Riociguat for the treatment of pulmonary arterial hypertension.

BACKGROUND: Riociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension. METHODS: In this phase 3, double-blind study, we randomly assigned 443 patients with symptomatic pulmonary arterial hypertension to receive placebo, riociguat in individually adjusted doses of up to 2.5 mg three times daily (2.5 mg-maximum group), or riociguat in individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg-maximum group). The 1.5 mg-maximum group was included for exploratory purposes, and the data from that group were analyzed descriptively. Patients who were receiving no other treatment for pulmonary arterial hypertension and patients who were receiving endothelin-receptor antagonists or (nonintravenous) prostanoids were eligible. The primary end point was the change from baseline to the end of week 12 in the distance walked in 6 minutes. Secondary end points included the change in pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, time to clinical worsening, score on the Borg dyspnea scale, quality-of-life variables, and safety. RESULTS: By week 12, the 6-minute walk distance had increased by a mean of 30 m in the 2.5 mg-maximum group and had decreased by a mean of 6 m in the placebo group (least-squares mean difference, 36 m; 95% confidence interval, 20 to 52; P<0.001). Prespecified subgroup analyses showed that riociguat improved the 6-minute walk distance both in patients who were receiving no other treatment for the disease and in those who were receiving endothelin-receptor antagonists or prostanoids. There were significant improvements in pulmonary vascular resistance (P<0.001), NT-proBNP levels (P<0.001), WHO functional class (P=0.003), time to clinical worsening (P=0.005), and Borg dyspnea score (P=0.002). The most common serious adverse event in the placebo group and the 2.5 mg-maximum group was syncope (4% and 1%, respectively). CONCLUSIONS: Riociguat significantly improved exercise capacity and secondary efficacy end points in patients with pulmonary arterial hypertension. (Funded by Bayer HealthCare; PATENT-1 and PATENT-2 ClinicalTrials.gov numbers, NCT00810693 and NCT00863681, respectively.).

Treatment of hypertension and adherence to treatment guidelines in clinical practice: an Italian study.

Despite the results from clinical trials in patients with hypertension and the development of a long list of guidelines for the management of hypertension, many physicians and other healthcare professionals still manage hypertension using approaches that clearly diverge at least partially from the recommendations of these guidelines. Whatever the underlying reasons for physicians' failure to adhere to these guidelines, it is one of the main causes of the high percentage of treated patients with uncontrolled hypertension. This article is a report of the outcomes of a project designed to identify specific discrepancies between hypertension guidelines and clinical practice in Italy then guide the physicians to reach a consensus on hypertension management through discussions with their peers. A total of 1120 internists from all 20 regions in Italy were recruited to participate in workshops conducted between June 2002 and July 2004. They were divided into 57 groups to discuss at least 7 key topics, including the blood pressure level at which to start drug therapy, target-organ damage, isolated systolic hypertension, pulse pressure, clinical trials, generic drugs, and fixed combination drug therapy. The project findings confirmed that the vast majority of internists agree with the guidelines but do not adhere to them completely in clinical practice. Through open discussions that allowed them to identify common viewpoints, the participants may have developed a better awareness of and insight into the guidelines for hypertension management. Hopefully this strategy for group participation will lead to improvements in the management of hypertension throughout Italy.

Blood pressure control by the nifedipine GITS-telmisartan combination in patients at high cardiovascular risk: the TALENT study.

BACKGROUND: Guidelines on hypertension regard combinations between two antihypertensive drugs to be the most important treatment strategy. Because of the complementary mechanism of action and the evidence of cardiovascular protective effects they include the combination of a calcium antagonist and an angiotensin receptor antagonist among the priorital ones to employ. AIMS: To determine in hypertensive patients at high cardiovascular risk whether combining Nifedipine GITS at low dose and telmisartan reduced ambulatory and clinic blood pressure (BP) more than the combination components, controlled BP early after treatment initiation and allowed to also obtain a better long-term BP control compared to initiating treatment with the combination components and moving to the combination later. METHODS: Four hundred and five patients with a clinic SBP ≥ 135 mmHg and with diabetes, a metabolic syndrome or organ damage were randomized to once-a-day telmisartan 80 mg, nifedipine GITS 20 mg or the combination of the two drugs in a 1: 1: 2 ratio for 8 weeks in the context of a multicenter double-blind study design. Patients on monotherapy were then moved to combination treatment and all three groups were followed for an additional 16-week period. Both 24-h and clinic BP were measured before treatment and at various times during treatment. RESULTS: In the per-protocol patients (n = 327), baseline demographic and clinical characteristics were similar between the three groups. Baseline 24-h SBP values were 136.2 ± 11.6 mmHg (mean ± SD), 137.2 ± 12.5 mmHg and 136.8 ± 11.7 mmHg in the telmisartan monotherapy, nifedipine GITS monotherapy and combination therapy, respectively. The corresponding clinic values were 151.7 ± 11.8, 151.3 ± 11.9 and 151.1 ± 11.8 mmHg, respectively. All treatments lowered 24-h SBP significantly (P < 0.0001) but combination treatment (8 weeks) reduced it significantly more than monotherapies (10.8 ± 0.8 vs. 6.6 ± 1.1 mmHg and 8.0 ± 1.2 mmHg; P = 0.001 and 0.037). Similar data were obtained for clinic SBP for which the combination showed a significantly greater BP reduction (12.6 ± 0.6 vs. 8.6 ± 0.7 mmHg and 9.3 ± 0.8 mmHg; P = 0.003 and 0.024) also after 2 weeks of treatment. Moving from monotherapy to combination therapy increased the antihypertensive effect and made both ambulatory and clinic SBP superimposable in the three groups after 16 and 24 weeks of treatment. Similar findings were obtained for DBP. CONCLUSION: Combination treatment with nifedipine GITS low dose and telmisartan provides a greater and earlier clinic and ambulatory BP reduction than the combination components in monotherapy. Initiating treatment with the combination did not result in any better longer term BP control compared to starting treatment with monotherapy and moving to the combination later.

A new solar-powered blood pressure measuring device for low-resource settings.

The management of high blood pressure (BP) is particularly inadequate in low-income countries, where the unavailability of a reliable, durable, and affordable BP-measurement device is a major obstacle to accurate diagnosis. Recognizing this, a World Health Organization committee was established to correct this deficiency by influencing manufacturers to produce a device according to predetermined criteria and to demonstrate the suitability of the device for low resource settings. A device, which fulfilled stipulated criteria in being inexpensive, semiautomated, and solar powered, was validated according to the International Protocol of the European Society of Hypertension; it was then subjected to field testing in 716 subjects from 2 centers in Uganda and 1 in Zambia. The Omron HEM-SOLAR having previously fulfilled accuracy criteria of the International Protocol for both systolic blood pressure (SBP) and diastolic blood pressure (DBP), fulfilled criteria for SBP, but not for DBP, when revalidated. In field testing, average SBPs and DBPs were 120.5 ± 21.6/74.6 ± 13.8 mm Hg and 122.3 ± 21.8/71.2 ± 14.0 mm Hg, respectively, with the auscultatory technique and the Omron HEM-SOLAR, respectively. Between-device agreement in defining SBP was 93.7%. The Omron HEM-SOLAR was favored over the mercury sphygmomanometer by both patients and investigators. In summary, considering the accuracy, robustness, relatively low cost, operational simplicity, and advantages such as solar power, the Omron HEM-SOLAR is likely to be a valuable device for improving BP measurement in low-resource settings with nonphysician health workers.