The good is today's article in the British Medical Journal that re-examines the association between use of antipsychotics in seniors and various forms of stroke.
The authors used a general practice research database which "contains information from over six million patients registered at over 400 general practice surgeries in the UK.11 Continuous information is recorded for each patient, including a record of each consultation, any diagnoses made, all prescribed medicine, and basic demographic data. The geographical distribution and size of general practices represented in the database are largely representative of the population of England and Wales, and the individuals registered on the database are representative of the whole UK population in terms of age and sex.12 The data held are rigorously checked and regularly audited and have been successfully used to conduct over 500 peer reviewed published studies. The information obtained from the database is entirely anonymous."
The authors were able to control for length of drug use, type of drug, and "measured the differential effects of typical and atypical antipsychotics among all patients and stratified by dementia status."
The most relevant results are here:
The authors note that only a handful of patients even received an atypical so it is hard to extrapolate beyond what previous studies have suggested: that people 80 and older are much more likely to have a stroke than other groups of patients and that a small statistical association between stroke and atypicals exists. However, it is unclear from the data whether the association is a function of dose or duration. In any event, the research provides a much needed systematic assessment of an important clinical issue dealing with the treatment of dementia.
Not so the rigged and biased attack Curt Furberg launches on all oral diabetic drugs....
"We reported [in the journal Diabetes Care] in June 2007 that thiazolidinediones doubled the risk of congestive heart failure in patients with type 2 diabetes...The increased heart failure appears to be a class effect."
Well, appearances are deceiving, especially when you are reporting on a highly selective group of studies....
A random-effects meta-analysis of three randomized controlled trials showed an odds ratio (OR) of 2.1 (95% CI 1.08-4.08; P = 0.03) for the risk of heart failure in patients randomized to TZDs compared with placebo. Four observational studies revealed an OR of 1.55 (1.33-1.80; P < 0.00001) for heart failure with TZDs. A dose-time-susceptibility analysis of 28 published reports and 214 spontaneous reports from the CADRMP database showed that heart failure was more likely to occur after several months (with median treatment duration of 24 weeks after initiation of therapy). Heart failure equally occurred at high and low doses. The adverse reaction was not limited to the elderly, with 42 of 162 (26%) of the reported cases occurring in patients aged <60 years. CONCLUSIONS: Our teleo-analysis confirms the increased magnitude of the risk of heart failure with TZDs. We estimate the number needed to harm with TZDs to be approximately 50 over 2.2 years. Existing guidelines and package inserts may have to be revised to incorporate these risk characteristics of TZDs..
Furberg also uses the ACCORD and ADVANCE studies to justify yanking Avandia off the market. According to ScienceDaily, here is Furberg's logic:
Yes, post market evaluation of meds is important. But it needs to be done right and honestly.
The authors used a general practice research database which "contains information from over six million patients registered at over 400 general practice surgeries in the UK.11 Continuous information is recorded for each patient, including a record of each consultation, any diagnoses made, all prescribed medicine, and basic demographic data. The geographical distribution and size of general practices represented in the database are largely representative of the population of England and Wales, and the individuals registered on the database are representative of the whole UK population in terms of age and sex.12 The data held are rigorously checked and regularly audited and have been successfully used to conduct over 500 peer reviewed published studies. The information obtained from the database is entirely anonymous."
The authors were able to control for length of drug use, type of drug, and "measured the differential effects of typical and atypical antipsychotics among all patients and stratified by dementia status."
The most relevant results are here:
| Any antipsychotic drug | Typical only | Atypical only |
| Patients with recorded dementia (n=1423) | |||
| No in group | 1423 | 1208 | 85 |
| Exposed v unexposed periods | 3.50 (2.97 to 4.12) | 3.26 (2.73 to 3.89) | 5.86 (3.01 to 11.38) |
| Days after treatment: | |||
| 1-35 | 4.03 (3.34 to 4.87) | 3.74 (3.05 to 4.59) | 5.70 (2.50 to 12.98) |
| 36-70 | 3.04 (2.33 to 3.96) | 2.92 (2.20 to 3.88) | 4.41 (1.40 to 13.89) |
| 71-105 | 2.71 (1.97 to 3.73) | 2.40 (1.69 to 3.41) | 3.50 (0.76 to 16.25) |
| 106-140 | 2.14 (1.45 to 3.15) | 2.16 (1.44 to 3.23) | 2.21 (0.28 to 17.34) |
| 141-175 | 1.53 (0.95 to 2.44) | 1.49 (0.90 to 2.44) | 2.40 (0.30 to 18.88) |
The authors note that only a handful of patients even received an atypical so it is hard to extrapolate beyond what previous studies have suggested: that people 80 and older are much more likely to have a stroke than other groups of patients and that a small statistical association between stroke and atypicals exists. However, it is unclear from the data whether the association is a function of dose or duration. In any event, the research provides a much needed systematic assessment of an important clinical issue dealing with the treatment of dementia.
Not so the rigged and biased attack Curt Furberg launches on all oral diabetic drugs....
"We reported [in the journal Diabetes Care] in June 2007 that thiazolidinediones doubled the risk of congestive heart failure in patients with type 2 diabetes...The increased heart failure appears to be a class effect."
Well, appearances are deceiving, especially when you are reporting on a highly selective group of studies....
A random-effects meta-analysis of three randomized controlled trials showed an odds ratio (OR) of 2.1 (95% CI 1.08-4.08; P = 0.03) for the risk of heart failure in patients randomized to TZDs compared with placebo. Four observational studies revealed an OR of 1.55 (1.33-1.80; P < 0.00001) for heart failure with TZDs. A dose-time-susceptibility analysis of 28 published reports and 214 spontaneous reports from the CADRMP database showed that heart failure was more likely to occur after several months (with median treatment duration of 24 weeks after initiation of therapy). Heart failure equally occurred at high and low doses. The adverse reaction was not limited to the elderly, with 42 of 162 (26%) of the reported cases occurring in patients aged <60 years. CONCLUSIONS: Our teleo-analysis confirms the increased magnitude of the risk of heart failure with TZDs. We estimate the number needed to harm with TZDs to be approximately 50 over 2.2 years. Existing guidelines and package inserts may have to be revised to incorporate these risk characteristics of TZDs..
Furberg also uses the ACCORD and ADVANCE studies to justify yanking Avandia off the market. According to ScienceDaily, here is Furberg's logic:
"They said that results from three large randomized clinical trials published this past June all failed to demonstrate that intensive control of blood sugar reduces mortality or events from cardiovascular disease in patients with type 2 diabetes.
The three trials were ACCORD, ADVANCE, and the Veterans Affairs Diabetes study. In ACCORD, the patients who received intensive treatment to control blood sugar actually had more cardiovascular disease mortality than patients receiving standard treatment."
Uh, maybe because they were sicker to begin with.
In any event, what has that to do with Avandia's risks and benefits. Nothing. But Furberg is grasping at straws here and he knows it.
Yes, post market evaluation of meds is important. But it needs to be done right and honestly.
