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Adverse events and tolerability of treatment with statins
338
XVII S.I.S.A. National Congress
ADVERSE EVENTS WITH STATINS
AND
TOLERABILITY
OF
TREATMENT
V Spagnuolo 1, C Cerallo 2, MP Citriniti 2, M Spagnuolo 3, E Garnier 4, A Moser 4, M Sprovieri 3 & L Vigna 1 1Internal Medicine, 3Emergency 4Universit~ de Paris 5 Pharmacie
Unit, Cosenza Hospital;
MEDIUM REDUCTION OF CHOLESTEROL W I T H USE OF A STANDARD DOSE OF HMG-COA I N H I B I T O R S I N AN OUTPATIENT SETFING V Spagnueloz MP Citriniti 1, M Spagnuolo, G Barene, M Nicoletti, M Sprovieri 2 & L Vigna
2Crotone;
Statins improve cardiovascular prognosis if assumed regularly. Statins are considered safe drugs but, in the common clinical practice, the adverse events could be remarkably more frequent than those reported in clinical trials. We have es~mated incidence of adverse events from statins and their tolerability in our outpatient clinic. In the table'the percentage of the adverse events of 300 consecutively patients is indicated. The number of the total visits for such patients has been of 2606 with average of 8.06 visit/patient (follow-up of 24.3 months approximately). CPK CPK Rhabdo- AST/ALT AST/ALT Other adverse I <3 >3 myolisis <3 1>3 [events 1.26 0.036 0 1.12 0.036 1.12 There were no cases of rhabdomyolis. The increase of the CPK more than three times has been episodic and only one case of major transaminase increase occurred. Also the tolerability was good. Only a small percentage complained of subjective symptoms. Between these: dyspepsia, dysgeusia, erectile dysfunction, asthenia, vertigos, tachycardia, pains, paraesthesias.
ROLE OF THE P60-KDA-C-TERMINAL FRAGMENT OF E-NOS I N THE REGULATION OF ENDOTHELIAL FUNCTION DURING APOPTOSIS. M Teseuro, D Lauro, M Federici, P Sbreccia, R Leer S Rizza, R Lauro.
Internal Medicine, ZEmergency Unit, Cosenza Hospital; 1Crotone. Recently it was pointed out that, in clinical practice, HMG-CoA inhibitors (statins) reduce cholesterolemia less than reported (26% against 34%) in clinical trials. We have estimated the average reduction of LDL cholesterol of 200 hypercholesterolemic outpatients (38 males and 162 females). These patients did not assume any statin before the first visit and they received a standard dose of statin. All these patients performed one successive control visit with that drug at least. In the table the average reductions of LDL cholesterol in all patients and according to different statins are indicated. Total
Atorva 10 mg 29.02 34.03 =Ell.32 =E9.28
Simva iPrava 20 mg 40 mg 20.12 29.02 ±9.40 +8.83
Ceriva 0.2 mg 33.72 =El1.37
Fluva 80 mg 25.57 ±12.57
Although in our outpatient clinic the medium reduction of LDL cholesterol has been lower than what was observed in trials, 85.5% of the subjects, with the standard dose, have achieved therapeutic goal (in agreement to NCEP guidelines). In average the goal, when obtained, was achieved after 2.45 months.
P L A S M A D - D I M E R LEVELS I N P A T I E N T S W I T H T R A N S I E N T ISCHAEMIC ATTACK Urselle S, Mazzone M, La Sale M, Portale G, Testa A, Pignataro G, Covino M t Forte P, Mirabella C, Gentiloni Silveri N Dip. Emergenza e AcceCtazione Policlinico Universitario A. Gemelli, Roma
[~ipartimento di Medicina Interna, Centro per L'Aterosclerosi, Universit,~ di Roma Tot Vergata. Nitric Oxide (NO) an important signaling molecule, is synthesized by a family of enzymes called nitric oxide synthase (NOS). Three NOS isoforms have been identified: one neuronal (nNOS), the inducible (iNOS) and endothelial (eNOS). NO has been shown to have an important role in apoptosis. NO can have both pro-and anti-apoptotic affects dependent on its concentration and the oxidative status of the cell. The endothelial nitric oxide synthase (eNOS) is believed to regulate the apoptotic process t~ough effects on caspases, a family of isoenzymes that mediate the two main apoptotic pathways. Considered this important role of eNOS in endothelial cell apoptosis, the effect of= staurosporine-induced apoptosis on eNOS activity was studied in COS7 transfected cells. Our results show an important reduction of eNOS activity during apoptosis, this effect coincided with the appearance of 60-kDa-c-terminal fragment of eNOS. This fragment demonstrate an inhibitory effect on eNOS activity. Dimerization of eNOS is required for activity. Lee et al (3BS 1995) demonstrated Chat eNOS c-and nterminal fragment co-expressed after transfection with full-length eNOS exerted a negative effect on eNOS activity. The diminished NO production during apoptosis leads to endothelial dysfunction with increased susceptibility to atherosclerosis. In this work we demonstrate that the p60 fragment generated during apoptosis may be the in vivo effector of caspases and regulate the endothelial function during apoptosis.
BACKGROUND: The measurement of markers of thrombosis has been proposed as a method to improve the prediction of risk in patients with vascular disease. The purpose of this study was to examine the hemostatic activation in patients with transient is haemic attack (TIA) and provide data on haemostatic variables in those patients. Literature data showed that D-dimer is important for determining not only the activation of fibrinolysis but also the severity of a hypercoagulabte state. We have studied the clinical utility of D-dimer in the early assessment of TIA in the Emergency Department lED). METHODS: We included 8 consecutive patients, 4 male and 4 female, with hypertension, (mean age =1=SD, 76 =E 9.5 years) presented in the ED with TIA. Every patient underwent neurological clinical examination, cerebral computerized tomography (CT), Doppler ultrasonography of precerebral arteries and measurement of plasmatic D-dimer levels. RESULTS: Patients presented: disartria (1), visual defects (1), amnesia (1), facial paralysis (2), 1 patient arrived in status of coma and 2 presented no neurological alterations in ED; CT scan showed in 3 patients chronic cerebrovascular disease, acute signs of ischaemia in 3 and no alterations in the last 2 patients; Doppler ultrasonography showed significant stenosis in 2 patients. Only in 1 patient D-dimer levels resulted higher than normal. CONCLUSIONS: In contrast with data concerning ischaemic stroke, this study showed no significant association between plasma levels of Ddimer and acute transient symptoms of cerebrovascular disease in the emergency setting.
XVII S.I.S.A. National Congress
ADVERSE EVENTS WITH STATINS
AND
TOLERABILITY
OF
TREATMENT
V Spagnuolo 1, C Cerallo 2, MP Citriniti 2, M Spagnuolo 3, E Garnier 4, A Moser 4, M Sprovieri 3 & L Vigna 1 1Internal Medicine, 3Emergency 4Universit~ de Paris 5 Pharmacie
Unit, Cosenza Hospital;
MEDIUM REDUCTION OF CHOLESTEROL W I T H USE OF A STANDARD DOSE OF HMG-COA I N H I B I T O R S I N AN OUTPATIENT SETFING V Spagnueloz MP Citriniti 1, M Spagnuolo, G Barene, M Nicoletti, M Sprovieri 2 & L Vigna
2Crotone;
Statins improve cardiovascular prognosis if assumed regularly. Statins are considered safe drugs but, in the common clinical practice, the adverse events could be remarkably more frequent than those reported in clinical trials. We have es~mated incidence of adverse events from statins and their tolerability in our outpatient clinic. In the table'the percentage of the adverse events of 300 consecutively patients is indicated. The number of the total visits for such patients has been of 2606 with average of 8.06 visit/patient (follow-up of 24.3 months approximately). CPK CPK Rhabdo- AST/ALT AST/ALT Other adverse I <3 >3 myolisis <3 1>3 [events 1.26 0.036 0 1.12 0.036 1.12 There were no cases of rhabdomyolis. The increase of the CPK more than three times has been episodic and only one case of major transaminase increase occurred. Also the tolerability was good. Only a small percentage complained of subjective symptoms. Between these: dyspepsia, dysgeusia, erectile dysfunction, asthenia, vertigos, tachycardia, pains, paraesthesias.
ROLE OF THE P60-KDA-C-TERMINAL FRAGMENT OF E-NOS I N THE REGULATION OF ENDOTHELIAL FUNCTION DURING APOPTOSIS. M Teseuro, D Lauro, M Federici, P Sbreccia, R Leer S Rizza, R Lauro.
Internal Medicine, ZEmergency Unit, Cosenza Hospital; 1Crotone. Recently it was pointed out that, in clinical practice, HMG-CoA inhibitors (statins) reduce cholesterolemia less than reported (26% against 34%) in clinical trials. We have estimated the average reduction of LDL cholesterol of 200 hypercholesterolemic outpatients (38 males and 162 females). These patients did not assume any statin before the first visit and they received a standard dose of statin. All these patients performed one successive control visit with that drug at least. In the table the average reductions of LDL cholesterol in all patients and according to different statins are indicated. Total
Atorva 10 mg 29.02 34.03 =Ell.32 =E9.28
Simva iPrava 20 mg 40 mg 20.12 29.02 ±9.40 +8.83
Ceriva 0.2 mg 33.72 =El1.37
Fluva 80 mg 25.57 ±12.57
Although in our outpatient clinic the medium reduction of LDL cholesterol has been lower than what was observed in trials, 85.5% of the subjects, with the standard dose, have achieved therapeutic goal (in agreement to NCEP guidelines). In average the goal, when obtained, was achieved after 2.45 months.
P L A S M A D - D I M E R LEVELS I N P A T I E N T S W I T H T R A N S I E N T ISCHAEMIC ATTACK Urselle S, Mazzone M, La Sale M, Portale G, Testa A, Pignataro G, Covino M t Forte P, Mirabella C, Gentiloni Silveri N Dip. Emergenza e AcceCtazione Policlinico Universitario A. Gemelli, Roma
[~ipartimento di Medicina Interna, Centro per L'Aterosclerosi, Universit,~ di Roma Tot Vergata. Nitric Oxide (NO) an important signaling molecule, is synthesized by a family of enzymes called nitric oxide synthase (NOS). Three NOS isoforms have been identified: one neuronal (nNOS), the inducible (iNOS) and endothelial (eNOS). NO has been shown to have an important role in apoptosis. NO can have both pro-and anti-apoptotic affects dependent on its concentration and the oxidative status of the cell. The endothelial nitric oxide synthase (eNOS) is believed to regulate the apoptotic process t~ough effects on caspases, a family of isoenzymes that mediate the two main apoptotic pathways. Considered this important role of eNOS in endothelial cell apoptosis, the effect of= staurosporine-induced apoptosis on eNOS activity was studied in COS7 transfected cells. Our results show an important reduction of eNOS activity during apoptosis, this effect coincided with the appearance of 60-kDa-c-terminal fragment of eNOS. This fragment demonstrate an inhibitory effect on eNOS activity. Dimerization of eNOS is required for activity. Lee et al (3BS 1995) demonstrated Chat eNOS c-and nterminal fragment co-expressed after transfection with full-length eNOS exerted a negative effect on eNOS activity. The diminished NO production during apoptosis leads to endothelial dysfunction with increased susceptibility to atherosclerosis. In this work we demonstrate that the p60 fragment generated during apoptosis may be the in vivo effector of caspases and regulate the endothelial function during apoptosis.
BACKGROUND: The measurement of markers of thrombosis has been proposed as a method to improve the prediction of risk in patients with vascular disease. The purpose of this study was to examine the hemostatic activation in patients with transient is haemic attack (TIA) and provide data on haemostatic variables in those patients. Literature data showed that D-dimer is important for determining not only the activation of fibrinolysis but also the severity of a hypercoagulabte state. We have studied the clinical utility of D-dimer in the early assessment of TIA in the Emergency Department lED). METHODS: We included 8 consecutive patients, 4 male and 4 female, with hypertension, (mean age =1=SD, 76 =E 9.5 years) presented in the ED with TIA. Every patient underwent neurological clinical examination, cerebral computerized tomography (CT), Doppler ultrasonography of precerebral arteries and measurement of plasmatic D-dimer levels. RESULTS: Patients presented: disartria (1), visual defects (1), amnesia (1), facial paralysis (2), 1 patient arrived in status of coma and 2 presented no neurological alterations in ED; CT scan showed in 3 patients chronic cerebrovascular disease, acute signs of ischaemia in 3 and no alterations in the last 2 patients; Doppler ultrasonography showed significant stenosis in 2 patients. Only in 1 patient D-dimer levels resulted higher than normal. CONCLUSIONS: In contrast with data concerning ischaemic stroke, this study showed no significant association between plasma levels of Ddimer and acute transient symptoms of cerebrovascular disease in the emergency setting.