L'atenololo ev nella fase acuta dell'ima: Indicazioni, controindicazioni, interazioni con i farmaci trombolitici nello studio GISSI-2

Translated title of the contribution: Intravenous atenolol in acute myocardial infarction: Results from the GISSI-2 study

A. Mafrici, F. Mauri, A. P. Maggioni, M. G. Franzosi, L. Santoro, C. De Vita

Research output: Contribution to journalArticlepeer-review


Background. In the pre-thrombolytic era, several studies showed the effectiveness of beta-blocker administration in the treatment of patients (pts) with acute Myocardial Infarction (MI). Results from the ISIS-1 and GISSI trials suggested that the combined administration of beta-blocker and of thrombolytic drugs in the acute phase of infarction could lead to a better prognosis. The possibility of synergic effects from the associated administration of these drugs was confirmed by small clinical trials. In GISSI-2 study a large number of patients treated with thrombolytic drugs were given i.v. atenolol (10 mg) as recommended therapy, not following a randomized study design. Aim. We reviewed the data of the GISSI-2 study population in order to evaluate: 1) the number of pts treated with i.v. atenolol; 2) the anamnestic and clinical characteristics of treated and untreated pts; 3) the causes of exclusion from the beta-blocker therapy; 4) the causes of scheduled dose withdrawal and the incidence of side effects related to atenolol administration; 5) the interaction between atenolol and streptokinase (SK) and rtPA; 6) the incidence of relevant clinical events and the causes of death during the in-hospital period. Results. Among 12377 evaluated pts, 5616 (45.4%) were given atenolol i.v., 2772 received SK (49.5%) and 2844 (50.5%) rtPA. Mean age was 59.5 ± 11.3 yrs in atenolol treated pts vs 63.4 ± 10.9 yrs in untreated pts (p <0.001); 34.1% of pts aged > 70 yrs vs 48.6% of younger pts (p <0.00001) and 42.1% of females vs 46.2% of males (p <0.003) received atenolol. Pts with previous MI received less frequently atenolol than those without MI (17.5% vs 13.5%, p <0.00001). 88.5% of the treated pts was in Killip class I at entry (untreated 69.5%, p <0.00001); anterior and lateral site, non-Q type and ≤ 5 electrocardiographic leads with ST segment elevation were more frequently found in atenolol treated pts, inferior and unknown site in untreated pts. Among 6761 untreated pts, 32% did not receive atenolol for the occurrence of bradycardia, 15.2% for hypotension, 14.1% for heart failure, 7.2% for bronchospasm or hystory of asthma, 6.2% for bradycardia and hypotension, 0.3% for death; in 25% of the untreated pts, none of the above-mentioned causes was detectable. 1064 pts (18.9%) did not complete the scheduled dose of atenolol for the occurrence of bradycardia or atrioventricular block ≤ II degree (7.3%), hypotension (7%), bradycardia and hypotension (1.8%), heart failure (0.7%), death (0.03%), other causes (1.9%). Transient hypotension was found more frequently in pts treated with SK than in those receiving rtPA (9.3% vs 4.8%, p <0.0001), but the rate of persistent hypotension was not different in both groups (4.6%). During the hospital phase a higher incidence of advanced atrioventricular block (12.3% vs 4.3%), need of temporary or permanent pacing (5.6% vs 1.9%), sustained ventricular tachycardia (4.5% vs 2.8%), heart failure (12% vs 7.1%), ventricular fibrillation (8% vs 4.9%) and death (11.9% vs 5.1%) were shown in pts that were not given i.v. atenolol. Heart failure was the main cause of death in both groups (untreated 2.3% vs 2.2%); ventricular fibrillation (0.2% vs 0.48%), cardiac rupture (0.5% vs 1.4%), and electromechanical dissociation (0.9% vs 1.9%) were less frequent in treated pts. Conclusions. The absence of randomized design of atenolol administration limits the value of the differences found in the clinical outcome of the two groups of pts. In spite of that, the low incidence of death and side effects in treated pts, and the high percentage of pts who completed the scheduled dose of atenolol, confirm that the i.v. administration of beta-blockers in acute phase of the myocardial infarction is safe, well tolerated and suitable in almost half of the patients submitted to thrombolytic therapy with SK or rtPA. Since the beta-blocker therapy alone is able to reduce mortality in pts with acute myocardial infarction, and thrombolytic drugs are ineffective in 20%-40% of the cases, we suggest treating with both drugs all pts without specific contraindications, utilizing their different mechanism of action in reducing early mortality.

Translated title of the contributionIntravenous atenolol in acute myocardial infarction: Results from the GISSI-2 study
Original languageItalian
Pages (from-to)353-364
Number of pages12
JournalGiornale Italiano di Cardiologia
Issue number3
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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