To the Editor: In their article on the effects of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure, Dr Nissen and colleagues1 found that the amlodipine group had both a significant decrease in cardiovascular events and a slower progression of coronary atherosclerosis as assessed by intravenous ultrasound (IVUS). We have some concerns about the study.
First, since no data on the mode of enrollment of patients in the IVUS substudy are provided, the likelihood of selection bias cannot be judged.
Second, the IVUS data in the amlodipine group should be compared with those in the Reversal of Atherosclerosis With Aggressive Lipid Lowering (REVERSAL) trial following equivalent methods.2 The nominal change in percentage atheroma volume (PAV) of 0.5% in the amlodipine group (83% of whom were taking statins) is comparable with the 0.6% change in PAV in the 80-mg atorvastatin group in the REVERSAL trial, suggesting equivalent antiatherosclerotic effects, despite major differences in low-density lipoprotein cholesterol levels. The improved outcome in the amlodipine group is mainly due to a reduction of hospitalization for angina and subsequent lower rate of revascularization, which, as the authors note, could be due to the anti-ischemic properties of amlodipine, in contrast with enalapril. No significant superiority of amlodipine for “hard” cardiac outcomes was found, in contrast with the major improvements in cardiovascular prognosis obtained by the use of statins.
Third, in contrast with the REVERSAL trial, the IVUS end point in the Comparison of Amlodipine vs Enalapril to Limit Occurrences of Thrombosis (CAMELOT) substudy was solely the nominal change in PAV corresponding to the difference of the external elastic membrane area (EEM) and the lumen cross-sectional area (LCS) divided by the EEM (PAV = (EEM − LCS)/EEM). Geometrically, a coronary vasodilation would increase both the EEM and LCS but proportionally more for the external area; this would mathematically decrease the PAV even with an unchanged plaque volume. The nominal change in PAV could therefore be affected by the vasodilatory effect of amlodipine, which would not be neutralized by the infusion of nitroglycerin3 prior to the IVUS study. Frielingsdorf et al4 demonstrated by quantitative coronary arteriography that in nonstenotic coronary arteries in patients with coronary artery disease, there is an additive vasodilation effect of nitroglycerin and calcium antagonists, of greater effect in hypertensive patients. These results could also explain the lower PAV change that was found in patients with baseline systolic blood pressure above the mean. Conversely, the vasodilator effect of nitrates is not potentiated by enalapril.5 We believe that it would have been better for the CAMELOT study to have used the total atheroma volume, which is less sensitive to drug-induced vasodilation effects, as the primary IVUS end point, as was done in the REVERSAL study.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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