[Stress bleeding. 2. Prophylaxis].
The seasonal occurrence and distribution of 69 pharmaceuticals along coastal watercourses during 6 sampling campaigns and their input through El Albujón watercourse to the Mar Menor lagoon were determined by UPLC-MS-MS, considering a total of 115 water samples. The major source of pharmaceuticals running into this watercourse was an effluent from the Los Alcazares WWTP, although other sources were also present (runoffs, excess water from irrigation, etc.). In this urban and agriculturally influenced watercourse different pharmaceutical distribution profiles were detected according to their attenuation, which depended on physicochemical water conditions, pollutant input variation, biodegradation and photodegradation rates of pollutants, etc. The less recalcitrant compounds in this study (macrolides, β-blockers, etc.) showed a relevant seasonal variability as a consequence of dissipation processes (degradation, sorption, etc.). Attenuation was lower, however, for diclofenac, carbamazepine, lorazepam, valsartan, sulfamethoxazole among others, due to their known lower degradability and sorption onto particulate matter, according to previous studies. The maximum concentrations detected were higher than 1000 ng L(-1) for azithromycin, clarithromycin, valsartan, acetaminophen and ibuprofen. These high concentration levels were favored by the limited dilution in this low flow system, and consequently some of them could pose an acute risk to the biota of this watercourse. Considering data from 2009 to 2010, it has been estimated that a total of 11.3 kg of pharmaceuticals access the Mar Menor lagoon annually through the El Albujón watercourse. The highest proportion of this input corresponded to antibiotics (46%), followed by antihypertensives (20%) and diuretics (18%).
At week 8, SiDBP changed by -9.93 (8.86) mm Hg in the fimasartan group and by -2.08 (9.47) mm Hg in the placebo group, which indicated significant antihypertensive efficacy (P < 0.0001). Efficacy was shown at week 4 as measured by SiDBP (-9.96 [7.73] vs -2.27 [7.85] mm Hg; P < 0.0001) or sitting systolic blood pressure (SiSBP) (-16.18 [14.44] vs -1.95 [13.48] mmHg; P < 0.0001) and at week 8 as determined by SiSBP (-15.35 [16.63] vs -2.30 [14.91] mm Hg; P < 0.0001). The fimasartan group exhibited more potent antihypertensive efficacy than the valsartan group both at week 4 (SiDBP, -9.96 [7.73] vs -6.53 [9.58] mm Hg [P = 0.0123]; SiSBP, -16.18 [14.4] vs -7.65 [12.89] mm Hg [P = 0.0002]) and at week 8 (SiDBP, -9.93 [8.86] vs -5.47 [8.96] mm Hg [P = 0.0021]; SiSBP, -15.35 [16.63] vs -7.49 [13.68] mm Hg [P = 0.0021]). Most treatment-emergent adverse events (TEAEs) were mild (89 of 95), and there were no serious TEAEs. The incidence of TEAEs was 19.1% in the fimasartan group, 22.6% in the placebo group, and 13.6% in the valsartan group, with no significant differences.
The study was designed to assess the antihypertensive effect of combined angiotensin-converting enzyme (ACE) inhibition and angiotensin II type 1 receptor (AT1) antagonism in patients with essential hypertension. Twenty patients with uncontrolled ambulatory diastolic blood pressure (BP) after 6 weeks of ACE inhibitor monotherapy (benazepril, 20 mg, o.d.) were randomized to receive double-blind valsartan, 80 mg, o.d. (AT1 antagonist) or matching placebo for 5 weeks while continuing to receive background benazepril. Then patients crossed over to the alternative regimen for a second 5-week period. The 24-h ambulatory BP was monitored on the final day of the benazepril monotherapy period and on the final day of each double-blind treatment period. Valsartan added to benazepril produced a significant antihypertensive effect with a benefit over placebo of 6.5 +/- 12.6/4.5 +/- 8.0 mm Hg (systolic/diastolic) for average awake ambulatory BP (p < 0.05), 7.1 +/- 9.4/5.6 +/- 6.5 mm Hg for asleep BP (p < 0.01), and 6.8 +/- 9.7/4.9 +/- 6.8 mm Hg for average 24-h ambulatory BP (p < 0.01). Pulse rate was unaffected. Plasma active renin was higher on the benazepril-valsartan combination compared with benazepril-placebo (p < 0.05). There was no change in routine biochemical variables when valsartan was added to benazepril. Six patients reported mild dizziness or fatigue (three also with placebo). These data suggest that in hypertensive patients uncontrolled with an ACE inhibitor, the addition of an AT1 antagonist provides a powerful and safe antihypertensive drug combination.
This was a study of the effects on sitting systolic BP (SBP)of 2 combinations of valsartan and hydrochlorothiazide (HCTZ) compared with valsartan monotherapy in patients with stage 2 or 3 systolic hypertension (SBP > or =160 mm Hg and < or =200 mm Hg) with or without other cardiovascular risk factors.
Both all-cause mortality and combined mortality and morbidity for patients not treated with ACE inhibitors were significantly reduced in the valsartan treatment group compared with the placebo group (17.3% vs. 27.1%, p = 0.017 and 24.9% vs. 42.5%, p < 0.001, respectively). Consistent with the data on clinical events, patients randomized to valsartan showed improvements in physiologic variables, such as ejection fraction, left ventricular internal diameter in diastole, and plasma neurohormone levels. Permanent discontinuation of study treatment because of adverse experiences was comparable between the two groups.