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To the Editor,
The timely retrospective US cohort study by Alonso et al.1 assessed the risk of hospitalisations for liver injury after initiation of oral anticoagulation in patients with non-valvular atrial fibrillation, an unresolved safety issue so far.
This study has key merits. First, it demonstrates the importance of conducting analytical research following safety signals emerging from spontaneous reporting systems2, to confirm or refute the drug-related hypothesis; this allows actual risk assessment and avoids unnecessary alarm, sometimes generated by pharmacovigilance analyses which do not recognize the limits of detected signals.
Second, it provides a significant contribution to the debate on targeted patients’ selection when prescribing DOACs. In fact, the authors found that hospitalization rates for liver injury were lower among DOAC initiators as compared to patients starting warfarin, with rivaroxaban and dabigatran associated with highest and lowest risk, respectively. They conclude that “dabigatran may be considered a safer option” in patients susceptible of liver complications. In this vulnerable population, our proposal when initiating DOAC administration is to early monitor hepatic enzymes (i.e., within the first month of therapy) and, subsequently, on a yearly basis, especially for rivaroxaban users.3
Although this study contributes to allay concern on the hepatotoxicity potential of DOACs, a residual aspect deserves attention. The...
To the Editor,
The timely retrospective US cohort study by Alonso et al.1 assessed the risk of hospitalisations for liver injury after initiation of oral anticoagulation in patients with non-valvular atrial fibrillation, an unresolved safety issue so far.
This study has key merits. First, it demonstrates the importance of conducting analytical research following safety signals emerging from spontaneous reporting systems2, to confirm or refute the drug-related hypothesis; this allows actual risk assessment and avoids unnecessary alarm, sometimes generated by pharmacovigilance analyses which do not recognize the limits of detected signals.
Second, it provides a significant contribution to the debate on targeted patients’ selection when prescribing DOACs. In fact, the authors found that hospitalization rates for liver injury were lower among DOAC initiators as compared to patients starting warfarin, with rivaroxaban and dabigatran associated with highest and lowest risk, respectively. They conclude that “dabigatran may be considered a safer option” in patients susceptible of liver complications. In this vulnerable population, our proposal when initiating DOAC administration is to early monitor hepatic enzymes (i.e., within the first month of therapy) and, subsequently, on a yearly basis, especially for rivaroxaban users.3
Although this study contributes to allay concern on the hepatotoxicity potential of DOACs, a residual aspect deserves attention. The authors acknowledge the fact that concerns/awareness about liver toxicity could have potentially resulted in selective prescribing towards DOACs of patients at higher hepatic risk, but did not discuss the resulting channeling bias. Notably, warfarin initiators were older, had higher CHA2DS2-VASc and HAS-BLED scores and higher prevalence of comorbidities, as compared to DOACs users. Therefore, it is plausible that this phenomenon generated confounding, which was not fully captured despite extensive adjustment strategies.4 Therefore, we believe that this first important piece of evidence cannot stand alone when it comes to selecting a given oral anticoagulant.
We encourage additional observational studies to replicate these findings, especially in different contexts, such as the European scenario and in patients with venous thromboembolism, which might be more prone to develop liver injury.3 Hopefully, collaborative multidisciplinary consortia will fill the mechanistic and clinical gaps to establish actual drug-event relationship and support risk stratification.
REFERENCES
1 Alonso A, MacLehose RF, Chen LY et al. Prospective study of oral anticoagulants and risk of liver injury in patients with atrial fibrillation. Heart 2017 Jan 5. pii: heartjnl-2016-310586. doi: 10.1136/heartjnl-2016-310586. [Epub ahead of print]
2 Raschi E, Poluzzi E, Koci A et al. Liver injury with novel oral anticoagulants: assessing post-marketing reports in the US Food and Drug Administration adverse event reporting system. Br J Clin Pharmacol 2015;80:285-93.
3 Raschi E, Bianchin M, Ageno W et al. Adverse events associated with the use of direct-acting oral anticoagulants in clinical practice: beyond bleeding complications. Pol Arch Med Wewn 2016;126:552-61.
4 Gorst-Rasmussen A, Lip GY, Bjerregaard Larsen T. Rivaroxaban versus warfarin and dabigatran in atrial fibrillation: comparative effectiveness and safety in Danish routine care. Pharmacoepidemiol Drug Saf 2016;25:1236-44.
We congratulate McDowell et al. on their educational and interesting case report.1 However, we would like to comment on their use of the term ‘near-drowning’. This, and other confusing and older terms which caused inconsistencies in the literature, have been abandoned by organisations such as the International Liaison Committee on Resuscitation (ILCOR) and the World Health Organisation (WHO) who recommend a more structured and clearer way of reporting drowning incidents.2,3 For several years now, drowning has been defined as ‘a process resulting in primary respiratory impairment from submersion/immersion in a liquid medium. Implicit in this definition is that a liquid/air interface is present at the entrance of the victim’s airway, preventing the victim from breathing air. The victim may live or die after this process, but whatever the outcome, he or she has been involved in a drowning incident’. 2,3 We would thus recommend that the authors and readers of your journal follow ILCOR and WHO recommendations, and simply use the term ‘drowning’ irrespective of the patient outcome. While this may seem pedantic, we do believe that it will assist with standardisation in drowning research and literature.
References
1. McDowell K, Carrick D, Weir R. Heart Published Online First: 18 may 2017. doi:10.1136/heartjnl-2016-311043.
2. Idris AH, Berg RA, Bierens J, Bossaert L, Branche CM, Gabrielli A, Graves SA, Handley AJ, Hoelle R, Morley PT, Papa L, Pepe...
We congratulate McDowell et al. on their educational and interesting case report.1 However, we would like to comment on their use of the term ‘near-drowning’. This, and other confusing and older terms which caused inconsistencies in the literature, have been abandoned by organisations such as the International Liaison Committee on Resuscitation (ILCOR) and the World Health Organisation (WHO) who recommend a more structured and clearer way of reporting drowning incidents.2,3 For several years now, drowning has been defined as ‘a process resulting in primary respiratory impairment from submersion/immersion in a liquid medium. Implicit in this definition is that a liquid/air interface is present at the entrance of the victim’s airway, preventing the victim from breathing air. The victim may live or die after this process, but whatever the outcome, he or she has been involved in a drowning incident’. 2,3 We would thus recommend that the authors and readers of your journal follow ILCOR and WHO recommendations, and simply use the term ‘drowning’ irrespective of the patient outcome. While this may seem pedantic, we do believe that it will assist with standardisation in drowning research and literature.
References
1. McDowell K, Carrick D, Weir R. Heart Published Online First: 18 may 2017. doi:10.1136/heartjnl-2016-311043.
2. Idris AH, Berg RA, Bierens J, Bossaert L, Branche CM, Gabrielli A, Graves SA, Handley AJ, Hoelle R, Morley PT, Papa L, Pepe PE, Quan L, Szpilman D, Wigginton JG, Modell JH, American Heart Association. Recommended guidelines for uniform reporting of data from drowning: the "Utstein style". Circulation 2003;108:2565-74.
3. van Beeck E, Branche C, Szpilman D, Modell J, Bierens J. A new definition of drowning: towards documentation and prevention of a global public health problem. Bull World Health Organ 2005;83:853-6.
We read with interest the Editorial on the recently updated National Institute for Health and Care Excellence (NICE) guidance for the assessment of suspected stable angina (1). The authors raise some salient points regarding the importance of careful history taking, the vexed question of the exercise ECG and the relative merits of the myriad non-invasive tests for diagnosing coronary artery disease (CAD). However, we believe they have adopted an unnecessarily alarmist tone in their criticisms and feel obliged to respond to several issues.
Although they suggest that the assessment of pretest probability (PTP) has been disregarded, this process has merely been made implicit rather than explicit. The guidelines emphasise the pivotal importance of the clinical history and, in the setting of suspected angina, the nature of the presenting symptoms is the dominant predictor of CAD. Existing risk tables (2) show that either typical or atypical angina essentially guarantees a PTP of CAD ≥ 10%, the threshold warranting further investigation in the earlier NICE guideline. The residual clinical risk seen in patients with non-anginal symptoms is best addressed through cardiovascular screening approaches with an emphasis of lifestyle modification and primary prevention.
Second, in arguing against the cost-effectiveness of the new approach, the authors imply that NICE are recommending “universal CTCA” which is incorrect. Non-anginal chest pain occurs in 40-60% of patients pre...
We read with interest the Editorial on the recently updated National Institute for Health and Care Excellence (NICE) guidance for the assessment of suspected stable angina (1). The authors raise some salient points regarding the importance of careful history taking, the vexed question of the exercise ECG and the relative merits of the myriad non-invasive tests for diagnosing coronary artery disease (CAD). However, we believe they have adopted an unnecessarily alarmist tone in their criticisms and feel obliged to respond to several issues.
Although they suggest that the assessment of pretest probability (PTP) has been disregarded, this process has merely been made implicit rather than explicit. The guidelines emphasise the pivotal importance of the clinical history and, in the setting of suspected angina, the nature of the presenting symptoms is the dominant predictor of CAD. Existing risk tables (2) show that either typical or atypical angina essentially guarantees a PTP of CAD ≥ 10%, the threshold warranting further investigation in the earlier NICE guideline. The residual clinical risk seen in patients with non-anginal symptoms is best addressed through cardiovascular screening approaches with an emphasis of lifestyle modification and primary prevention.
Second, in arguing against the cost-effectiveness of the new approach, the authors imply that NICE are recommending “universal CTCA” which is incorrect. Non-anginal chest pain occurs in 40-60% of patients presenting to chest pain clinics in the United Kingdom (3, 4), creating the opportunity for many more individuals to be discharged without further investigation. In addition, the Scottish COmputed Tomography of the Heart (SCOT-HEART) trial (3) did not demonstrate an overall increase in invasive coronary angiograms or revascularisation rates, perhaps reflecting a more nuanced response to coronary disease in the modern era.
Third, although correct in noting the borderline statistical significance of the reduction in fatal and non-fatal myocardial infarction after 1.7 years follow-up of the SCOT-HEART trial (3), the primary pre-specified timeframe for reporting this outcome is 5 years, with final results due early 2018.
Finally, the authors will be pleased to learn that we will shortly present a comprehensive analysis of the clinical impact of the revised NICE guidelines when applied to the SCOT-HEART trial population, addressing the questions and allaying the concerns raised in this Editorial.
References:
1. Cremer PC, Nissen SE. The National Institute for Health and Care Excellence update for stable chest pain: poorly reasoned and risky for patients. Heart. 2017:heartjnl-2017-311410.
2. European Society of Cardiology Task Force. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013;34(38):2949-3003.
3. The SCOT-HEART investigators. CT coronary angiography in patients with suspected angina due to coronary heart disease (SCOT-HEART): an open-label, parallel-group, multicentre trial. The Lancet. 2015;385(9985):2383-91.
4. McKavanagh P, Lusk L, Ball PA, Verghis RM, Agus AM, Trinick TR, Duly E, Walls GM, Stevenson M, James B, Hamilton A, Harbinson MT, Donnelly PM. A comparison of cardiac computerized tomography and exercise stress electrocardiogram test for the investigation of stable chest pain: the clinical results of the CAPP randomized prospective trial. Eur Heart J Cardiovasc Imaging. 2015;16(4):441-8.
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.
To the Editor,
Show MoreThe timely retrospective US cohort study by Alonso et al.1 assessed the risk of hospitalisations for liver injury after initiation of oral anticoagulation in patients with non-valvular atrial fibrillation, an unresolved safety issue so far.
This study has key merits. First, it demonstrates the importance of conducting analytical research following safety signals emerging from spontaneous reporting systems2, to confirm or refute the drug-related hypothesis; this allows actual risk assessment and avoids unnecessary alarm, sometimes generated by pharmacovigilance analyses which do not recognize the limits of detected signals.
Second, it provides a significant contribution to the debate on targeted patients’ selection when prescribing DOACs. In fact, the authors found that hospitalization rates for liver injury were lower among DOAC initiators as compared to patients starting warfarin, with rivaroxaban and dabigatran associated with highest and lowest risk, respectively. They conclude that “dabigatran may be considered a safer option” in patients susceptible of liver complications. In this vulnerable population, our proposal when initiating DOAC administration is to early monitor hepatic enzymes (i.e., within the first month of therapy) and, subsequently, on a yearly basis, especially for rivaroxaban users.3
Although this study contributes to allay concern on the hepatotoxicity potential of DOACs, a residual aspect deserves attention. The...
Sir,
We congratulate McDowell et al. on their educational and interesting case report.1 However, we would like to comment on their use of the term ‘near-drowning’. This, and other confusing and older terms which caused inconsistencies in the literature, have been abandoned by organisations such as the International Liaison Committee on Resuscitation (ILCOR) and the World Health Organisation (WHO) who recommend a more structured and clearer way of reporting drowning incidents.2,3 For several years now, drowning has been defined as ‘a process resulting in primary respiratory impairment from submersion/immersion in a liquid medium. Implicit in this definition is that a liquid/air interface is present at the entrance of the victim’s airway, preventing the victim from breathing air. The victim may live or die after this process, but whatever the outcome, he or she has been involved in a drowning incident’. 2,3 We would thus recommend that the authors and readers of your journal follow ILCOR and WHO recommendations, and simply use the term ‘drowning’ irrespective of the patient outcome. While this may seem pedantic, we do believe that it will assist with standardisation in drowning research and literature.
References
1. McDowell K, Carrick D, Weir R. Heart Published Online First: 18 may 2017. doi:10.1136/heartjnl-2016-311043.
Show More2. Idris AH, Berg RA, Bierens J, Bossaert L, Branche CM, Gabrielli A, Graves SA, Handley AJ, Hoelle R, Morley PT, Papa L, Pepe...
We read with interest the Editorial on the recently updated National Institute for Health and Care Excellence (NICE) guidance for the assessment of suspected stable angina (1). The authors raise some salient points regarding the importance of careful history taking, the vexed question of the exercise ECG and the relative merits of the myriad non-invasive tests for diagnosing coronary artery disease (CAD). However, we believe they have adopted an unnecessarily alarmist tone in their criticisms and feel obliged to respond to several issues.
Show MoreAlthough they suggest that the assessment of pretest probability (PTP) has been disregarded, this process has merely been made implicit rather than explicit. The guidelines emphasise the pivotal importance of the clinical history and, in the setting of suspected angina, the nature of the presenting symptoms is the dominant predictor of CAD. Existing risk tables (2) show that either typical or atypical angina essentially guarantees a PTP of CAD ≥ 10%, the threshold warranting further investigation in the earlier NICE guideline. The residual clinical risk seen in patients with non-anginal symptoms is best addressed through cardiovascular screening approaches with an emphasis of lifestyle modification and primary prevention.
Second, in arguing against the cost-effectiveness of the new approach, the authors imply that NICE are recommending “universal CTCA” which is incorrect. Non-anginal chest pain occurs in 40-60% of patients pre...
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...
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