Lipids Online: Educational Resources in Atherosclerosis
Several large-scale, controlled, randomized clinical trials have provided evidence that statins are effective in reducing CHD events in both primary- and secondary-prevention populations. Their efficacy in CHD risk reduction is truly impressive. Nonfatal myocardial infarction and CHD death were reduced by about 25-40% after just 5 years of treatment; ischemic events requiring hospitalization were reduced by 26-36% after just 18 months of statin therapy. All the statins studied demonstrated the ability to reduce CHD risk—lovastatin in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), simvastatin in the Scandinavian Simvastatin Survival Study (4S), and pravastatin in the Cholesterol and Recurrent Events (CARE) trial, Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial, and West of Scotland Coronary Prevention Study (WOSCOPS). Neither the Atorvastatin versus Revascularization Treatment (AVERT) nor Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial showed significant reductions in hard CHD endpoints; both were short-term trials and not powered to show such a difference. A trend toward benefit on CHD events was shown in the Lipoprotein and Coronary Atherosclerosis Study (LCAS), but this angiographic trial was not powered for clinical events; the effect of fluvastatin on CHD events is being studied in the ongoing Lescol Intervention Prevention Study (LIPS) and Assessment of Lescol in Renal Transplantation (ALERT). The available data suggest that CHD risk reduction by statins is a class effect and that the LDL-C reduction is the key event driving the change in risk.
What makes these studies and their results impressive is that they are "end point" studies. That is to say, they base the results on endpoints, such as heart attack or death, not simply a hypothesis about the potentials based on assumed relationships.
There is no panacea, and there are money interests, to say the least. However, these studies cover several different statins on thousands and thousands of patients with many hundreds of academic researchers involved. The data are impressive.
Lipids Online: Educational Resources in Atherosclerosis
Several large-scale, controlled, randomized clinical trials have provided evidence that statins are effective in reducing CHD events in both primary- and secondary-prevention populations. Their efficacy in CHD risk reduction is truly impressive. Nonfatal myocardial infarction and CHD death were reduced by about 25-40% after just 5 years of treatment; ischemic events requiring hospitalization were reduced by 26-36% after just 18 months of statin therapy. All the statins studied demonstrated the ability to reduce CHD risk—lovastatin in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), simvastatin in the Scandinavian Simvastatin Survival Study (4S), and pravastatin in the Cholesterol and Recurrent Events (CARE) trial, Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial, and West of Scotland Coronary Prevention Study (WOSCOPS). Neither the Atorvastatin versus Revascularization Treatment (AVERT) nor Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial showed significant reductions in hard CHD endpoints; both were short-term trials and not powered to show such a difference. A trend toward benefit on CHD events was shown in the Lipoprotein and Coronary Atherosclerosis Study (LCAS), but this angiographic trial was not powered for clinical events; the effect of fluvastatin on CHD events is being studied in the ongoing Lescol Intervention Prevention Study (LIPS) and Assessment of Lescol in Renal Transplantation (ALERT). The available data suggest that CHD risk reduction by statins is a class effect and that the LDL-C reduction is the key event driving the change in risk.
What makes these studies and their results impressive is that they are "end point" studies. That is to say, they base the results on endpoints, such as heart attack or death, not simply a hypothesis about the potentials based on assumed relationships.
There is no panacea, and there are money interests, to say the least. However, these studies cover several different statins on thousands and thousands of patients with many hundreds of academic researchers involved. The data are impressive.
You stated "..they base the results on endpoints, such as heart attack or death", but the article you referenced above doesn't exactly say that. It says "Nonfatal myocardial infarction and CHD death were reduced" It says death as a result of heart disease was reduced, but makes no mention of death from other causes or if total mortality was reduced with statins. That is a key point in my opinion.
Also note that the reductions listed in CHD events/death are likely relative risks, not total risk reductions. I don't have the exact numbers from those studies, but lets say there were 100 controls and 100 on statins. If you have 4 people in the control group that had a CHD event/death during the study period but only 3 people in the statin group that had a CHD event/death, then you are looking at a 25% reduction in relative risk. The actual numbers in these studies rarely look as impressive as the changes in relative risk as a precentage.
Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).
It states in part "All-cause mortality was similar for the 2 groups..., with 6-year mortality rates of 14.9% for pravastatin vs 15.3% with usual care. CHD event rates were not significantly different between the groups..., with 6-year CHD event rates of 9.3% for pravastatin and 10.4% for usual care."
Also from the study "CONCLUSIONS: Pravastatin did not reduce either all-cause mortality or CHD significantly when compared with usual care in older participants with well-controlled hypertension and moderately elevated LDL-C."
"They only demonstrate that in tens of thousands involved in the studies, there is significant reduction in heart attack and death."
Uh, I hate to bust your bubble pcovers, but I wrote the National Institute of Health about how they were getting the high percentages in these studies, when the data clearly showed the difference in say death rate, in taking a statin and not taking a statin was less than 1 percent. I got a reply from a supervisor with the National Cholesterol Education Program. She replied that I was right, but they use a "Cox mathematical model" to report the percentages, and the NIH does not do the study, they just report it. Ok, you mention the WOSCOPS study. I happen to have the figures on that and other studies. I like this one because it is of healthy people with high cholesterol, and the study is used to show they benefit from a statin drug. There were 3302 people in the study that were treated with pravastatin, and in 4.4 years they had 106 deaths from all causes. (you can't fudge the deaths, it is a good solid figure). This is 3.2 percent of the group. There were 3293 people in the study that were not treated, and in 4.4 years they had 135 deaths. This is 4.1 percent of the group. The actual decrease in dying was .9 of one percent! This is in 4.4 years! A cox model uses these figures and says it is 22 percent! Every study, every category, uses this model. It gives a distorted result. Articles you read say 22 percent, not .9. They don't explain that they used a cox model. So all your talk about end results does not fly. Joe
"They only demonstrate that in tens of thousands involved in the studies, there is significant reduction in heart attack and death."
Uh, I hate to bust your bubble pcovers, but I wrote the National Institute of Health about how they were getting the high percentages in these studies, when the data clearly showed the difference in say death rate, in taking a statin and not taking a statin was less than 1 percent. I got a reply from a supervisor with the National Cholesterol Education Program. She replied that I was right, but they use a "Cox mathematical model" to report the percentages, and the NIH does not do the study, they just report it. Ok, you mention the WOSCOPS study. I happen to have the figures on that and other studies. I like this one because it is of healthy people with high cholesterol, and the study is used to show they benefit from a statin drug. There were 3302 people in the study that were treated with pravastatin, and in 4.4 years they had 106 deaths from all causes. (you can't fudge the deaths, it is a good solid figure). This is 3.2 percent of the group. There were 3293 people in the study that were not treated, and in 4.4 years they had 135 deaths. This is 4.1 percent of the group. The actual decrease in dying was .9 of one percent! This is in 4.4 years! A cox model uses these figures and says it is 22 percent! Every study, every category, uses this model. It gives a distorted result. Articles you read say 22 percent, not .9. They don't explain that they used a cox model. So all your talk about end results does not fly. Joe
It is fascinating that you can present data, assess the data, and draw conclusions from the data in such an economical fashion. Those trained researchers and statisticians could learn a thing or two from your unique statistical modeling protocol. I hope you shared your unique methods with your stats professor.
In all seriousness, there is no busted bubble here and no smoking gun. Interpretation of data is not so simple as you would like to present. The Cox Model is not some evil or sneaky equation thought up by the drug companies to fool unsuspecting lay persons into believing an otherwise untruth. The Cox Model is a standard statistical model used in all types of studies looking at survival. It is a norm, not an exception. I would recommend anyone interested do a search on "What is a Cox Model" and read the very informative and easy to read commentary on its purpose, application, and interpretation.
One might also want to do a search on, "Cox and Gompertz Regression Models: An assessment with empirical estimates". It really is a well prepared research paper on a comparison of these two statistical models.
You see, it requires the utilization of a statistical modeling methodology in order to support the conclusions presented in the assessment of the data. Presenting the data and conclusion as you have would be completely and universally dismissed by any researcher or peer review group.
Models, such as Cox, are not used by researchers and statisticians simply because corporations are paying them to muddy the waters. They are used because they are the norms - the standards - necessary tools of the trade of those that collect and assess empirical data.
Whether or not every statin study used the Cox model has not been definitively established. Regardless, if they did, one can rest assured that the results have been derived from a statistical modeling algorithm that is among the accepted norms.
