Coronary Angiographic Results of ASTEROID
Abstract & Commentary
By Michael H. Crawford, MD
Source: Ballantyne, CM et al. Effect of rosuvastatin therapy on coronary artery stenoses assessed by quantitative coronary angiography. Circulation. 2008;117:2458-2466.
A study to evaluate the effect of rosuvastatin on intravascular ultrasound derived coronary atheroma burden (ASTEROID) was designed to assess the effects of rosuvastatin monotherapy on the progression of coronary atherosclerosis in patients undergoing catheterization. The primary end point was plaque volume, as determined by intravascular ultrasound (IVUS), the beneficial results of which have already been reported. Rosuvastatin showed regression of all IVUS measures of atheroma volume. The current report reveals the results of the secondary end point of quantitative coronary artery (QCA) luminal measurements. ASTEROID was a multicentered, open-label trial of the effect of rosuvastatin 40 mg daily for 24 months on lumen percent diameter stenosis and minimal lumen diameter (MLD) in 507 patients. Angiography was performed before and after the study period in 75% of the patients, and of these, 77% had lesions with > 25% stenoses that could be matched on the two angiograms. A total of 292 patients with 613 matched segments represented the final study group. Rosuvastatin decreased the baseline LDL cholesterol of 132mg/dL by 53% and increased the baseline HDL cholesterol of 43 by 14%. Mean percent diameter stenosis decreased from 37% to 36% (P < .001) and MLD increased from 1.65 to 1.68 mm (P < .001). By either measure, over half the patients showed regression and about 5% were unchanged vs 41% who showed progression. Clinically relevant regression occurred in about 10% of patients and clinically relevant progression was exhibited by about 5%. Ballantyne and colleagues concluded that rosuvastatin treatment that brought mean LDL cholesterol to below 70 mg/dL and increased HDL cholesterol by 13%, resulted in significant decreases in percent diameter stenosis and increases in MLD by QCA in patients with evident coronary atherosclerosis.
Commentary
This study used surrogate markers to assess the ability of rosuvastatin, the most potent statin on the market, to regress coronary atherosclerosis. The primary end point was IVUS measures, and these results have already been already published. IVUS measures atheroma volume, and it was reduced significantly. However, IVUS is limited to examining the proximal major coronary arteries. This paper reports the secondary end point of QCA data, which is concordant with the IVUS data. Mean QCA measures were significantly changed in a direction supporting regression. QCA only examines the lumen of coronary arteries, but it can assess more distal segments. Also, QCA has been shown to be predictive of coronary events in other studies.
Other monotherapy studies with statins have shown, on average, less progression, but no regression. So this study is the first to show net regression; however, if you examine the individual data, the majority exhibited plaque regression, but 41% showed progression. The change in mean QCA measurement values is very small. When Ballantyne et al analyzed what they considered were clinically meaningful changes, most patients showed stabilization and a few either regressed (10%) or progressed (5%). When compared to other trials, there seems to be a relation between the amount of reduction in LDL cholesterol and favorable changes in QCA measures. Rosuvastatin, being a potent agent, was able to achieve LDL cholesterol targets that met any guideline; < 70mg/dL and > 50% drop.
There are some limitations to this study. There were no controls, but the angiographic analyses were blinded. Also, there was a 25% drop out rate for repeat angiography, but this is consistent with many other trials and better than some. In addition, QCA does not assess plaque composition, which may be important for future events. Finally, there is no clinical outcome data and the trial was not powered to assess outcomes.
The role of HDL-cholesterol is unclear in this study. It was significantly increased in the study; a feat no other statin monotherapy trial has accomplished. When analyzed vs other trials, there seems to be a relation between change in HDL and QCA data, but the same is true of LDL cholesterol, as discussed above. Thus, whether this increase in HDL was an important component of the results of ASTEROID, or whether the data can be completely explained by the changes in LDL is unknown. The magnitude of the HDL change was small (+5 mg/dL, 13%) but statistically significant. The role of HDL in atherosclerosis, in general, is a controversial topic currently.
Although the results of this study support statin therapy for patients with atherosclerosis regardless of their initial LDL cholesterol level (average baseline value 131 in this cohort), it does not clarify what dose to use. Almost all statin atherosclerosis studies have used fixed doses of statins, instead of titrating, to target LDL levels. For example, we know atorvastatin 80 mg is better than 10 mg, but what about 20 or 40? We can infer from these studies that the lower the LDL the better, but what are the thresholds? The COURAGE trial showed excellent results at an average LDL of about 85mg/dL. In this study, LDL was < 70mg/dL. Whether 40 mg of rosuvastatin is required to get these results no matter what the LDL is, is unknown.
A study to evaluate the effect of rosuvastatin on intravascular ultrasound derived coronary atheroma burden (ASTEROID) was designed to assess the effects of rosuvastatin monotherapy on the progression of coronary atherosclerosis in patients undergoing catheterization.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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