- Email: [email protected]
The statin wars
CORRESPONDENCE
COMMENTARY
CORRESPONDENCE e-mail submissions to [email protected]
The statin wars Sir—In your Oct 25 Editorial,1 you write that “Physicians must tell their patients the truth about Crestor (rosuvastatin)”. Readers of The Lancet are entitled to no less from their Editor. Your readers should know the following. Crestor is an extensively studied and well tolerated drug with a safety profile comparable to other marketed statins combined with a greater ability to get patients to their cholesterol goals than any other single product. More than 80% of patients reach their LDL cholesterol goals on the starting dose of 10 mg which also significantly increases HDL cholesterol—a profile unmatched by competitor drugs. AstraZeneca developed and submitted for regulatory approval the largest clinical database for any statin with more than 10 000 patients studied in clinical trials. Eight full primary publications of Crestor data have appeared in prestigious peer review journals including the American Heart Journal, American Journal of Cardiology, and the Journal of Cardiovascular Risk. All of the safety and efficacy data on Crestor have been reviewed in great depth by regulatory authorities globally, who have assessed the benefit-risk profile of the product and approved it in a very demanding regulatory climate. For example, the whole database was publicly scrutinised at a meeting of the Food and Drug Administration Advisory Committee, with all nine members unanimously supporting the recommendation for approval of Crestor 5–40 mg for long-term lipid control. More than 30 regulatory authorities worldwide have approved Crestor to date and more approvals are pending. Over 200 000 patients worldwide have now been treated with Crestor. Postmarketing surveillance confirms its safety profile to be similar to that of other marketed products in the statin class. Outcome data are rarely available for any new medicine at the time of launch, and have never been available for cholesterol-lowering and hypertensive drugs at this stage. Mandating outcomes data for any drug before approval would stifle innovation and needlessly delay the introduction of new therapeutic
1498
advances. External clinical opinion leaders were so impressed by the Crestor clinical trial data that AstraZeneca started a comprehensive outcomes programme before approval. However these studies, including trials in heart failure, are long-term and it will be a number of years before they reach maturity. Lipid surrogate endpoints are necessary, widely accepted, and form the basis of clinical decision making. Large studies have established that an increased concentration of LDL cholesterol is a risk factor for the development of atherosclerosis. In turn, atherosclerosis is a major cause of cardiovascular mortality and morbidity. Crestor has an impressive, reproducible, and reliable effect on these surrogates, and this evidence is the basis for the Crestor GALAXY Programme. Millions of people are at risk of cardiovascular disease because they are either untreated or not being effectively treated with current lipid-lowering therapies. With this compelling medical need, it is unthinkable that we should desist from our efforts to make this medicine more widely available to physicians and patients. Regulators, doctors, and patients as well as AstraZeneca have been poorly served by your flawed and incorrect editorial. I deplore the fact that a respected scientific journal such as The Lancet should make such an outrageous critique of a serious, well studied, and important medicine. Tom McKillop Chief Executive, AstraZeneca PLC 1
Editorial. The statin wars: why AstraZeneca must retreat. Lancet 2003; 362: 1341.
Separating inflammation from speculation in autism Sir—The report by Michael Kidd and colleagues (Sept 6, p 832)1 of measlesassociated encephalitis in children with renal transplants emphasises the grave risks posed to immunosuppressed children by low uptake of the measles mumps and rubella (MMR) vaccine. Calculations of outbreak size indicate that low MMR uptake has left the UK
on the edge of major measles outbreaks.2 Uptake as low as 61%1 makes almost certain the return of endemicity.2 Additionally, the near elimination of congenital rubella syndrome by MMR will surely reverse. I write as an author of an Early report for The Lancet3 and a paediatric gastroenterologist for many autistic children. Although subsequent studies4 have lent support to and extended the gastrointestinal findings associated with autism noted in this report, the same is not true for any link with MMR; many epidemiological studies have been undertaken, the results of which indicate no causal relation. No other vaccine has ever been studied in such depth, and the evidence for its overall safety is comprehensive. The response by all consultant paediatricians in the Early report3 was to support MMR vaccination without reservation,5 although this fact went largely unreported. The points made by us in this letter remain valid. This department has continued to assess children with autism on straightforward clinical grounds, since large numbers show improvement in abdominal pain and sleep disturbance if constipation, gastritis, or colonic inflammation are recognised and treated.5 However, not all children with autism show such response, a finding that needs further study. That any reports that characterise gut inflammation in autistic children are reported in the media as supporting the idea that MMR is causative is deeply frustrating, since it is simply not so. I and my colleagues have seen similar intestinal changes in children with no history of regression, in unvaccinated children, and in children whose first autistic symptoms clearly predated MMR administration. Several genes implicated in autism are expressed in the intestine and immune systems, and it is possible that subtle abnormality in these systems is an unrecognised component of autistic-spectrum disorders. This area remains one of legitimate interest, but should be clearly separated from the MMR issue. MMR immunisation, which should be an easy decision, has become a worrying issue for many British parents.
THE LANCET • Vol 362 • November 1, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.
COMMENTARY
CORRESPONDENCE e-mail submissions to [email protected]
The statin wars Sir—In your Oct 25 Editorial,1 you write that “Physicians must tell their patients the truth about Crestor (rosuvastatin)”. Readers of The Lancet are entitled to no less from their Editor. Your readers should know the following. Crestor is an extensively studied and well tolerated drug with a safety profile comparable to other marketed statins combined with a greater ability to get patients to their cholesterol goals than any other single product. More than 80% of patients reach their LDL cholesterol goals on the starting dose of 10 mg which also significantly increases HDL cholesterol—a profile unmatched by competitor drugs. AstraZeneca developed and submitted for regulatory approval the largest clinical database for any statin with more than 10 000 patients studied in clinical trials. Eight full primary publications of Crestor data have appeared in prestigious peer review journals including the American Heart Journal, American Journal of Cardiology, and the Journal of Cardiovascular Risk. All of the safety and efficacy data on Crestor have been reviewed in great depth by regulatory authorities globally, who have assessed the benefit-risk profile of the product and approved it in a very demanding regulatory climate. For example, the whole database was publicly scrutinised at a meeting of the Food and Drug Administration Advisory Committee, with all nine members unanimously supporting the recommendation for approval of Crestor 5–40 mg for long-term lipid control. More than 30 regulatory authorities worldwide have approved Crestor to date and more approvals are pending. Over 200 000 patients worldwide have now been treated with Crestor. Postmarketing surveillance confirms its safety profile to be similar to that of other marketed products in the statin class. Outcome data are rarely available for any new medicine at the time of launch, and have never been available for cholesterol-lowering and hypertensive drugs at this stage. Mandating outcomes data for any drug before approval would stifle innovation and needlessly delay the introduction of new therapeutic
1498
advances. External clinical opinion leaders were so impressed by the Crestor clinical trial data that AstraZeneca started a comprehensive outcomes programme before approval. However these studies, including trials in heart failure, are long-term and it will be a number of years before they reach maturity. Lipid surrogate endpoints are necessary, widely accepted, and form the basis of clinical decision making. Large studies have established that an increased concentration of LDL cholesterol is a risk factor for the development of atherosclerosis. In turn, atherosclerosis is a major cause of cardiovascular mortality and morbidity. Crestor has an impressive, reproducible, and reliable effect on these surrogates, and this evidence is the basis for the Crestor GALAXY Programme. Millions of people are at risk of cardiovascular disease because they are either untreated or not being effectively treated with current lipid-lowering therapies. With this compelling medical need, it is unthinkable that we should desist from our efforts to make this medicine more widely available to physicians and patients. Regulators, doctors, and patients as well as AstraZeneca have been poorly served by your flawed and incorrect editorial. I deplore the fact that a respected scientific journal such as The Lancet should make such an outrageous critique of a serious, well studied, and important medicine. Tom McKillop Chief Executive, AstraZeneca PLC 1
Editorial. The statin wars: why AstraZeneca must retreat. Lancet 2003; 362: 1341.
Separating inflammation from speculation in autism Sir—The report by Michael Kidd and colleagues (Sept 6, p 832)1 of measlesassociated encephalitis in children with renal transplants emphasises the grave risks posed to immunosuppressed children by low uptake of the measles mumps and rubella (MMR) vaccine. Calculations of outbreak size indicate that low MMR uptake has left the UK
on the edge of major measles outbreaks.2 Uptake as low as 61%1 makes almost certain the return of endemicity.2 Additionally, the near elimination of congenital rubella syndrome by MMR will surely reverse. I write as an author of an Early report for The Lancet3 and a paediatric gastroenterologist for many autistic children. Although subsequent studies4 have lent support to and extended the gastrointestinal findings associated with autism noted in this report, the same is not true for any link with MMR; many epidemiological studies have been undertaken, the results of which indicate no causal relation. No other vaccine has ever been studied in such depth, and the evidence for its overall safety is comprehensive. The response by all consultant paediatricians in the Early report3 was to support MMR vaccination without reservation,5 although this fact went largely unreported. The points made by us in this letter remain valid. This department has continued to assess children with autism on straightforward clinical grounds, since large numbers show improvement in abdominal pain and sleep disturbance if constipation, gastritis, or colonic inflammation are recognised and treated.5 However, not all children with autism show such response, a finding that needs further study. That any reports that characterise gut inflammation in autistic children are reported in the media as supporting the idea that MMR is causative is deeply frustrating, since it is simply not so. I and my colleagues have seen similar intestinal changes in children with no history of regression, in unvaccinated children, and in children whose first autistic symptoms clearly predated MMR administration. Several genes implicated in autism are expressed in the intestine and immune systems, and it is possible that subtle abnormality in these systems is an unrecognised component of autistic-spectrum disorders. This area remains one of legitimate interest, but should be clearly separated from the MMR issue. MMR immunisation, which should be an easy decision, has become a worrying issue for many British parents.
THE LANCET • Vol 362 • November 1, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet.