The article by Wouters and colleagues (1) presents an exhaustive overview on how QALYs can be used in cost-effectiveness analysis. In this framework, the authors also mention the incremental cost-effectiveness ratio (ICER), which is the parameter typically employed to express the results of a cost-effectiveness study. The article, however, does not discuss the net monetary benefit (NMB), which is another parameter employed to express the results of a cost-effectiveness study.
The incremental cost (deltaC) and the incremental effectiveness (deltaE) are the two main parameters of pharmacoeconomics and cost-effectiveness analysis, along with the willingness-to-pay threshold (lambda). The decision rule (e.g. in the case of a favourable pharmacoeconomic result) is (deltaC/deltaE)<lambda (Equation 1), if based on the ICER, or (deltaE x lambda - deltaC) > 0 (Equation 2), if based on the NMB. Likewise, an unfavourable pharmacoeconomic result is when (deltaC/deltaE)>lambda or when (deltaE x lambda - deltaC) < 0; NMB is defined as deltaE x lambda - deltaC, while ICER is defined as deltaC/deltaE.
Despite its apparent complexity, most part of pharmacoeconomic methodology is described by the two simple equations reported above (i.e. Equations 1 and 2), but whether the ICER or the NMB is the best parameter for the purposes of pharmacoeconomic decision-making remains on open question.
The study by Cowper et al evaluating new versus old oral antic...
The article by Wouters and colleagues (1) presents an exhaustive overview on how QALYs can be used in cost-effectiveness analysis. In this framework, the authors also mention the incremental cost-effectiveness ratio (ICER), which is the parameter typically employed to express the results of a cost-effectiveness study. The article, however, does not discuss the net monetary benefit (NMB), which is another parameter employed to express the results of a cost-effectiveness study.
The incremental cost (deltaC) and the incremental effectiveness (deltaE) are the two main parameters of pharmacoeconomics and cost-effectiveness analysis, along with the willingness-to-pay threshold (lambda). The decision rule (e.g. in the case of a favourable pharmacoeconomic result) is (deltaC/deltaE)<lambda (Equation 1), if based on the ICER, or (deltaE x lambda - deltaC) > 0 (Equation 2), if based on the NMB. Likewise, an unfavourable pharmacoeconomic result is when (deltaC/deltaE)>lambda or when (deltaE x lambda - deltaC) < 0; NMB is defined as deltaE x lambda - deltaC, while ICER is defined as deltaC/deltaE.
Despite its apparent complexity, most part of pharmacoeconomic methodology is described by the two simple equations reported above (i.e. Equations 1 and 2), but whether the ICER or the NMB is the best parameter for the purposes of pharmacoeconomic decision-making remains on open question.
The study by Cowper et al evaluating new versus old oral anticoagulants in patients with atrial fibrillation (2) is a typical ICER-based cost-effectiveness analysis in which the ICER of apixaban versus warfarin is compared against a willingness-to-pay threshold. This analysis can be taken as an example for comparing ICER vs NMB.
In one of the base-case analyses of the study by Cowper et al, QALYs per patient were 7.94 for apixaban and 7.54 for warfarin, while pharmacological costs per patient were $22,934 and $4,392, respectively. These data yielded, for apixaban versus warfarin, an ICER of $46,355 per QALY gained, a value that remains within the willingness-to-pay threshold of $50,000 per QALY gained and is therefore considered favourable (or “high value care”). As pointed our by Hlatky (3), in interpreting a specific ICER value, more than a single willingness-to-pay threshold is frequently considered (e.g. the threshold between $50,000 and $150,000 or the threshold above $150,000), and this allows us to better understand a pharmacoeconomic result expressed on the basis of an ICER.
In the methodology of pharmacoeconomics, the net monetary benefit (NMB) plays a role similar to that of ICER, but some differences are important.
Firstly, the ICER –by definition- has always an incremental nature and consequently the absolute cost-effectiveness ratio (calculated for a single treatment in the absence of any comparison) makes little sense and, for this reason, is rarely employed. In contrast, the NMB can be calculated for a single treatment in the absence of any comparison (absolute NMB) or can conversely be calculated as an incremental parameter [according to the equation: (incremental NMB) = (incremental QALYs per patient) x (willingness-to-pay threshold) – (incremental cost per patient)]. Another feature of NMB is that the incremental NMB for the comparison of A vs B can be estimated as the absolute NMB calculated for A minus the absolute NMB calculated for B. In this sequence of calculations, calculating the absolute NMB makes sense because the absolute NMB (separately calculated for the experimental treatment and for the control treatment) represents an intermediate step in the calculation of the incremental NMB (Table 1)
The values of absolute NMB for apixaban and warfarin (Table 1) are, respectively, 374,066 and $372,608 per patient (calculated according to Equation 2). Hence, the incremental NMB for apixaban vs warfarin is simply the difference of the above two values, i.e. $1,458 per patient.
References
1. Wouters OJ, Naci H, Samani NJ. QALYs in cost-effectiveness analysis: an overview for cardiologists. Heart. 2015 Dec;101(23):1868-73.
2. Cowper PA, Sheng S, Lopes RD, Anstrom KJ, Stafford JA, Davidson-Ray L, Al-Khatib SM, Ansell J, Dorian P, Husted S, McMurray JJ, Steg PG, Alexander JH, Wallentin L, Granger CB, Mark DB. Economic Analysis of Apixaban Therapy for Patients With Atrial Fibrillation From a US Perspective: Results From the ARISTOTLE Randomized Clinical Trial. JAMA Cardiol. 2017 Mar 29. doi:10.1001/jamacardio.2017.0065. [Epub ahead of print]
3. Hlatky MA. Are Novel Anticoagulants Worth Their Cost? JAMA Cardiol. 2017 Mar 29. doi: 10.1001/jamacardio.2017.0126. [Epub ahead of print]
Table 1. Cost-effectiveness of apixaban vs warfarin in atrial fibrillation: base-case analysis reported by Cowper et al. (2)
___________________________________________________
a) STARTING VALUES
Apixaban: QALYs per patient = 7.94, cost per patient = $22,934
Warfarin: QALYs per patient = 7.54, cost per patient = $4,392
Sawhney et al. reported that nurse-led, physician-directed moderate sedation during cardiac electrophysiology procedures is safe (1). All of the patients undergoing cardiac electrophysiological (EP) procedures and cardiac implantable electronic device (CIED) implantation during the last 12 years were moderately sedated. Since this study is a retrospective study, we could not comprehend why all patients were sedated despite the fact that routine sedation during all cardiac EP procedures and all CIED implantation is not recommended.
Moreover, as mentioned in the article, sedation is a continuum and it is not always possible to predict how individual patients will respond. Therefore, a gradual increase of doses of the sedatives during sedation may be needed which may possibly increase the procedure duration. Did authors ascertain any prolongation of the procedures due to sedative administration?
Furthermore, sedation may diminish arrythmia induction during EP procedures, particularly in patients with catecholamine-sensitive ventricular tachycardias (2). Did authors have any data questioning this issue?
As a conclusion, the aim of sedation is to diminish the anxiety and to relieve the pain during the procedure. Therefore, using moderate sedation selectively in patients with anxiety or hyperalgesia may be more practical and rational rather than its routine use due to the fact that as mentioned in the article, researches and audit demonstrate continued avoidabl...
Sawhney et al. reported that nurse-led, physician-directed moderate sedation during cardiac electrophysiology procedures is safe (1). All of the patients undergoing cardiac electrophysiological (EP) procedures and cardiac implantable electronic device (CIED) implantation during the last 12 years were moderately sedated. Since this study is a retrospective study, we could not comprehend why all patients were sedated despite the fact that routine sedation during all cardiac EP procedures and all CIED implantation is not recommended.
Moreover, as mentioned in the article, sedation is a continuum and it is not always possible to predict how individual patients will respond. Therefore, a gradual increase of doses of the sedatives during sedation may be needed which may possibly increase the procedure duration. Did authors ascertain any prolongation of the procedures due to sedative administration?
Furthermore, sedation may diminish arrythmia induction during EP procedures, particularly in patients with catecholamine-sensitive ventricular tachycardias (2). Did authors have any data questioning this issue?
As a conclusion, the aim of sedation is to diminish the anxiety and to relieve the pain during the procedure. Therefore, using moderate sedation selectively in patients with anxiety or hyperalgesia may be more practical and rational rather than its routine use due to the fact that as mentioned in the article, researches and audit demonstrate continued avoidable morbidity and mortality from sedation.
Kind Regards
REFERENCES
1) Sawhney V, Bacuetes E, Wray M, et al. Moderate sedation in cardiac electrophysiology laboratory: a retrospective safety analysis. Heart. 2017 Mar 1. pii: heartjnl-2016-310676. doi: 10.1136/heartjnl-2016-310676.
2) EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhytmias. Aliot EM, Stevenson WG, Almendral-Garrote JM, et al. Europace. 2009 Jun;11(6):771-817. doi: 10.1093/europace/eup098.
This is good to read a research article on "Tea consumption and risk
of ischaemic heart disease"
This is the largest prospective study (cohort of Chinese adults) published
to assess the association between tea consumption and incidence of IHD
and showed that daily tea consumption is beneficial in reducing risk of
IHD.
Study has more limitations (although the investigators rightly said
this).The is observational study,ma...
This is good to read a research article on "Tea consumption and risk
of ischaemic heart disease"
This is the largest prospective study (cohort of Chinese adults) published
to assess the association between tea consumption and incidence of IHD
and showed that daily tea consumption is beneficial in reducing risk of
IHD.
Study has more limitations (although the investigators rightly said
this).The is observational study,mainly subjective and lack causal
relationship.Tea consumption was measured in gram using tea leaves but
not exactly reflect the intake amount of active ingredient. The study
design revealed that cohort was compared with participants who did not
consumed tea during the previous 12 months, "compelling to believe but
difficult to believe it" also the inclusion and exclusion criteria were
designed that may best fit to conclude.
Studies revealed the health benefits of tea consumption like antioxidant
property, anticancer property, anticaries effect of tea and consumption of
green tea benefits ethanol intoxication [1].
The present study fail to reach conclusion that "daily tea consumption was
associated with a reduced risk of IHD".
Regards
Rajiv Kumar
Faculty
Dept. of Pharmacology, Government Medical College & Hospital
Chandigarh. India.
DRrajiv.08@gmail.com
References:
1. Sharma VK, Bhattacharya A, Kumar A, Sharma HK. Health Benefits of
Tea Consumption. Trop J Pharm Res, September 2007; 6 (3)
We read with interest the article by Varcoe et al (Heart Jan 15 th 20917) “Impact of call-to-balloon time on 30-day mortality in contemporary practice” We were not surprised by the results which indicate yet again that patients with delays to reperfusion suffer worse mortality rates - the concept of timely reperfusion in STEMI has been previously very well documented, and its importance recognised for some time. Thus de Lucca (1), Cannon (2) and others (3) reported data >10 years ago which supported the concept that mortality rates increase when important time metrics are not achieved. Time dependent infarct size is considered the cause (4)
When the National Infarct Angioplasty Project (NIAP) was established in 2008 with the explicit aim of rolling out P-PCI in the UK, everyone involved in care of STEMI patients thought it was a good idea to go with a policy of one STEMI management strategy, for simplicity. No-one doubted that P-PCI should become the standard of care. Some (including the authors of this letter - one of whom served on NIAP) voiced concerns however that, based on the published data, achieving guideline mandated times was essential, and that this might be difficult to achieve with P-PCI in patients transferred from more rural regions. There was assurance from Department of Health that >95% of patients were “within distance” of a P-PCI centre. We tried to point out that being “within distance”, and being within the mandated times were very differe...
We read with interest the article by Varcoe et al (Heart Jan 15 th 20917) “Impact of call-to-balloon time on 30-day mortality in contemporary practice” We were not surprised by the results which indicate yet again that patients with delays to reperfusion suffer worse mortality rates - the concept of timely reperfusion in STEMI has been previously very well documented, and its importance recognised for some time. Thus de Lucca (1), Cannon (2) and others (3) reported data >10 years ago which supported the concept that mortality rates increase when important time metrics are not achieved. Time dependent infarct size is considered the cause (4)
When the National Infarct Angioplasty Project (NIAP) was established in 2008 with the explicit aim of rolling out P-PCI in the UK, everyone involved in care of STEMI patients thought it was a good idea to go with a policy of one STEMI management strategy, for simplicity. No-one doubted that P-PCI should become the standard of care. Some (including the authors of this letter - one of whom served on NIAP) voiced concerns however that, based on the published data, achieving guideline mandated times was essential, and that this might be difficult to achieve with P-PCI in patients transferred from more rural regions. There was assurance from Department of Health that >95% of patients were “within distance” of a P-PCI centre. We tried to point out that being “within distance”, and being within the mandated times were very different indeed. We predicted that about 20% of patients could not achieve the call to balloon times in the UK probably for reasons in part related to transport times. And so it turns out. Data from the USA (5) indeed suggested that while door to balloon times fall, mortality does not, supporting the concept that it is the total ischaemic time that is crucial . This has thus again been confirmed by the data reported in this Heart paper.
In this context there are issues with these data in addition: In particular we are not provided with any data on total ischaemic times. It is clear that total ischemic time is best metric so the following is not an excuse to minimize its importance - quote “The STB time is a measure of total ischemic time, but symptom onset may be difficult to define accurately because of recall bias, prodromal anginal symptoms and silent or atypical presentations”. Other data bases manage to report this metric. Thus the authors cannot say “In our study, symptom-to-call time was not associated with 30-day mortality, whereas call-to-door and DTB times were (table 4), thus suggesting that pre-hospital and hospital-based emergency care are equally important contributors to patient outcome” since they havn’t considered the time from symptom onset. Again it is total ischaemic timer that is the issue. Furthermore whilst there is of course some value in measuring the 150 or 120 min CTB, time alone fails to recognize the key prognostic variables of territory at risk or demographics (anterior, young patient).
Inability to attain Guideline mandated times may occur for a number of reasons some of which are suggested in this paper. However since it is not patient level data, important issues such as individual transport times, other than inter-hospital transfer, which has always shown been shown to add time and lead to worse outcomes, cannot be determined. For the 18.5% patients in the ‘transfer’ cohort, the mean DTB time from first hospital admission was an unacceptable 133 min (median 123 min, IQR 95–161 min).
Difficulty in attaining Guideline agreed optimal times to reperfusion is not uncommon in other countries such as Australia, USA and parts of South America where geography and local conditions (e.g known times of traffic congestion) mean these times may be regularly missed, with the consequent impact on outcomes.
It was for the reasons of difficulty in achieving symptom to balloon times, because of transport delays that we devised, ran and published in 2013 the STREAM trial (6) which showed that if P-PCI could not be delivered within one hour of first medical contact, then a pharmaco-invasive strategy (immediate pre-hospital thrombolysis (with a reduced dose>75 years), then transfer to a PCI capable centre and intervention on those who needed rescue angioplasty and routine angiography+/- angioplasty between 6 and 24 hours in all others) resulted in equivalent outcomes to those randomised to timely P-PCI. As such recommendations, based on this study and others (7), have been incorporated into the European Guidelines (8). The authors allude to all of this a mere last sentence of their discussion.
The concept of pre-hospital timings are worth emphasizing more than this however. If those who could not receive timely P-PCI had in fact received a pharmaco-invasive strategy then the robust published data suggests they would have had the same outcomes as if they had received timely P-PCI (6).
Rather than one line in a discussion, we should robustly address the issue of whether it is indeed time (if transport delays because of geography are an issue in the UK) to re-think the reperfusion strategy and be a bit smarter and nuanced as to how we deliver reperfusion to ensure all patients do as well as those who receive timely P-PCI. They and all the others who missed the mandated Guideline time metrics may have done better with the pharmaco-invasive strategy. We worried about this previously, now UK data also supports this. Mixed models work in other countries who struggle to meet total ischaemic time challenges, why shouldn’t they in the UK?
Tony Gershlick
Frans van der Werf
Paul Armstrong
1) De Luca G1, Suryapranata H, Ottervanger JP, Antman EM. Time delay to treatment and mortality in primary angioplasty for acute myocardial infarction: every minute of delay counts. Circulation. 2004 Mar 16;109(10):1223-5. Epub 2004 Mar 8.
2) Cannon CP1, Gibson CM, Lambrew CT, Shoultz DA, Levy D, French WJ, Gore JM, Weaver WD, Rogers WJ, Tiefenbrunn AJ. Relationship of symptom-onset-to-balloon time and door-to-balloon time with mortality in patients undergoing angioplasty for acute myocardial infarction. JAMA. 2000 Jun 14;283(22):2941-7.
3) McNamara RL, Herrin J, Bradley EH, Portnay EL, Curtis JP, Wang Y, Magid DJ, Blaney M, Krumholz HM; NRMI Investigators.Hospital improvement in time to reperfusion in patients with acute myocardial infarction, 1999 to 2002.J Am Coll Cardiol. 2006 Jan 3;47(1):45-51.
4) Francone M, Bucciarelli-Ducci C, Carbone I, Canali E, Scardala R, Calabrese FA, Sardella G, Mancone M, Catalano C, Fedele F, Passariello R, Bogaert J, Agati L Impact of primary coronary angioplasty delay on myocardial salvage, infarct size, and microvascular damage in patients with ST-segment elevation myocardial infarction: insight from cardiovascular magnetic resonance. J Am Coll Cardiol. 2009 Dec 1;54(23):2145-53. doi: 10.1016/j.jacc.2009.08.024.
5) A Flynn, M Moscucci, D Share, Smith D, LaLonde T, Changezi H, Riba A, Gurm HS. Trends in door-to-balloon time and mortality in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention Arch Intern Med, 170 (2010), pp. 1842–1849
6) Armstrong PW, Gershlick AH, Goldstein P, Wilcox R, Danays T, Lambert Y, Sulimov V, Rosell Ortiz F, Ostojic M, Welsh RC, Carvalho AC, Nanas J, Arntz HR, Halvorsen S, Huber K, Grajek S, Fresco C, Bluhmki E, Regelin A, Vandenberghe K, Bogaerts K, Van de Werf F; STREAM Investigative TeamFibrinolysis or primary PCI in ST-segment elevation myocardial infarction. N Engl J Med. 2013 Apr 11;368(15):1379-87
7) Bonnefoy E, Steg PG, Boutitie F, Dubien PY, Lapostolle F, Roncalli J, Dissait F, Vanzetto G, Leizorowicz A, Kirkorian G; CAPTIM Investigators, Mercier C, McFadden EP, Touboul P Comparison of primary angioplasty and pre-hospital fibrinolysis in acute myocardial infarction (CAPTIM) trial: a 5-year follow-up. Eur Heart J. 2009 Jul;30(13):1598-606. doi: 10.1093/eurheartj/ehp156. Epub 2009 May 8.
8) Eur Heart J. 2012 Oct;33(20):2569-619. doi: 10.1093/eurheartj/ehs215. Epub 2012 Aug 24.
9) Steg PG, James SK, Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, van 't Hof A, Widimsky P, Zahger D ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012 Oct;33(20):2569-619.
We would like to thank Sarah Blake et al, for their thoughtful and insightful comments.
Firstly, we agree that "palliative PCI" can be a very useful treatment in this elderly patient population. Locally at our institution, via our heart team meeting, we can offer an elderly symptomatic patient with multiple co-morbidities percutaneous coronary intervention (PCI), which often fails to achieve complete re-vasculari...
We would like to thank Sarah Blake et al, for their thoughtful and insightful comments.
Firstly, we agree that "palliative PCI" can be a very useful treatment in this elderly patient population. Locally at our institution, via our heart team meeting, we can offer an elderly symptomatic patient with multiple co-morbidities percutaneous coronary intervention (PCI), which often fails to achieve complete re-vascularisation (even with small territories left ischaemic) but offers significant improvement in symptoms and can leave them safer in the presence of left main stem (LMS) or proximal left anterior decending (LAD) disease. Unlike the younger population, these patients prioritise symptomatic relief, and quality of life (Qol) over prognostic benefit, preferring a quick and immediate return over life years gained.
Secondly, in elderly patients with chest pains treated medically who re-present to the emergency department , a more definitive intervention can certainly help prevent re-admissions. However a careful and full discussion of the risks and benefits of PCI in this high risk cohort needs to be made often in conjunction with family members and it is crucial to consider bleeding risk from DAPT.
Finally, interventional cardiology in general has realised the need to shift outcomes away from procedural success to more patient orientated outcomes, such as QoL and angina status. The only issue with these is that they are qualitative rather than quantitative outcomes and often subjective. However we agree that this may need to be the focus along with bleeding risk in elderly interventional trials.
We read with interest this manuscript which demonstrated in a large
clinical registry that patients with chronic kidney disease with
indications for anticoagulation were often treated sub-therapeutically
(1). A more aggressive approach was therefore advocated.
We would like to point out that, while this study should be commended
for including a large number of patients, it did not show data on the key
clinical...
We read with interest this manuscript which demonstrated in a large
clinical registry that patients with chronic kidney disease with
indications for anticoagulation were often treated sub-therapeutically
(1). A more aggressive approach was therefore advocated.
We would like to point out that, while this study should be commended
for including a large number of patients, it did not show data on the key
clinical outcomes of stroke or bleeding. We feel, therefore, that a clear
association cannot be made between low time in the therapeutic range (TTR)
and any negative clinic outcome. In fact, paradoxically, our experience
from a large tertiary cardiac and renal service differs. We agree with the
authors that haemodialysis patients often have a suboptimal TTR, but we
believe there is no convincing data implying that increased time spent in
therapeutic range is beneficial in preventing embolic or thrombotic events
(2).
In addition, there is substantial evidence that haemodialysis
patients are at significantly increased risk of major bleeding events,
contributed to by uraemic platelet dysfunction, hypergastrinaemia and
anticoagulation required for the extracorporeal circuit. This risk of
major bleeding (bleeds into a critical organ, requiring transfusion or
admission, or fatal) is increased compared with non-dialysis patients, and
this risk has been shown to increase with the addition of antiplatelet
treatment or oral anticoagulation (3).
We would, therefore, advocate a cautious approach to anticoagulation
in patients with dialysis-requiring end-stage kidney disease. Our policy
is not to anticoagulate these patients in light of the fact that the
significant bleeding risk per annum in our haemodialysis patients without
addition anticoagulation is already nearly 4% (4). We believe there is an
urgent need for clinical outcome data in order to better inform our
clinical decision making in this complex patient group.
References.
References.
1. Yang et al. Heart online. 2016. doi:10.1136/heartjnl-2016-309266.
2. Chen et al. Circulation. 2016;133:265-272.
3. Holden et al. CJASN. 2008;3:105-110.
4. Nadarajah et al. Clin Nephrology 2015;85(5):274-9.
I read with great interest the article by Morris et al entitled,
"Marginal role for 53 common genetic variants in cardiovascular disease
prediction" (1). The article analyzed a large sample of 11, 851
individuals from 7 prospective studies aimed at primary prevention of
fatal or non-fatal coronary heart disease (CHD) or stroke.
The study incorporated susceptibility variants for CHD and str...
I read with great interest the article by Morris et al entitled,
"Marginal role for 53 common genetic variants in cardiovascular disease
prediction" (1). The article analyzed a large sample of 11, 851
individuals from 7 prospective studies aimed at primary prevention of
fatal or non-fatal coronary heart disease (CHD) or stroke.
The study incorporated susceptibility variants for CHD and stroke
into a genetic risk score (GRS), to match the two conditions predicted by
a conventional risk score QRISK-2. Results for population-wide utility of
the GRS, and estimates from a sequential screening strategy proposed for
individuals at intermediate risk, were provided. The study extrapolated
that 462 intermediate-risk individuals would need to be screened in order
to prevent one coronary heart disease or stroke event in 10 years.
Based on these results, a GRS could become a novel method for
determining which intermediate-risk individuals should be managed
aggressively, if reclassified to high-risk. However, before these results
are adopted in clinical practice, the following should be considered.
First, the extrapolated estimates should be confirmed prospectively.
Second, the 53 variants include 46 for CHD and 7 for stroke. The CHD
variants are not necessarily found to associate with stroke, and vice
versa. This may limit predictions for each disorder. Third, 46 CHD
variants account for 10% of heritability, and do not capture the entire
contribution of genetics estimated at 40-60% (3). Fourth, the GRS included
29 variants unique for CHD, as well as 17 additional variants that also
associate with CHD risk factors, such as cholesterol, blood pressure, and
diabetes (3); these risk factors are already accounted for in QRISK2 and
are not providing independent information. Fifth, the GRS did not
incorporate 10 additional variants recently discovered (4).
Reclassification and discrimination analyses should be redone with only 29
variants (then adding in the 10 new variants) in population-wide analysis
and for intermediate-risk individuals. Finally, a weak effect on mortality
was reported. This is likely due to the GRS being developed using case-
control prevalence and not incidence.
Overall, there is still work to be done before these excellent
results can be implemented.
References
1. Morris RW, Cooper JA, Shah T, Wong A, Drenos F, Engmann J, et al.
Marginal role for 53 common genetic variants in cardiovascular disease
prediction. Heart. 2016 Jun 30. 2. Kullo IJ, Jouni H, Austin EE, Brown SA,
Kruisselbrink TM, Isseh IN, et al. Incorporating a Genetic Risk Score Into
Coronary Heart Disease Risk Estimates: Effect on Low-Density Lipoprotein
Cholesterol Levels (the MI- GENES Clinical Trial). Circulation. 2016
Mar;133(12):1181-8. 3. Deloukas P, Kanoni S, Willenborg C, Farrall M,
Assimes TL, Thompson JR, et al. Large-scale association analysis
identifies new risk loci for coronary artery disease. Nat Genet. 2013
Jan;45(1):25-33. 4. Nikpay M, Goel A, Won HH, Hall LM, Willenborg C,
Kanoni S, et al. A comprehensive 1,000 Genomes-based genome-wide
association meta-analysis of coronary artery disease. Nat Genet. 2015
Oct;47(10):1121-30.
We read with great interest the manuscript by Faden et al. (1)
entitled "A nationwide evaluation of spontaneous coronary artery
dissection in pregnancy and the puerperium" when it was published online
July 13. Using the Healthcare Cost and Utilization Project national
database, the authors evaluated over 4 million pregnancy-related
discharges, looking at the prevalence and outcomes of pregnancy-associated
spontaneous cor...
We read with great interest the manuscript by Faden et al. (1)
entitled "A nationwide evaluation of spontaneous coronary artery
dissection in pregnancy and the puerperium" when it was published online
July 13. Using the Healthcare Cost and Utilization Project national
database, the authors evaluated over 4 million pregnancy-related
discharges, looking at the prevalence and outcomes of pregnancy-associated
spontaneous coronary artery dissection (P-SCAD). By applying the
International Classification of Diseases, 9th Revision (ICD-9) 79 cases of
P-SCAD were identified, resulting in a prevalence of 1.81 per 100,000
pregnancies. Although this study stands out as the largest cohort thus far
assessing P-SCAD, a few shortcomings should be highlighted. First, the
methodology for P-SCAD search and identification included the ICD-9
medical code 412.12 represents a general definition of coronary artery
dissection; there is no specific classification for SCAD in either the ICD
-9 or in the recent ICD-10-CM (diagnosis code I25.42). Therefore, the 79
cases identified by the investigators may have included coronary artery
dissections arising from other causes including atherosclerosis. The
genuine classification of SCAD should be non-atherosclerotic. In addition,
other ambiguous findings by angiography, such as thrombus, may also mimic
SCAD (2). Prior study evaluating pregnant and postpartum women with
myocardial infarction showed that its pathophysiology includes SCAD in 43%
of cases, atherosclerosis in 27%, intracoronary thrombus in 17%, and
normal coronary arteries in 11% (3). Second, despite its well-known
limitations, invasive coronary angiography is still the main tool for
recognizing this condition; other intravascular imaging such as
intravascular ultrasound and optical coherence tomography have been
recently used to enhanced its diagnostic accuracy. Of note, the
pathognomonic appearance of SCAD on angiography--contrast dye staining of
arterial wall with multiple radiolucent lumen--is less prevalent among all
the findings, making the diagnostic ability of invasive angiography
limited and challenging (5). In the present study by Faden et al. there is
no mention about the angiographic findings of those patients, making the
definite and final diagnosis of P-SCAD debatable. Had the authors
reassessed all coronary invasive angiography, the ability to definitively
diagnosis SCDA would have been improved; indeed, 10% of cases did not
undergo invasive angiography, so the final diagnosis P-SCDA could only be
extracted from the data set alone. Finally, when assessing the risk
factors for P-SCAD, the authors demonstrated that chronic hypertension and
lipid profile abnormalities were highly prevalent in relation to SCAD,
which is in disagreement with prior studies showing that most patients had
no risk factors for coronary artery disease (4). Likewise, a high rate of
prior coronary angioplasty and, specifically, coronary artery bypass graft
surgery (34%) in this cohort may suggest the inclusion of patients with
coronary atherosclerosis.
References:
1. Faden MS, Bottega N, Benjamin A, Brown RN. A nationwide evaluation
of spontaneous coronary artery dissection in pregnancy and the puerperium.
Heart 2016;0:1-6. doi:10.1136/heartjnl-2016-309403.
2. Cade JR, Abizaid A, Caixeta A. Organized Thrombus Mimicking
Spontaneous Coronary Artery Dissection. JACC Cardiovasc Interv. 2014;
7(12):1458.
3. Elkayam U, Jalnapurkar S, Barakkat MN, Khatri N, Kealey AJ, Mehra
A, et al. Pregnancy-associated acute myocardial infarction: a review of
contemporary experience in 150 cases between 2006 and 2011. Circulation.
2014;129(16):1695-702.
4. Cade JR, Szarf G, de Siqueira ME, Chaves A, Andrea JC, Figueira
HR, et al. Pregnancy-associated spontaneous coronary artery dissection:
insights from a case series of 13 patients. Eur Heart J Cardiovasc
Imaging. 2016 [Epud ahead of print].
5. Saw J. Coronary angiogram classification of spontaneous coronary
artery dissection. Catheter Cardiovasc Interv. 2014;84(7):1115-22.
On reading the review on coronary revascularisation in the elderly by
Cockburn et al (1) I must agree that more trials are needed to focus on
the benefit of PCI in elderly populations.
When assessing these patients, clinicians should consider the impact
of symptom relief versus procedural risk. If a patient is experiencing
recurrent and debilitating chest pain requiring frequent hospital
a...
On reading the review on coronary revascularisation in the elderly by
Cockburn et al (1) I must agree that more trials are needed to focus on
the benefit of PCI in elderly populations.
When assessing these patients, clinicians should consider the impact
of symptom relief versus procedural risk. If a patient is experiencing
recurrent and debilitating chest pain requiring frequent hospital
admission then the risks of PCI, despite multiple comorbidities, could
easily be rationalised when the benefit to the patient is clear. In such
patients this "palliative PCI" approach, aiming to improve quality of life
but not necessarily prolong it, should be at the forefront of the
clinicians mind. Each patient should be assessed with consideration of the
benefits to the individual and with a clear understanding of the values of
the patient.
An interesting additional consideration not mentioned in the review
is the potential benefit of PCI in elderly patients in terms of cost to
hospitals. Although complications and poor outcomes may be increased in
this population, the burden of elderly patients deemed unfit for PCI
presenting with recurrent admissions due to chest pain must be taken into
account. I noted that in a paragraph on future research the authors
mentioned further trials of PCI in elderly patients that looked at
myocardial infarction and mortality as their primary outcomes. This may no
longer be as relevant in elderly patients where quality of life is more
important than quantity. A trial involving predominantly elderly patients
assessing quality of life both before and after PCI as the primary outcome
could be useful.
References:
1.Cockburn J, Hildick-Smith D, Trivedi U, de Belder A. Heart 2016;0:1-9.
doi:10.1136/heartjnl-2015-308999
Nehme and coworkers tested out the effect of air versus oxygen on
myocardial injury in ST-elevation myocardial infarction (STEMI).1 When
administered in the first 12 hours after STEMI oxygen was associated with
a dose-dependent increase in troponin and creatine kinase. In 2015 the
same group of investigators published a study in Circulation showing that
air instead of oxygen supplementation in STEMI led to improved outco...
Nehme and coworkers tested out the effect of air versus oxygen on
myocardial injury in ST-elevation myocardial infarction (STEMI).1 When
administered in the first 12 hours after STEMI oxygen was associated with
a dose-dependent increase in troponin and creatine kinase. In 2015 the
same group of investigators published a study in Circulation showing that
air instead of oxygen supplementation in STEMI led to improved outcome.
The conclusions of these two studies seem to be that supplemental oxygen
therapy in patients with STEMI but without hypoxia may increase early
myocardial injury and is associated with larger myocardial infarct size
assessed at 6 months.
In 1980 we were the first to suggest that due to production of oxygen free
radicals air could be better than oxygen supplementation during
reoxygenation.2 During the next 30 years we performed a series of studies
demonstrating that air compared to 100% oxygen caused significantly less
oxidative stress and less myocardial and kidney injury, and resulted in
higher survival rates in newborn infants needing resuscitation at birth.
In animal studies we demonstrated that 100% oxygen induced injury or
inflammation of several organs as the brain and heart.3,4 We also have
worked intensively with the basic mechanisms explaining such findings.
Based on these and other studies international recommendations for newborn
resuscitation were changed in 2010 from starting with 100% oxygen to air.
We have always been surprised that colleagues in adult medicine
apparently have not been aware of these results. The mechanisms of
reoxygenation injury are probably similar in adults as in newborn. We are
therefore delighted that Nehme et al1 and Stub et al performed their
studies, although 30 years after we challenged the present oxygen dogma.
It is therefore with surprise we don't find any references in their
publications 1 to our basic experimental and clinical studies. Thirty
years of extensive research with internationally acknowledged
translational results have not been credited by the authors, reviewers as
well as the editors responsible for publishing these results.
We truly believe that now is the time when adult medicine should recognize
progress in neonatal medicine which has helped unravel pathophysiological
mechanisms that have improved the survival and quality of life of human
beings independently of their age.
References
1. Nehme Z, Stub D, Bernard S, et al. Effect of supplemental oxygen
exposure on myocardial injury in ST- elevation myocardial infarction.
Heart 2016;102: 444-51
2. Saugstad OD, Aasen AO. Plasma hypoxanthine concentrations in pigs. A
prognostic aid in hypoxia. Eur Surg Res 1980;12:123-9.
3. Saugstad OD, Ramji S, Vento M. Resuscitation of depressed newborn
infants with ambient air or pure oxygen: a meta-analysis. Biol Neonate
2005;87:27-34
4. Saugstad OD. Resuscitation of newborn infants: from oxygen to room air.
Lancet 2010;376:1970-1
The article by Wouters and colleagues (1) presents an exhaustive overview on how QALYs can be used in cost-effectiveness analysis. In this framework, the authors also mention the incremental cost-effectiveness ratio (ICER), which is the parameter typically employed to express the results of a cost-effectiveness study. The article, however, does not discuss the net monetary benefit (NMB), which is another parameter employed to express the results of a cost-effectiveness study.
The incremental cost (deltaC) and the incremental effectiveness (deltaE) are the two main parameters of pharmacoeconomics and cost-effectiveness analysis, along with the willingness-to-pay threshold (lambda). The decision rule (e.g. in the case of a favourable pharmacoeconomic result) is (deltaC/deltaE)<lambda (Equation 1), if based on the ICER, or (deltaE x lambda - deltaC) > 0 (Equation 2), if based on the NMB. Likewise, an unfavourable pharmacoeconomic result is when (deltaC/deltaE)>lambda or when (deltaE x lambda - deltaC) < 0; NMB is defined as deltaE x lambda - deltaC, while ICER is defined as deltaC/deltaE.
Despite its apparent complexity, most part of pharmacoeconomic methodology is described by the two simple equations reported above (i.e. Equations 1 and 2), but whether the ICER or the NMB is the best parameter for the purposes of pharmacoeconomic decision-making remains on open question.
The study by Cowper et al evaluating new versus old oral antic...
Show MoreSawhney et al. reported that nurse-led, physician-directed moderate sedation during cardiac electrophysiology procedures is safe (1). All of the patients undergoing cardiac electrophysiological (EP) procedures and cardiac implantable electronic device (CIED) implantation during the last 12 years were moderately sedated. Since this study is a retrospective study, we could not comprehend why all patients were sedated despite the fact that routine sedation during all cardiac EP procedures and all CIED implantation is not recommended.
Show MoreMoreover, as mentioned in the article, sedation is a continuum and it is not always possible to predict how individual patients will respond. Therefore, a gradual increase of doses of the sedatives during sedation may be needed which may possibly increase the procedure duration. Did authors ascertain any prolongation of the procedures due to sedative administration?
Furthermore, sedation may diminish arrythmia induction during EP procedures, particularly in patients with catecholamine-sensitive ventricular tachycardias (2). Did authors have any data questioning this issue?
As a conclusion, the aim of sedation is to diminish the anxiety and to relieve the pain during the procedure. Therefore, using moderate sedation selectively in patients with anxiety or hyperalgesia may be more practical and rational rather than its routine use due to the fact that as mentioned in the article, researches and audit demonstrate continued avoidabl...
This is good to read a research article on "Tea consumption and risk of ischaemic heart disease" This is the largest prospective study (cohort of Chinese adults) published to assess the association between tea consumption and incidence of IHD and showed that daily tea consumption is beneficial in reducing risk of IHD. Study has more limitations (although the investigators rightly said this).The is observational study,ma...
We read with interest the article by Varcoe et al (Heart Jan 15 th 20917) “Impact of call-to-balloon time on 30-day mortality in contemporary practice” We were not surprised by the results which indicate yet again that patients with delays to reperfusion suffer worse mortality rates - the concept of timely reperfusion in STEMI has been previously very well documented, and its importance recognised for some time. Thus de Lucca (1), Cannon (2) and others (3) reported data >10 years ago which supported the concept that mortality rates increase when important time metrics are not achieved. Time dependent infarct size is considered the cause (4)
Show MoreWhen the National Infarct Angioplasty Project (NIAP) was established in 2008 with the explicit aim of rolling out P-PCI in the UK, everyone involved in care of STEMI patients thought it was a good idea to go with a policy of one STEMI management strategy, for simplicity. No-one doubted that P-PCI should become the standard of care. Some (including the authors of this letter - one of whom served on NIAP) voiced concerns however that, based on the published data, achieving guideline mandated times was essential, and that this might be difficult to achieve with P-PCI in patients transferred from more rural regions. There was assurance from Department of Health that >95% of patients were “within distance” of a P-PCI centre. We tried to point out that being “within distance”, and being within the mandated times were very differe...
We would like to thank Sarah Blake et al, for their thoughtful and insightful comments.
Firstly, we agree that "palliative PCI" can be a very useful treatment in this elderly patient population. Locally at our institution, via our heart team meeting, we can offer an elderly symptomatic patient with multiple co-morbidities percutaneous coronary intervention (PCI), which often fails to achieve complete re-vasculari...
We read with interest this manuscript which demonstrated in a large clinical registry that patients with chronic kidney disease with indications for anticoagulation were often treated sub-therapeutically (1). A more aggressive approach was therefore advocated.
We would like to point out that, while this study should be commended for including a large number of patients, it did not show data on the key clinical...
Dear Editor,
I read with great interest the article by Morris et al entitled, "Marginal role for 53 common genetic variants in cardiovascular disease prediction" (1). The article analyzed a large sample of 11, 851 individuals from 7 prospective studies aimed at primary prevention of fatal or non-fatal coronary heart disease (CHD) or stroke.
The study incorporated susceptibility variants for CHD and str...
We read with great interest the manuscript by Faden et al. (1) entitled "A nationwide evaluation of spontaneous coronary artery dissection in pregnancy and the puerperium" when it was published online July 13. Using the Healthcare Cost and Utilization Project national database, the authors evaluated over 4 million pregnancy-related discharges, looking at the prevalence and outcomes of pregnancy-associated spontaneous cor...
Dear Editor
On reading the review on coronary revascularisation in the elderly by Cockburn et al (1) I must agree that more trials are needed to focus on the benefit of PCI in elderly populations.
When assessing these patients, clinicians should consider the impact of symptom relief versus procedural risk. If a patient is experiencing recurrent and debilitating chest pain requiring frequent hospital a...
Nehme and coworkers tested out the effect of air versus oxygen on myocardial injury in ST-elevation myocardial infarction (STEMI).1 When administered in the first 12 hours after STEMI oxygen was associated with a dose-dependent increase in troponin and creatine kinase. In 2015 the same group of investigators published a study in Circulation showing that air instead of oxygen supplementation in STEMI led to improved outco...
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