Global Use of Idarucizumab in Clinical Practice: Outcomes of the RE-VECTO Surveillance Program.

Idarucizumab was approved for the reversal of dabigatran in 2015. We investigated whether postapproval usage patterns of idarucizumab in a real-world setting reflect those observed in the pivotal trials. No safety or efficacy data were collected in this medical record-based observational study. RE-VECTO, a global postapproval, international, surveillance program, involved hospital pharmacies in countries where idarucizumab was licensed and dispensed (August 2016-June 2018). Characteristics of sites prescribing idarucizumab and of eligible patients (≥ 18 years old and receiving idarucizumab regardless of prior oral anticoagulant use), as well as idarucizumab utilization data, were collected and analyzed descriptively. Sixty-one sites enrolled 359 patients. Most pharmacies (85.2%) were centralized, and the median idarucizumab units stocked per hospital was 2.0 (interquartile range, 1.0-3.0). Almost three-quarters of patients were elderly (74.9% aged > 70 years), and only four (1.1%) had received idarucizumab before. Nearly all patients were treated with dabigatran (97.5%). There was a low frequency of unapproved dabigatran dosage regimens (3.3%). Life-threatening or uncontrolled bleeding was the most frequent indication for idarucizumab (57.7%), followed by emergency surgery/urgent procedure (35.9%). Of the life-threatening bleeding events, the most frequent were gastrointestinal tract (44.4%) and intracranial (38.6%). Most patients (95.0%) were given the full dose of two vials (2 × 2.5 g) of idarucizumab initially, and very few (1.7%) received a second dose. Of those patients requiring emergency or scheduled/planned surgery/procedures, 25.5% underwent gastrointestinal and/or abdominal surgery/procedures. Real-world usage patterns of idarucizumab provide valuable insights into emergency reversal strategies. Off-label use was minimal.

Effects of the angiotensin II receptor blockers telmisartan versus valsartan in combination with hydrochlorothiazide: a large, confirmatory trial.

In 2004-2005, the antihypertensive effects of telmisartan 80 mg versus valsartan 160 mg combined with hydrochlorothiazide 25 mg were assessed in a large placebo-controlled trial in patients with stages 1 and 2 hypertension and demonstrated that both agents were highly effective in lowering blood pressure (BP) compared with placebo and that telmisartan lowered BP significantly greater than valsartan. To confirm this finding according to Food and Drug Administration guidelines, we performed a second large trial using the same design in an entirely separate patient population. The trial was double-blind with a 4 : 4 : 1 randomization scheme to compare once daily telmisartan 80 mg plus hydrochlorothiazide 25 mg versus once daily valsartan 160 mg plus hydrochlorothiazide 25 mg versus once daily placebo on reductions in seated clinic BP in patients with stages 1 and 2 hypertension. The primary endpoints were the changes from baseline in seated diastolic and systolic BP at the end of the 8-week treatment period. Safety endpoints included adverse events, changes in laboratory parameters and pulse rate. In total, 1185 patients were randomized (of which 1181 were treated and included in the primary analysis: 528 in the telmisartan-hydrochlorothiazide group, 523 in the valsartan-hydrochlorothiazide group, and 130 in the placebo group), changes from baseline in BP following telmisartan-hydrochlorothiazide (-24.6/-18.2 mmHg) were significantly greater than both placebo (-4.1/-6.1 mmHg) and valsartan-hydrochlorothiazide (-22.5/-17.0 mmHg) (versus placebo, P<0.0001 for systolic and diastolic BP; versus valsartan-hydrochlorothiazide, P=0.017 for systolic BP and P=0.025 for diastolic BP). The total number of patients with at least one adverse event reported was similar among the three treatment groups (placebo, 42%, telmisartan-hydrochlorothiazide, 36%, and valsartan-hydrochlorothiazide, 37%). Thus, this large, second trial confirms that telmisartan-hydrochlorothiazide at doses of 80/25 mg lowered both systolic and diastolic BP to a greater extent than valsartan-hydrochlorothiazide at doses of 160/25 mg in stages 1-2 hypertension. Although these are not the highest doses of these agents at present, at the time that the studies were conducted, they were the maximally approved dosages. Both studies support the strategy of using angiotensin receptor blockers with a higher dose of a thazide diuretic (25 mg) for enhancing the control of hypertension.

Effects of the angiotensin II receptor blockers telmisartan vs valsartan in combination with hydrochlorothiazide 25 mg once daily for the treatment of hypertension.

To attain recent goals of blood pressure (BP) control, multiple drug therapy combinations are required, including higher doses of thiazide diuretics in combination with other classes of antihypertensive drug therapy. Thus, the authors evaluated the antihypertensive effects of telmisartan vs valsartan when combined with hydrochlorothiazide (HCTZ) 25 mg in a large (N=1066), placebo-controlled trial in patients with stage 1 or 2 hypertension. The primary end points were the changes from baseline in seated diastolic and systolic BP at the end of the 8-week treatment period. Safety end points included adverse events, changes in laboratory parameters, and pulse rate. Changes from baseline in BP following telmisartan-HCTZ (-24.0/-17.6 mm Hg) were significantly greater than both placebo (-4.4/-6.8 mm Hg) and valsartan-HCTZ (-21.2/-16.1 mm Hg) (vs placebo, P<.001 for systolic and diastolic BP; vs valsartan-HCTZ, P=.004 for systolic BP and P=.019 for diastolic BP). The total number of patients with at least 1 adverse event reported were similar among the 3 treatment groups (placebo, 49%; telmisartan-HCTZ, 43%; and valsartan-HCTZ, 38%). In conclusion, telmisartan-HCTZ at doses of 80/25 mg lowered both systolic and diastolic BP to a greater extent than valsartan-HCTZ at doses of 160/25 mg. These data support using a higher dose of a thiazide diuretic (25 mg) with a long-acting angiotensin receptor blocker as a useful strategy for improving hypertension control.