Correspondence
Long-Term Follow-up of the West of Scotland Coronary Prevention Study
N Engl J Med 2008; 358:193-195January 10, 2008
- Article
To the Editor:
Ford et al. (Oct. 11 issue)1 report long-term follow-up data from the West of Scotland Coronary Prevention Study (WOSCOPS), which showed that statin treatment for 5 years provided an ongoing reduction in cardiovascular events for an additional 10 years. Stabilization of existing plaque, slowing of the progression of coronary artery disease, and possibly regression of atherosclerosis are suggested as potential mechanisms for this benefit.
This follow-up study adjusted for the presence or absence of a history of diabetes at entry. Previous data from WOSCOPS have shown that randomized assignment to pravastatin therapy resulted in a 30% reduction in the risk of the development of diabetes.2 Could this reduction in the incidence of diabetes during the 5-year trial period account, in part, for the observed reduction in future cardiovascular events in the 10 years after completion of the trial?
2 ReferencesJohn W. McEvoy, M.B., M.R.C.P.I.
Ronan Margey, M.B., M.R.C.P.I.
Gavin J. Blake, M.D., F.R.C.P.I.
Mater Misericordiae University Hospital, Dublin 7, Ireland
gblake@mater.ie 1
Ford I ,Murray H ,Packard CJ ,Shepherd J ,Macfarlane PW ,Cobbe SM . Long-term follow-up of the West of Scotland Coronary Prevention Study. N Engl J Med 2007;357:1477-1486
Full Text | Web of Science | Medline2
Freeman DJ ,Norrie J ,Sattar N , et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001;103:357-362
Web of Science | Medline
To the Editor:
Ford et al. report that the use of pravastatin was associated with a significant reduction in coronary events in men with hypercholesteremia. Lately, the immunosuppressive effect of statins has been highlighted.1 Immunocompromised patients, including those with AIDS,2 and recipients of solid-organ or hematopoietic-cell transplants3 are at increased risk for lymphoid cancers.
The present study failed to show any significant association between the incidence of all cancers and the use of pravastatin, whereas a small case–control study showed that pravastatin use was associated with an elevated risk of lymphoid cancers in a dose-related fashion.4 It is difficult to draw definite conclusions about the influence of pravastatin on the development of lymphoid cancers on the basis of this study.4 We would be grateful if the authors could provide us the information on the association between the development of lymphoid cancers and pravastatin use in WOSCOPS.
4 ReferencesMasaharu Tsubokura, M.D.
Kameda Medical Center, Kamogawa 296-8602, Japan
tsubokura-tky@umin.ac. jp Masahiro Kami, M.D.
University of Tokyo, Tokyo 108-8639, Japan1
Kwak B ,Mulhaupt F ,Myit S ,Mach F . Statins as a newly recognized type of immunomodulator. Nat Med 2000;6:1399-1402
CrossRef | Web of Science | Medline2
Franceschi S ,Dal Maso L ,La Vecchia C . Advances in the epidemiology of HIV-associated non-Hodgkin's lymphoma and other lymphoid neoplasms. Int J Cancer 1999;83:481-485
CrossRef | Web of Science | Medline3
Bhatia S ,Ramsay NK ,Steinbuch M , et al. Malignant neoplasms following bone marrow transplantation. Blood 1996;87:3633-3639
Web of Science | Medline4
Iwata H ,Matsuo K ,Hara S , et al. Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies. Cancer Sci 2006;97:133-138
CrossRef | Web of Science | Medline
To the Editor:
On the basis of the long-term follow-up of WOSCOPS, Ford et al. conclude that 5 years of treatment with pravastatin was associated with a significant reduction in fatal and nonfatal coronary events for a subsequent 10 years. We would ask that the authors further explore their results by presenting analyses stratified according to post-trial statin use or nonuse (Figure 1Figure 1
Treatment-Scenario Comparisons.). Among subjects not taking a statin during follow-up (scenario A), the comparison would assess whether statins provide ongoing risk reduction after cessation of therapy. A similar comparison among subjects taking a statin after the trial (scenario B) would provide insight regarding the benefits of early versus delayed statin therapy in primary prevention, which might have important implications for current treatment guidelines, which are largely based on 10-year event rates.1 1 ReferencesAndrew P. DeFilippis, M.D.
Sandeep Bansal, M.D., M.P.H.
Roger S. Blumenthal, M.D.
Johns Hopkins Ciccarone Preventive Cardiology Center, Baltimore, MD 21287
apdef@yahoo.com 1
Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III): final report. Bethesda, MD: National Heart, Lung, and Blood Institute, September 2002. (NIH publication no. 02-5215.)
Author/Editor Response
We agree with McEvoy et al. that our findings could theoretically be explained in part by a reduction in the number of participants in whom diabetes developed. However, our assertion1 that pravastatin might prevent new-onset diabetes was based on a post hoc analysis that has not, to our knowledge, been reproduced in other studies. Furthermore, even in our previous analysis, only approximately 25 cases of new diabetes were prevented during an average of 5 years of follow-up. Hence, we believe, as we indicate in our report, that the main explanations for the ongoing benefit are stabilization of existing plaque, slowing of the progression of coronary artery disease, and possibly regression of atherosclerosis.
Tsubokura and Kami refer to a previous report of a small case–control study2 suggesting that pravastatin was associated with an elevated risk of lymphoid cancers. In our long-term follow-up study, we observed 28 cases of lymphoid cancers in the placebo group and 24 cases in the pravastatin group (hazard ratio in the pravastatin group as compared with the placebo group, 0.83 [95% confidence interval, 0.48 to 1.43]). Hence, our data do not support the hypothesis that pravastatin treatment has an adverse effect on the rate of lymphoid cancers.
DeFilippis et al. propose that we reanalyze our data after subgrouping according to whether the WOSCOPS participants were treated with a statin in the period after the original double-blind trial. The creation of subgroups on the basis of post-randomization data is generally contraindicated in the analysis of clinical trials. For this reason, we do not agree that this approach will provide useful additional insights. The obvious reason in this instance is that the post-trial use of statins is not independent of study outcomes. Participants who had a cardiovascular event during or after the trial were much more likely to be given a prescription for a statin after the original trial results were reported. Hence, subgrouping according to post-trial treatment creates a subgroup that has artificially low event rates among patients not treated with a statin after the trial and artificially high event rates among those treated with a statin after the trial. In fact, there is approximately a doubling of event rates in the second group in comparison with the first.
2 ReferencesIan Ford, Ph.D.
Heather Murray, M.Sc.
Stuart M. Cobbe, M.D.
University of Glasgow, Glasgow G12 8QQ, United Kingdom1
Freeman DJ ,Norrie J ,Sattar N , et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 2001;103:357-362
Web of Science | Medline2
Iwata H ,Matsuo K ,Hara S , et al. Use of hydroxy-methyl-glutaryl coenzyme A reductase inhibitors is associated with risk of lymphoid malignancies. Cancer Sci 2006;97:133-138
CrossRef | Web of Science | Medline
