The Jupiter Trial has found that Rosuvastatin reduces the risk of major cardiovascular events in patients with elevated C-reactive Protein (CRP) levels. Another journal also suggested that the guidelines for primary prevention may be re-evaluated in the light of these results.
But is it really time to change the way we assess patients CVD risk? First, it is essential to understand what the trial actually tells us and then to consider the implications of those findings.
The Jupiter Trial was a randomised, controlled trial which enrolled 17,802 patients with a median age of 66 years, More than 60% of participants were men and 70% were white. Participants had no apparent vascular disease, an LDL cholesterol of less than 3.4 mmol/l (median 2.8 mmol/l) and a high sensitivity CRP concentration of 2.0 mg/l or higher.
Patients were randomised to either rosuvastatin 20 mg daily or placebo. The primary endpoint was a composite of myocardial infarction, stroke, arterial revascularisation, hospital admission for unstable angina and death from cardiovascular causes.
The trial was stopped after a median of 1.9 years because of a highly significant improvement in the primary end-point in the rosuvastatin group. The median LDL cholesterol levels in patients receiving rosuvastatin had been reduced to 1.4 mmol/l and their had been 142 events in the statin group compared with 251 in the placebo group (HR 0.56, 95% Cl 0.46-0.69, P=< 0.00001). This effect was consistent across all subgroups. Rosuvastatin was well tolerated with no significant imcrease in myopathy.
The Jupitar Trail has shown Resuvastatin to be effective and safe. However, it was not compared with other low-cost statins, such as simvastatin.
Although the reletive risk reductions seen were impressive, the actual number of events was low (142/8901 or 1.6% in the statin group and 251/8901 or 2.8% in the placebo group), and therefore the absolute risk reduction is less impressive. This is further illustrated by looking at the effect on all-cause mortality, with 198 deaths in the rosuvastatin group compared with 247 in the placebo group (HR 0.80, 95% Cl 0.67-0.97, P=0.02).
It is also noteworthy that 41% of the study population had the metabolic syndrome and that half of the trial participants had a 1- year Framingham risk of >10%; one would expect statin therapy to have a fairly impressive impact in these patients. The incidence of diabetes was also higher in the rosuvastatin group, with 270 cases compared with 216 in the placebo group. This would somewhat offset the benefit of statin therapy.
It is not clear if testing for CRP provodes an incremental benefit over and above traditional risk factors in identifying cardiovascular risk. The routine measurement of CRP can not be recommended in cardiovascular risk algorithms until further evidence becomes available.
If a trial can show the benefit of CRP measurement in cardiovascular risk assessment, it may find a place to aid clinical decision making in patients with intermediate cardiovascular risk who sit on the threshold of intervention. However, even then lifestyle modification should be the first-line intervention. Drug therapy should only be considered if lifestyle changes are unsuccessful, and treatment should not be dependant on a single agent targeting a single risk factor.
The Jupiter Trial has generated further discussion about the primary prevention of CVD. However, i suspect that most clinicians will not change their practice on the basis of this trial and will continue to identify and treat patients at risk of CVD using established methods.
But is it really time to change the way we assess patients CVD risk? First, it is essential to understand what the trial actually tells us and then to consider the implications of those findings.
The Jupiter Trial was a randomised, controlled trial which enrolled 17,802 patients with a median age of 66 years, More than 60% of participants were men and 70% were white. Participants had no apparent vascular disease, an LDL cholesterol of less than 3.4 mmol/l (median 2.8 mmol/l) and a high sensitivity CRP concentration of 2.0 mg/l or higher.
Patients were randomised to either rosuvastatin 20 mg daily or placebo. The primary endpoint was a composite of myocardial infarction, stroke, arterial revascularisation, hospital admission for unstable angina and death from cardiovascular causes.
The trial was stopped after a median of 1.9 years because of a highly significant improvement in the primary end-point in the rosuvastatin group. The median LDL cholesterol levels in patients receiving rosuvastatin had been reduced to 1.4 mmol/l and their had been 142 events in the statin group compared with 251 in the placebo group (HR 0.56, 95% Cl 0.46-0.69, P=< 0.00001). This effect was consistent across all subgroups. Rosuvastatin was well tolerated with no significant imcrease in myopathy.
The Jupitar Trail has shown Resuvastatin to be effective and safe. However, it was not compared with other low-cost statins, such as simvastatin.
Although the reletive risk reductions seen were impressive, the actual number of events was low (142/8901 or 1.6% in the statin group and 251/8901 or 2.8% in the placebo group), and therefore the absolute risk reduction is less impressive. This is further illustrated by looking at the effect on all-cause mortality, with 198 deaths in the rosuvastatin group compared with 247 in the placebo group (HR 0.80, 95% Cl 0.67-0.97, P=0.02).
It is also noteworthy that 41% of the study population had the metabolic syndrome and that half of the trial participants had a 1- year Framingham risk of >10%; one would expect statin therapy to have a fairly impressive impact in these patients. The incidence of diabetes was also higher in the rosuvastatin group, with 270 cases compared with 216 in the placebo group. This would somewhat offset the benefit of statin therapy.
It is not clear if testing for CRP provodes an incremental benefit over and above traditional risk factors in identifying cardiovascular risk. The routine measurement of CRP can not be recommended in cardiovascular risk algorithms until further evidence becomes available.
If a trial can show the benefit of CRP measurement in cardiovascular risk assessment, it may find a place to aid clinical decision making in patients with intermediate cardiovascular risk who sit on the threshold of intervention. However, even then lifestyle modification should be the first-line intervention. Drug therapy should only be considered if lifestyle changes are unsuccessful, and treatment should not be dependant on a single agent targeting a single risk factor.
The Jupiter Trial has generated further discussion about the primary prevention of CVD. However, i suspect that most clinicians will not change their practice on the basis of this trial and will continue to identify and treat patients at risk of CVD using established methods.
