Cuffless Blood Pressure Measurement Using a Smartphone-Case Based ECG Monitor with Photoplethysmography in Hypertensive Patients.

The availability of simple, accurate, and affordable cuffless blood pressure (BP) devices has the potential to greatly increase the compliance with measurement recommendations and the utilization of BP measurements for BP telemonitoring. The aim of this study is to evaluate the correlation between findings from routine BP measurements using a conventional sphygmomanometer with the results from a portable ECG monitor combined with photoplethysmography (PPG) for pulse wave registration in patients with arterial hypertension. METHODS: The study included 500 patients aged 32-88 years (mean 64 ± 7.9 years). Mean values from three routine BP measurements by a sphygmomanometer with cuff were selected for comparison; within one minute after the last measurement, an electrocardiogram (ECG) was recorded for 3 min in the standard lead I using a smartphone-case based single-channel ECG monitor (CardioQVARK®-limited responsibility company "L-CARD", Moscow, Russia) simultaneously with a PPG pulse wave recording. Using a combination of the heart signal with the PPG, levels of systolic and diastolic BP were determined based on machine learning using a previously developed and validated algorithm and were compared with sphygmomanometer results. RESULTS: According to the Bland-Altman analysis, SD for systolic BP was 3.63, and bias was 0.32 for systolic BP. SD was 2.95 and bias was 0.61 for diastolic BP. The correlation between the results from the sphygmomanometer and the cuffless method was 0.89 (p = 0.001) for systolic and 0.87 (p = 0.002) for diastolic BP. CONCLUSION: Blood pressure measurements on a smartphone-case without a cuff are encouraging. However, further research is needed to improve the accuracy and reliability of clinical use in the majority of patients.

E-Health in Hypertension Management: an Insight into the Current and Future Role of Blood Pressure Telemonitoring.

PURPOSE OF REVIEW: Out-of-office blood pressure (BP) monitoring techniques, including home and ambulatory BP monitoring, are currently recommended by hypertension guidelines worldwide to confirm the diagnosis of hypertension and to monitor the appropriateness of treatment. However, such techniques are not always effectively implemented or timely available in the routine clinical practice. In recent years, the widespread availability of e-health solutions has stimulated the development of blood pressure telemonitoring (BPT) systems, which allow remote BP tracking and tighter and more efficient monitoring of patients' health status. RECENT FINDINGS: There is currently strong evidence that BPT may be of benefit for hypertension screening and diagnosis and for improving hypertension management. The advantage is more significant when BPT is coupled with multimodal interventions involving a physician, a nurse or pharmacist, and including education on lifestyle and risk factors and drug management. Several randomized controlled studies documented enhanced hypertension management and improved BP control of hypertensive patients through BPT. Potential additional effects of BPT are represented by improved compliance to treatment, intensification, and optimization of drug use, improved quality of life, reduction in risk of developing cardiovascular complications, and cost-saving. Applications based on m-health and making use of wearables or smartwatches integrated with machine learning models are particularly promising for the future development of efficient BPT solutions, and they will provide remarkable support decision tools for doctors. BPT and telehealth will soon disrupt hypertension management. However, which approach will be the most effective and whether it will be sustainable in the long-term still need to be elucidated.

Telemedicine During the COVID-19 in Italy: A Missed Opportunity?

In the time of COVID-19 epidemic, Italy was found unprepared to manage lockdown patients with chronic diseases, due to limited availability and diffusion of large-scale telemedicine solutions. The scattered distribution and heterogeneity of available tools, the lack of integration with the electronic health record of the national health system, the poor interconnection between telemedicine services operating at different levels, the lack of a real multidisciplinary approach to the patient's management, the heavy privacy regulations, and lack of clear guidelines, together with the lack of reimbursement, all hinder the implementation of effective telemedicine solutions for long-term patients' management. This COVID-19 epidemic should help promote better use and a larger integration of telemedicine services in the armamentarium of health care services. Telemedicine must no longer be considered as an option or add-on to react to an emergency.

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 α(q,τ), function of the scale τ, 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 α(q, τ) surfaces of cardiovascular series differ between daytime and night-time. We estimated α(q,τ) with -5 ≤ q ≤ 5 and 8 ≤ τ ≤ 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 α(q,τ) surfaces, we estimated short-term (<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 α(q,τ) between 128 and 256 s affecting heart rate and blood pressure similarly, and multifractal short-term modulations at q < 0 for the heart rate and at q > 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 α(q,τ) area reflecting this rhythm. Furthermore, nonlinear components in the nocturnal α(q,τ) at q ≠ 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.

Simultaneous double arm automated blood pressure measurement for the screening of subjects with potential vascular disease: a community study.

PURPOSE: Hypertension guidelines recommend measuring blood pressure (BP) on both arms, since an abnormal inter-arm difference (IAD) in BP is associated with an increased risk of vascular abnormalities and cardiovascular (CV) disease. We tested whether an automatic oscillometric BP monitor allowing simultaneous both arm BP measurement might be effective for screening of subjects with potential vascular disease. MATERIALS AND METHODS: 220 consecutive subjects from an unselected sample of individuals of a small Italian community were screened using an automated upper-arm electronic BP monitor (Microlife WatchBP Office). Seated BP was measured in triplicate at 1 min interval. Demographic and clinical data were collected prior to any BP measurement. An average IAD difference >20 mmHg for systolic (S) and/or >10 mmHg for diastolic (D) BP was considered abnormal. RESULTS: In 9 subjects (4.1%) an abnormal IAD was found, with lower BPs measured in the non-dominant arm (147 ± 28/78 ± 9 vs. 154 ± 15/92 ± 11 mmHg dominant, p<.01). Subjects with a significant IAD were significantly older (71 ± 8 vs. 57 ± 15 years, p=.005), had a greater body mass index (BMI: 32 ± 7 vs. 25 ± 4 kg/m2, p=.0001), higher BP levels (154 ± 15/92 ± 11 vs. 133 ± 18/80 ± 10 mmHg, p=.001) and were more likely to report obesity (56 vs. 13%, p=.001), a history of hypertension (67 vs. 35%, p=.044) or cardiovascular disease (33 vs. 10%, p=.034) than subjects with normal IAD. In a multivariate analysis, a higher BMI [odds ratio (95% confidence interval): 1.29 (1.11, 1.51)] and SBP [1.06 (1.01, 1.10)] were significantly associated with a larger risk of an abnormal IAD (p=.001 and p=.012, respectively). CONCLUSIONS: An abnormal IAD in BP is associated with a larger prevalence of CV risk factors and CV disease. Our study confirms that simultaneous both arm BP measurement must always be accomplished in subjects at risk for or with established CV disease.

Effects of the concomitant administration of xanthine oxidase inhibitors with zofenopril or other ACE-inhibitors in post-myocardial infarction patients: a meta-analysis of individual data of four randomized, double-blind, prospective studies.

BACKGROUND: Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival. OBJECTIVE: We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies. METHODS: One hundred sixty-five (31.4%) patients were treated with XOIs (79 under zofenopril, 86 placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril, 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes). RESULTS: MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p = 0.034 across groups). Rate of survival free from MACE was significantly larger under treatment with zofenopril + XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06-4.91), p = 0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54-2.64), p = 0.669] or vs. placebo or other ACEIs + XOIs [1.82 (0.78-4.26), p = 0.169]. CONCLUSIONS: Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.

Self-monitoring of blood pressure in hypertension: A systematic review and individual patient data meta-analysis.

BACKGROUND: Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. METHODS AND FINDINGS: Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. CONCLUSIONS: Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions.

Smartphone Applications for Hypertension Management: a Potential Game-Changer That Needs More Control.

PURPOSE OF THE REVIEW: This review article will summarize available data on mobile applications for the management of hypertension, by highlighting their potential for clinical use, the current limitations and the yet pending issues to be addressed in future studies. RECENT FINDINGS: The number of available applications related to arterial hypertension and their usage by smartphone owners is constantly increasing. However, most applications lack standardization and scientific validation, and security flaws could be an important, yet still underrated, issue. Small studies showed that treatment strategies based on telemonitoring of home blood pressure with mobile applications could improve blood pressure control, but there are no data on strong outcomes and the high heterogeneity of available studies severely limits the possibility of reaching a definitive conclusion on the impact of such strategies. Smartphone applications for arterial hypertension represent a great chance to improve management of this condition. Results from small studies are promising, but there is a strong need for large, long-term, well-designed clinical trials, before these potential solutions might be reliably applied in real-life patients' care.

Early Treatment With Zofenopril and Ramipril in Combination With Acetyl Salicylic Acid in Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: Results of a 5-Year Follow-up of Patients of the SMILE-4 Study.

The SMILE-4 study showed that in patients with left ventricular dysfunction (LVD) after acute myocardial infarction, early treatment with zofenopril plus acetyl salicylic acid is associated with an improved 1-year survival, free from death or hospitalization for cardiovascular (CV) causes, as compared to ramipril plus acetyl salicylic acid. We now report CV outcomes during a 5-year follow-up of the patients of the SMILE-4 study. Three hundred eighty-six of the 518 patients completing the study (51.2%) could be tracked after the study end and 265 could be included in the analysis. During the 5.5 (±2.1) years of follow-up, the primary endpoint occurred in 27.8% of patients originally randomized and treated with zofenopril and in 43.8% of patients treated with ramipril [odds ratio (OR) and 95% confidence interval, 0.65 (0.43-0.98), P = 0.041]. Such a result was achieved through a significantly larger reduction in CV hospitalization under zofenopril [OR: 0.61 (0.37-0.99), P = 0.047], whereas reduction in mortality rate with zofenopril did not achieve statistical significance versus ramipril [OR: 0.75 (0.36-1.59), P = 0.459]. These results were in line with those achieved during the initial 1-year follow-up. Benefits of early treatment of patients with LVD after acute myocardial infarction with zofenopril are sustained over many years as compared to ramipril.

Efficacy of Zofenopril Compared With Placebo and Other Angiotensin-converting Enzyme Inhibitors in Patients With Acute Myocardial Infarction and Previous Cardiovascular Risk Factors: A Pooled Individual Data Analysis of 4 Randomized, Double-blind, Controlled, Prospective Studies.

In the Survival of Myocardial Infarction Long-term Evaluation (SMILE) 1, 3, and 4 studies, early administration of zofenopril in acute myocardial infarction showed to be prognostically beneficial versus placebo or ramipril. The SMILE-2 showed that both zofenopril and lisinopril are safe and showed no significant differences in the incidence of major cardiovascular (CV) complications. In this pooled analysis of individual data of the SMILE studies, we evaluated whether the superior efficacy of zofenopril is maintained also in patients with ≥1 CV risk factor (CV+, n = 2962) as compared to CV- (n = 668). The primary study end point was set to 1-year combined occurrence of death or hospitalization for CV causes. The risk of CV events was significantly reduced with zofenopril versus placebo either in the CV+ (-37%; hazard ratio: 0.63; 95% confidence interval: 0.51-0.78; P = 0.0001) or in the CV- group (-55%; hazard ratio: 0.45; 0.26-0.78; P = 0.004). Also, the other angiotensin-converting enzyme inhibitors reduced the risk of major CV outcomes, though the reduction was not statistically significant versus placebo (CV+: 0.78; 0.58-1.05; P = 0.107; CV-: 0.71; 0.36-1.41; P = 0.334). The benefit was larger in patients treated with zofenopril than other angiotensin-converting enzyme inhibitors, with a statistically significant difference for CV+ (0.79; 0.63-0.99; P = 0.039) versus CV- (0.62; 0.37-1.06; P = 0.081). In conclusion, zofenopril administered to patients after acute myocardial infarction has a positive impact on prognosis, regardless of the patient's CV risk profile.

Cardioprotective role of zofenopril in hypertensive patients with acute myocardial infarction: a pooled individual data analysis of the SMILE studies.

PURPOSE: The four SMILE studies demonstrated that early administration of zofenopril following acute myocardial infarction is prognostically beneficial compared to placebo or other angiotensin-converting enzyme (ACE) inhibitors. In the present retrospective pooled analysis of individual SMILE studies, we evaluated the efficacy of zofenopril on cardiovascular (CV) outcomes in 1880 hypertensive and 1662 normotensive patients. MATERIALS AND METHODS: Four hundred and forty-nine hypertensives and 486 normotensives were treated with placebo, 980 and 786 with zofenopril 30-60 mg daily, 252 and 259 with lisinopril 5-10 mg daily, 199 and 131 with ramipril 10 mg daily, for 6 to 48 weeks. RESULTS: The 1-year risk of death or hospitalization for CV causes was significantly reduced with zofenopril and lisinopril vs. placebo in both hypertensive (HR: 0.65; 95%CI: 0.48-0.86; p = .003 and .60, .36-.99; p = .049, respectively) and normotensive patients (0.56, 0.42-0.75; p = .0001 and .51, .28-.90; p = .020), whereas this was not the case for ramipril (hypertensives: 1.02, 0.69-1.52; p = .918; normotensives: 0.91, 0.59-1.41; p = .670). Zofenopril significantly reduced the risk of CV outcomes vs. the other two ACE-inhibitors pooled together in hypertensive (0.76; 0.58-0.99; p = .045), but not in normotensive patients (0.77; 0.55-1.10; p = .150). CONCLUSIONS: In cardiac patients of the SMILE studies with arterial hypertension treatment with the ACE-inhibitor zofenopril was beneficial in reducing the 1-year risk of CV events as compared to placebo and ramipril. An efficacy similar to that of zofenopril was observed with lisinopril.

Twenty-Four-Hour Ambulatory Pulse Wave Analysis in Hypertension Management: Current Evidence and Perspectives.

The predictive value of vascular biomarkers such as pulse wave velocity (PWV), central arterial pressure (CAP), and augmentation index (AIx), obtained through pulse wave analysis (PWA) in resting conditions, has been documented in a variety of patient groups and populations. This allowed to make appropriate recommendations in clinical practice guidelines of several scientific societies. Due to advances in technologies, largely operator-independent methods are currently available for estimating vascular biomarkers also in ambulatory conditions, over the 24 h. According to the acceptable accuracy and reproducibility of 24-h ambulatory PWA, it appears to be a promising tool for evaluating vascular biomarkers in daily life conditions. This approach may provide an opportunity to further improve the early cardiovascular screening in subjects at risk. However, concerning the clinical use of PWA over the 24 h in ambulatory conditions at the moment, there is no sufficient evidence to support its routine clinical use. In particular, long-term outcome studies are needed to show the predictive value of 24-h PWV, CAP, and AIx values, provided by these devices, over and beyond peripheral blood pressure, and to answer the many technical and clinical questions still open. To this regard, the VASOTENS Registry, an international observational prospective study recently started, will help providing answers on a large sample of hypertensive patients recruited worldwide.

The role of telemedicine in hypertension management: focus on blood pressure telemonitoring.

This review aims at updating and critically assessing the role of telemedicine, and in particular, of home blood pressure telemonitoring (HBPT), in the management of the hypertensive patient. Result from several randomized trials suggest that HBPT represents a promising tool for improving blood pressure (BP) control of hypertensive patients, in particular, those at high risk. Most studies documented a significant BP reduction with regular HBPT compared to usual care. HBPT interventions showed a very high degree of acceptance by patients, helped improving the patients' quality of life, and were associated with lower medical costs than standard care, even though such costs were offset by those of the technology, thus reducing the overall cost-effectiveness of HBPT. The high heterogeneity of the technologies, study designs, and type of patients in the various studies suggest that further well-designed, large cohort, prospective studies are needed to identify key elements of HBPT approach to be able to give impact on specific outcomes. Likely, patients who need a constant monitoring of multiple vital signs and a tight BP control, such as high risk patients with chronic diseases (ischemic heart disease or heart failure, diabetes, etc.), as well as non-adherent patients, may particularly benefit from HBPT. In general, HBPT can be an advantageous choice when a network among healthcare professionals (doctors, nurses, and pharmacists) is needed to improve the screening and management of hypertension and related comorbidities and to achieve an effective prevention of cardiovascular diseases in the community.

Early (≤ 1-h) vs. late (>1-h) administration of frovatriptan plus dexketoprofen combination vs. frovatriptan monotherapy in the acute treatment of migraine attacks with or without aura: a post hoc analysis of a double-blind, randomized, parallel group study.

The early use of triptan in combination with a nonsteroidal anti-inflammatory drug after headache onset may improve the efficacy of acute migraine treatment. In this retrospective analysis of a randomized, double-blind, parallel group study, we assessed the efficacy of early or late intake of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex 25 and FroDex 37.5) vs. frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks. In this double-blind, randomized parallel group study 314 subjects with acute migraine with or without aura were randomly assigned to Frova, FroDex 25, or FroDex 37.5. Pain free (PF) at 2-h (primary endpoint), PF at 4-h and pain relief (PR) at 2 and 4-h, speed of onset at 60, 90, 120 and 240-min, and sustained pain free (SPF) at 24-h were compared across study groups according to early (≤1-h; n = 220) or late (>1-h; n = 59) intake. PF rates at 2 and 4-h were significantly larger with FroDex 37.5 vs. Frova (early intake, n = 71 FroDex 37.5 and n = 75 Frova: 49 vs. 32 % and 68 vs. 52 %, p < 0.05; late intake, n = 20 Frodex 37.5, and n = 18 Frova: 55 vs. 17 %, p < 0.05 and 85 vs. 28 %, p < 0.01). Also with FroDex 25, in the early intake group (n = 74) PF episodes were significantly higher than Frova. PR at 2 and 4-h was significantly better under FroDex 37.5 than Frova (95 % vs. 50 %, p < 0.001, 100 % vs. 72 %, p < 0.05) in the late intake group (n = 21). SPF episodes at 24-h after early dosing were 25 % (Frova), 45 % (FroDex 25) and 41 % (FroDex 37.5, p < 0.05 combinations vs. monotherapy), whereas they were not significantly different with late intake. All treatments were equally well tolerated. FroDex was similarly effective regardless of intake timing from headache onset.

Efficacy of frovatriptan as compared to other triptans in migraine with aura.

BACKGROUND: The treatment of migraine attacks with aura by triptans is difficult since triptans most probably are not efficacious when taken during the aura phase. Moreover, there are insufficient data from randomised studies whether triptans are efficacious in migraine attacks with aura when taken during the headache phase. In this metaanalysis, we aimed to compare the efficacy of frovatriptan versus rizatriptan, zolmitriptan, and almotriptan. METHODS: Five double-blind, randomized, controlled crossover trials were pooled. All trials had an identical design. Patients were asked to treat three consecutive migraine attacks with frovatriptan 2.5 mg and three consecutive migraine attacks with a comparative triptan (rizatriptan 10 mg; zomitriptan 2.5 mg; almotriptan 12.5 mg). RESULTS: In this analysis, 117 migraine attacks with aura could be included (intention-to-treat population). The mean headache intensity after 2 hours was 1.2 +/- 1.0 for frovatriptan and 1.6 +/- 1.0 for the other triptans (p<0.05); all triptans showed significant improvement of headache. Frovatriptan resulted in significantly lower relapse rates at 24 hours and 48 hours when taken in migraine attacks with aura. CONCLUSIONS: Our data suggest that frovatriptan is efficacious and even superior in some endpoints also when taken during the headache phase in migraine attacks with aura. This is of particular importance for those many patients who have migraine attacks both without and with aura.

Gender and triptan efficacy: a pooled analysis of three double-blind, randomized, crossover, multicenter, Italian studies comparing frovatriptan vs. other triptans.

Migraine is three times as common in females as in males, and attacks may be more severe and difficult to treat in women. However, no study specifically addressed possible gender differences in response to antimigraine therapy. The objective of this study was to review the efficacy of frovatriptan vs. other triptans, in the acute treatment of migraine in subgroups of subjects classified according to gender (men vs. women) through a pooled analysis of three individual randomized Italian studies. 414 patients suffering from migraine with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1-3 episodes of migraine in no more than 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, traditional migraine endpoints were compared between the 66 men and 280 women of the intent-to-treat population. At baseline, long-term and debilitating migraine attacks were more frequently reported by women than men. During the observation period, the proportion of pain-free attacks at 2 h did not significantly differ between frovatriptan and the comparators in either men (32 vs. 38 %, p = NS) or women (30 vs. 33 %, p = NS). Pain relief was also similar between treatments for both genders (men: 56 % frovatriptan vs. 57 % comparators; women: 55 vs. 57 %; p = NS for both). The rate of relapse was significantly lower with frovatriptan than with the comparators in men (24 h: 10 vs. 30 %; 48 h: 21 vs. 39 %; p < 0.05) as well as in women (24 h: 14 vs. 23 %; 48 h: 28 vs. 40 %; p < 0.05). The rate of adverse drug reactions was significantly larger with comparators, irrespectively of gender. Although migraine presents in a more severe form in women, frovatriptan seems to retain its good efficacy and favorable sustained antimigraine effect regardless of the gender.

Efficacy of frovatriptan and other triptans in the treatment of acute migraine of normal weight and obese subjects: a review of randomized studies.

An association between obesity and migraine has been observed in recent studies and it is supported by plausible biological mechanisms. The objective of this study is to evaluate the efficacy of frovatriptan and other triptans in the acute treatment of migraine, in patients enrolled in three randomized, double-blind, crossover, Italian studies and classified according to body mass index (BMI) levels, as normal weight or non-obese (NO, BMI 18.5-24.9 kg/m(2)) and overweight or obese subjects (O, BMI ≥ 25 kg/m(2)). 414 migraineurs with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). After treating up to three episodes of migraine in 3 months with the first treatment, patients switched to the alternate treatment for the next 3 months. The present analysis assessed triptan efficacy in 220 N and in 109 O subjects of the 346 individuals of the intention-to-treat population. The proportion of pain free at 2 h did not significantly differ between frovatriptan and the comparators in either NO (30 vs. 34 %) or O (24 vs. 27 %). However, the rate of pain free at 2 h was significantly (p < 0.05) larger in NO than in O, irrespective of the type of triptan. Pain relief at 2 h was also similar between drug treatments for either subgroup. Pain relapse occurred at 48 h in significantly (p < 0.05) fewer episodes treated with frovatriptan in both NO (26 vs. 36 %) and O (27 vs. 49 %). The rate of 48-h relapse was similar in NO and O with frovatriptan, while it was significantly (p < 0.05) higher in O with the comparators. Frovatriptan, in contrast to other triptans, retains a sustained antimigraine effect in NO and even more so in O subjects.

Efficacy of early vs. late use of frovatriptan combined with dexketoprofen vs. frovatriptan alone in the acute treatment of migraine attacks with or without aura.

Early triptan use after headache onset may help improve the efficacy of acute migraine treatment. This may be particularly the case when triptan therapy is combined with a nonsteroidal anti-inflammatory drug (NSAID). The objective of this is to assess whether the combination of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex25 and FroDex37.5) is superior to frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks in patients who took the drug within 30 min from the onset of pain (early use) or after (late use). A total of 314 subjects with a history of migraine with or without aura were randomized into a double-blind, multicenter, parallel group, pilot study to Frova, FroDex25 or FroDex37.5 and were required to treat at least one migraine attack. In the present post hoc analysis, traditional migraine endpoints were compared across study drugs for subgroups of the 279 patients of the full analysis set according to early (n = 172) or late (n = 107) drug use. The proportion of patients pain free at 2 h in the early drug use subgroup was 33 % with Frova, 50 % with FroDex25 and 51 % with FroDex37.5 mg (p = NS combinations vs. monotherapy), while in the late drug use subgroup was 22, 51 and 50 % (p < 0.05 FroDex25 and FroDex37.5 vs. Frova), respectively. Pain-free episodes at 4 h were 54 % for early and 34 % for late use of Frova, 71 and 57 % with FroDex25 and 74 and 68 % with FroDex37.5 (p < 0.05 for early and p < 0.01 for late use vs. Frova). The proportion of sustained pain free at 24 h was 26 % under Frova, 43 % under FroDex25 mg and 40 % under FroDex37.5 mg (p = NS FroDex25 or 37.5 vs. Frova) in the early drug intake subgroup, while it was 19 % under Frova, 43 % under FroDex25 mg and 45 % under FroDex37.5 mg (p < 0.05 FroDex25 and FroDex37.5 vs. Frova) in the late drug intake subgroup. Risk of relapse at 48 h was similar (p = NS) among study drug groups (Frova: 25 %, FroDex25: 21 %, and FroDex37.5: 37 %) for the early as well as for the late drug use subgroup (14, 42 and 32 %). FroDex was found to be more effective than Frova taken either early or late. The intrinsic pharmacokinetic properties of the two single drug components made FroDex combination particularly effective within the 2-48-h window from the onset of the acute migraine attack. The efficacy does not seem to be influenced by the time of drug use relative to the onset of headache.

Cardiac index assessment: validation of a new non-invasive very low current thoracic bioimpedance device by thermodilution.

INTRODUCTION: The accuracy of impedance cardiography for cardiac index assessment is matter of debate, with available studies reporting inconsistent results. Our study aimed at evaluating the agreement between measurements of cardiac index provided by a new-generation thoracic electrical bioimpedance device (Hotman System) and an invasive approach based on thermodilution in humans. METHODS: Cardiac index was assessed simultaneously with thoracic electrical bioimpedance and conventional thermodilution through comparison of five consecutive measurements in 51 cardiac patients, hospitalized in an intensive care unit (mean± SD age: 60 ± 11 years; 68% males). The agreement between cardiac index values measured by both methods was assessed by the Bland-Altman approach, adjusted for repeated measures. The repeatability coefficient and the intraclass correlation coefficient were used to assess reproducibility of replicates. RESULTS: Average (± SD) cardiac index was 3.05 ± 0.91 l/min/m(2) with Hotman System and 3.14 ± 1.12 l/min/m(2) with thermodilution. The bias of precision was -0.09 ± 0.41. The coefficients of repeatability and intraclass correlation coefficients were high and similar for the two techniques (0.95 l/min/m(2) and 0.91 for Hotman System vs 0.78 l/min/m(2) and 0.90 for thermodilution). CONCLUSIONS: Cardiac index values yielded by Hotman system compares favorably with that obtained with thermodilution in cardiac patients.

Blood pressure in atrial fibrillation and in sinus rhythm during ambulatory blood pressure monitoring: data from the TEMPLAR project.

The coexistence of hypertension and atrial fibrillation (AF) is common and accounts for a worse prognosis. Uncertainties exist regarding blood pressure (BP) measurements in AF patients by automated oscillometric devices. The Microlife WatchBP 03 AFIB ambulatory BP monitoring (ABPM) device including an AF algorithm with each measurement was used in 430 subjects aged >65 years referred for ABPM and with assumed paroxysmal AF to perform intra-individual comparisons of BP during both AF-indicated and sinus rhythm. Only subjects with >30% of measurements indicating AF and episodes >30 min for assumed AF and for sinus rhythm were included. Mean age was 78 ± 7 years, 43% were male, 77% hypertensive, and 72% were treated. Compared to sinus rhythm, 24-h mean arterial pressure was similar (87.2 ± 9.5 vs 87.5 ± 10.6 mm Hg, p = 0.47), whereas 24-h systolic BP tended to be lower (123.6 ± 13.9 vs 124.7 ± 16.1 mm Hg, p = 0.05) and night-time diastolic BP higher (64.6 ± 10.9 vs 63.3 ± 10.4 mm Hg, p = 0.01) in assumed AF. Diastolic (not systolic) BP variability was higher in AF (p < 0.001). Results were similar with heart rates <90 and ≥90 bpm. In conclusion, this is the first study to use intra-individual comparisons of averaged BP during an ABPM in assumed paroxysmal AF and sinus rhythm. Our results imply that ABPM is feasible and informative also in patients with AF. We also suggest that an AF detection algorithm offers a new approach to evaluate the reliability of averaged BP values in AF compared to SR during an ABPM.