Dario Zava

Comparison of frovatriptan plus dexketoprofen (25 mg or 37.5 mg) with frovatriptan alone in the treatment of migraine attacks with or without aura: A randomized study

Background Drugs for migraine attacks include triptans and NSAIDs; their combination could provide greater symptom relief. Methods A total of 314 subjects with history of migraine, with or without aura, were randomized to frovatriptan 2.5 mg alone (Frova), frovatriptan 2.5 mg + dexketoprofen 25 mg (FroDex25) or frovatriptan 2.5 mg + dexketoprofen 37.5 mg (FroDex37.5) and treated at least one migraine attack. This was a multicenter, randomized, double-blind, parallel-group study. The primary end point was the proportion of pain free (PF) at two hours. Secondary end points were PF at one and four hours, pain relief (PR) at one, two, four hours, sustained PF (SPF) at 24 and 48 hours, recurrence at 48 hours, resolution of nausea, photophobia and phonophobia at two and four hours, the use of rescue medication and the judgment of the treatment. Results The results were assessed in the full analysis set (FAS) population, which included all subjects randomized and treated for whom at least one post-dose intensity of headache was recorded. The proportions of subjects PF at two hours (primary end point) were 29% (27/93) with Frova compared with 51% (48/95 FroDex25 and 46/91 FroDex37.5) with each combination therapies (p < 0.05). Proportions of SPF at 24 hours were 24% (22/93) for Frova, 43% (41/95) for FroDex25 (p < 0.001) and 42% (38/91) for FroDex37.5 (p < 0.05). SPF at 48 hours was 23% (21/93) with Frova, 36% (34/95) with FroDex25 and 33% (30/91) with FroDex37.5 (p = NS). Recurrence was similar for Frova (22%, 6/27), FroDex25 (29%, 14/48) and FroDex37.5 (28%, 13/46) (p = NS), meaning a lack of improvement with the combination therapy. Statistical adjustment for multiple comparisons was not performed. No statistically significant differences were reported in the occurrence of total and drug-related adverse events. FroDex25 and FroDex37.5 showed a similar efficacy both for primary and secondary end points. There did not seem to be a dose response curve for the addition of dexketoprofen. Conclusion FroDex improved initial efficacy at two hours compared to Frova whilst maintaining efficacy at 48 hours in this study. Tolerability profiles were comparable. Intrinsic pharmacokinetic properties of the two single drugs contribute to this improved efficacy profile.

Zofenopril and ramipril and acetylsalicylic acid in postmyocardial infarction patients with left ventricular systolic dysfunction: a retrospective analysis in hypertensive patients of the SMILE-4 study.

Background: Antecedent hypertension represents a risk factor for adverse outcomes in survivors of acute myocardial infarction (AMI). Prognosis of such patients might be greatly improved by drugs enhancing blood pressure control. In the present retrospective analysis of the randomized, double-blind, parallel-group, SMILE-4 study we compared the efficacy of zofenopril 60 mg and acetylsalicylic acid (ASA) 100 mg versus ramipril 10 mg and ASA in patients with AMI complicated by left ventricular dysfunction, classified according to a history of hypertension. Methods: The primary study end-point was 1-year combined occurrence of death or hospitalization for cardiovascular causes. Hypertension was defined according to medical history and current blood pressure values at entry and could be determined in 682 of 716 patients of the intention-to-treat analysis. Results: One hundred and fifty-seven patients (23%) were normotensives and 525 (77%) hypertensives. In the normotensive population the primary end-point occurred in 19 of 76 zofenopril-treated patients (25%) and in 23 of 81 ramipril-treated patients (28%) [odds ratio (95% confidence interval): 0.84 (0.41–1.71), P = 0.631]. In the hypertensive population, major cardiovascular outcomes were reported in 84 of 273 zofenopril-treated patients (31%) and in 99 of 252 ramipril-treated patients (39%), with a 31% significantly (P = 0.041) lower risk with zofenopril [0.69 (0.48–0.99)]. The superiority of zofenopril versus ramipril was particularly evident in patients with isolated systolic hypertension [n = 131, 0.48 (0.23–0.99), P = 0.045]. Conclusion: This retrospective analysis of the SMILE-4 study confirmed the good efficacy of zofenopril and ASA in the prevention of long-term cardiovascular outcomes also in the subgroup of patients with hypertension.

Frovatriptan vs other triptans in the treatment of menstrual migraine: pooled analysis of three double-blind, randomized, cross-over studies

Methods Subjects with a history of migraine with or without aura were randomized to F 2.5 mg or R 10 mg (study 1), F or Z 2.5 mg (study 2), and F or A 12.5 mg (study 3). The studies had an identical multicenter, randomized, double blind, cross-over design. After treating 3 episodes of migraine in no more than 3 months with the first treatment, patients had to switch to the next treatment for other 3 months.

Erratum: Comparison of frovatriptan plus dexketoprofen (25 mg or 37.5 mg) with frovatriptan alone in the treatment of migraine attacks with or without aura: A randomized study (Cephalalgia (2014) 34 (434-445) DOI:10.1177/0333102413515342)

Vincenzo Tullo, Fabio Valguarnera, Piero Barbanti, Pietro Cortelli, Giuliano Sette, Gianni Allais, Florindo d’Onofrio, Marcella Curone, Dario Zava, Deborha Pezzola, Chiara Benedetto, Fabio Frediani and Gennaro Bussone. Comparison of frovatriptan plus dexketoprofen (25 mg or 37.5 mg) with frovatriptan alone in the treatment of migraine attacks with or without aura: A randomized study. Cephalalgia 2014; 34: 434–445. DOI: 10.1177/0333102413515342. In the published version of this article, the author names and affiliations were represented as below: Vincenzo Tullo1, Fabio Valguarnera2, Piero Barbanti3, Pietro Cortelli4, Giuliano Sette5, Gianni Allais6, Florindo d’Onofrio7, Marcella Curone1, Dario Zava8, Deborha Pezzola8, Chiara Benedetto6, Fabio Frediani9 and Gennaro Bussone1 1Department of Clinical Neuroscience, National Neurological Institute Carlo Besta, Italy 2Sestri Ponente Hospital “Padre Antero Micone”, Italy 3Unit for treatment and research of headaches and pain, IRCCS San Raffaele Pisana, Italy 4Neurological Clinic, Department of Neurological Science, University of Bologna, Italy 5Sant’Andrea Hospital, Italy 6Department of Gynecology and Obstetrics, Women’s Headache Center, University of Turin, Italy 7San Giuseppe Moscati Hospital, Italy 8Istituto Luso Farmaco d’Italia, Peschiera Borromeo, Italy 9Ospedale S. Carlo Borromeo, Italy However, the affiliation for Pietro Cortelli4 should have been written correctly as follows: 4Neurological Clinic, Department of Biomedical and Neuromotor Science, University of Bologna, Italy and IRCCS Institute of Neurological Sciences of Bologna, Bologna, Italy The authors apologize for this mistake.

Cost-effectiveness of zofenopril in patients with left ventricular systolic dysfunction after acute myocardial infarction: a post hoc analysis of SMILE-4.

Background In SMILE-4 (the Survival of Myocardial Infarction Long-term Evaluation 4 study), zofenopril + acetylsalicylic acid (ASA) was superior to ramipril + ASA in reducing the occurrence of major cardiovascular events in patients with left ventricular dysfunction following acute myocardial infarction. The present post hoc analysis was performed to compare the cost-effectiveness of zofenopril and ramipril. Methods In total, 771 patients with left ventricular dysfunction and acute myocardial infarction were randomized in a double-blind manner to receive zofenopril 60 mg/day (n = 389) or ramipril 10 mg/day (n = 382) + ASA 100 mg/day and were followed up for one year. The primary study endpoint was the one-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n = 716). Cost data were drawn from the National Health Service databases of the European countries participating in the study. The incremental cost-effectiveness ratio was used to quantify the cost per event prevented with zofenopril versus ramipril. Results Zofenopril significantly (P = 0.028) reduced the risk of the primary study endpoint by 30% as compared with ramipril (95% confidence interval, 4%–49%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril. The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n = 365) than with ramipril (165.12 Euros per patient per year, n = 351). The cost related to the occurrence of major cardiovascular events requiring hospitalization averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The incremental cost-effectiveness ratio for zofenopril versus ramipril was 2125.45 Euros per event prevented (worst and best case scenario in the sensitivity analysis was 3590.09 and 3243.96 Euros, respectively). Conclusion Zofenopril is a viable and cost-effective treatment for managing patients with left ventricular dysfunction after acute myocardial infarction.

564 ZOFENOPRIL AND RAMIPRIL PLUS ASA IN POST- MYOCARDIAL INFARCTION PATIENTS WITH LEFT VENTRICULAR SYSTOLIC DYSFUNCTION: A POST-HOC ANALYSIS IN PATIENTS WITH ARTERIAL HYPERTENSION

Background: In the randomized, double-blind, parallel-group, multicenter, international SMILE-4 Study zofenopril (Z) 60 mg plus ASA was more effective than ramipril (R) 10 mg plus acetyl salicylic acid (ASA) 100 mg in reducing 1-year occurrence of major cardiovascular events in patients with acute myocardial infarction complicated by left ventricular dysfunction. Objective: To compare efficacy of Z and R plus ASA in patients with arterial hypertension from the SMILE-4 Study. Methods: The primary study end-point was 1-year combined occurrence of death or hospitalization for cardiovascular causes. Results: In the main study population (n = 716) the primary outcome was significantly reduced by Z vs. R (odds ratio, OR and 95% confidence interval, CI: 0.70, 0.51–0.96; p = 0.028). The majority of patients (437, 64.1%) had arterial hypertension and showed a rate of major cardiovascular events slightly, but not significantly, lower under Z than under R (32.1% vs. 39.5%; OR: 0.72, 0.49–1.07; p = 0.106). This was the case also for the group of patients without hypertension (24.1% Z vs. 32.3% R; OR: 0.67, 0.38–1.17; p = 0.156). However, in the group with an entry systolic blood pressure ≥140 mmHg the 1-year hazard of cardiovascular events was significantly (p = 0.003) lower under Z (28.9% vs. 43.9% R; OR: 0.52, 0.34–0.80). The reduction in the risk of cardiovascular events was similar in patients with and without hypertension. Conclusions: This retrospective analysis of the SMILE-4 Study confirmed the good efficacy of Z plus ASA in the prevention of long-term cardiovascular outcomes also in the subgroup of patients with arterial hypertension.