This week we were inundated with reports of a major study with near miraculous results. Just under 18,000 participants in the Jupiter study either received rosuvastatin (Crestor) or placebo. Patients were chosen to participate if they had low LDL cholesterol (under 130 mg/deciliter) and elevated C-reactive protein (above 2 mg/liter). The results, as summarized, in a accompanying editorial :
“ The trial of nearly 18,000 patients was stopped, with only 1.9 of its proposed 4 years of follow-up concluded, when the data and safety monitoring board noted a significant reduction in the primary end point among participants assigned to receive rosuvastatin (142 primary events, vs. 251 in the placebo group; hazard ratio, 0.56; 95% confidence interval [CI], 0.46 to 0.69). There was a similar reduction in a combination of the more important hard outcomes: myocardial infarction, stroke, or death from cardiovascular causes (83 events in the rosuvastatin group vs. 157 in the placebo group; hazard ratio, 0.53; 95% CI, 0.40 to 0.69). “
The study also reported virtually no extra side effects among the study patients. “Total numbers of reported serious adverse events were similar in the rosuvastatin and placebo groups (1352 and 1377, respectively; P=0.60) Nineteen myopathic events were reported (in 10 subjects receiving rosuvastatin and 9 receiving placebo, P=0.82)” There was one case of major muscle lysis problems (rhabdomylysis) in a 90 year old man after the study was completed. Virtually all other toxicity was equivalent between drug and placebo.
Medicynical note: As noted above the finding that there was no difference in side-effects between the drug and placebo is at least a little strange. That the reported side effects occurred much less frequently even than the incidence in the FDA drug insert also is remarkable. It could indicate patient selection or bias from in this drug company sponsored trial. Interestingly 25% of patients were reported not taking the drug at the end of the study. Why? That’s left to the imagination.
From the drug insert:
“ In clinical studies of 10,275 patients, 3.7% were discontinued due to adverse experiences attributable to rosuvastatin. The most frequent adverse events thought to be related to rosuvastatin were myalgia, constipation, asthenia, abdominal pain, and nausea.”
“ Uncomplicated myalgia has been reported in rosuvastatin-treated patients (see Creatine kinase (CK) elevations (>10 times upper limit of normal) occurred in 0.2% to 0.4% of patients taking rosuvastatin at doses up to 40 mg in clinical studies. Treatment-related myopathy, defined as muscle aches or muscle weakness in conjunction with increases in CK values >10 times upper limit of normal, was reported in up to 0.1% of patients “
The NEJM editorial about the study also noted:
“ On the other side of the balance, of concern are the significantly higher glycated hemoglobin levels and incidence of diabetes in the rosuvastatin group in JUPITER (3.0%, vs. 2.4% in the placebo group; P=0.01). There are also no data on the long-term safety of lowering LDL cholesterol to the level of 55 mg per deciliter (1.4 mmol per liter), as was attained with rosuvastatin in JUPITER, which is lower than in previously reported trials. Long-term safety is clearly important in considering committing low-risk subjects without clinical disease to 20 years or more of drug treatment.”
An additional concern is cost.
“The proportion of participants with hard cardiac events in JUPITER was reduced from 1.8% (157 of 8901 subjects) in the placebo group to 0.9% (83 of the 8901 subjects) in the rosuvastatin group; thus, 120 participants were treated for 1.9 (Medicynical note: 693 days) years to prevent one event.“
At a cost of $3.45/day treating 120 patients for 693 days is a total of almost $300,000 spent to prevent one event. This is far above any reasonable cost/effective intervention. It’s obvious why this information was not included in this drug company sponsored study. It is, however, one of the major concerns we all should have in this time of crisis in health care.
Having patients commit to take a medication for the duration of their lives to prevent serious medical problems is the dream of drug companies. But in order to seriously consider such an intervention, it must be very effective, have low toxicity and be affordable both for the patient and the health care system. Use of rosuvastatin to prevent cardiovascular disease doesn’t fully meet these criteria and as such, the report should be viewed as an interesting approach that merits further study, not wholesale adoption.
In the press I noted comment that other statins that are available as generics may have the same beneficial effect at lower cost. It’s unlikely however, that drug company sponsored studies of these low cost alternatives will ever be done.
It appears that journalists have a short memory. Only four year ago, Dr. David Graham, associate director in the FDA’s Office of Drug Safety gave senate testimony that Crestor was one of five drugs with safety concerns. The drug causes muscle breakdown and renal failure. To read more…