Dear Editor,

We read with interest the article by Sutton et al. entitled ‘Predictors of outcome after percutaneous treatment for cardiogenic shock.’ [1]. We would like to congratulate the authors on attempting to identify risk factors that predict outcome in patients with cardiogenic shock who undergo percutaneous coronary intervention (PCI). We would, however, like to make a few points regarding the study that may have influenced its findings.

The study was conducted between 1995 to 2002 with a total of 113 patients recruited. The use of coronary stents in the study was only 48% and use of abciximab only 25%. Advances in stent technology and increasing evidence from trials on the use of abciximab during PCI suggest that both these treatment options improve outcomes in patients undergoing PCI [2,3]. The use of stents in the study by Sutton et al. is low and probably reflects the fact that stents were not being used routinely for PCI in the mid to late 90’s. Modern management has changed considerably, with stent use in acute myocardial infarction being better than just balloon angioplasty [4]. Along with this trend of increasing stent usage, the use of glycoprotein IIb/IIIa receptor antagonists has also increased with several large trials showing clear benefit of the use of such agents [3]. Evidence also exists for the use of clopidogrel in all patients undergoing PCI, unless contraindicated; emerging data also suggests that the initial loading dose should be 600mg [5]. Sutton et al. only used clopidogrel if one or more stents were used and even then ticlopidine may have been used instead. Less than 50% would therefore have received clopidogrel in this trial and those that did would have received a lower than recommended dose.

The low use of stents, glycoprotein IIb/IIIa receptor antagonists, and clopidogrel are all likely to have influenced the outcome of the trial and hence the conclusions drawn by the investigators. While we welcome the study and, once again, congratulate the authors on their attempts at identifying those at highest risk of death we would like to point out the limitations of the study in relation to advances in stent and drug use.

References

1. Sutton AGC, Finn P, Hall JA, et al. Predictors of outcome after percutaneous treatment for cardiogenic shock. Heart 2005; 91: 339-344.

2. ACC/AHA guidelines for the management of patients with ST- elevation myocardial infarction-executive summary. Circulation 2003; 110: 588-636.

3. Randomized, placebo-controlled trial of platelet glycoprotein IIb/IIIa blockade with primary angioplasty for acute myocardial infarction. Circulation 1998; 98: 734-741.

4. Schomig A, Ndrepepa G, Mehilli J, et al. A randomized trial of coronary stenting versus balloon angioplasty as a rescue intervention after failed thrombolysis in patients with acute myocardial infarction. J Am Coll Cardiol. 2004; 44 :2073-2079.

5. Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. High clopidogrel loading dose during coronary stenting: effects on drug response and interindividual variability. Eur Heart J. 2004; 25: 1903-1910.

Dear Editor,

The study of Mukherjee and co-workers [1] on the problem of statin and clopidogrel interaction is certainly of clinical interest. The study is similar to the re-evaluation of the CREDO-data [2] and the MITRAplus- data [3] but there are some limitations to consider: The study is retrospective and not randomised, and the subgroups differ substantially in many aspects. The major criticism is that the authors do not describe the initial therapeutic procedure of acute coronary syndrome (ACS) in their patients (primary percutaneous coronary intervention (PCI) with/without stenting, thrombolysis, coronary artery bypass grafting (CABG)) as these factors may have more impact on the clinical outcome than the combined use of statins and clopidogrel. The clopidogrel-statin drug-drug interaction may be of particular interest in patients undergoing stenting because of the risk of stent thrombosis in the case of a diminished clopidogrel effect. Therefore adequate endpoints could be stent thrombosis, myocardial infarction or revascularization of the target vessel. None of these conditions were analyzed by the authors. Instead they used overall death, myocardial infarction (irrespectively of the target vessel), and stroke (which appears not relevant regarding the working hypothesis). These composite endpoints may not be sufficient to analyse a possible adverse effect because of clopidogrel-statin interaction. Furthermore other important details were ignored in the paper: The data on the dosage of statins and the number of different statins used are lacking and it is not apparent how long the patients were given statin medication. In the discussion Mukherjee et al. emphasized that the presented data are in line with the report by Muller [4] et al. (600mg clopidogrel loading dosage), but it is not clear when and how the clopidogrel therapy was initiated (300mg loading or no loading) and how long it was sustained in their study group.

On the whole, the study presented by Mukherjee et al. retrospectively assesses statin co-medication on patients treated with clopidogrel without contributing very much to the on-going discussion on the clinical relevance of this clopidogrel-statin drug-drug interaction as they disregard other important factors on the clinical outcome of patients with ACS. Therefore randomized, prospective trials are an absolute must!

Dr. Horst Neubauer, Prof. Dr. Andreas Mügge,
Clinic of Cardiology & Angiology, BG Kliniken Bergmannsheil/St. Josef-Hospital, University Hospitals, Ruhr-University Gudrunstrasse 56, 44791 Bochum, Germany E-Mail: Horst.Neubauer@rub.de

References:

[1] Mukherjee D, Kline-Rogers E, Fang J et al. Lack of clopidogrel-CYP3A4 statin interaction in patients with acute coronary syndrome. Heart 2005;91:23-6.

[2] Saw J, Steinhubl SR, Berger PB et al. Lack of adverse clopidogrel- atorvastatin clinical interaction from secondary analysis of a randomized, placebo-controlled clopidogrel trial. Circulation 2003;108:921-4.

[3] Wienbergen H, Gitt AK, Schiele R et al. Comparison of clinical benefits of clopidogrel therapy in patients with acute coronary syndromes taking atorvastatin versus other statin therapies. Am J Cardiol 2003;92:285-8.

[4] Muller I, Besta F, Schulz C et al. Effects of statins on platelet inhibition by a high loading dose of clopidogrel. Circulation 2003;108:2195-7.

Dear Editor,

Jackson and colleagues [1] review of the predictors of cardiac rehabilitation participation addresses a serious international health problem. However, throughout, the review conflates prediction with causality- a confusion that has significant implications for the clarity of its recommendations for practice.

While a number of common predictors of participation are identified by the review (most notably physician’s endorsement, age and sex), these are presented as causes of participation in the subsequent discussion. This confusion is maintained in the conclusion that ‘obstacles’ such as age, sex and educational attainment ‘cannot be changed.’ As these are predictors and not themselves obstacles, their identification provides evidence of which patient groups are excluded but does not identify the causes of low participation in women, older adults and low income groups. Our own work has shown in a national study of Scotland [2] that, though age may predict lower cardiac rehabilitation participation, the actual causes of this pattern are complex and related to limited program capacity, resources and flexibility. To improve participation in older patients these underlying health systems factors should be addressed.

Secondly, by focusing on single factors, the review fails to identify the complex ways in which factors interact in the individual patient to influence not only willingness but also capacity to participate. Beneath even the seemingly straightforward single reasons voiced by patients for non-attendance, such as a lack of transport, we have shown that there lies a web of complex cost-benefit calculations, perceptions and values [3]. Again, to increase participation, these underlying factors must be understood and addressed.

Identifying predictors can assist the targeting of additional intervention to increase attendance. However, attempts to increase participation in cardiac rehabilitation will only be successful, if clinicians focus on the systems and individual factors that causally inhibit attendance in defined populations.

References

(1). Jackson L, Leclerc J, Erksine Y, Linden W. Getting the most out of cardiac rehabilitation: a review of referral and adherence patterns. Heart 2005;91:10-14.

(2). Clark AM, Sharp C, MacIntyre PD. The role of age in moderating access to cardiac rehabilitation in Scotland. Ageing and Society 2002;22:501-515.

(3). Clark AM, Barbour RS, White M, MacIntyre PD. Promoting participation in cardiac rehabilitation : Patients' choices and experiences. Journal of Advanced Nursing 2004;47(1):5-14.