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European Journal of Heart Failure 2007 9(4):415-423; doi:10.1016/j.ejheart.2006.10.003
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© 2007 European Society of Cardiology

Effects of applying a standardised management algorithm for moderate to severe renal dysfunction in patients with chronic stable heart failure

Ramesh de Silvaa,*, Nikolay P. Nikitina, Klaus K.A. Wittea, Alan S. Rigbya, Huan Loha, Anthony Nicholsonb, Sunil Bhandaric, Andrew L. Clarka and John G.F. Clelanda

a Department of Cardiology, University of Hull, Castle Hill Hospital Kingston upon Hull, East Yorkshire, HU16 5JQ, United Kingdom
b Department of Vascular Radiology, Leeds General Infirmary Leeds, West Yorkshire, LS1 3EX, United Kingdom
c Department of Nephrology, Hull Royal Infirmary Kingston upon Hull, East Yorkshire, HU3 2JZ, United Kingdom

* Corresponding author. Tel.: +44 1482 624073, +44 7931 581 623(Mobile); fax: +44 1482 624085. E-mail address: ramesh{at}desilva84.freeserve.co.uk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Background: No specific guidelines exist on how to manage renal dysfunction (RD) in patients with chronic heart failure (CHF).

Aims: To identify the proportion of patients with moderate to severe RD and CHF who showed an improvement in their renal function in response to a systematic management algorithm.

Methods: Stable patients with CHF and RD (defined by a serum creatinine (SCr) of >130 µmol/l (>1.5 mg/dl)) were enrolled into a systematic management algorithm. The following changes were implemented: switching aspirin to clopidogrel, halving the dose of both diuretics and angiotensin converting enzyme (ACE) inhibitors and switching between bisoprolol and carvedilol.

Results: Two thirds of patients in whom diuretics were reduced, and one fifth of patients in whom ACE inhibitors were reduced, improved their SCr by >25.5 µmol/l (0.3 mg/dl). All these changes were more marked in the presence of bilateral renal artery stenosis. Compared to a reference group, in whom no changes were implemented, the treatment group showed an improvement in their mean SCr by 35 µmol/l (0.4 mg/dl), p<0.001.

Conclusion: Manipulation of pharmacological therapy for patients with CHF and RD results in a substantial recovery of renal function in a minority of patients.

Key Words: Chronic heart failure • Renal dysfunction • Renal artery stenosis

Received April 22, 2006; Revised August 2, 2006; Accepted October 4, 2006


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 
Renal dysfunction (RD) is common in patients with chronic heart failure (CHF) and predicts a worse outcome [1,2], which may be because it is a marker of worse cardiovascular function or because it reflects important comorbidity. RD might contribute by a variety of mechanisms, including impairment of salt and water excretion [3], increased neuro-endocrine activation [4], accumulation of uraemic factors and vascular, endothelial and haemostatic dysfunction [5]. RD may also limit the use of effective treatments for heart failure, such as angiotensin converting enzyme (ACE) inhibitors [6,7], angiotensin receptor blockers and aldosterone antagonists [8] and attenuate salt and water excretion in response to diuretics [9].

Recommendations for the management of RD in CHF rely mainly on anecdote, which quantify neither the proportion of patients who respond to intervention nor the magnitude of response. We therefore conducted a prospective study lasting 5 months to assess the effects on renal function of a systematically applied algorithm using a series of four standardised therapeutic interventions in patients with stable heart failure and chronic renal impairment. Two of these steps reflected management decisions used in clinical practice, such as reducing the doses of diuretics and angiotensin converting enzyme (ACE) inhibitors. The other two interventions were based on reports showing a theoretical advantage in improving renal function in patients with CHF, and included substituting aspirin with clopidogrel and switching between the two beta-blockers, bisoprolol and carvedilol.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Conclusion
 References
 
2.1. Ethical approval
All participants provided written informed consent, and the study was carried out in accordance with the Helsinki Declaration II and the European Standards for Good Clinical Research Practice. Ethical approval was granted by the Local Research Ethics Committee.

2.2. Study design
The study was a single centre, experimental trial with one treatment group prospectively followed for a period of five months. Patients with stable left ventricular systolic dysfunction (LVSD) and RD (as defined below) were included in a standardised treatment algorithm (Fig. 1). The primary objective was to determine whether a series of changes in therapy had any effect on renal function. The principal outcome of interest was the proportion of patients in whom a substantial improvement in renal function occurred between baseline and the end of the management algorithm. A secondary objective was to identify which, if any, individual treatment change had the greatest impact on renal function.


Figure 01
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  		Fig. 1 Standardised treatment flow chart. ACEi = angiotensin converting enzyme inhibitor.

 
2.3. Participants
Patients with a prior diagnosis of heart failure (determined by the presence of appropriate symptoms and signs, and a left ventricular ejection fraction <40%) and RD (defined as the presence of both a serum creatinine (SCr) of >130 µmol/l (1.5 mg/dl) and a calculated glomerular filtration rate (GFR) of <60 ml/min) were recruited from a community based heart failure programme. All patients were on stable treatment for a minimum of 8 weeks prior to entry. Exclusion criteria used were patients aged <18 years, pregnancy, inability to give informed consent, requirement for chronic renal dialysis or renal transplantation.

Patients with LVSD and RD who consented for investigations into their renal dysfunction and to be observed for 5 months, but who declined to take part in the management algorithm because of the number of additional hospital visits, provided a reference group in which the natural history of renal dysfunction without a systematic management programme could be observed.

2.4. Assessment and definition of renal dysfunction
SCr and the GFR were used to assess renal function. The GFR is usually regarded as the best overall index of the level of kidney function because SCr is determined by a number of factors other than GFR, such as sex, age, muscle mass and ethnicity. The GFR was calculated using a formula developed and validated in the Modification of Diet in Renal Disease (MDRD) study [10] as follows: GFR (ml/min/1.73 m2)=186.3x(SCr (mg/dl)–1.154)x(age (years)–0.203)x1.212 (if black)x0.742 (if female).

The following definitions, as recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines [11], were used to describe renal function in our population; GFR>90 ml/min/1.73 m2 = normal, GFR 60 to 89 ml/min/1.73 m2 = mild impairment, GFR 30 to 59 ml/min/1.73 m2 = moderate impairment and a GFR of <30 ml/min/1.73 m2 = severe impairment of renal function.

2.5. Baseline clinical assessment
All patients had a standard history and examination performed along with documentation of their past medical history and therapy. Daily doses of diuretics were expressed in furosemide equivalents (bumetanide 1 mg=furosemide 40 mg). Doses of agents blocking the renin-angiotensin-aldosterone system were expressed as the percentage of the maximum recommended daily dose for heart failure [12]. Other tests obtained at baseline were a 6-minute corridor walk test and a transthoracic echocardiogram to measure the ejection fraction, performed in the left lateral decubitus position at rest, using a Vingmed System V (GE Vingmed Ultrasound, Horten, Norway) with a 2.5 MHz transducer. Blood tests included urea, creatinine, potassium, sodium, and a full blood count. Urine was analysed for microalbuminuria.

2.6. Magnetic resonance angiography to assess renal artery stenosis
Patients with no contraindications underwent magnetic resonance angiography (MRA) to assess their renal arteries and kidney size. A non-nephrotoxic contrast agent, gadopentetate dimeglumine (Amersham Health, UK) was administered intravenously via a power injector over 2 s at a dose of 0.2 mmol/kg followed by 30 ml of normal saline as a flush to acquire MRA images of the renal arteries. Bolus tracking was used to optimise images. The images obtained were reported by one of us (AN) blinded to the clinical details of the patient. The degree of renal artery stenosis (RAS) was graded as follows: none, mild (<50% stenosis), moderate (51-69% stenosis) and severe (>70% stenosis). These were further classified as either bilateral or unilateral lesions.

2.7. Interventions
Patients without an obvious, readily correctable cause of renal dysfunction entered a standardised clinical algorithm designed to identify whether manipulation of therapy can improve renal function without worsening the heart failure. The process was five months in duration and implemented by the same physician (RDS) who was non-blinded. The therapeutic changes were implemented at four-weekly intervals as follows.

Baseline visit — Gathering of baseline data and review of medication to identify and, if possible, replace potentially nephrotoxic drugs.
Visit one — If patients were taking aspirin, this was stopped and substituted with clopidogrel. If the patient was already taking clopidogrel and/or warfarin, these were continued. No intervention was performed at this visit if patients were not on aspirin.
Visit two — Patients continued with the changes made at previous visits. The dose of diuretic was halved. If already on a minimum dose (<20 mg of furosemide or equivalent), the diuretic was stopped. Diuretic doses could be restored if the patient exhibited signs and symptoms of progressive fluid retention.
Visit three — If the patients remained stable, the reduced dose of the diuretic implemented previously was continued. If the patient was not already receiving the lowest available dose of an ACE inhibitor, the dose of the ACE inhibitor was halved.
Visit four — Patients taking bisoprolol were switched to carvedilol and vice versa, at the appropriate dose scale (e.g.: if on bisoprolol 5 mg od, carvedilol 12.5 mg bd was started). Previous reductions in ACE inhibitors or diuretic dose were continued, unless worsening of symptoms and signs occurred.
Final visit — Renal function was reassessed as described before. At the end of the study all medications were restored to pre-study doses.

At each visit patients were asked to report any change in symptoms or well being, and had their blood pressure measured, along with a blood sample to assess renal function and electrolytes. The SCr thus obtained reflected any changes in the renal function attributable to the pharmacological manipulation performed 4 weeks ago. The reference group had their renal function assessed at the end of the 5-month period. Changes were reported for each individual intervention and cumulatively from baseline.

2.8. Statistical methods
The principal form of analysis was descriptive, showing the numbers of patients in whom interventions were attempted, tolerated and successful. Statistical analysis was mainly confined to within group comparisons of the mean change (assuming normal distribution of change) and of the proportion of patients who responded. For mean change, the population of interest were those patients who tolerated the intervention. The proportion of patients responding was described both in relationship to the number of patients in whom the intervention was attempted and in whom the intervention was tolerated. A minor response was classified as a change >10 µmol/l (0.11 mg/dl) and a major response as a change >26.5 µmol/l (0.3 mg/dl). This latter figure was chosen as several investigators have reported a significant change in prognosis following improvement or deterioration of renal function by this amount [13-17].

Continuous variables were described by means and standard deviations and categorical data were described by percentages. We also present the same data stratified by the various degrees of RAS that were present. Analysis was performed using commercially available software (SPSS Inc, Chicago, Illinois, USA).


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Conclusion
 References
 
One hundred and twenty four patients who fulfilled the inclusion criteria were identified, of whom 72 patients agreed to participate in the management algorithm. The remaining 52 constituted the reference group. There were no significant differences between groups. The mean age of the patients was 73 (±9) years and 23 (19%) were women. Other baseline characteristics are shown in Table 1. Almost a quarter of the total population had microalbuminuria.


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  		Table 1 Baseline characteristics for both treatment and reference groups

 
One third of patients did not have MRA due to contraindications such as permanent pacemakers, claustrophobia or other reasons. Significant renal artery stenosis, defined as unilateral or bilateral narrowing of more than 50%, was seen in two thirds of the patients who were scanned (Table 2). Only a minority of patients had renal arteries that were free of any atherosclerosis.


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  		Table 2 Renal artery stenosis (RAS) as determined by contrast enhanced magnetic resonance angiography (MRA)

 
3.1. Response to interventions
The proportions of patients responding to interventions are given in Fig. 2 and the changes in the SCr observed are presented in Table 3.


Figure 02
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  		Fig. 2 Proportion of patients with changes in their renal function as measured by serum creatinine following treatment changes at each visit.

 


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  		Table 3 Changes in serum creatinine in the treatment group at each visit depending on the presence or absence of renal artery stenosis (RAS), and the overall change observed

 
3.1.1. Visit 1: substituting aspirin for clopidogrel
Forty (56%) patients were not taking aspirin. Of these, 6 were taking warfarin, 3 were taking clopidogrel and 31 were taking no anti-thrombotic agent. 32 patients were taking aspirin and were switched to clopidogrel. The mean SCr of these 32 patients fell by 8 (SD 19) µmol/l (within group comparison p=0.013) but rose by 7 (SD 34) µmol/l in the 40 patients who were not taking aspirin, and who therefore had no change in therapy (p=0.019 for the difference). SCr fell by >10 µmol/l (0.11 mg/dl) in 14 (44%) and by >26.5 µmol/l (0.3 mg/dl) in 7 (22%) of the patients who switched from aspirin to clopidogrel compared to 10 (25%) and 3 (8%) respectively in whom no change was made. Mean serum sodium, potassium, urea and haemoglobin did not change significantly (data not shown).

3.1.2. Visit 2: halving dose of diuretic
Eighteen patients had their loop diuretic stopped, 25 patients had their diuretic halved from 80 mg (in furosemide equivalents) to 40 mg od, 12 had their diuretic halved from 40 mg to 20 mg od, 9 had their diuretic halved from 160 mg to 80 mg od and 4 had their diuretic halved from 120 mg to 60 mg od. Four patients were not taking diuretics and one patient died due to a myocardial infarction prior to this visit.

7 of 18 (39%) patients were unable to tolerate discontinuation and 18 of 50 (36%) patients were unable to tolerate a reduction in diuretics. The reasons included an increase in shortness of breath (11 (44%)), increased ankle swelling and weight gain (7 (28%)) or both (7 (28%)).

Changes in SCr in the 42 patients who could tolerate dose reduction are shown in Table 3. Reduction of diuretics was associated with a modest improvement in mean serum creatinine, though 16 patients (38%) improved their SCr by >25.5 µmol/l (Fig. 2). Serum sodium, potassium and systolic blood pressure did not change in either group of patients.

Stopping or changing the dose of diuretics was not tolerated by 25 (37%) of the remaining 67 patients originally on diuretics. These patients had a higher mean SCr at the start of the study period when compared to the group tolerating the reduction in diuretics. (199 (±73) µmol/l vs. 159 (±43) µmol/l (2.3 (±0.8) mg/dl vs. 1.8 (±0.5) mg/dl) p=0.007. None of these 25 patients showed an improvement in their SCr by >25.5 µmol/l.

3.1.3. Visit 3: halving the dose of ACE inhibitor
68 (96%) patients were taking either an ACE inhibitor or an angiotensin receptor blocker, on average at 75% of the maximum recommended daily dose of the drug. 3 patients were not on ACE inhibitors and one patient died prior to this visit. There was no increase in symptoms following halving (or stopping in 4 cases already on a low dose) of the ACE inhibitor. Mean SCr fell from 170 (±55) µmol/l to 164 (±46) µmol/l, (1.9 (±0.6) mg/dl to 1.8 (±0.5) mg/dl) (within group comparison p=0.11) but serum urea, sodium and potassium were unchanged (data not shown). However, following dose reduction, one fifth of patients showed an improvement in their SCr by >26.5 µmol/l (0.3 mg/dl). Mean systolic blood pressure was unchanged in the 68 patients who had ACE inhibitors reduced or withdrawn but rose by >10 mm Hg in 22 (32%) patients.

3.1.4. Visit 4: switching of beta-blockers
65 (90%) of the 71 remaining patients in the treatment group were taking beta-blockers at the start of visit 4. 23 (32%) patients were switched from bisoprolol to carvedilol and 30 (42%) patients were switched from carvedilol to bisoprolol. 11 patients preferred not to have any changes made to their beta-blockers due to previously experiencing adverse effects with the alternative, 6 patients were not on any beta-blockers, one patient had died earlier, and another patient died of worsening heart failure before the final visit despite reintroduction of full dose ACE inhibition, and is not included. No significant changes were observed either in the change in SCr, sodium, potassium, urea or blood pressure. No adverse events due to side effects were reported. 4 patients in each arm showed an improvement of their SCr by more than 26.5 µmol/l (0.3 mg/dl) (Fig. 2).

3.1.5. Final visit
2 patients from the treatment group and 3 patients from the reference group had died by the end of the 5-month follow-up period (4% overall mortality). In the treatment group, two thirds of patients achieved a reduction in their SCr by >10 µmol/l (0.11 mg/dl), and nearly half achieved a reduction in their SCr by >26.5 µmol/l (0.3 mg/dl) (Fig. 2). 17 (24%) patients achieved a serum creatinine <130 µmol/l. Renal function deteriorated (rise in serum creatinine by 26.5 µmol/l (0.3 mg/dl)) in only 5 (7%) patients. Amongst patients who tolerated reductions in diuretic and ACE inhibitor dose, 15 out of 41 (37%) had a reduction SCr by >26.5 µmol/l (0.3 mg/dl). Amongst patients who withdrew from aspirin and tolerated reductions in both diuretic and ACE inhibitor dose, 9 out of 18 (50%) had a reduction SCr by >26.5 µmol/l (0.3 mg/dl). Patients in the reference group fared less well, with a deterioration in renal function (rise in serum creatinine by 26.5 µmol/l (0.3 mg/dl)) in 14 (29%) patients. The mean difference between the two groups was 35 µmol/l (confidence interval –50, –19 µmol/l, (0.4 mg/dl (confidence interval –0.6, –0.2) p<0.001) (Table 4). After adjustment for baseline SCr, a multi-variable analysis showed that no variables were significantly associated with an improvement in RD when considering it as a binary outcome measure.


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  		Table 4 Proportion of patients in whom serum creatinine (SCr) improved from baseline to the end of study after entering the standardised treatment algorithm in the presence or absence of varying degrees of renal artery stenosis (RAS)

 
3.2. Changes in the presence or absence of RAS
Changes in the SCr observed following manipulation of treatment at each visit stratified according to the presence or absence or RAS are shown in Table 4. After halving the dose of the ACE inhibitor, there was a striking reduction in SCr in patients with bilateral RAS but statistical heterogeneity across subgroups according to RAS could not be demonstrated.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Conclusion
 References
 
To our knowledge, this is the first study showing that systematic changes in treatment can improve renal function in patients with stable chronic RD and CHF and the first to investigate the influence or RAS. The application of a package of changes in pharmacological therapy causes, on average, a moderate overall improvement in renal function. However, SCr fell substantially, by >26.5 µmol/l (0.3 mg/dl), in 40% of patients in response to manipulation of therapy. A worsening of this magnitude appears to have prognostic significance [13-17]. Most of the improvement in renal function was due to reducing the dose of diuretics and ACE inhibitors, provided these could be tolerated. Improvement in renal function appeared more marked in the presence of underlying bilateral RAS although this could not be confirmed statistically, perhaps reflecting small numbers of patients. Despite these positive findings, it is also clear that application of existing clinical practice has little impact on renal function in the majority of patients with chronic RD and CHF.

4.1. Treatment changes
Aspirin inhibits the synthesis of prostaglandins by binding to cyclo-oxygenase [18]. This might reduce GFR, as renal vasodilator prostaglandins help maintain renal blood flow in the face of activated vasonconstrictor systems. Clopidogrel exerts its anti-platelet effects by binding to the ADP receptor on platelets, and therefore does not interfere with prostaglandin synthesis. The Warfarin and Antiplatelet Therapy in Chronic Heart failure (WATCH) trial suggested that patients with heart failure taking aspirin had more hospitalisations for worsening heart failure than did patients randomised to warfarin [19]. In WATCH, the rate of hospitalisation for worsening heart failure amongst patients randomised to clopidogrel was intermediate and not significantly different from either warfarin or aspirin. Based on the above and other evidence, Guidelines of the European Society of Cardiology do not advocate the routine use anti-thrombotic agents for the management of patients with heart failure including those with coronary disease [20]. Substituting aspirin with clopidogrel has been advocated in patients with CRD and CHF but this suggestion has not been adequately explored [21]. Our study is inconclusive partly due to the small number of patients taking aspirin. Substitution of aspirin with clopidogrel was associated with a small fall in SCr by 8 µmol/l that was of statistical significance and one in five of these patients had a substantial fall in SCr (>26.5 µmol/l (0.3 mg/dl)).

Chronic diuretic therapy leads to activation of the sympathetic nervous system [22], vasopressin and angiotensin II, and a reduction in arterial pressure, resulting in a decline in renal perfusion pressure, blood flow and GFR [23]. Identifying the smallest dose of diuretic that controls symptoms and oedema could minimise the adverse effects of these agents on renal function. However, in patients with intrinsic disease of the kidney, higher doses of diuretic may be required to maintain sodium balance. Patients in the present trial who were unable to tolerate a reduction in diuretics had higher SCr levels compared to the patients who tolerated the dose reduction. Most patients tolerated a reduction in diuretic dose but this did not result in a significant mean change in renal function. It is possible that further reductions in diuretic dose might have had a greater effect but may have been less well tolerated. However, the response to diuretic reduction was variable. Amongst the 58% of patients who tolerated a reduction in diuretic dose, 38% had a substantial improvement in SCr. Indeed, reduction in diuretic dose led to a substantial improvement in SCr in more patients than for any other intervention.

Angiotensin II causes efferent glomerular arteriolar constriction that helps maintain GFR in the face of a fall in perfusion pressure [22]. Activation of the RAS helps defend GFR in the face of a fall in arterial pressure or renal artery stenosis. Reducing the dose of ACE may allow restoration of some efferent arteriolar tone and improvement in GFR. Also, most ACE inhibitors are excreted by the kidneys, and therefore chronic RD will increase plasma concentration and duration of action of ACE inhibitors. In this study, reduction in the dose of the ACE inhibitor did not lead to a change in symptoms or blood pressure. Overall, the effects on renal function were modest but one in five patients had a substantial fall in SCr when the ACE inhibitor dose was reduced. The effects appeared greatest in patients with bilateral RAS although the study did not have adequate power to show that this effect was different from other patient-groups. Substantial improvement in SCr in some without RAS may reflect disease of small intra-renal vessels or afferent arteriolar dysfunction.

Beta-blockers may have a reno-protective effect in patients with CHF. In the Carvedilol Or Metoprolol European Trial (COMET) study patients randomised to carvedilol had less long-term deterioration in renal function than patients randomised to metoprolol [24]. In addition, improvements in the GFR and renal blood flow, measured by radioisotopes, have been documented in a small study using carvedilol [25]. Our data show that in routine clinical practice changing beta-blockers is not associated with an important effect on short-term renal function or blood pressure.

4.2. Renal artery stenosis
Prevalence rates for significant RAS in patients with CHF vary from between 12% and 34% [26,27]. Two thirds of the patients with RD in our study had evidence of significant RAS affecting at least one renal artery. However, doubt exists about the clinical and functional significance of RAS identified by MRA [28]. This study suggests that RAS identified by MRA does identify patients who are somewhat more likely to improve their renal function in response to reductions in therapy. If these results are confirmed, investigation for RAS might be considered routinely in patients with heart failure and RD. It is unclear whether renal angioplasty is an appropriate therapy for such patients [29] and the outcome of randomised control trials comparing renal angioplasty vs. standard medical that includes patients with heart failure are awaited [30].

4.3. Limitations
This was not a randomised controlled trial. A series of randomised controlled trials would be necessary to provide conclusive evidence of the effect of these interventions. However, the chosen study is essentially a pilot study, that allows calculations to be done on the size of study required to show an effect. The sample size calculations assume two groups of equal size with a power of 80% and 5% significance (two-tailed). Furthermore, we have not taken into account any loss to follow-up. Hence, to show a difference in SCr of ≥26.5 µmol/l (0.3 mg/dl) in patients switching from aspirin to clopidogrel we would need 100 patients per group. This calculation assumes that 22% of patients would improve their renal function when switching treatment compared to 8% not switching treatment. The change we observed in the diuretic group was larger (38%) which implies a smaller sample size (30 per group — again assuming an 8% difference in the comparator group). If approximately one third of patients were unable to tolerate a reduction in diuretics (from 25/67) the sample size would have to be increased upwards by an appropriate amount (100/70). The sample size for those on ACE would be similar to that of the aspirin-clopidogrel change.

An important limitation of our study is the inability to look at the longer term effects of changes in therapy and it is possible that the effects of switching away from aspirin, reducing the dose of diuretic and ACE inhibitor take a longer time to become fully apparent. For this reason, changes in renal function from baseline to the end of study, which was the principal outcome, might be due to the cumulative effects of these interventions. A randomised control trial of approximately 60 per group would be required to prove the overall efficacy of the management algorithm, assuming that 40% improved in the algorithm group compared to 18% in the usual care group. Whether reducing or changing medications proven to improve mortality and morbidity in CHF will offset the benefit observed in the reduction of mortality and morbidity in the presence of a falling GFR will need further prospective studies. The follow-up period was too short to consider these outcomes in our study. The prevalence of significant RAS in our study is higher than reported before, and may reflect a combination of selection bias and overestimation of the severity of the lesion using contrast enhanced MRA. And finally, the control group did not have their renal function checked at the same time points as the intervention group.


   5. Conclusion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
References
 
Manipulation of pharmacological therapy for patients with CHF and RD results in a substantial recovery of renal function in a minority of patients. It is probably the overall package of care rather than the sequence in which it was implemented that is important. Whether failure to respond reflects the presence of irreversible intrinsic renal disease, severe RAS or poor cardiac function awaits the results of further randomised control trials. Clearly, measures other than those we tested are required to reverse RD in this clinical setting. Patients with bilateral RAS may be more likely to respond to changes in pharmacological therapy but renal angioplasty might also be considered, although the safety and efficacy of this strategy must be tested.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Conclusion
 References
 

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Y. Amsalem, M. Garty, R. Schwartz, A. Sandach, S. Behar, A. Caspi, S. Gottlieb, D. Ezra, B. S. Lewis, and J. Leor
Prevalence and significance of unrecognized renal insufficiency in patients with heart failure
Eur. Heart J., April 2, 2008; 29(8): 1029 - 1036.
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