Zofenopril and incidence of cough: a review of published and unpublished data.

open2noOBJECTIVE: Cough is a typical side effect of angiotensin-converting enzyme (ACE) inhibitors, though its frequency quantitatively varies among the different compounds. Data on the incidence of cough with the lipophilic third-generation ACE inhibitor zofenopril are scanty and never systematically analyzed. The purpose of this paper is to give an overview on the epidemiology, pathophysiology, and treatment of ACE inhibitor-induced cough and to assess the incidence of cough induced by zofenopril treatment. METHODS: Published and unpublished data from randomized and postmarketing zofenopril trials were merged together and analyzed. RESULTS: Twenty-three studies including 5794 hypertensive patients and three studies including 1455 postmyocardial infarction patients exposed for a median follow-up time of 3 months to zofenopril at doses of 7.5-60 mg once-daily were analyzed. The incidence of zofenopril-induced cough was 2.6% (range 0%-4.2%): 2.4% in the hypertension trials (2.4% in the double-blind randomized studies and 2.4% in the open-label postmarketing studies) and 3.6% in the doubleblind randomized postmyocardial infarction trials. Zofenopril-induced cough was generally of a mild to moderate intensity, occurred significantly (P < 0.001) more frequently in the first 3-6 months of treatment (3.0% vs 0.2% 9-12 months), and always resolved or improved upon therapy discontinuation. Zofenopril doses of 30 mg and 60 mg resulted in significantly (P = 0.042) greater rate of cough (2.1% and 2.6%, respectively) than doses of 7.5 mg and 15 mg (0.4% and 0.7%, respectively). In direct comparison trials (enalapril and lisinopril), incidence of cough was not significantly different between zofenopril and other ACE inhibitors (2.4% vs 2.7%). CONCLUSION: Evidence from a limited number of studies indicates a relatively low incidence of zofenopril-induced cough. Large head-to-head comparison studies versus different ACE inhibitors are needed to highlight possible differences between zofenopril and other ACE inhibitors in the incidence of cough.openOmboni S.; Borghi C.Omboni S.; Borghi C

Zofenopril plus hydrochlorothiazide fixed combination in the treatment of hypertension and associated clinical conditions.

Zofenopril, is a highly lipophilic ACE inhibitor, characterized by long-lasting tissue penetration and sustained cardiac ACE inhibition, indicated for the treatment of hypertension and myocardial infarction. Comparative studies with different antihypertensive drug classes have demonstrated the good efficacy and tolerability of this compound in the management of the patient with mild-moderate hypertension. Zofenopril may also be combined with hydrochlorothiazide, a combination which has proved to be effective and safe as compared with monotherapy with either agent in three studies, including more than 600 patients. In addition, recent post hoc analyses in high-risk patients, such as those with the metabolic syndrome, impaired fasting glucose or diabetes, atherogenic dyslipidemia, and impaired renal function, have confirmed the superiority of zofenopril 30 mg plus hydrochlorothiazide 12.5 mg once-daily combination as compared with zofenopril monotherapy also in these high-risk populations of patients with hypertension. These data suggest the usefulness of this fixed combination in the treatment of patients with hypertension requiring more prompt, intensive, and sustained blood pressure reduction, according to guidelines recommendation. © 2009 Blackwell Publishing Ltd

Day and Night Changes of Cardiovascular Complexity: A Multi-Fractal Multi-Scale Analysis

Recently, a multifractal-multiscale approach to detrended fluctuation analysis (DFA) was proposed to evaluate the cardiovascular fractal dynamics providing a surface of self-similarity coefficients alpha(q,tau), function of the scale tau, and moment order q. We hypothesize that this versatile DFA approach may reflect the cardiocirculatory adaptations in complexity and nonlinearity occurring during the day/night cycle. Our aim is, therefore, to quantify how alpha(q, tau) surfaces of cardiovascular series differ between daytime and night-time. We estimated alpha(q,tau) with -5 &lt;= q &lt;= 5 and 8 &lt;= tau &lt;= 2048 s for heart rate and blood pressure beat-to-beat series over periods of few hours during daytime wake and night-time sleep in 14 healthy participants. From the alpha(q,tau) surfaces, we estimated short-term (&lt;16 s) and long-term (from 16 to 512 s) multifractal coefficients. Generating phase-shuffled surrogate series, we evaluated short-term and long-term indices of nonlinearity for each q. We found a long-term night/day modulation of alpha(q,tau) between 128 and 256 s affecting heart rate and blood pressure similarly, and multifractal short-term modulations at q &lt; 0 for the heart rate and at q &gt; 0 for the blood pressure. Consistent nonlinearity appeared at the shorter scales at night excluding q = 2. Long-term circadian modulations of the heart rate DFA were previously associated with the cardiac vulnerability period and our results may improve the risk stratification indicating the more relevant alpha(q,tau) area reflecting this rhythm. Furthermore, nonlinear components in the nocturnal alpha(q,tau) at q not equal 2 suggest that DFA may effectively integrate the linear spectral information with complexity-domain information, possibly improving the monitoring of cardiac interventions and protocols of rehabilitation medicine

Evaluation of 24-Hour Arterial Stiffness Indices and Central Hemodynamics in Healthy Normotensive Subjects versus Treated or Untreated Hypertensive Patients: A Feasibility Study

Objective. Central blood pressure (BP) and vascular indices estimated noninvasively over the 24 hours were compared between normotensive volunteers and hypertensive patients by a pulse wave analysis of ambulatory blood pressure recordings. Methods. Digitalized waveforms obtained during each brachial oscillometric BP measurement were stored in the device memory and analyzed by the validated Vasotens technology. Averages for the 24 hours and for the awake and asleep subperiods were computed. Results. 142 normotensives and 661 hypertensives were evaluated. 24-hour central BP, pulse wave velocity (PWV), and augmentation index (AI) were significantly higher in the hypertensive group than in the normotensive group (119.3 versus 105.6 mmHg for systolic BP, 75.6 versus 72.3 mmHg for diastolic BP, 10.3 versus 10.0 m/sec for aortic PWV, −9.7 versus −40.7% for peripheral AI, and 24.7 versus 11.0% for aortic AI), whereas reflected wave transit time (RWTT) was significantly lower in hypertensive patients (126.6 versus 139.0 ms). After adjusting for confounding factors a statistically significant between-group difference was still observed for central BP, RWTT, and peripheral AI. All estimates displayed a typical circadian rhythm. Conclusions. Noninvasive assessment of 24-hour arterial stiffness and central hemodynamics in daily life dynamic conditions may help in assessing the arterial function impairment in hypertensive patients

A similar 24‐h blood pressure control is obtained by zofenopril and candesartan in primary hypertensive patients

Objective. To compare the antihypertensive effect of treatment with zofenopril vs candesartan by office and ambulatory blood pressure (BP). Design and methods. Following a 2‐week wash‐out from previous treatment, 236 grade I–II primary hypertensive patients were randomized double‐blind to 12 weeks treatment with zofenopril 30 mg or candesartan 8 mg od. After 4 weeks, treatment was doubled in responder non‐normalized (office systolic BP⩾140 mmHg and office diastolic BP reduction ⩾10 mmHg) or non‐responder patients (office systolic BP⩾140 mmHg and office diastolic BP reduction <10 mmHg). Following a further 4 weeks, non‐responder or non‐normalized patients were withdrawn. Results. In the intention‐to‐treat population, office systolic BP and diastolic BP reductions after 12 weeks of treatment were similar between the two groups (zofenopril: 21±11/15±8 mmHg, n = 114 vs C: 20±11/15±7 mmHg, n = 122; p = NS). In the 163 patients of the per‐protocol population, office BP dropped by 22±11/15±8 mmHg (zofenopril) an..

Clinical Study Blood Pressure Response to Zofenopril or Irbesartan Each Combined with Hydrochlorothiazide in High-Risk Hypertensives Uncontrolled by Monotherapy: A Randomized, Double-Blind, Controlled, Parallel Group, Noninferiority Trial

In this randomized, double-blind, controlled, parallel group study (ZENITH), 434 essential hypertensives with additional cardiovascular risk factors, uncontrolled by a previous monotherapy, were treated for 18 weeks with zofenopril 30 or 60 mg plus hydrochlorothiazide (HCTZ) 12.5 mg or irbesartan 150 or 300 mg plus HCTZ. Rate of office blood pressure (BP) response (zofenopril: 68% versus irbesartan: 70%; = 0.778) and 24-hour BP response (zofenopril: 85% versus irbesartan: 84%; = 0.781) was similar between the two treatment groups. Cardiac and renal damage was equally reduced by both treatments, whereas the rate of carotid plaque regression was significantly larger with zofenopril. In conclusion, uncontrolled monotherapy treated hypertensives effectively respond to a combination of zofenopril or irbesartan plus a thiazide diuretic, in terms of either BP response or target organ damage progression

Efficacy of frovatriptan in the acute treatment of menstrually related migraine: analysis of a double-blind, randomized, multicenter, Italian, comparative study versus zolmitriptan

Menstrually related migraine (MRM) is a particularly difficult-to-treat pain condition, associated with substantial disability. Aim of this study was to compare the efficacy and safety of frovatriptan and zolmitriptan in the treatment of MRM attacks, analyzing data from a multicenter, randomized, double blind, cross-over study. We analyzed the subset of 76 regularly menstruating women who participated in one head-to-head multicenter, randomized, double blind, cross-over clinical trial and who took the study drugs to treat MRM attacks. In a randomized sequence, each patient received frovatriptan 2.5 mg or zolmitriptan 2.5 mg: after treating three episodes of migraine in no more than 3 months with the first treatment, the patient had to switch to the other treatment. MRM was defined according to the criteria listed in the Appendix of the last Classification of Headache disorders of the International Headache Society. A total of 73 attacks, classified as MRM, were treated with frovatriptan and 65 with zolmitriptan. Rate of pain relief at 2 h was 52% for frovatriptan and 53% for zolmitriptan (p = NS), while rate of pain free at 2 h was 22 and 26% (p = NS), respectively. At 24 h, 74 and 83% of frovatriptan-treated and 69 and 82% of zolmitriptan-treated patients were pain free and had pain relief, respectively (p = NS). Recurrence at 24 h was significantly (p < 0.05) lower with frovatriptan (15 vs. 22% zolmitriptan). Frovatriptan proved to be effective in the immediate treatment of MRM attacks, similarly to zolmitriptan, but showed lower recurrence rates, and thus a better sustained relief