{'fraction_non_alphanumeric': 0.01764014112112897, 'fraction_numerical': 0.0003920031360250882, 'mean_word_length': 5.428211586901763, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Hypertension and Diabetes and the Fosinopril Versus Amlodipine Cardiovascular Events Trial (FACET): More ammunition against surrogate end points

MEDICAL THERAPY OF CHRONIC DISEASES— The report from the Fosinopril versus Amlodipine Cardiovascular Events Trial (FACET) in this issue of Diabetes Care (1) provides further evidence of a major dilemma for clinicians and patients. We can be certain that widespread prescription of therapies for chronic diseases without validation of the true effects of these therapies on major clinical outcomes will, with some frequency, result in proliferation of therapies detrimental to the well being of the patients we are serving. The methodology and the technology now exist to limit this problem; but successful implementation of a strategy to measure the impact of specific therapies on medical outcomes in chronic diseases requires a cultural change in the practice of medicine and a major alteration in the clinical research infrastructure. If we take this randomized clinical trial (FACET) at face value, we have randomized trial evidence that in patients with diabetes and hypertension, those treated with the ACE inhibitor, fosinopril, have a lower rate of major vascular events than patients treated with the calcium-channel blocker, amlodipine. The measures of renal function, LDL cholesterol and triglycerides, and diabetes control were almost identical in the two groups, providing no clue as to why events would be lowered with fosinopril. However, the systolic blood pressure was lowered significantly more in the amlodipine group, a paradoxical finding if the main mechanism of event prevention in patients with hypertension is lowering the blood pressure. Of interest, the HDL cholesterol rose slightly more with fosinopril, and the fibrinogen dropped somewhat more with fosinopril. The reader is left with three possible explanations for the observed excess vascular events in patients treated with amlodipine. It is possible that both agents are effective, but fosinopril is more effective than amlodipine in preventing vascular events. Alternatively, perhaps amlodipine is actually detrimental in that it causes an excess of vascular events, and patients would be better off on placebo than on amlodipine. Finally, we cannot exclude the possibility that the findings are simply due to the play of chance. This single trial cannot provide a definitive answer to which of these is true. Nevertheless, careful consideration from this latest chapter in the calcium-channel blocker story is merited.