Author + information
- Alan D. Guerci, MD, FACC⁎ ( and )
- David Newstein, DrPH
- ↵⁎St. Francis Hospital, 100 Port Washington Boulevard, Roslyn, New York 11576
As Dr. Tousoulis and colleagues point out, the design of the St. Francis Heart Study Randomized Clinical Trial (two cells of a 2 × 2 factorial) does not permit a definitive conclusion as to whether statins alone retard the progression of coronary calcification. However, there are other reasons to believe that statins do not reduce the rate of coronary calcification, or, if they do, that said reduction in the rate of progression is not proportional to their clinical benefit.
First, the study by Achenbach et al. (1), in which patients served as their own controls, was small (n = 66) and neither randomized, double-blind, nor controlled. Contrary to the assertion by Dr. Tousoulis and colleagues that “statins do decrease both the progression of coronary calcification and cardiovascular events,” the study by Achenbach et al. did not report event rates.
Second, with permission of our institutional review board, donations of atorvastatin and matching placebo from Pfizer, and informed consent from 233 participants among those with the highest calcium scores, we extended the St. Francis Heart Study Randomized Clinical Trial for another 12 months. Antioxidant treatment was discontinued, the atorvastatin dose was increased from 20 mg daily to 80 mg daily (four 20-mg tablets), and the dose of placebo was increased from one to four tablets daily. All subjects remained in their originally assigned group, all continued to receive aspirin 81 mg daily, and all clinical staff remained blinded to treatment. No differences in baseline characteristics occurred.
Whereas treatment with atorvastatin reduced low-density lipoprotein (LDL) cholesterol by 40% in the original randomized clinical trial, atorvastatin 80 mg daily reduced LDL cholesterol by 49% to 53% (from 144 mg/dl to 67 to 73 mg/dl). As can be seen in Table 1,however, 12 months of high-dose atorvastatin without antioxidants also failed to retard the process of coronary calcification.
“Baseline” refers to calcium scores in these 233 subjects at the beginning of the St. Francis Heart Study Randomized Clinical Trial (2). “Exit” refers to their calcium scores at the end of the original randomized clinical trial, and “Exit + 1 year” refers to calcium scores after 12 months of treatment with high-dose atorvastatin or placebo.
Values at any point in time were skewed upwards and are presented as 25th/50th/75th percentiles. Changes in calcium scores were normally distributed and are presented as mean ± SD.
In the recently published Beyond Endorsed Lipid Lowering with EBT Scanning (BELLES) study, coronary calcium increased by similar amounts in groups with one year of intensive and moderate reduction of LDL-C (47% and 25%, respectively) with statin monotherapy (3).
Last but not least, the Heart Protection Study tested simvastatin, antioxidants, both, or neither in over 20,000 high-risk subjects for five years. The antioxidant cocktail (vitamins C, E, and beta-carotene) neither enhanced nor reduced the benefit of simvastatin (4).
In summary, and effects on endothelial function notwithstanding, in randomized clinical trials, statins—alone or in combination with antioxidants—have had no effect on the process of coronary calcification. These findings are consistent not only with the results of clinical megatrials like the Heart Protection Study, in that antioxidant supplements have no effect on atherosclerotic cardiovascular disease rates, but with an unexpected result of the St. Francis Heart Study Randomized Clinical Trial: that calcium scores and the clinical benefit of statins are dissociated, at least for as much as four years of therapy.
- American College of Cardiology Foundation
- Achenbach S.,
- Ropers D.,
- Pohle H.,
- et al.
- Arad Y.,
- Spadaro L.A.,
- Roth M.,
- Newstein D.,
- Guerci A.D.
- Raggi P.,
- Davidson M.,
- Callister T.Q.,
- et al.