To the Editor: We read with great interest the article by Mascherbauer and coworkers, (1) in which they reported the short-term and long-term mortality results of moderate patient-prosthesis mismatch (PPM) after valve replacement for severe aortic stenosis. PPM, generates a great controversy with respect to its clinical relevance and in relation to its effect on survival after operation. Evidence of an association between PP...
As suggested in your editorial comment (1), the divergent trends in
incident (falling) and recurrent (rising) myocardial infarction (MI) in
New Zealand described by Chan and colleagues are puzzling.(2) We
believe that this finding could well be an artifact resulting from the way
in which they have defined incident MI. In their paper, incident
admissions for MI are described as those having no admission for ANY form
o...
As suggested in your editorial comment (1), the divergent trends in
incident (falling) and recurrent (rising) myocardial infarction (MI) in
New Zealand described by Chan and colleagues are puzzling.(2) We
believe that this finding could well be an artifact resulting from the way
in which they have defined incident MI. In their paper, incident
admissions for MI are described as those having no admission for ANY form
of CHD coded as a primary or secondary diagnosis in the previous five
years. Such cases will exclude some persons who are nevertheless having
their first-ever admission for MI and who are thus defined by default as
recurrent cases. The better alternative would have been be to simply
define incident cases as those in which there was no admission for MI
(whether primary or secondary diagnosis) in the previous five years.
In Perth, Western Australia, where a similar record-linkage system
exists (dating from 1980), we have shown consistent downward trends in
admissions for MI up until 1997 when rates levelled out, probably because
of the rapid uptake after that date of troponin tests for diagnosing
MI.(3) More recent analysis of trends in admissions of first MI since
1996 (defined as no admission for MI in the previous ten years) shows
only modest declines in rates.(unpublished data)
As in New Zealand, CHD admissions in Western Australia increased
rapidly from 1960s before levelling-off in late 1990s. This was at least
partly driven by rapid increases in coronary artery revascularization
procedures, associated admissions for coronary angiography and repeat
procedures, particularly following percutaneous interventions (PCI).(4)
This gained further momentum with the introduction of bare-metal stents in
1995 and drug-eluting stents in 2002. Many of these admissions were for
elective procedures for chronic CHD, reflecting changes in the capacity of
revascularization services as much as any underlying trends in acute CHD.
A second factor leading to an apparent increase in CHD admissions in this
period was a marked general increase in the use secondary diagnostic
fields in the early 1990s in anticipation of case-mix funding of public
hospitals, which may or may not apply in other jurisdictions.
In Western Australia, this apparent rapid increase in CHD admissions
has almost certainly led to an increase in the prevalence of persons in
the population who have had admissions for CHD in the past five years,
which is not necessarily due to any increase in incidence. Definition of
incident MI as described in the New Zealand study would bias trends in the
direction of increasing rates of recurrent MI and decreasing rates of
incident MI.
References
1. Avendano M, Soerjomataram I. Monitoring trends in acute coronary
syndrome: can we use hospital admission registries? Heart 2008;94:1524-
1525.
2. Chan WC, Wright C, Tobias M, Mann S, Jackson R. Explaining trends
in coronary heart disease hospitalisations in New Zealand: trend for
admissions and incidence can be in opposite directions. Heart 2008;94;1589
-1593.
3. Sanfilippo FM, Hobbs MST, Knuiman MW, Hung J. Impact of New
Biomarkers of Myocardial Damage on Trends in Myocardial Infarction
Hospital Admission Rates from Population-based Administrative Data. Am J
Epidemiol 2008;168:225–233.
4. Hobbs MST, McCaul KA, Knuiman MW, Rankin JM, Gilfillan I. Trends
in coronary artery revascularisation procedures in Western Australia,
1980–2001. Heart 2004;90:1036–1041.
The editorial by Avendano and Soerjomataram (Heart 2008; 94; 1524-
1525) identifies some of the key difficulties of using routine data to
monitor trends in coronary heart disease (CHD) incidence, but fails to
mention that researchers and statisticians have been using Scottish linked
hospital discharge and deaths data for many years to produce the sort of
analyses recommended. We have routinely used...
The editorial by Avendano and Soerjomataram (Heart 2008; 94; 1524-
1525) identifies some of the key difficulties of using routine data to
monitor trends in coronary heart disease (CHD) incidence, but fails to
mention that researchers and statisticians have been using Scottish linked
hospital discharge and deaths data for many years to produce the sort of
analyses recommended. We have routinely used probability linkage methods
to identify first admissions, to take account of confounders such as age,
to look at a cross section of CHD diagnoses and to take out of hospital
deaths into account.
The linked dataset maintained by the Information Services Division
(ISD) of NHS National Services Scotland is an extremely valuable asset to
researchers in Scotland’s health services. The SliDE - Studies Linking ISD
Data for Epidemiology - Group (Simon Capewell of Liverpool University, Jim
Chalmers and ISD colleagues, John McMurray, Jill Pell and colleagues in
Glasgow and Edinburgh universities) have conducted projects examining
trends, prognosis and deprivation effects in CHD patients (funded by the
British Heart Foundation). Subsequent studies have focused on coronary
artery bypass grafting surgery, atrial fibrillation, unstable angina,
chest pain, and the burden of CHD in primary care. We are now conducting
comparable studies in stroke (Principal Investigator, Dr Kate Macintyre
of the University of Glasgow).
Routine statistical analyses of trends in incidence (including both
hospital admission and out of hospital deaths) are published on our
website- www.isdscotland.org/chd - and will be updated on 25 November
2008. Data for the previous decade shows a steady decline in the incidence
of both acute myocardial infarction (AMI) and overall CHD.
The linked data set dates back to the early 1980s. The linkage method
is highly accurate, based on name, date of birth, postcode, sex and other
relevant fields. We list below some of the publications produced using
these linked data.
Yours sincerely,
Adam Redpath
CHD and Stroke Programme,
ISD Scotland
South Gyle Crescent
Edinburgh, EH12 9EB.
Professor Simon Capewell,
Department of Public Health,
University of Liverpool,
Liverpool
L69 3GB
Publications:
Capewell S, Murphy NF, MacIntyre K, Frame S, Stewart S, Chalmers JW,
Boyd J, Finlayson A, Redpath A, McMurray JJ. Short-term and long-term
outcomes in 133,429 emergency patients admitted with angina or myocardial
infarction in Scotland, 1990-2000: population-based cohort study. Heart.
2006 Nov;92(11):1563-70.
Murphy NF, Simpson CR, MacIntyre K, McAlister FA, Chalmers J,
McMurray JJ. Prevalence, incidence, primary care burden and medical
treatment of angina in Scotland: age, sex and socioeconomic disparities:.
Heart. 2006 Aug;92(8):1047-54.
MacIntyre K, Murphy NF, Chalmers J, Capewell S, Frame S, Finlayson A,
Pell J, Redpath A, McMurray JJ.
Murphy NF, MacIntyre K, Stewart S, Hart CL, Hole D, McMurray JJ.
Long-term cardiovascular consequences of obesity: 20-year follow-up of
more than 15 000 middle-aged men and women (the Renfrew-Paisley study).
Eur Heart J. 2006 Jan;27(1):96-106.
Murphy NF, MacIntyre K, Stewart S, Capewell S, McMurray JJ. Reduced
between-hospital variation in short term survival after acute myocardial
infarction: the result of improved cardiac care? Heart. 2005 Jun;91(6):726
-30.
Murphy NF, Stewart S, MacIntyre K, Capewell S, McMurray JJ. Seasonal
variation in morbidity and mortality related to atrial fibrillation. Int J
Cardiol. 2004 Nov;97(2):283-8.
Murphy NF, Simpson CR, McAlister FA, Stewart S, MacIntyre K,
Kirkpatrick M, Chalmers J, Redpath A, Capewell S, McMurray JJ.
National survey of prevalence, incidence, primary care burden, &
treatment of heart failure in Scotland. Heart. 2004 Oct;90:1129-36.
Murphy NF, MacIntyre K, Capewell S, Stewart S, Pell J, Chalmers J,
Redpath A, Frame S, Boyd J, McMurray JJ. Hospital discharge rates for
suspected acute coronary syndromes between 1990 and 2000: population based
analysis. BMJ. 2004 ;328(7453):1413-4.
McAlister FA, Murphy NF, Simpson CR, Stewart S, MacIntyre K,
Kirkpatrick M, Chalmers J, Redpath A, Capewell S, McMurray JJ.
Influence of socioeconomic deprivation on the primary care burden and
treatment of patients with a diagnosis of heart failure in general
practice in Scotland: population based study. BMJ. 2004 May
8;328(7448):1110.
Stewart S, MacIntyre K, Capewell S, McMurray JJ. Heart failure and
the aging population: an increasing burden in the 21st century?
Heart. 2003 Jan;89(1):49-53.
Stewart S, Hart CL, Hole DJ, McMurray JJ. A population-based study of
the long-term risks associated with atrial fibrillation: 20-year follow-up
of the Renfrew/Paisley study. Am J Med. 2002 Oct 1;113(5):359-64.
Stewart S, Blue L, Walker A, Morrison C, McMurray JJ. An economic
analysis of specialist heart failure nurse management in the UK; can we
afford not to implement it? Eur Heart J. 2002 Sep;23(17):1369-78.
Stewart S, Jenkins A, Buchan S, McGuire A, Capewell S, McMurray JJ.
The current cost of heart failure to the National Health Service in the
UK. Eur J Heart Fail. 2002 Jun;4(3):361-71.
Stewart S, Demers C, Murdoch DR, McIntyre K, MacLeod ME, Kendrick S,
Capewell S, McMurray JJ. Substantial between-hospital variation in outcome
following first emergency admission for heart failure. Eur Heart J. 2002
Apr;23(8):650-7.
Stewart S, McIntyre K, Capewell S, McMurray JJ. Heart failure in a
cold climate. Seasonal variation in heart failure-related morbidity and
mortality. J Am Coll Cardiol. 2002 Mar 6;39(5):760-6.
Stewart S, MacIntyre K, Chalmers JW, Boyd J, Finlayson A, Redpath A,
Pell JP, Capewell S, McMurray JJ.
Trends in case-fatality in 22968 patients admitted for the first time
with atrial fibrillation in Scotland, 1986-1995. Int J Cardiol. 2002
Mar;82(3):229-36.
Pell JP, MacIntyre K, Walsh D, Capewell S, McMurray JJ, Chalmers JW,
Boyd JH, Finlayson AR, Stewart S, Redpath AD.
Time trends in survival and readmission following coronary artery bypass
grafting in Scotland, 1981-96: retrospective observational study. BMJ.
2002 Jan 26;324(7331):201-2.
Stewart S, Hart CL, Hole DJ, McMurray JJ. Population prevalence,
incidence, and predictors of atrial fibrillation in the Renfrew/Paisley
study. Heart. 2001 Nov;86(5):516-21.
Capewell S, MacIntyre K, Stewart S, Chalmers JW, Boyd J, Finlayson A,
Redpath A, Pell JP, McMurray JJ. Age, sex, and social trends in out-of-
hospital cardiac deaths in Scotland 1986-95: a retrospective cohort study.
Lancet. 2001 Oct 13;358(9289):1213-7.
MacIntyre K, Stewart S, Capewell S, Chalmers JW, Pell JP, Boyd J,
Finlayson A, Redpath A, Gilmour H, McMurray JJ. Gender and survival: a
population-based study of 201,114 men and women following a first acute
myocardial infarction. J Am Coll Cardiol. 2001 Sep;38(3):729-35.
Stewart S, MacIntyre K, Hole DJ, Capewell S, McMurray JJ. More
'malignant' than cancer? Five-year survival following a first admission
for heart failure. Eur J Heart Fail. 2001 Jun;3(3):315-22.
Macintyre K, Stewart S, Chalmers J, Pell J, Finlayson A, Boyd J,
Redpath A, McMurray J, Capewell S. Relation between socioeconomic
deprivation and death from a first myocardial infarction in Scotland:
population based analysis. BMJ. 2001 May 12;322(7295):1152-3.
Stewart S, MacIntyre K, MacLeod MM, Bailey AE, Capewell S, McMurray
JJ. Trends in hospital activity, morbidity and case fatality related to
atrial fibrillation in Scotland, 1986--1996. Eur Heart J. 2001
Apr;22(8):693-701.
Stewart S, Blue L, Capewell S, Horowitz JD, McMurray JJ. Poles apart,
but are they the same? A comparative study of Australian and Scottish
patients with chronic heart failure. Eur J Heart Fail. 2001 Mar;3(2):249-
55.
Stewart S, MacIntyre K, MacLeod MM, Bailey AE, Capewell S, McMurray
JJ. Trends in hospitalization for heart failure in Scotland, 1990-1996. An
epidemic that has reached its peak? Eur Heart J. 2001 Feb;22(3):209-17.
Capewell S, Livingston BM, MacIntyre K, Chalmers JW, Boyd J,
Finlayson A, Redpath A, Pell JP, Evans CJ, McMurray JJ. Trends in case-
fatality in 117 718 patients admitted with acute myocardial infarction in
Scotland. Eur Heart J. 2000 Nov;21(22):1833-40.
MacIntyre K, Capewell S, Stewart S, Chalmers JW, Boyd J, Finlayson A,
Redpath A, Pell JP, McMurray JJ.
Evidence of improving prognosis in heart failure: trends in case
fatality in 66 547 patients hospitalized between 1986 and 1995.
Circulation. 2000 Sep 5;102(10):1126-31.
Evans C, Chalmers J, Capewell S, Redpath A, Finlayson A, Boyd J, Pell
J, McMurray J, Macintyre K, Graham L. "I don't like Mondays"-day of the
week of coronary heart disease deaths in Scotland: study of routinely
collected data. BMJ. 2000 Jan 22;320(7229):218-9.
Capewell S, Pell JP, Morrison C, McMurray J. Increasing the impact of
cardiological treatments. How best to reduce deaths.
Eur Heart J. 1999 Oct;20(19):1386-92.
Capewell S, Morrison CE, McMurray JJ. Contribution of modern
cardiovascular treatment and risk factor changes to the decline in
coronary heart disease mortality in Scotland between 1975 and 1994. Heart.
1999 Apr;81(4):380-6.
Murdoch DR, Love MP, Robb SD, McDonagh TA, Davie AP, Ford I, Capewell
S, Morrison CE, McMurray JJ.
Importance of heart failure as a cause of death. Changing
contribution to overall mortality and coronary heart disease mortality in
Scotland 1979-1992. Eur Heart J. 1998 Dec;19(12):1829-35.
Davie AP, Caesar D, Caruana L, Clegg G, Spiller J, Capewell S,
Starkey IR, Shaw TR, McMurray JJ. Outcome from a rapid-assessment chest
pain clinic. QJM. 1998 May;91(5):339-43.
McMurray J, McDonagh T, Morrison CE, Dargie HJ. Trends in
hospitalization for heart failure in Scotland 1980-1990. Eur Heart J. 1993
Sep;14(9):1158-62.
Taylor GL, Murphy NF, Berry C, Christie J, Finlayson A, MacIntyre K,
Morrison C, McMurray J. Long-term outcome of low-risk patients attending
a rapid-assessment chest pain clinic. Heart. 2008 May;94(5):628-32.
Carrington M, Murphy NF, Strange G, Peacock A, McMurray JJ, Stewart
S. Prognostic impact of pulmonary arterial hypertension: a population-
based analysis. Int J Cardiol. 2008 Feb 29;124(2):183-7.
Peacock AJ, Murphy NF, McMurray JJ, Caballero L, Stewart S. An
epidemiological study of pulmonary arterial hypertension.
Eur Respir J. 2007 Jul;30(1):104-9.
Murphy NF, Simpson CR, Jhund PS, Stewart S, Kirkpatrick M, Chalmers
J, MacIntyre K, McMurray JJ. A national survey of the prevalence,
incidence, primary care burden and treatment of atrial fibrillation in
Scotland. Heart. 2007 May;93(5):606-12.
Stewart S, Murphy NF, McMurray JJ, Jhund P, Hart CL, Hole D. Effect
of socioeconomic deprivation on the population risk of incident heart
failure hospitalisation: an analysis of the Renfrew/Paisley Study. Eur J
Heart Fail. 2006 Dec;8(8):856-63.
Murphy NF, Stewart S, Hart CL, MacIntyre K, Hole D, McMurray JJ. A
population study of the long-term consequences of Rose angina: 20-year
follow-up of the Renfrew-Paisley study. Heart. 2006 Dec;92(12):1739-46.
Stewart S, Murphy NF, Walker A, McGuire A, McMurray JJ. Cost of an
emerging epidemic: an economic analysis of atrial fibrillation in the UK.
Heart. 2004 Mar;90(3):286-92.
Stewart S, Murphy NF, Walker A, McGuire A, McMurray JJ. The current
cost of angina pectoris to the National Health Service in the UK. Heart.
2003 Aug;89(8):848-53.
As regards clinical effectiveness, we must not confuse effectiveness
in reducing restenosis and the need for repeat treatment (about which
there is no doubt) and the potential for a reduction in later morbidity
and mortality (about which there is continuing debate). The point is that
we cannot exclude the latter possibility and this raises the issue of...
As regards clinical effectiveness, we must not confuse effectiveness
in reducing restenosis and the need for repeat treatment (about which
there is no doubt) and the potential for a reduction in later morbidity
and mortality (about which there is continuing debate). The point is that
we cannot exclude the latter possibility and this raises the issue of
sensitivity analyses in cost-effectiveness analyses. The NICE models of
cost-effectiveness usually result in a black-and-white view of the world,
when there are many criteria that influence treatment decisions in
individual patients. There is considerable uncertainty in these economic
models, which should be recognised.
Dr Mohindra writes that any balance to be struck is between value and
cost, not between clinical and cost-effectiveness, with value being seen
both in terms of effectiveness and how the patient perceives this. Many
others have discussed the limitation of relying wholly on an assessment of
cost per QALYs in this regard and so there is nothing new here. NICE
itself has stated that it does not have a threshold at which cost-
effectiveness becomes unacceptable, although greater reliance on other
factors is required for costs per QALY of more than £20,000.(1) He is
right to point out though that I did not highlight this distinction in my
editorial.
As regards the cost of stents, he is right in pointing out that this
is something that currently depends on market forces; because of this, the
cost can vary across the country. I am informed that the NICE committee
had some difficulty dealing with this issue and ultimately decided to use
an “average” cost of a bare metal stent, although for some reason they
were provided with costs that were significantly lower than the costs
identified by other means.
The value of a treatment as perceived by the patient is clearly very
important. Take a “low risk” scenario where a patient treated with a bare
metal stent has a 10% risk of angiographic restenosis and a clinical
restenosis rate of 5% (i.e. a 1 in 20 chance of requiring a second
treatment). For the same patient a drug eluting stent might offer a 5-6%
chance of angiographic restenosis with a 2-3% chance of clinical
restenosis (i.e. a 1 in 50 chance of requiring a second treatment). I
don’t think many patients would find this choice very difficult but,
depending on the relative costs of the stents, the NHS might find the 2-3%
absolute difference unacceptable. One would have to be extremely sure of
the reliability of cost-effectiveness analyses before denying this benefit
to patients.
Because value is more difficult to establish than effectiveness, the
current NICE methodology puts great pressure on clinicians to deny
patients a superior treatment. In calling for this difference between
effectiveness and value to be considered, Dr Mohindra calls for greater
involvement of politicians in the process and yet NICE claims to be an
“independent body”. He has not outlined what sort of involvement he would
find helpful. There is a possibility that greater political involvement
might lead to a reduction in the range of cost per QALYs that is deemed
acceptable and so greater political involvement might make matters worse
rather than better. Politicians in committee will always ask for a line to
be drawn somewhere (although they sometimes react differently when
confronted with a specific constituent’s medical problems), whereas
patient groups and clinicians will always want what is “best”, regardless
of cost. Some system is needed if only to avoid “the tragedy of commons”,
whereby the individual demand by every patient for the currently best
treatment regardless of cost leads to a level of healthcare spending that
cannot be provided.(2) Introducing an ethicist into the process might
help, if only to outline the dilemmas when cost-effectiveness analyses
fall into the zone when additional justification is required to support
the use of a new treatment.
Dr Mohindra has written elsewhere about the “affordability gap”, i.e.
the gap between evidence-based treatments and NICE-approved treatments.(3)
This is currently under great scrutiny, especially in the world of cancer
treatment, where we might see that the value of a few additional weeks of
life outweighs the results of cost-effectiveness analyses. In a recent
presentation to the British Cardiovascular Society, I suggested that NICE
does affect the clinician’s role as the patient’s advocate, but its system
of appraisal, however imperfect, does at least provide a societal
framework that both doctors and clinicians can live with as long as it is
fair, consistent, intellectually robust and transparent. Many feel that
the NICE review of drug-eluting stents has been anything but.
The debate about how to value a treatment will continue.
Yours sincerely
Mark de Belder
1. Raftery J. Review of NICE’s recommendations, 1999-2005. Br.Med.J.
2006;332:1266-8
2. Ferner RE, McDowell SE. How NICE may be outflanked. Br.Med.J.
2006;332:1268-71
3. Mohindra RK, Hall JA. Desmond’s non-NICE choice: dilemmas from
drug-eluting stents in the affordability gap. Clinical Ethics 2006;192:105
-8
Professor NS Levitt recently reviewed the epidemiology, management
and health care challenges related to diabetes in Africa [1], however not
including data from the Seychelles. We would like to add some information
from the Republic of Seychelles, an island state located 1800 km east of
Kenya where more than 80% of the population is of African descent.
Based on two independent population-based surveys in 1989 an...
Professor NS Levitt recently reviewed the epidemiology, management
and health care challenges related to diabetes in Africa [1], however not
including data from the Seychelles. We would like to add some information
from the Republic of Seychelles, an island state located 1800 km east of
Kenya where more than 80% of the population is of African descent.
Based on two independent population-based surveys in 1989 and 2004,
the prevalence of diabetes (fasting blood glucose >=7 mmol/l and/or
treatment) increased from 6.2% to 9.6% in men and from 6.1% to 9.2% in
women [2-4]. The prevalence reached 11.5 % in 2004 when also considering
results of the oral glucose tolerance test. The prevalence of obesity
increased markedly in the interval [4,5] and overweight accounted for 49%
of all cases of diabetes in 2004 [4]. Furthermore, pre-diabetes was found
in an additional 22% of the population [4].
Of all cases of diabetes in the population aged 25-64, 54% were aware
of the diagnosis [4]. However less than a fifth of diabetic persons under
treatment had blood glucose, blood pressure and blood cholesterol below
the recommended targets [4]. Furthermore, we found that persons with pre-
diabetes already had worsened levels of several cardiometabolic risk
factors and were therefore at increased cardiovascular risk [6]. We also
confirmed the strong association between diabetes and microalbuminuria in
the Seychelles [7] and found a high prevalence of the metabolic syndrome
[8].
Our figures further contribute to map the "diabesity" epidemic in the
African region. Limited therapeutic control among diabetic patients in the
Seychelles is challenging since this occurred while the population is well
aware of diabetes following sustained awareness campaigns since the late
1980s and health care, including medications in all major therapeutic
classes, is provided at no direct cost through an easily accessible
network of health centers. The situation in the Seychelles may provide a
good case study for current and future trends in rapidly developing
countries in the continent and, possibly, for middle-income countries in
other regions.
Conflict of interest statement: We declare that we have no conflict
of interest
References
1) Levitt N. Diabetes in Africa: Epidemiology, management and healthcare
challenges. Heart 2008;94:1376-82.
2) Tappy L, Bovet P, Shamlaye C. Prevalence of diabetes and obesity in the
adult population of the Seychelles. Diab Med 1991;8:448-52.
3) Bovet P, Shamlaye C, Gabriel A, Riesen W, Paccaud F. Prevalence of
cardiovascular risk factors in a middle-income country and estimated cost
of a treatment strategy. BMC Public Health 2006,6:9.
4) Faeh D, William J, Tappy L, Ravussin E, Bovet P. Prevalence, awareness
and control of diabetes in the Seychelles and relationship with excess
body weight. BMC Public Health 2007;7:163.
5) Bovet P, Chiolero A, Shamlaye C, Paccaud F. Prevalence of overweight in
Seychelles: 15-year trends and association with socio-economic status.
Obes Rev 2008; 2008;9:511-7.
6) Faeh D, William J, Yerli P, Paccaud F, Bovet P. Diabetes and pre-
diabetes are associated with cardiovascular risk factors and
carotid/femoral intima-media thickness independently of markers of insulin
resistance and adiposity. Cardiovasc Diab 2007;6:32.
7) Pruijm MT, Madeleine G, Riesen W, Burnier M, Bovet P. Prevalence of
microalbuminuria in the general population of Seychelles. J Hypertens
2008;26:871-77.
8) Kelliny C, William J; Riesen W; Paccaud; Bovet P. Metabolic syndrome
according to different definitions in a rapidly developing country of the
African region. Cadiovasc Diab 2008;18;7:27.
SIR, Dr M De Belder asks the question how to determine the worth of
drug-eluting stent? (1) The answer to this question does not lie in the
trial data. The function of the trial data is to establish the extent of
clinical-effectiveness to a given degree of certainty. In this context,
whilst a trend may be hypothesis generating it does not establish clinical
-effectiveness.
SIR, Dr M De Belder asks the question how to determine the worth of
drug-eluting stent? (1) The answer to this question does not lie in the
trial data. The function of the trial data is to establish the extent of
clinical-effectiveness to a given degree of certainty. In this context,
whilst a trend may be hypothesis generating it does not establish clinical
-effectiveness.
There is no balance between clinical and cost-effectiveness. Clinical
effectiveness necessarily precedes cost-effectiveness. If there is a
balance to be struck it lies between value and cost. The cost is set by
the market and by negotiation between the respective parties. Once this is
settled the remaining key variable left to be determined is the value
placed upon the degree of benefit demonstrated by the clinical trial
evidence.
The value of the intervention to the patient as perceived by the NHS
has to be balanced against its cost to the NHS as payer. It is this
combination of clinical-effectiveness, cost and value (2) that presently
falls to be considered by NICE.
Importantly, observe that the value to the patient of the treatment
is judged not by the patient but by the payer. Because of this critical
point the process should possess a stronger political component than it
presently does. This is because it is the politicians and not NICE who are
directly accountable to the key stakeholders i.e. the public whose dual
guise as patients and tax payers drives this dilemma. (3)
Questions of clinical effectiveness can yield to randomised
controlled clinical trials. However it is clear, from the principle of
fact-value distinction first expressed by David Hume (4), that the value
of an intervention cannot be determined from the trial data because trial
data only ever returns a factual conclusion. Questions of value do yield
to the principles of ethics. Questions of cost yield to principles of
economics.
As the present situation with drug-eluting stents demonstrates there
seems to be a need for doctors who can wield the full spectrum of such
principles to be engaged with the aim of better protecting the interests
of patients.
References
(1) Mark A de Belder NICE Guidelines for the use of drug-eluting
stents: how do we establish worth? Published Online First: 26 August 2008.
doi:10.1136/hrt.2008.144055
(2) Rawlins M., Culyer AJ. National Institute for Clinical Excellence
and its value judgments. BMJ 2004;329:224-227
(3) Burke K. NICE needs sweeping changes to maintain credibility, say
MPs. BMJ 2002;325:5
(4) Hume D. Treatise on Human Nature.1738. Book III part 1
Sir,
I was interested in Elliott and Spirito's lucid description of the
arrhythmogenic substrate in HCM (1) in their recent review article.
Although they quote no evidence for their assertions, I have advanced this
hypothesis on many occasions in the last 16 years and have gathered
substantial clinical evidence that is consistent with the
electrophysiological effects of disarray leading to lethal arrhythmias.
Sir,
I was interested in Elliott and Spirito's lucid description of the
arrhythmogenic substrate in HCM (1) in their recent review article.
Although they quote no evidence for their assertions, I have advanced this
hypothesis on many occasions in the last 16 years and have gathered
substantial clinical evidence that is consistent with the
electrophysiological effects of disarray leading to lethal arrhythmias.
Paced electrogram fractionation in HCM has recently been shown, in a
prospective study, to be strongly predictive of arrhythmic events (2).
Furthermore, the same study prospectively evaluated the prediction of
sudden death by "risk factors" and showed that the predictions of risk
factors are only just distinguishable from being purely random. This has
clear implications for prevention of sudden death using ICDs.
Prospective evaluation of hypotheses is a normal part of the
scientific process; I wonder why Drs Elliott and Spirito have been
unwilling to test their assertions on the prediction of sudden death,
constructed by retrospective analysis of databases, in a rigorously
designed, properly conducted prospective trial?
Yours sincerely
Richard Saumarez
1) Elliot P, Spirito P. Prevention of hypertrophic cardiomyopathy-
related deaths: theory and practice. Heart; 2008:94;1269-1275.
2)Saumarez R, Pytkowski M, Sterlinski M et al. Paced ventricular
electrogram fractionation predicts sudden death in hypertrophic
cardiomyopathy. European Heart Journal 2008;29:1653-1661.
Re: Comment to Acute pulmonary embolism revisited published in Heart
2008;94:795-802.
We have read with great interest the review article by Dr
Konstantinides1 on acute pulmonary embolism (PE) published in the June
issue of the journal. Unfortunately this very comprehensive review failed
to mention the use of levosimendan in the treatment of right ventricular
failure and acute pulmonar...
Re: Comment to Acute pulmonary embolism revisited published in Heart
2008;94:795-802.
We have read with great interest the review article by Dr
Konstantinides1 on acute pulmonary embolism (PE) published in the June
issue of the journal. Unfortunately this very comprehensive review failed
to mention the use of levosimendan in the treatment of right ventricular
failure and acute pulmonary hypertension in the critically unstable
patient with massive PE. Levosimendan has been successfully used as rescue
therapy in this particular group of patients. The high mortality of
massive PE is correlated with the presence of shock due to right
ventricular failure whereas mortality for massive PE without the presence
of shock versus submassive PE is approximately the same2 This is important
as submassive PE can eventually result in massive PE.
Levosimendan is a calcium sentitizer, a new inodilator that displays
lusitropic properties by increasing the sensitivity of the myosin
filaments to calcium and by activation of the ATP-sensitive potassium
channels reducing the afterload3. In both human4 and animal5 l studies
levosimendan has shown to restore the right ventricular-vascular coupling
via pulmonary vasodilation and enhanced myocardial contractility, hence
improving right ventricular performance. Similar findings were seen in
patients with ARDS treated with this new inodilator4 . Powell et al6
successfully used Levosimendan as a rescue therapy in a patient with
obstructive shock secondary to a massive PE where thrombolysis was not an
option due to the presence of active dyspepsia and a known duodenal
ulcer. In our experience, the use of levosimendan is relatively safe if no
loading dose is given at 0.1 to 0.2 mcg/kg/min. Although the SURVIVE3
trial failed to show a survival difference between dobutamine and
levosimendan in acute heart failure, patients with right ventricular
failure were not included in the study.
Dr B L De Keulenaer, MD, FJFICM
Dr B P Powell
Dr I R Jenkins
Correspondence to:
Dr B L De Keulenaer, MD, FJFICM
Intensivist
Fremantle Hospital
Alma street
6160 Fremantle
WA
Australia
Email: bdekeul@hotmail.com
Phone +61 08 9431 3333
Fax + 61 08 9431 3009
References
1. Konstantinides SV. Acute pulmonary embolism revisited. Heart
2008;94:795-802.
2.Alpert JS, Smith R, Carlson J et al. Mortality in patients treated for
pulmonary embolism.JAMA. 1976 Sep 27;236:1477-80.
3. Mebazaa A, Nieminen M, Packer M et al. SURVIVE Investigators.
Levosimendan vs dobutamine for patients with acute decompensated heart
failure: the SURVIVE Randomized Trial. JAMA 2007;297:1883-1891.
4. Morelli A, Terboul JL, Maggiore SM et al. Effects of levosimendan on
right ventricular afterload in patients with acute respiratory distress
syndrome: a pilot study. Crit Care Med 2006;34:2287-2293.
5. Kerbaul F, Rondelet B, Demester JP et al. Effetcs of levosimendan
versus dobutamine on pressure load-induced right ventricular failure. Crit
Care Med 2006;34:2814-2819.
6. Powell BP, Simes D. Levosimendan in acute pulmonary embolism. Anaesth
Intensive Care. 2007 Oct;35:771-2.
.
Sir,
I was interested to note the omission from the review by Elliot and
Spirito (1) of an important paper by Saumarez and colleagues (2)
describing an electrophysiological method of risk assessment in
hypertrophic cardiomyoptahy(2). The substrate for sudden death is almost
certainly fibre disarray and fibrosis. Based on this knowledge, Saumarez
and colleagues in 1992 (1) hypothesised that pacing induced electrogram
fra...
Sir,
I was interested to note the omission from the review by Elliot and
Spirito (1) of an important paper by Saumarez and colleagues (2)
describing an electrophysiological method of risk assessment in
hypertrophic cardiomyoptahy(2). The substrate for sudden death is almost
certainly fibre disarray and fibrosis. Based on this knowledge, Saumarez
and colleagues in 1992 (1) hypothesised that pacing induced electrogram
fractionation might predict risk of death from VF or a similar arrhythmia.
The results of the small initial investigation were impressive and
represented an important step in risk stratification of HCM. The
ACC/AHA/ESC guidelines (ESC 2006) referred to by Elliot and Spirito (their
ref 25) mention the Saumerez paper but overlook its central point which is
pacing induced electrogram fractionation NOT induction of arrhythmia. A
large scale multicentre trial published 16 years later has confirmed the
initial hypothesis (3). One wonders why this technique of paced
electrogram fractionation analysis (PEFA) does not even deserve a mention
in the current review?
1. Elliot P, Spirito P. Prevention of hypertrophic cardiomyopathy-
related deaths: theory and practice. Heart; 2008:94;1269-1275.
2. Saumarez R, Camm AJ, Panagos A et al. Ventricular fibrillation in HCM
is associated with increased fractionation of paced right ventricular
electrograms Circulation 1992;92:467-74.
3. Saumarez R, Pitkowski M, Sterlinski M et al. Paced ventricular
electrogram fractionation predicts sudden death in hypertrophic
cardiomyopathy. European Heart Journal 2008;29:1653-1661.
With interest we read the article by Leschka and colleagues
concerning the assessment of coronary atherosclerosis by dual-source
computed tomography coronary angiography (CTCA) and calcium scoring
(CS).[1] The authors propose an imaging pathway consisting of dual-source
CTCA and selective CS in patients with suspicion of significant coronary
atherosclerosis. We have two remarks.
With interest we read the article by Leschka and colleagues
concerning the assessment of coronary atherosclerosis by dual-source
computed tomography coronary angiography (CTCA) and calcium scoring
(CS).[1] The authors propose an imaging pathway consisting of dual-source
CTCA and selective CS in patients with suspicion of significant coronary
atherosclerosis. We have two remarks.
Firstly, as the authors indicate in the Results and in Table 1 and 2,
no significant stenoses were detected in patients without coronary
calcium. However, in Figure 2, six patients without coronary stenosis are
considered to have a negative calcium score. We assume this is an error
and that this number should be zero. Then, the total number of patients
with a calcium score of 0 or >= 400 add up to 46, consistent with the
total number of patients mentioned under CS in Table 2.
The sensitivity of coronary calcium for presence of significant
stenoses and the negative predictive value reported by the authors are
100%, in concordance with previous studies that used the gold standard,
electron-beam tomography (EBT) to derive calcium scores.[2,3] In view of
the reported negative predictive value, we propose that CS should be the
initial test in case of suspected significant coronary atherosclerosis.
Thus, further diagnostic imaging procedures with associated radiation dose
and contrast effects can be withheld in almost one-fifth of the clinical
population (14/74). Earlier generations of multi-detector computed
tomography (MDCT) up to single source 64-MDCT were found to underestimate
the amount of coronary calcium compared to EBT.[4] Thus, the prevalence of
coronary calcium is underestimated with single-source MDCT, leading to
unability to reliably exclude coronary calcium. With dual-source CT the
temporal resolution of EBT is approximated. We recently found that dual-
source CT-derived calcium scores are closer to calcium scores derived by
EBT than those by MDCT.[5]
Dual-source CT studies in larger prospective populations should
confirm these findings.
References
1. Leschka S, Scheffel H, Desbiolles L, et al. Combining dual-source
computed tomography coronary angiography and calcium scoring: added value
for the assessment of coronary artery disease. Heart 2008;94:1154-61.
2. Breen JF, Sheedy PF II, Schwartz RS, et al. Coronary artery
calcification detected with ultrafast CT as an indication of coronary
artery disease. Radiology 1992;185 : 435-439.
3. Laudon DA, Vukov LF, Breen JF, Rumberger JA, Wollan PC, Sheedy PF II.
Use of electron-beam computed tomography in the evaluation of chest pain
patients in the emergency department. Ann Emerg Med1999; 33:15 -21
4. Greuter MJ, Dijkstra H, Groen JM, et al. 64 slice MDCT generally
underestimates coronary calcium scores as compared to EBT: a phantom
study. Med Phys 2007;34:3510-9.
5. Groen JM, Greuter MJ, Vliegenthart R, et al. Calcium scoring using 64-
slice MDCT, dual source CT and EBT: a comparative phantom study. Int J
Cardiovasc Imaging 2008;24:547-56.
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Sir, I was interested in Elliott and Spirito's lucid description of the arrhythmogenic substrate in HCM (1) in their recent review article. Although they quote no evidence for their assertions, I have advanced this hypothesis on many occasions in the last 16 years and have gathered substantial clinical evidence that is consistent with the electrophysiological effects of disarray leading to lethal arrhythmias.
P...
To the editor,
Re: Comment to Acute pulmonary embolism revisited published in Heart 2008;94:795-802.
We have read with great interest the review article by Dr Konstantinides1 on acute pulmonary embolism (PE) published in the June issue of the journal. Unfortunately this very comprehensive review failed to mention the use of levosimendan in the treatment of right ventricular failure and acute pulmonar...
Sir, I was interested to note the omission from the review by Elliot and Spirito (1) of an important paper by Saumarez and colleagues (2) describing an electrophysiological method of risk assessment in hypertrophic cardiomyoptahy(2). The substrate for sudden death is almost certainly fibre disarray and fibrosis. Based on this knowledge, Saumarez and colleagues in 1992 (1) hypothesised that pacing induced electrogram fra...
With interest we read the article by Leschka and colleagues concerning the assessment of coronary atherosclerosis by dual-source computed tomography coronary angiography (CTCA) and calcium scoring (CS).[1] The authors propose an imaging pathway consisting of dual-source CTCA and selective CS in patients with suspicion of significant coronary atherosclerosis. We have two remarks.
Firstly, as the authors indicat...
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