placebo groups. The neutral outcome in PEACE is thus consistent with the blood pressure argument.
A meta-analysis of outcome data from the HOPE, EUROPA, and PEACE studies is shown in Fig. 2a and b.
|
In summary, PEACE reinforces the notion that ACE inhibitors reduce vascular events in patients at increased risk. The effect in all three studies is modest but consistent. Society and the medical profession should decide what absolute level of risk and absolute benefit justifies taking an extra tablet each day. Controversially, trials comparing the safety and efficacy of revascularisation with contemporary interventions to that of medical therapy are urgently required since this is an area of medical practice that lacks an adequate evidence base.
|
4. CREATE: clinical trial of metabolic modulation in acute MI treatment evaluation |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
This study of more than 20,000 patients tested two hypotheses in patients with acute MI. The first hypothesis was that a glucose/insulin/potassium regimen would reduce mortality (it did not). Major morbidity was also not reduced and there were more adverse events. The second hypothesis was to test the effect of a low-molecular-weight heparin, reviparin, on 7- and 30-day incidence of death, MI, or stroke. Reviparin reduced the composite outcome at both time points, mainly due to an effect on death and MI.
The benefit from reviparin was greater the earlier it was given. The majority of these patients received thrombolysis with streptokinase, in whom antithrombotic treatment is commonly withheld or delayed for several hours (as compared with patients receiving alteplase/tenecteplase). CREATE should encourage earlier use of low-molecular-weight heparin in patients who have received streptokinase.
|
5. SHIELD: Shock Inhibition Evaluation with Azimilide |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
Azimilide is an antiarrhythmic drug with potassium channel-blocking properties that prolongs the cardiac action potential and refractory periods and is theoretically useful for the prevention of VT/VF. This double-blind, placebo-controlled trial randomised patients (mean LVEF 34%) with an ICD and recent VT or VF to azimilide (at two dose levels) or placebo and followed them for 1 year. Azimilide was not associated with a significant reduction in shocks but did reduce shocks or episodes of markedly symptomatic VT terminated by pacing (Table 2). Mortality was not reduced, but cardiovascular hospitalisations, including those for heart failure, were reduced by the lower dose. The reduction was either due to fewer ICD shocks (which may cause myocardial damage) or suppression of supraventricular and ventricular arrhythmias. There were five patients in the azimilide group and one patient in the placebo group who developed torsades de pointes. Because the patients had ICDs, they were protected from the worst effects of this outcome.
|
|
6. A-HeFT: African–American Heart Failure Trial |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
This study has recently been published in the New England Journal of Medicine [9,10]. Briefly, 1050 African–American patients with NYHA III/IV heart failure were randomised to placebo or Bidil (a combination of hydralazine/isosorbide dinitrate) on top of treatment with ACE inhibitors, beta-blockers, and diuretics. The rationale for this was the observation that only African–American patients received benefit with the combination in V-HeFT I [11] and that ‘Bidil— outperformed enalapril in this subgroup in V-HeFT II [11]. African–American patients may not have benefited from enalapril in SOLVD [12], although data on this latter point are conflicting [13]. However, in neither V-HeFT trial was there a significant interaction on mortality between race and treatment (Table 3).
|
The primary endpoint of the study included death, hospitalisation, and patient well-being. The study was stopped early by its DSMB after only 86 deaths had occurred and only a mean of 10 months of follow-up accrued due to a 43% reduction in mortality with Bidil. This is unfortunate since studies stopped early for benefit tend to overestimate effects, and the number of deaths is not large enough to convince all observers. However, the result is encouraging. The use of ACE inhibitors and beta-blockers other than carvedilol [14] must now be questioned in this population. Whether Bidil is effective in other racial groups is presumably the next big question. Data have not so far provided convincing evidence that either nitrates or hydralazine used alone adds to the benefits of ACE inhibition [15].
|
7. GEMINI: glycemic effects in diabetes mellitus: carvedilol–metoprolol comparison in hypertensives |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
This randomised study of 1235 hypertensive patients suggested that carvedilol (target dose 25 mg, bid; mean achieved dose 17.5, mg bid) had fewer adverse effects on insulin sensitivity and diabetes control compared to metoprolol tartrate (target dose 200 mg, bid; mean achieved dose 128 mg, bid). There were more problems with bradycardia in those assigned to metoprolol [16]. It is unclear as to what extent the difference observed is due to dose or drug, although its findings are in keeping with other studies in heart failure [17,18].
|
8. Vitamin E meta-analysis |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
This meta-analysis suggested that high-dose vitamin E supplements were associated with increased mortality, although these data may not apply to patients with heart failure who were poorly represented in the analysis [19].
|
9. ESCAPE: Evaluation Study of CHF and Pulmonary Artery Catheterisation Effectiveness |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
This randomised controlled trial assessed the value of a pulmonary artery catheter (PAC) for the management of patients admitted to hospitals with severe heart failure not already treated with inotropic agents [20]. Only patients with LVEF <30% and systolic blood pressure <125 mm Hg were included to ensure higher risk, but patients with serum creatinine >3.5 mg/dl (about 300 µmol/l) were excluded as these patients might not have tolerated effective treatments for heart failure. The immediate therapeutic goal in the clinically managed group was resolution of the symptoms and signs of heart failure. The immediate goal in the intervention group was the same but also to reduce the PCWP to <15 mm Hg and right atrial pressure to <8 mm Hg. The primary outcome was the number of days dead or hospitalised over 6 months.
A total of 218 patients were randomised to clinical management and 215 to the PAC. The mean age of the patients was 56 years, 26% were women, and 56% had ischaemic heart disease. The mean ejection fraction was 19%, systolic BP 106 mm Hg, sodium 136 mmol/l, and creatinine 1.5 mg/dl (about 130 µmol/l). The 6-min walk test was 400 ft (the patients could walk) and Minnesota QoL score was 74 (versus 75 in REMATCH [21]). PCWP was 25 mm Hg (dropping to 17 mm Hg on therapy), right atrial pressure 14 mm Hg (dropping to 10 mm Hg on therapy), and cardiac index 1.9 l/min/m2 (rising to 2.4 l/min/m2). Patients randomised to clinical care tended to receive more diuretics and beta-blockers.
During 6 months follow-up, patients spent a median of about 11 days in hospital (average 17 days); mortality was about 19% and 21% of the 180 days of follow-up (average 38 days; median 13 days) were lost due to death or hospitalisation (Table 4). Patients managed clinically had fewer serious adverse events and tended to have a lower mortality; but otherwise, there was no difference in outcome. There was no difference in index hospitalisation duration (about 8 days). Eighteen percent of control patients crossed over to catheterisation. There were no PAC-related deaths.
|
In conclusion, this result suggests that clinicians should be conservative about their use of pulmonary catheters. However, pulmonary catheterisation may still have a place in the management of hypotensive patients (i.e., those with systolic BP <100 mm Hg). No subgroup analyses were presented.
|
10. CARP: Coronary Artery Revascularization Prophylaxis trial |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
This study investigated the use of routine prophylactic coronary revascularisation by CABG or PCI for stable coronary disease prior to major surgery for abdominal aortic (33%) or peripheral (leg) vascular disease [22,23]. The primary endpoint was long-term all-cause mortality. The study was adequately powered for this endpoint. A total of 5859 patients were screened for inclusion and 80% were excluded mainly because the patient/procedure was considered to have such a low risk that angiography was not necessary, or because the vascular surgery was urgent and had to proceed without delay. A total of 1190 had an angiogram. This showed no coronary obstruction in only 5%, no revascularisable lesion in 20%, and left main coronary disease in 8%. These patients were excluded. Eventually, 510 were randomised. Thirty-five percent of this group had three-vessel coronary disease, 44% had myocardial perfusion imaging indicating moderate or high risk, and their mean age was 66 years. Eighty percent of patients were on a beta-blocker and 50% on a statin. Coronary revascularisation was by percutaneous intervention in 59% of cases and 41% had CABG. Coronary revascularisation led to about 7 weeks delay (versus 1–3 weeks in the control group) in vascular surgery during which 10 patients died.
Perioperative outcome following peripheral vascular surgery was similar in each group in terms of mortality and MI. During a median follow-up of 2.7 years, all-cause mortality was similar in the two groups at about 23%. Only 25% of deaths were from coronary disease in each group (Table 5).
|
These data suggest, with few caveats, that routine preoperative revascularisation for vascular—and probably by extension of other types—surgery is not warranted. Preoperative assessment by stress echo or nuclear cardiology tests will identify patients at increased risk, but as intervention has not been shown to decrease risk, the value of such tests should be questioned. However, noninvasive techniques could have a role in excluding left main coronary disease. It may be better to focus on the use of beta-blockers and statins in this setting rather than investigating and intervening on coronary disease.
|
11. SCD-HeFT cost-effectiveness study |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
Governments increasingly use estimates of cost-effectiveness to decide which interventions to adopt. These calculations should be performed on locally derived data since costs (mainly salaries) may vary widely. However, estimates from one country provide a starting point for others. In the United States and UK, a cost per life year gained (LYG) of less than US$50,000 is generally considered cost-effective, whilst costs in excess of US$100,000 would generally be considered cost-ineffective. However, governments implement many interventions that are not cost-effective (for instance, air bags in cars or some railway safety measures, both of which are thought to cost in excess of 1 million per LYG).
This analysis of the SCD-HeFT trial [24] suggested that ICDs were fairly cost-effective. The analysis assumed that the average cost of a simple device with leads but not implantation costs in the United States was US$17,500 (range US$13,000–23,700) and that the average cost of 5-year management in the control group was about US$43,000 and in the ICD group was US$62,000 per patient (Table 6). The primary analysis extrapolated the within-trial follow-up to lifetime expectation. The median longevity in the control group was estimated to be 8.4 years, rising to 10.9 years with an ICD.
|
On this basis, the calculation suggests that the cost per life year gained is US$33,000, similar to that estimated for MADIT II (about US$50,000 per LYG). There was a powerful interaction between NYHA class and outcome (p=0.0002). ICDs did not appear effective (and therefore not cost-effective) in patients who had NYHA III heart failure. Patients with milder NYHA II heart failure had a cost of US$26,000 per LYG. If this interaction was ignored and the benefits were assumed to be the same regardless of NYHA class, the cost-effectiveness was still higher in NYHA III patients (US$35,000 vs. US$45,000). If only cost over the lifetime of the study is considered, the cost rises to US$77,000 per LYG. If quality-adjusted life years (QALY) are considered, then the estimated cost per QALY was about US$35,000. Analysis of other subgroups including age >65 years, LVEF <30%, and QRS width >120 ms showed little variation in cost-effectiveness.
Clearly, this analysis suggests that ICDs are cost-effective by current criteria. Are there any reasons not to implant them in most patients with low ejection fraction heart failure? In fact, there are many reasons to be cautious. Firstly, ICDs are not as cost-effective to implement as ACE inhibitors, beta-blockers, or spironolactone, nor as cost-effective as some other measures, such as heart failure nurses or telemonitoring. Implementation rates for these effective, inexpensive treatments are low. Only once an adequate protocol for the implementation and monitoring of pharmacological treatment is in place should ICDs be considered. Secondly, new technologies such as CRT may provide most or all of the mortality benefits of ICDs at lower cost, whilst also improving patient symptoms. Thirdly, it is possible that properly informed patients may decide that they do not want a device, knowing that more than 90% of recipients will not benefit from the device over 5 years and that 10–20% of patients will get inappropriate shocks. Finally, only considering new cases of heart failure and assuming that only 25% of patients receive an ICD because the patient has refused the device or is considered too frail then a regional centre covering a population of 2 million people will need to implant about 500 devices per year. Once steady state has been reached, the excess treatment costs may be about 
20 million per year, based on this model. Even though ICDs might be cost-effective, it is possible that health services will be unable to afford to implement therapy.
Ultimately, the best solution is to target ICD use more accurately. Unfortunately, no technology or strategy has convincingly shown that it can usefully detect who will and who will not benefit from an ICD.
|
References |
|---|
|
TopAbstract1. ACORN Cardiac Support...2. Primary care-based trial...3. PEACE: Prevention of...4. CREATE: clinical trial...5. SHIELD: Shock Inhibition...6. A-HeFT: African-American...7. GEMINI: glycemic effects...8. Vitamin E meta-analysis9. ESCAPE: Evaluation Study...10. CARP: Coronary Artery...11. SCD-HeFT cost-effectiveness...References |
|---|
- Mann D.L., Acker M.A., Jessup M., Sabbah H.N., Starling R.C., Kubo S.H.On behalf of the ACORN Investigators. Rationale, design and methods for a pivotal randomised clinical trial for the assessment of a cardiac support device in patients with New York Heart association Class III–IV heart failure. J. Card. Fail. (2004) 10(3):185–192.[CrossRef][Web of Science][Medline]
- Louis A.A., Turner T., Gretton M., Baksh A., Cleland J.G.F. A systematic review of telemonitoring for the management of heart failure. Eur. J. Heart Fail. (2003) 5:583–590.
[Abstract/Free Full Text] - Gonseth J., Gullar-Castillon P., Banegas J.R., Rodriguez-Artalejo. The effectiveness of disease management programmes in reducing hospital re-admission in older patients with heart failure: a systematic review and meta-analysis of published reports. Eur. Heart J. (2004) 25:1570–1595.
[Abstract/Free Full Text] - Fox K.F., Cowie M.R., Wood D.A., Coates A.J., Poole-Wilson P.A., Sutton G.C. A rapid access heart failure clinic provides a prompt diagnosis and appropriate management of new heart failure presenting in the community. Eur. J. Heart Fail. (2000) 2(423):429.
- Wright S.P., Walsh H., Ingley K.M., Muncaster S.A., Gamble G.D., Pearl A., et al. Uptake of self-management strategies in a heart failure management programme. Eur. J. Heart Fail. (2003) 5:371–380.
[Abstract/Free Full Text] - Yusuf S., Zucker D., Peduzzi P., Fisher L.D., Takaro T., Kennedy J.W., et al. Effect of coronary artery bypass graft surgery on survival: overview of 10 year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet (1994) 344:563–570.[CrossRef][Web of Science][Medline]
- The PEACE Trial Investigators. Angiotensin converting enzyme inhibition in stable coronary artery disease. N. Engl. J. Med. (2004) 351:2058–2068.
[Abstract/Free Full Text] - Svensson P., de Faire U., Sleight P., Yusuf S., Stergren J. Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE substudy. Hypertension (2001) 38:e28–e32.[CrossRef][Web of Science][Medline]
- Franciosa J.A., Taylor A.L., Cohn J.N., Yancy C.W., Ziesche S., Olukotun A., et alA-HeFT Investigators. African–American Heart Failure Trial (A-HeFT): rationale, design and methodology. J. Card. Fail. (2002) 8(3):128–135.[CrossRef][Web of Science][Medline]
- Taylor A.L., et alFor the A-HeFT Trial Investigators. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N. Engl. J. Med. (2004) 351:2049–2057.
[Abstract/Free Full Text] - Carson P., et alFor the V-HeFT Trial Study Group. Racial differences in response to therapy for heart failure: analysis of the vasodilator—heart failure trials. J. Card. Fail. (1999) 5(3):178–187.[CrossRef][Medline]
- Exner D.V., Dries D.L., Domanski M.J., Cohn J.N. Lesser response to ACE inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N. Engl. J. Med. (2001) 344:1351–1357. [Ref. ID 5269].
[Abstract/Free Full Text] - Dries D.L., Strong M.H., Cooper R., Drazner M.H. Efficacy of angiotensin converting enzyme inhibition in reducing progression from asymptomatic left ventricular dysfunction to symptomatic heart failure in black and white patients. J. Am. Coll. Cardiol. (2002) 40:311–317.
[Abstract/Free Full Text] - Yancy C.W., et alFor the US Carvedilol Heart Failure Study Group. Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure. N. Engl. J. Med. (2001) 344:1358–1365.
[Abstract/Free Full Text] - Massie B.M., Packer M., Hanlon J.T., Combs D.T. Hemodynamic responses to combined therapy with captopril and hydralazine in patients with severe heart failure. J. Am. Coll. Cardiol. (1983) 2:338–344.[Abstract]
- Bakris G.L., et alFor the GEMINI Investigators. Metabolic effects of carvedilol vs. metoprolol in patients with type 2 diabetes mellitus and hypertension. JAMA (2004) 292(18):2227–2236.
[Abstract/Free Full Text] - Refsgaard J., Thomsen C., Andreassen F., Gotzsche O. Carvedilol does not alter the insulin sensitivity in patients with congestive heart failure. Eur. J. Heart Fail. (2002) 4:445–453.
[Abstract/Free Full Text] - Nodari S., Metra M., Cas A.D., Cas L.D. Efficacy and tolerability of the long term administration of carvedilol in patients with chronic heart failure with and without concomitant diabetes mellitus. Eur. J. Heart Fail. (2003) 5:803–809.
[Abstract/Free Full Text] - Miller E.R., Pastor-Barriuso R., Dalal D., Riemersma R.A., Appel J.L., Guallar E. Meta-analysis: high dose vitamin E supplementation may increase all-cause mortality. Ann. Intern. Med. (2004) 142. [in press].
- Shah M.A., et alFor the ESCAPE Investigators. Evaluation study of congestive heart failure and pulmonary artery catheterisation effectiveness (ESCAPE): design and rationale. Am. Heart J. (2001) 141:528–535.[CrossRef][Web of Science][Medline]
- Rose E.A., et alFor the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) Study Group. Long-term use of a left ventricular assist device for end-stage heart failure. N. Engl. J. Med. (2001) 345(20):1435–1443.
[Abstract/Free Full Text] - McFalls E.O., Ward H.B., Krupski W.C., Goldman S., Littooy F., Eagle K., et al. Prophylactic coronary artery revascularisation for elective vascular surgery: study design. Control. Clin. Trials (1999) 20:297–308.[CrossRef][Web of Science][Medline]
- Pierpont G.L., Mortiz T.E., Goldman S., Krupski W.C., Littooy F., Ward H.B., et alCurrent Opinion on Revascularisation Study Investigators. Disparate opinions regarding indications for coronary artery revascularisation before elective vascular surgery. Am. J. Cardiol. (2004) 94(9):1124–1128.[CrossRef][Web of Science][Medline]
- Cleland J.G.F., Ghosh J., Freemantle N., Kaye G.C., Nasir M., Clark A.L., et al. Clinical trials update and cumulative meta-analyses from the American College of Cardiology: WATCH, SCD-HeFT, DINAMIT, CASINO, INSPIRE, STRATUS-US, RIO-LIPIDS and cardiac resynchronisation therapy in heart failure. Eur. J. Heart Fail. (2004) 6:501–508.
[Abstract/Free Full Text] - Galbreath A.D., Krasuski R.A., Smith B., Stajdhuhar K.C., Kwan M.D., Ellis R., et al. Long-term healthcare and cost outcomes of disease management in a large randomised community based population with heart failure. Circulation (2004) 110. [in press].
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Z. Xia, K.-H. Kuo, P. R. Nagareddy, F. Wang, Z. Guo, T. Guo, J. Jiang, and J. H. McNeill N-acetylcysteine attenuates PKC{beta}2 overexpression and myocardial hypertrophy in streptozotocin-induced diabetic rats Cardiovasc Res, March 1, 2007; 73(4): 770 - 782. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Fisher Who Needs a Defibrillator?: The Beat Goes On J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1727 - 1728. [Full Text] [PDF]
|
|
|
|
 |
|
 J. G.F. Cleland, A. P. Coletta, M. Lammiman, K. K. Witte, H. Loh, M. Nasir, and A. L. Clark Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS-III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE Eur J Heart Fail, October 1, 2005; 7(6): 1070 - 1075. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Developed in Collaboration With the American Colle, Endorsed by the Heart Rhythm Society, S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure) J. Am. Coll. Cardiol., September 20, 2005; 46(6): 1116 - 1143. [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Hunt, W. T. Abraham, M. H. Chin, A. M. Feldman, G. S. Francis, T. G. Ganiats, M. Jessup, M. A. Konstam, D. M. Mancini, K. Michl, et al. ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult--Summary Article: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: Endorsed by the Heart Rhythm Society Circulation, September 20, 2005; 112(12): 1825 - 1852. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||