Significance of initial blood pressure and comorbidity for the efficacy of a fixed combination of an angiotensin receptor blocker and hydrochlorothiazide in clinical practice

Roland E Schmieder1, Markus Schwertfeger2, Peter Bramlage31Department of Nephrology and Hypertension, University Hospital of Erlangen; Germany; 2Sanofi-Aventis Deutschland GmbH, Berlin, Germany; 3Institute of Cardiovascular Pharmacology and Epidemiology, Mahlow, GermanyBackground: Two-thirds of all patients with arterial hypertension need drug combinations to achieve blood pressure (BP) goals. Fixed combinations have high efficacy and result in high patient compliance. 300 mg irbesartan plus 25 mg hydrochlorothiazide (HCTZ) has been investigated only in clinical trials but not in daily practice.Methods: A multicenter, noninterventional, noncontrolled observational study with 8123 patients seen by 1604 physicians in daily practice. BP reduction (office measurements), co-morbid disease and tolerability were documented over a 6-month observational period.Results: At mean baseline BP of 161 ± 15/94 ± 10 mmHg, administering of fixed combination resulted in a substantial BP reduction averaging 28 ± 15/14 ± 10 mmHg (P < 0.001). Decrease of systolic BP ran parallel with increasing systolic baseline BP (Spearman’s Rho –0.731; P < 0.0001; diastolic BP vs diastolic baseline BP Rho 0.740; P < 0.0001), independent from patient characteristics (age, obesity, diabetes or nephropathy) but enhanced with short history of hypertension (P < 0.0001 vs long history), prior beta blockers (P = 0.001 vs prior angiotensin receptor blockers [ARBs]), prior calcium channel blockers (P = 0.046 vs prior ARBs) and no prior medication (P = 0.012 vs prior ARBs). High compliance (>98%) and low incidence of adverse events (0.66%) were documented.Conclusions: The fixed combination of 300 mg irbesartan with 25 mg HCTZ was efficacious and tolerable in an unselected patient population in primary care.Keywords: hypertension, combination therapy, obesity, irbesartan, noninterventional study, diuretic

Transcranial Doppler ultrasound to assess cerebrovascular reactivity: reliability, reproducibility and effect of posture

Transcranial Doppler ultrasound (TCD) allows measurement of blood flow velocities in the intracranial vessels, and can be used to assess cerebral vasodilator responses to a hypercapnic stimulus. The reliability of this technique has not been established, nor is there agreement about whether the technique should be performed in sitting or lying postures. We tested the intra- and inter-rater reliability of measures of cerebrovascular reactivity (CVR) in 10 healthy adults, in sitting and lying postures. Participants underwent triplicate bilateral ultrasound assessment of flow velocities in the middle cerebral arteries whilst sitting and lying supine prior to and during inhalation of Carbogen (5% CO2, 95% O2) for 2 min. This procedure was performed twice by each of two raters for a total of four sessions. CVR was calculated as the difference between baseline and the peak blood flow velocity attained during CO2 inhalation. Intraclass correlation coefficients (ICCs) for intra-rater reliability were greater sitting than lying for both raters (e.g. Rater 1 ICC sitting = 0.822, lying = 0.734), and inter-rater reliability was also greater in sitting (e.g. sitting ICC = 0.504, lying = 0.081). These results suggest that assessment of CVR using TCD should be performed with participants sitting in order to maximise CVR measurement reliability

Updated European Heart Rhythm Association practical guide on the use of non-vitamin-K antagonist anticoagulants in patients with non-valvular atrial fibrillation: Executive summary

In 2013, the European Heart Rhythm Association (EHRA) published a Practical Guide on the use of non-VKA oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) (Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, European Heart Rhythm A. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P. EHRA practical guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation: executive summary. Eur Heart J 2013;34:2094-2106). The document received widespread interest, not only from cardiologists but also from neurologists, geriatricians, and general practitioners, as became evident from the distribution of > 350 000 copies of its pocket version (the EHRA Key Message Booklet) world-wide. Since 2013, numerous new studies have appeared on different aspects of NOAC therapy in AF patients. Therefore, EHRA updated the Practical Guide, including new information but also providing balanced guiding in the many areas where prospective data are still lacking. The outline of the original guide that addressed 15 clinical scenarios has been preserved, but all chapters have been rewritten. Main changes in the Update comprise a discussion on the definition of 'non-valvular AF' and eligibility for NOAC therapy, inclusion of finalized information on the recently approved edoxaban, tailored dosing information dependent on concomitant drugs, and/or clinical characteristics, an expanded chapter on neurologic scenarios (ischaemic stroke or intracranial haemorrhage under NOAC), an updated anticoagulation card and more specifics on start-up and follow-up issues. There are also many new flow charts, like on appropriate switching between anticoagulants (VKA to NOAC or vice versa), default scenarios for acute management of coronary interventions, step-down schemes for longterm combined antiplatelet-anticoagulant management in coronary heart disease, management of bleeding, and cardioversion under NOAC therapy. The Updated Guide is available in full in EP Europace (Heidbuchel H, Verhamme P, Alings M, Antz M, Diener HC, HackeW, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, Advisors. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507), while additional resources can be found at the related ESC/EHRA website (www.NOACforAF.eu)

Peripheral Arterial Disease as an Independent Predictor for Excess Stroke Morbidity and Mortality in Primary-Care Patients: 5-Year Results of the getABI Study

Background:There is controversial evidence with regard to the significance of peripheral arterial disease (PAD) as an indicator for future stroke risk. We aimed to quantify the risk increase for mortality and morbidity associated with PAD. Methods:In an open, prospective, noninterventional cohort study in the primary care setting, a total of 6,880 unselected patients ≧65 years were categorized according to the presence or absence of PAD and followed up for vascular events or deaths over 5 years. PAD was defined as ankle-brachial index (ABI) <0.9 or history of previous peripheral revascularization and/or limb amputation and/or intermittent claudication. Associations between known cardiovascular risk factors including PAD and cerebrovascular mortality/events were analyzed in a multivariate Cox regression model. Results:During the 5-year follow-up [29,915 patient-years (PY)], 183 patients had a stroke (incidence per 1,000 PY: 6.1 cases). In patients with PAD (n = 1,429) compared to those without PAD (n = 5,392), the incidence of all stroke types standardized per 1,000 PY, with the exception of hemorrhagic stroke, was about doubled (for fatal stroke tripled). The corresponding adjusted hazard ratios were 1.6 (95% confidence interval, CI, 1.1–2.2) for total stroke, 1.7 (95% CI 1.2–2.5) for ischemic stroke, 0.7 (95% CI 0.2–2.2) for hemorrhagic stroke, 2.5 (95% CI 1.2–5.2) for fatal stroke and 1.4 (95% CI 0.9–2.1) for nonfatal stroke. Lower ABI categories were associated with higher stroke rates. Besides high age, previous stroke and diabetes mellitus, PAD was a significant independent predictor for ischemic stroke. Conclusions:The risk of stroke is substantially increased in PAD patients, and PAD is a strong independent predictor for stroke.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich