Outcome Results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in Patients With Hypertension and NIDDM

Abstract

Fosinopril and amlodipine had similar effects on biochemical measures, but the patients randomized to fosinopril had a significantly lower risk of major vascular events, compared with the patients randomized to amlodipine.

Systolic Hypertension in Europe (Syst-Eur) Trial Phase 2: objectives, protocol, and initial progress

“…For this reason, a first-ever-event analysis could have been helpful to correctly interpret the ABCD results, but was not presented. 18 In the Fosinopril versus Amlodipine Cardiovascular Events Randomized Trial (FACET), 17 the patients receiving fosinopril had a significantly lower risk of the combined outcome of acute myocardial infarction, stroke, or hospitalized angina pectoris than those receiving amlodipine (14/189 vs 27/191 events). However, the FACET trial had an open design and events were monitored by 'asking' the patients if they had been hospitalized or had experienced any other event.…”

“…In contrast to the ABCD trial, 18 the worse outcome on amlodipine compared with the converting-enzyme inhibitor was not due to myocardial infarction (13 vs 10), but was driven by hospitalized angina (4 vs 0) and stroke (10 vs 4). The interpretation of the FACET results 17 is also rendered difficult, because 58 patients randomised to fosinopril (30.7%) and 50 of the amlodipine group (26.2%) crossed over and received the combination of both drugs. A recent subgroup analysis of the Syst-Eur trial 29 showed that in patients with diabetes mellitus active treatment reduced all-cause mortality by 55%, cardiovascular mortality by 76%, all cardiovascular end-points by 69%, fatal and nonfatal stroke by 73% and all cardiac end-points by 63%.…”

“…The median follow-up of 2 years in the Syst-Eur trial 3 may have been too short to reveal the suspected adverse effects of dihydropyridines, such as cancer, 12,13 gastrointestinal bleeding, 14 or coronary complications in patients with pre-existing coronary heart disease 4,15,16 or diabetes mellitus. [17][18][19][20][21][22] Syst-Eur 2 will answer these reservations. Of the patients enrolled, 2.3% already experienced a major cardiovascular complication prior to the end of the Syst-Eur trial proper, and 12.2% have diabetes mellitus.…”

“…One of the arguments used is that the median follow-up of the Syst-Eur patients was only 2 years and that therefore they may not have been exposed to nitrendipine 2 for a period sufficiently long to elicit adverse effects, such as cancer, 12,13 gastro-intestinal bleeding, 14 or coronary complications in patients with pre-existing coronary heart disease 4,15,16 or diabetes mellitus. [17][18][19][20][21][22] In keeping with the expert recommendation 8 that wellconducted observational studies may answer issues of drug safety, the Syst-Eur patients will remain in open follow-up to confirm the safety and, ultimately the cost-effectiveness, of antihypertensive therapy based on a dihydropyridine calcium-channel blocker.…”

The Appropriate Blood Pressure Control in Diabetes (ABCD) Trial

“…14 In this open labelled study that randomised participants to either an ACE inhibitor or a long acting dihydropyridine CCA, the cardiac event rate was approximately double in the amlodipine alone group vs the ACE inhibitor group. Moreover, the trial was stopped early due to this trend.…”