Effects of fosinopril on exercise tolerance and clinical deterioration in patients with chronic congestive heart failure not taking digitalis. Fosinopril Heart Failure Study Group.

A total of 241 men and women with mild to moderately severe chronic heart failure (New York Heart Association functional class II [90%] or III) and a mean (+/- SD) left ventricular ejection fraction of 25 +/- 7%, entered a 24-week, prospective, double-blind, placebo-controlled trial of 10 or 20 mg/day of fosinopril, a phosphinic acid angiotensin-converting enzyme inhibitor. Patients received concomitant diuretic therapy but not digitalis. Primary end points were mean change in maximal treadmill exercise time and occurrence of prospectively defined clinical events indicative of worsening heart failure (most to least severe): death, withdrawal for worsening heart failure, hospitalization for worsening heart failure, need for supplemental diuretic or emergency room visit for worsening heart failure, and no event. At study end point, treadmill exercise time had improved in the fosinopril versus the placebo group (+28.4 vs -13.5 seconds, p = 0.047). New York Heart Association functional class had improved at end point more frequently (24% vs 13%) and deteriorated less frequently (18% vs 32%) in the fosinopril group (p = 0.003). More patients treated with fosinopril (66% vs 50%) remained free of clinical events indicative of worsening heart failure, and fosinopril-treated patients had less severe clinical events (p = 0.004). Dyspnea, fatigue, and paroxysmal nocturnal dyspnea improved more often and worsened less often in this group (p < or = 0.002), and edema showed a trend toward improvement (p = 0.088). These clinical benefits did not require concomitant digitalis therapy. Fosinopril was associated with an acceptable safety profile.

Acute occupational respiratory diseases in hospital discharge data.

We investigated the feasibility of using hospital discharge diagnoses of ICD codes 506, 507, and 508, respiratory diseases from external sources, to identify occupational sentinel health events [SHE(O)]. Two hundred sixty-nine records were reviewed and 66 (25%) were incidents where the work-relatedness of the respiratory diseases was documented in the medical records. Twenty-six percent of the 269 records contained no exposure information. Sixty-four of the 66 occupational cases were from ICD codes 506.0-506.9, with the largest number classified as ICD codes 506.0 (bronchitis and pneumonitis due to fumes and vapors) and 506.3 (other acute and subacute respiratory conditions due to fumes and vapors). We conclude that surveillance of ICD codes in the 506 series, where 39% of the cases were secondary to occupational exposures, is a valuable component of a surveillance system for preventable occupational lung disease.

Accumulated exposure to ozone and measurement of health effects in children and counselors at two summer camps.

In the summer of 1988 a multiorganizational field health study was conducted at two summer day camps in suburban-central New Jersey. Thirty-four campers and counselors had daily pulmonary function tests performed each afternoon while attending camp during the month of July. The subjects ranged from 9 to 35 years of age. A mobile medical screening van was used to house the spirometric equipment and travel to each camp. Continuous ozone measurements were collected over the 19-test day study period. An intense ozone episode was recorded just prior to and during the first 2 weeks of the study. The campers had an increase in respiratory symptoms with increases in ozone concentrations above 120 ppb. Exposures below 120 ppb ozone were not significantly associated with symptoms. Peak expiratory flow rate in children was the only lung function measure associated with increasing ozone concentrations, with an average loss of 4.74 ml/sec/ppb (P-value = 0.05) for the 8-hr ozone exposure measure. Furthermore, it appears that the early intense exposure to ozone produced a persistent decrease in lung function and baseline shift for three days after the episode that obscured the daily dose-response relationship.

Fosinopril attenuates clinical deterioration and improves exercise tolerance in patients with heart failure. Fosinopril Efficacy/Safety Trial (FEST) Study Group.

This study was a 12-week, double-blind, placebo-controlled, multinational trial of fosinopril in 308 patients with mild to moderately severe heart failure (New York Heart Association [NYHA] functional class IIS 17%, IIM 48%, and III 35%; mean ejection fraction [+/-SD] 26.5% [+/-6.9%]; bicycle exercise duration 1 to 11 min). An initial dose of 10 mg once daily was titrated as tolerated to 40 mg once daily. Patients all received diuretic therapy; digoxin was optional. The primary endpoint was maximal bicycle exercise time; a secondary endpoint was occurrence of the following prospectively defined, ordered clinical events indicative of worsening heart failure: death, study discontinuation, hospitalization, emergency room visits, and need for supplemental diuretic. At study endpoint (last value obtained for each patient), bicycle exercise time increased more with fosinopril (38.1 s) than with placebo (23.5 s) (P = 0.101 by ANCOVA and 0.010 by prospectively defined dropout-adjusted endpoint analysis). More patients remained free of clinical events indicative of worsening heart failure when treated with fosinopril (89%) than with placebo (75%), and the worst events of fosinopril-treated patients tended to be less severe than those of placebo patients (P = 0.001). Analysis of the occurrence of individual clinical events showed that the need for supplemental diuretic was markedly reduced with fosinopril (8% vs 20%, of patients, P = 0.002), as were hospitalizations (3% vs 12% of patients, P = 0.002) and study discontinuations (2% vs 12% of patients, P < 0.001) for worsening heart failure; the two groups had similar incidences of death (3% of patients in the fosinopril group vs 2% in the placebo group, P = 0.723). In addition, symptoms of dyspnoea (P = 0.017), fatigue (P = 0.019), and NYHA functional class (P = 0.008) improved with fosinopril relative to placebo. In conclusion, fosinopril, at an initial dose of 10 mg once daily, subsequently titrated as tolerated to 40 mg once daily, increased exercise tolerance and reduced the frequency of clinical events indicative of worsening heart failure.

Effects of fosinopril on exercise tolerance, symptoms, and clinical outcomes in patients with decompensated heart failure.

The purpose of this prospective, multicenter, randomized, double blind, placebo controlled study was to determine the clinical effects of fosinopril in patients with decompensated or worsening heart failure (HF). Patients >/=18 years with New York Heart Association (NYHA) functional class II-IV HF who had been hospitalized or seen in the ER or outpatient clinic for treatment of worsening or decompensated HF were eligible. Patients had to be on diuretic therapy and have a left ventricular ejection fraction (LVEF) /=90 mm Hg). ETTs (modified Naughton protocol) were performed at weeks 1, 3, 6, and 12. A total of 206 patients (mean age 62 years) were randomized to fosinopril (n=102) or placebo (n=104). Most patients were NYHA functional class III (58%) or IV (30%) at presentation; 145 patients completed 12 weeks of treatment (fosinopril, n=85; placebo, n=60). After adjustment for baseline imbalances and investigator effects, fosinopril-treated patients had a 513 second mean exercise duration at endpoint vs. a 489 second duration in placebo-treated patients (p=0.353). When the analysis was adjusted for the impact of dropouts on ETT time, fosinopril-treated patients had a greater exercise duration than those treated with placebo (p=0.043). Fewer patients in the fosinopril group were discontinued from study medication (p=0.008) or hospitalized (p=0.005) for worsening HF. At endpoint, more patients improved their NYHA Functional Class and fewer had worsened with fosinopril vs. placebo (p=0.018); fosinopril-treated patients showed improvements in dyspnea (p=0.054), fatigue (p=0.052), edema (p=0.012), and paroxysmal nocturnal dyspnea (p=0.003) vs. the placebo group. Once-daily fosinopril had a favorable effect on dropout-adjusted exercise tolerance, reduced the frequency of discontinuations or hospitalizations for worsening HF, improved HF signs and symptoms, and was safe and well tolerated. (c)1999 by CHF, Inc.

The hemodynamic effects of long-term ACE inhibition with fosinopril in patients with heart failure. Fosinopril Hemodynamics Study Group.

The objective of this study was to evaluate the hemodynamic and clinical effects of fosinopril in patients with heart failure. This was a prospective, multicenter, double-blind, randomized, parallel-group study. Patients 18 to 80 years of age who were receiving diuretics with a systolic blood pressure (SBP) > or = 90 mm Hg, New York Heart Association (NYHA) functional class II-IV, left ventricular ejection fraction < or = 40%, pulmonary capillary wedge pressure (PCWP) > or = 18 mm Hg, and a cardiac index (CI) < or = 2.6 L/min/m(2) were eligible. A total of 179 patients were randomized to a single, double-blind oral dose of placebo or fosinopril at 1, 20, or 40 mg, and hemodynamic monitoring was performed for 24 hours postdose; 155 patients with SBP > or = 90 mm Hg were re-randomized to 10 weeks of double-blind fosinopril at 1, 20, or 40 mg once daily. Hemodynamic monitoring was repeated at the last visit, beginning at 24 hours postdose (trough) and continuing for 12 hours thereafter. Significant decreases in preload (PCWP) and afterload (mean arterial blood pressure [MABP] and systemic vascular resistance [SVR]) were evident 3 to 4 hours after a single dose of fosinopril at 20 and 40 mg and continuing for up to 8 to 12 hours postdose for PCWP and SVR and for up to 24 hours postdose for MABP (P < or = .05 v placebo and baseline). Sustained decreases in PCWP, MABP, SVR, and heart rate and increases in CI and stroke volume index were observed after 10 weeks of treatment with fosinopril at 20 and 40 mg once daily (P < or = .05 v 1 mg group for PCWP and MABP at most time points and P < or = .05 v baseline for other parameters at most time points). Dose-related trends toward reduced supplemental diuretic use (P = .027) and reduced symptoms of dyspnea (P = .008) were observed with the 20-mg and 40-mg fosinopril dose groups. Once daily administration of fosinopril at 20 and 40 mg was safe and well tolerated, provided a sustained beneficial hemodynamic effect, improved left ventricular performance, and reduced symptoms of dyspnea, resulting in a reduced need for supplemental diuretic therapy.