On 24 June the National Institute of Clinical Excellence (NICE)
issued their Appraisal consultation document: coronary artery
stents.[1] With the proviso that ‘the decision to use a bare metal
stent or drug-eluting stent (DES) will depend on the anatomy of
the target vessel for stenting and the severity of the disease’
(presumably reflecting issues of deliverability of the stent
platforms on offer), t...
On 24 June the National Institute of Clinical Excellence (NICE)
issued their Appraisal consultation document: coronary artery
stents.[1] With the proviso that ‘the decision to use a bare metal
stent or drug-eluting stent (DES) will depend on the anatomy of
the target vessel for stenting and the severity of the disease’
(presumably reflecting issues of deliverability of the stent
platforms on offer), the key point was that a ‘DES is
recommended .. [when] .. the target artery is less than 3mm in
diameter or the lesion to be stented is longer than 20mm.’
We applaud the NICE philosophy of selective DES implantation
in a resource-hungry health service. It must be appreciated by
interventional cardiologists, however, that this guideline will
reduce, but not abolish, restenosis. As we recently argued,[2]
there is a law of diminishing returns with DESs; escalating
numbers (and, therefore, costs) would be required to squeeze the
last few % points of restenosis out of the system. Clearly, NICE
have grasped this reality and are endorsing a policy of scientific
rationing, the science providing some targeting of the few DESs
permitted to the lesions most likely to restenose.
What are the implications of the NICE guidelines? Applying
them to our institution reveals that a DES would be used in about
34% of lesions. This would reduce our clinical recurrence (re-
PCI) rate - the only restenosis parameter a centre not performing
routine follow-up angiography can count – from 9% to 5.1%. A
considerable disadvantage of the NICE system would be that no
stents of certain important and commonly used sizes would be
permitted, such as 3 x16mm, 3 x 18mm or any stent of 3.5mm
calibre, even if the target lesion is a long stenosis in the proximal
left anterior descending artery of a diabetic patient. If, instead,
we allotted DES according to our recommended system, based
upon a matrix of restenosis risk,[2] we find that a 34% DES rate
would yield an almost identical overall institutional recurrence
risk (5.2%), with the advantage that we would have DES
available for the sizes and indications mentioned above. Stock
control would also be simpler (important if the DES in question
has a limited shelf life) because rarely used sizes would not be
stocked.
We were interested to read the recent scientific letter from Pollard et al published in Heart.[1]
The authors evaluated the safety of a
protocol for earlier sit up and mobilisation after routine transfemoral
cardiac catheterisation in contemporary practice. Patients were
randomised to be mobilised after 2½ hours or 4½ hours bed rest. The
authors report that a significant reduction in...
We were interested to read the recent scientific letter from Pollard et al published in Heart.[1]
The authors evaluated the safety of a
protocol for earlier sit up and mobilisation after routine transfemoral
cardiac catheterisation in contemporary practice. Patients were
randomised to be mobilised after 2½ hours or 4½ hours bed rest. The
authors report that a significant reduction in the duration of bed rest
was achieved in the early mobilisation protocol group with no adverse
effect on vascular complications. They also report that early
mobilisation was associated with a reduction in pain and discomfort,
although this data is not presented. On this basis, the authors call into
question the role of alternative arterial access sites for diagnostic
cardiac catheterisation.
The published data does not support this viewpoint. Firstly, the
early mobilisation protocol still required 2½ hours of bed rest. There is
extensive published evidence that bed rest after medical procedures has
few benefits and a wide range of adverse effects.[2] The combination of
back pain related to bed rest and groin pain related to femoral puncture
and pressure haemostasis delays mobilisation and return to normal activity
after discharge in at least one third of patients.[3] Secondly, despite
studying only a selected low risk group of patients (only some elective
patients with chest pain undergoing diagnostic angiography were eligible
for the study. Patients with a difficult femoral puncture, those
undergoing percutaneous revascularisation, receiving adjunctive
antithrombotic therapy or with previously treated peripheral vascular
disease were excluded) haematomas re-bleeding and vaso-vagal reactions
were common. Indeed this study suggests that these problems occur in 15-
20% of these low risk patients. In contrast to this, we have recently
reported on a series of 1000 consecutive transradial cases, in which a
third of the study subjects had major risk factors for vascular
complications.[4] Patients undergoing diagnostic angiography or
percutaneous intervention were mobilised immediately, removing the
potential for adverse effects from bed rest. Avoiding a groin puncture
will facilitate a rapid return to normal activity after discharge. In
this high risk population the incidence of both major and minor vascular
complications was less than 1%. The data from the North Staffordshire
series is entirely compatible with other published case series and
randomised trials, which consistently show that use of the transradial
access site is associated with short mobilisation and discharge times, a
reduction in procedure costs and vascular complications, and a consistent
improvement in patient quality of life when compared to the femoral access
site.[5-7]
In our view the data presented (a 2½ hour period of bed rest and 15-
20% incidence of access site problems) strengthens the case for selecting
the radial artery (no bed rest and less than 1% incidence of access site
problems) in the majority of patients undergoing routine diagnostic
cardiac catheterisation.
References
(1) Pollard SD, Munks K, Wales C, Crossman DC, Cumberland DC, Oakley
GDG, Gunn J. Position and mobilisation post-angiography study. (PAMAS): a
comparison of 4.5 hours and 2.5 hours bed rest. Heart 2003;89:447-448.
(2) Allen C, Glasziou P, Del Mar C. Bed rest: a potentially harmful
treatment needing more careful evaluation. Lancet 1999;354:1229-1233.
(3) Foulger V. Patients’ views of day-case cardiac catheterisation.
Professional Nurse 1997;12:478-480.
(4) Eccleshall SC, Banks M, Carroll R, Jaumdally R, Fraser D, Nolan J.
Implementation of a diagnostic and interventional transradial programme:
resource and organisational implications. Heart 2003;89:561-562.
(5) Eccleshall S, Muthusamy T, Nolan J. The transradial access site
for cardiac procedures: a clinical perspective. Stent 1999;2(3):74-9.
(6) Al-Allaf K, Eccleshall S, Kaba R, et al. Arterial access for
cardiac procedures utilising the percutaneous transradial approach. Br J
Cardiol 2000;7:548-52.
(7) Kiemeneij F, Laarman GJ, Odekerken D et al. A randomised
comparison of percutaneous transluminal coronary angioplasty by the
radial, brachial and femoral approaches: the Access study. J Am Coll
Cardiol 1997;29(6):1269-75.
I read the article by Barrera-Ramirez et al. with interest and have some comments.
I think this case is an extensive myocardial stunning induced by emotional stress. Some stunning occured with emotional stress, cerebrovascular attack,
and surgery. Symathetic denervation is involved in such cases. Prolonged T
wave inversion would indicate the change in repolarization related to the
sympathetic...
I read the article by Barrera-Ramirez et al. with interest and have some comments.
I think this case is an extensive myocardial stunning induced by emotional stress. Some stunning occured with emotional stress, cerebrovascular attack,
and surgery. Symathetic denervation is involved in such cases. Prolonged T
wave inversion would indicate the change in repolarization related to the
sympathetic activation. The discrepancy between remarkable ST elevation and
mild elevation of myocardial enzymes would indicate myocardial stunning with
sympathetic denervation. Although some Japanese docotrs call such a clinical
state ampulla cardiomyopathy, it is contoversial. Apical thrombus has
firstly described all over the world.[2]
References
(1) Barrera-Ramirez CF, Jimenez-Mazuecos JM, Alfonso F. Apical thrombus associated with left ventricular apical ballooning. Heart 2003;89:927.
(2) Tetsuya Sato et al. Extensive myocardial stunning showing transient regression of prolonged T wave inversion and prolonged sympathetic
denervation. Internal Med 2001;40:312-319.
We read the review paper by Tousoulis et al. with great interest. We applaud their thoroughness in describing the molecular and cellular
mechanisms involved in the inflammatory mechanisms and haemostatic factors
leading to coronary atherosclerosis. They also describe the role of
chronic infection in this process.[1] However, they omit an important
factor that is common to the majority of patients su...
We read the review paper by Tousoulis et al. with great interest. We applaud their thoroughness in describing the molecular and cellular
mechanisms involved in the inflammatory mechanisms and haemostatic factors
leading to coronary atherosclerosis. They also describe the role of
chronic infection in this process.[1] However, they omit an important
factor that is common to the majority of patients suffering from this
condition – current or previous cigarette smoking.
We have undertaken an investigation into the relationship between
smoking habit, notably quantitative measurement of nicotine intake and
factors involved in the formation of the plaque and the inflammatory
process. Due to ‘social desirability bias’ associated with smoking
patients frequently under-report or deny their smoking habit. It would
seem therefore that the greater the clinical impact of smoking the greater
the patient guilt enhancing the likelihood of denial.
To improve the accuracy of information about smoking a 6-minute point
-of-care test to detect nicotine metabolites (including cotinine), called
SmokeScreen® was developed.[2] The easy to use colorimetric urine test
can provide qualitative, semi-quantitative and quantitative measurements
of nicotine intake. With this test we undertook an audit of smoking habits
of 154 new patients attending a large inner-city hospital cardiology
outpatient clinic, comparing the test identification of smoking with self-
completed questionnaire of current smoking habit. The results identified
112 (72.7%) as non-smokers, 30 (19.5%) as confessed smokers and 12 (7.8%)
as ‘smoking deceivers’.
We followed this with another study of the same population (n=85, 33
smokers and 52 never-smokers) to examine the interaction of smoking with
risk factors associated coronary artery disease, as assessed by a
biochemical screen and a blood count. Interestingly, none of the
parameters measured in the biochemical screen, such as cholesterol, HDL
and triglycerides; urea and electrolytes and liver function tests were
associated with smoking habit or quantitative assessment of nicotine
intake. Whereas white blood cell count (WBC) was significantly higher in
smokers (p=0.002), in particular neutrophils (p=0.01) and eosinophils
(p=0.02). Lymphocytes, monocytes and basophiles were higher but failed to
reach significance. Quantitative assessment of nicotine intake of the
smokers further revealed a positive correlation with WBC (p<_0.0001 neutrophils="neutrophils" p0.001="p0.001" eosinophils="eosinophils" p0.004="p0.004" and="and" lymphocytes="lymphocytes" p0.02="p0.02" with="with" monocytes="monocytes" approaching="approaching" significance="significance" p="p"/> It would seem from this pilot study that smoking or the amount of
tobacco consumed doesn’t influence the biochemical risk factors for
coronary artery disease, such as cholesterol and HDL, but does increase
many of the cellular factors which Tousoulis et al. identified as
contributors to the inflammatory response and to the formation and
instability of the atheromatous plaque.[1]
We suggest that identification of smokers, feedback from the point-of-care
test and subsequent advice on smoking cessation could have a significant
impact on reducing many of the risk factors associated with coronary
atherosclerosis and lower cardiovascular events and mortality.
References
(1) Tousoulis D, Davies G, Stefanadis, Toutouzas P, Ambrose JA.
Inflammatory and thrombotic mechanisms in coronary atherosclerosis. Heart 2003;89:993-997.
(2) Cope GF, Nayyar P, Holder R, Gibbons J, Bunce R. A simple near-patient
test for nicotine and its metabolites in urine to assess smoking habit. Clin Chim Acta 1996;256:135-149.
Bosi and colleagues [1] suggested that significant volume
load of the heart as a result of chronic anaemia in young adults with beta
thalassaemia major is the main culprit of the so-called 'beta thalassaemic
cardiomyopathy'. Their findings, based on echocardiographic assessment of
left ventricular function, were similar to those reported
previously.[2,3] Nonetheless, the role of arterial dysfunction in th...
Bosi and colleagues [1] suggested that significant volume
load of the heart as a result of chronic anaemia in young adults with beta
thalassaemia major is the main culprit of the so-called 'beta thalassaemic
cardiomyopathy'. Their findings, based on echocardiographic assessment of
left ventricular function, were similar to those reported
previously.[2,3] Nonetheless, the role of arterial dysfunction in the
pathogenesis of myocardial contractile dysfunction has likewise been
ignored.
The fact that both the end systolic meridional and circumferential
wall stress were increased in their patients would suggest an elevated
left ventricular afterload. The importance of optimal ventriculo-arterial
interaction in enhancing mechanical efficiency of the heart cannot be
overemphasized. Unexpectedly, the systemic vascular resistance, which
reflects the static vascular load, was significantly lower in their
patients than controls. Furthermore, the significance of the pulsatile
vascular load has not been discussed.
We have previously shown that teenagers and young adults with beta-
thalassaemia major have arterial endothelial dysfunction and increased
arterial stiffness.[4] The increase in arterial stiffness, relating
probably to structural alteration as a result of iron overload and
endothelial dysfunction, and increased wave reflection as a result of a
faster pulse wave velocity increase the pulsatile afterload. Interaction
between left ventricular ejection and systemic arterial impedance may thus
render less favorable as the impedance modulus may no longer be the least
at where the flow harmonics are highest.[5]
Our previous findings support the view of a multi-factorial etiology
of LV failure in patients with beta-thalassaemia major.[6] Apart from
myocardial iron deposition, myocarditis and immunogenetic profile,
arterial dysfunction is also contributory.
References
(1) Bosi G, Crepaz R, Gamberini MR, et al. Left ventricular
remodelling, and systolic and diastolic function in young adults with b
thalassaemia major: a Doppler echocardiographic assessment and correlation
with haematological data. Heart 2003;89:762-766.
(2) Lewis SB, Rachmilewitz AE, Amitai N, et al. Left ventricular function
in b-thalassemia and the effect of multiple transfusion. Am Heart J 1978;96:636-645.
(3) Kremastinos DT, Tsiapras DP, Tsetos GA, et al. Left ventricular
diastolic Doppler characteristics in beta-thalassemia major. Circulation 1993;88:1127-1135.
(4) Cheung YF, Chan GCF, Ha SY. Arterial stiffness and endothelial function
in patients with beta-thalassaemia major. Circulation 2002;106;2561-2566.
(5) Nichols WW, O'Rourke MF. Vascular impedance. In McDonalds's Blood
Flow in Arteries: Theoretical, Experimental and Clinical Principles. 4th
ed. London: Edward Arnold; 1998:54-97, 243-293.
(6) Jessup M, Manno CS. Diagnosis and management iron-induced heart disease
in Cooley's anemia. Ann N Y Acad Sci 1998;850:242-250.
In the report by Palka et al,[1] and in previous such reports [2,3]
the phenotypic variation seen in supposedly genetically identical
monozygotic (MZ) twins with hypertrophic cardiomyopathy (HCM) is
interpreted as a measure of the importance of environmental influences.
However, although environmental factors undoubtedly contribute to the
phenotype in HCM, there is substantial evidence that d...
In the report by Palka et al,[1] and in previous such reports [2,3]
the phenotypic variation seen in supposedly genetically identical
monozygotic (MZ) twins with hypertrophic cardiomyopathy (HCM) is
interpreted as a measure of the importance of environmental influences.
However, although environmental factors undoubtedly contribute to the
phenotype in HCM, there is substantial evidence that discordance between
MZ twins in fact has a genetic component. MZ twins develop from a
separation of the embryonic cells at any point from the two-cell stage up
until as late as day 8 when the primordial streak has already started to
form.[4] The timing of the separation has consequences for the genetic
composition of each twin, as the cells become more heterogeneous with time
with respect to the mitochondria they carry [5] and the pattern of
methylation, and hence potential gene expression, they display.[6]
Mitochondria are inherited through the maternal line only and contain
their own genome which encodes a subset of mitochondrial proteins. During
mitosis mitochondria can segregate unequally between the daughter cells.
Where the oocyte contains a mixed population of mitochondrial DNA variants
somatic mosaicism can arise, one consequence of which is that one MZ twin
may inherit a different complement of mitochondrial DNA than the other.
While such a difference in mitochondrial DNA is often of only theoretical
relevance, it would be of particular importance in HCM. Not only do many
of the mitochondrial DNA mutation syndromes display HCM-like features, but
common variants in mtDNA are associated with susceptibility to
cardiomyopathy [7] and co-inheritance of mitochondrial variants with
sarcomeric mutations produces a much more extreme phenotype .[8] These
findings can be explained by the recent recognition that perturbations of
myocardial energetics play a central role in HCM pathogenesis.[9]
DNA methylation plays a recognised role in regulation of gene
expression, and important changes in the methylation of genes occur during
embryogenesis. In particular the male gametic genome is first demethylated
[10] and then selectively re-methylated in a step wise fashion up to the
stage of the blastocyst.[5] Hence, some of the observed discordance
between MZ twins can also be due to separation of a heterogeneously
methylated group of cells, with discordant patterns of gene expression.
It is through these epigenetic modifying phenomena that we may begin
to explain the differences in phenotypic expression of HCM, not only in MZ
twins but also that seen within and between pedigrees containing the same
causal mutant gene.
References
(1) Palka P, A Lange, DJ Burstow. Different presentation of
hypertrophic cardiomyopathy in monozygotic twins. Heart 2003;89(7):751.
(2) Reid JM, AB Houston, E Lundmark. Hypertrophic
cardiomyopathy in identical twins. Br Heart J 1989;62(5):384-8.
(3) Ko YL et al. Idiopathic hypertrophic cardiomyopathy in
identical twins. Morphological heterogeneity of the left ventricle. Chest1992;102(3):783-5.
(4) Gringras, P. and W. Chen, Mechanisms for differences in monozygous
twins. Early Hum Dev 2001;64(2):105-17.
(5) Youssoufian H, RE Pyeritz. Mechanisms and consequences of somatic mosaicism in humans. Nat Rev Genet 2002;3(10):748-58.
(6) Singh SM, B Murphy, R O'Reilly. Epigenetic contributors
to the discordance of monozygotic twins. Clin Genet 2002;62(2):97-103.
(7) Khogali SS et al. A common mitochondrial DNA variant
associated with susceptibility to dilated cardiomyopathy in two different
populations. Lancet 2001;357(9264):1265-7.
(8) Arbustini E. et al. Coexistence of mitochondrial DNA and beta
myosin heavy chain mutations in hypertrophic cardiomyopathy with late
congestive heart failure. Heart 1998;80(6):548-58.
(9) Blair E. et al. Mutations in the gamma(2) subunit of AMP-
activated protein kinase cause familial hypertrophic cardiomyopathy:
evidence for the central role of energy compromise in disease
pathogenesis. Hum Mol Genet 2001;10(11):1215-20.
(10) Mayer W et al. Demethylation of the zygotic paternal genome. Nature 2000;403(6769):501-2.
We do not agree that our study population was highly selected. The
only exclusion criteria in our study were severe psychiatric problems
and/or dementia, planned admission to a nursing home, not taking care of
their own medication (e.g. filled or administered by relatives or district
nurses) and/or life expectancy of less than 3 months.
We feel that we sufficiently described the characteristics of our...
We do not agree that our study population was highly selected. The
only exclusion criteria in our study were severe psychiatric problems
and/or dementia, planned admission to a nursing home, not taking care of
their own medication (e.g. filled or administered by relatives or district
nurses) and/or life expectancy of less than 3 months.
We feel that we sufficiently described the characteristics of our
population (co-morbidity, physical examination and medication that
describe our population). We choose not to report cardio thoracic ratio
and echocardiography data, because although they were available on the
majority of patients, there were many differences in the way these data
were reported between the participating hospitals. More objective
assesments of cardiac function such as ejection fraction or fractional
shortening were mostly missing.
Once more we want to emphasise that the major aim of our study was to
develop a comprehensive and easily applicable prognostic model predicting
the risk of death in patients with heart failure, based on information
that is readily available in daily care. In their study Kearney et al.[1] did
not include co-morbidity and relatively easy to obtain characteristics
from physical examination such as weight, ankle oedema and blood pressure.
In addition patients with diabetes were excluded in their study.[2] In
our opinion it is very important to first study whether these relatively
easily obtainable characteristics are predictive, before assessing the
additional value of more difficult to obtain data from cardiovascular
imaging. We also want to emphasise that several similarities between
Kearney’s and our study are noticeable. Both studies find renal function
as an important predictor. We used a history of renal insufficiency as a
binomial value, but inclusion of the continuous variables serum creatinine
or creatinine clearance (calculated with Cockroft and Gault’s formula) led
to similar findings. Kearney et al find a predictive value of low sodium
levels. We also found low sodium levels to be predictive, although
slightly less than other variables and therefore not included in the
model.
Mean frusemide dose (or bumetanide equivalent) in our study was 124
mg/day. We did not include dose in the model, but high frusemide dose and
low ACE-inhibitor dose could also be important and readily available
predictors of mortality and might be subject of future studies.
Although not reported bootstrapping was performed and yielded similar
results.
References
(1) Kearney MT, Fox KA, Lee AJ et al. Predicting death due to progressive
heart failure in patients with mild-to-moderate chronic heart failure. J
Am Coll Cardiol 2002;40:1801-8.
(2)
Bouvy ML, Heerdink ER, Leufkens HGM, Hoes AW. Predicting mortality
in patients with heart failure: a pragmatic approach. Heart 2003;89:605-609.
We read with great interest the article recently published in "Heart"
on the current use of anticoagulation for non-valvar atrial fibrillation
[1].
This article analyses the use of aspirin and anticoagulant treatment
in 313 consecutive patients, presented with chronic atrial fibrillation of
non-valvar etiology, in a single hospital in Northern Italy, from January
1 to June 30 2000. From th...
We read with great interest the article recently published in "Heart"
on the current use of anticoagulation for non-valvar atrial fibrillation
[1].
This article analyses the use of aspirin and anticoagulant treatment
in 313 consecutive patients, presented with chronic atrial fibrillation of
non-valvar etiology, in a single hospital in Northern Italy, from January
1 to June 30 2000. From this cohort, 168 patients with no
contraindications to anticoagulation were identified. These patients were
classified as being at high risk for embolic stroke, hence anticoagulation
was indicated according to recent guidelines.[2] Bo et al. [1] reported
appropriate use of warfarin therapy in only 75 (44%) of patients, with a
substantial proportion (42%) receiving subtherapeutic dosage. Furthermore,
the use of anticoagulation declined with increasing age, despite the
greater net benefit of such use in older patients.
Our group has previously reported on 628 patients presenting with non
-valvar atrial fibrillation in the region of North-Western Greece
(representing mostly rural areas) from March 1 to November 1 1998.[3] We
thought that the similarities in the patient population characteristics,
as well as the inclusion and exclusion criteria, enable a useful
comparison between the two studies.
In our patient population,[3] of the 628 patients, 188 (29.9%) were
excluded from the analysis by criteria similar to those used by Bo et al
[1]. Of the 440 remaining patients, 328 (74.5%) were classified as being
at high risk for embolic stroke, and of them, 95 (29%) were on
anticoagulant therapy, 133 (40.5%) on aspirin and 100 (30.5%) on neither
treatment. In concert with the results reported by Bo et al,[1] a
subtherapeutic dose was given in 50% of our patients, and the use of
anticoagulation declined with increasing age.
We attempted to compare the use of anticoagulation and aspirin in the two
patient cohorts, using chi-square.
Study
Anticoag.
Aspirin
None
Sum
Italian [1]
75
54
39
168
Greek [3]
95
133
100
328
Sum
170
187
139
496
Chi square= 12.42, p<_0.01 p="p"/> This comparison reinforces the conclusions drawn by Bo et al.[1]
Anticoagulation treatment for non-valvar atrial fibrillation is
substantially underused, especially in older patients, with therapeutic
doses being achieved in only approximately half of the patients.
Furthermore, these limitations appear even more prominent in rural areas,
most likely due to additional difficulties in monitoring international
normalized ratio (INR) values, compared to urban areas.
References
(1) Bo S, Ciccone G, Scaglione L, Taliano C, Piobbici M, Mereletti F,
Pagano G. Warfarin for non-valvar atrial fibrillation: still underused in
the 21st century? Heart 2003;89:553-554.
(2) Scottish Intercollegiate Guidelines Network (SIGN). Antithrombotic
therapy. A national guideline. Edinburgh: SIGN, 1999, SIGN publication
number 36.
(3) Patsouras D, Vakalis I, Giogakas V, Kitsanou M, Sioros L,
Oikonomidis K, Goudevenos J. Status of anticoagulation therapy for
patients with atrial fibrillation in north-western Greece. Hellenic J
Cardiol (Athens) 1998;39:237-245.
I thank John Polito for his lengthy reply to my article. I will try
to discuss some of his points as far as I understand them.
Firstly, no, my article is not a "commercial" for nicotine
replacement! If anything it is a "commercial" for specialist psychological
support. My intention was to present the data and these indicate that
there is a role for both types of treatment for smokers. The data I...
I thank John Polito for his lengthy reply to my article. I will try
to discuss some of his points as far as I understand them.
Firstly, no, my article is not a "commercial" for nicotine
replacement! If anything it is a "commercial" for specialist psychological
support. My intention was to present the data and these indicate that
there is a role for both types of treatment for smokers. The data I cite
in support of pharmacotherapy come from independent and authoratitive
sources (NICE, Cochrane, WHO, UK & US Clinical Guidelines). The main
gist of what I wrote concerned the need to encourage doctors and others to
intervene with smokers by referring them to specialist smoking cessation
clinics where intensive behavioural/psychological support can be provided
alongside pharmacotherapy. As a clinical psychologist who has specialised
in treating smokers for 17 years I know only too well the importance of
helping smokers develop new skills and behaviours to protect against
relapse back to smoking.
Mr Polito disputes the evidence from the Cochrane Review Group and
the US Guidelines showing that adding NRT to any level of behavioural
support is better than that level of behavioural support given alone. He
reaches this conclusion by assuming that using NRT (or placebo) in RCT's
in some way diffuses or undermines the behavioural support and diminishes
it’s effectiveness. This is certainly not my experience, either in
conducting trials or in clinical practice. Behavioural support
concentrates on aspects of quitting smoking not related to NRT use. It has
to, because we know only to well that NRT only partially relieves tobacco
withdrawal symptoms and craving. It does not remove the need for the
smoker to make a concerted effort to modify their behaviour and
cognitions. If it were the case that behavioural support was reduced when
combined with NRT in trials this should apply equally to both active and
placebo groups, so that any additional effect of NRT can still be
accurately delineated. Over many trials this has been found to be of
substantial clinical value.
Mr Polito also forgets that some NRT trials have been conducted
without a placebo using behavioural therapy alone as the control group. In
these trials the behavioural support was clearly not focussed on NRT, and
Cochrane report that these trials give results similar to those with
placebo. One area where we do not have a strong evidence base is in
comparing brief behavioural support plus NRT with more intensive
behavioural support alone. Perhaps this is what Mr Polito was alluding to?
Although I am sure these two treatments would give similar success rates
(see Figure 1, bars 3 & 4), this comparison is of little interest,
because we know we can do even better in the intensive support group by
adding NRT or bupropion (see Figure 1 bar 5).
Mr Polito is incorrect in saying that on ceasing NRT use nicotine
withdrawal symptoms “peak in intensity”. This would only be the case if
NRT was discontinued during the first week or so, when tobacco withdrawal
symptoms are at their peak. Many smokers stopping smoking using the
nicotine patch, for instance, simply forget to use it after a few weeks.
If this caused an upsurge in withdrawal symptoms they would soon remember
to use it again! If stopping using NRT is associated with an increase in
withdrawal symptoms, then we might expect this to be reflected in higher
relapse rates when people come off NRT, which is not the case. The large
scale CEASE trial compared relapse rates in an abrupt NRT patch cessation
arm compared to a gradual nicotine weaning arm and there was no suggestion
of a differential relapse rate subsequently.
Contrary to Mr Polito's view that having a small dose of nicotine in
a placebo patch would diminish the likelihood of quitting, I believe the
opposite has been found in trials. In the dose-ranging trials I have seen,
the very low doses did as well, if not better, than pure placebos.
My article concerned clinician-supported treatment for smokers, not
self-help OTC NRT. These scenarios differ considerably. The latter does
not include the type of behavioural support, which my article makes clear,
is essential to increase success rates. The California study to which Mr
Polito refers has already been seriously and vociferouly questioned in
JAMA and elsewhere for its use of self-selected smokers as well as on
several other methodological grounds. Regardless of the interpretation of
those findings, it is a single study, in one unique population. I give
more weight to evidence from the meta-analysis of OTC NRT studies to which
he refers. These do not show NRT “generating a 93% midyear relapse rate”,
but rather that NRT enables a 7% success rate. This is very much in line
with the 5% additional success rate due to NRT that my 12-month success
rate graph (see Figure 1) would suggest by subtracting the brief advice alone
(bar 2) from the brief advice plus NRT (bar 3). Furthermore, the majority
of these smokers did not stop for any length of time, so cannot be
regarded as having “relapsed”. For those who did have a substantial period
of abstinence followed by relapse, this cannot have been due to NRT, or
there would be no 7% excess benefit from NRT.
Mr Polito may see the efficacy of NRT as an emperor without clothes,
but I would ask him to take a longer and less emotive look at all the
evidence. The first essential point to realise is that NRT is not the
emperor in the field of smoking cessation, nor has anyone tried to pretend
that it is. NRT is just one useful component which adds a modest, but
worthwhile boost to the likelihood of success.
On his next point I can agree. If a smoker can get access to
professional counselling support (with or without NRT) , as all smokers
now can in the UK, this will give them by far the best chance of success
and I would not advise a smoker to make a self-help attempt with OTC NRT
if they are prepared to attend a formal behavioural treatment programme.
Unfortunately, many smokers are not prepared to attend these even when
they are readily accessible - at least not initially - so the real
question is whether they are better off with OTC NRT or nothing. The
balance of evidence still remains firmly in favour of the former, although
we cannot be comfortable about the fact that so many choose to take this
route when there are far better options, at least in the UK. I also agree
that the more active, knowledgeable, and engaged physicians are, then the
more success they will achieve. Finally although there are many online
cessation sites, these are of very mixed quality and have not yet been
adequately evaluated so I would not recommend them as the best evidenced-
based sources. As with all things WWW, one has to be discriminating, and
the unwary can easily be misled.
We read the recent published paper by Mueller and co-workers.[1]
They demonstrate convincingly that the neutrophil count is a strong
predictor for future coronary events in patients with acute coronary
syndromes. Smoking habits, however, may to some extent confound their
results.[2] To verify the assumption we want to publish this scientific
note.
We read the recent published paper by Mueller and co-workers.[1]
They demonstrate convincingly that the neutrophil count is a strong
predictor for future coronary events in patients with acute coronary
syndromes. Smoking habits, however, may to some extent confound their
results.[2] To verify the assumption we want to publish this scientific
note.
Neutrophil granulocytes are a well-recognised risk factor for
coronary heart disease [3] closely related to smoking.[2] The neutrophils
are increased in conjunction with acute myocardial infarctions (MI) [3]
and predictive for coronary recurrence.[1] Before elective coronary
angiography we measured neutrophil counts in 74 patients with stable
angina pectoris (Table 1, see below). All participants were males and below 75 years
of age. Patients with an acute MI within the previous 3 months were
disqualified, as were individuals with unstable angina pectoris, rheumatic
arthritis or diabetes mellitus. At blood sampling, 11 individuals were
smokers whereas the remainder (n=63) did not smoke. In this homogeneous
cohort smokers had enhanced neutrophil counts (4.8 ± 1.5(SD) x 1012/L) as
compared with non-smokers (3.4 ± 1.1(SD) x 1012/L). The difference is highly
significant (p<_0.001. consequently="consequently" in="in" conjunction="conjunction" with="with" the="the" data="data" provided="provided" by="by" mueller="mueller" i="i"/>et al.[1] our results show a possible
pathophysiological mechanism explaining the deleterious effects of smoking
in male coronary heart disease patients. A leukocyte mediated
hypercoagulable state and subsequent neutrophil microvascular plugging
could offer tenable explanations. Thus, longitudinal measurements of the
neutrophil count could provide the physician with additional arguments
when persuading patients with coronary heart disease to stop smoking.
References
(1) Mueller C, Neumann FJ, Perruchoud AP, Buettner HJ. White blood cell
count and long time mortality after non-ST elevation acute coronary
syndrome treated with very early revascularisation. Heart 2003:89:389-392.
(2) Zalokar JB, Richard JL, Claude JR. Leukocyte count, smoking, and
myocardial infarction. N Engl J Med 1981:304:465-468.
(3) Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-
reactive protein, albumin, or leukocyte count with coronary heart disease.
Meta-analyses of prospective studies. JAMA 1998:279:1477-1482.
(4) Järemo P, Hansson G, Nilsson O. Elevated inflammatory parameters are
associated with lower platelet density in acute myocardial infarctions
with ST-elevation. Thromb Res 2000:100:471-478.
Dear Editor
On 24 June the National Institute of Clinical Excellence (NICE) issued their Appraisal consultation document: coronary artery stents.[1] With the proviso that ‘the decision to use a bare metal stent or drug-eluting stent (DES) will depend on the anatomy of the target vessel for stenting and the severity of the disease’ (presumably reflecting issues of deliverability of the stent platforms on offer), t...
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Dear Editor
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Dear Editor
I thank John Polito for his lengthy reply to my article. I will try to discuss some of his points as far as I understand them.
Firstly, no, my article is not a "commercial" for nicotine replacement! If anything it is a "commercial" for specialist psychological support. My intention was to present the data and these indicate that there is a role for both types of treatment for smokers. The data I...
Dear Editor
We read the recent published paper by Mueller and co-workers.[1] They demonstrate convincingly that the neutrophil count is a strong predictor for future coronary events in patients with acute coronary syndromes. Smoking habits, however, may to some extent confound their results.[2] To verify the assumption we want to publish this scientific note.
Neutrophil granulocytes are a well-recogn...
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