Branco Mautner

Randomised trial of roxithromycin in non-Q-wave coronary syndromes: ROXIS pilot study

BACKGROUND There is serological evidence for an association between Chlamydia pneumoniae and coronary heart disease. We investigated the hypothesis that an antichlamydial macrolide antibiotic, roxithromycin, can prevent or reduce recurrent major ischaemic events in patients with unstable angina. METHODS The effect of roxithromycin was assessed in a double-blind, randomised, prospective, multicentre, parallel-group, placebo-controlled pilot study of 202 patients with unstable angina or non-Q-wave myocardial infarction. Patients were randomly assigned either roxithromycin 150 mg orally twice a day (n = 102) or placebo orally twice a day (n = 100). The treatment was for 30 days. Patients were followed up for 6 months. We report the primary clinical endpoints (cardiac ischaemic death, myocardial infarction, and severe recurrent ischaemia), assessed at day 31, in 202 patients on an intention-to-treat basis. FINDINGS A statistically significant reduction in the primary composite triple endpoint rates was observed in the roxithromycin group: p = 0.032. The rate of severe recurrent ischaemia, myocardial infarction, and ischaemic death was 5.4%, 2.2%, and 2.2% in the placebo group and 1.1%, 0%, and 0%, in the roxithromycin group, respectively. No major drug-related adverse effects were observed. INTERPRETATION Antichlamydial antibiotics may be useful in therapeutic intervention in addition to standard medication in patients with coronary-artery disease. Large-scale trials are needed to confirm these preliminary observations.

Low molecular weight heparin versus regular heparin or aspirin in the treatment of unstable angina and silent ischemia

OBJECTIVES This study was designed to test the hypothesis that low molecular weight heparin may lessen the severity of ischemic events in patients with unstable angina. BACKGROUND Unstable angina is a thrombotic process that requires intensive medical treatment. Although current treatments can reduce the number of complications, serious bleeding continues to occur. Nadroparin calcium, a low molecular weight heparin, seems to be a safe therapeutic agent that does not require laboratory monitoring. METHODS A total of 219 patients with unstable angina entered the study at a mean time of 6.17 h after the last episode of rest pain. Patients were randomized to receive aspirin (200 mg/day [group A]), aspirin plus regular heparin (400 IU/kg body weight per day intravenously and titered by activated partial thromboplastin time [group B]) and aspirin plus low molecular weight heparin (214 UIC/kg anti-Xa twice daily subcutaneously [group C]). The major end points determined for the in-hospital period were 1) recurrent angina, 2) myocardial infarction, 3) urgent revascularization, 4) major bleeding, and 5) death. Minor end points were 1) silent myocardial ischemia, and 2) minor bleeding. Event rates were tested by chi-square analysis. RESULTS Recurrent angina occurred in 37%, 44% and 21% of patients in groups A, B and C, respectively, and was significantly less frequent in group C than in either group A (odds ratio 2.26, 95% confidence interval [CI] 1 to 5.18, p = 0.03) or group B (odds ratio, 3.07, 95% CI 1.36 to 7.00, p = 0.002). Nonfatal myocardial infarction was present in seven patients in group A, four in group B and none in group C (group B vs. A, p = 0.5; group C vs. A, p = 0.01). Urgent revascularization was performed in nine patients in group A, seven in group B and one in group C (C vs. A, p = 0.01). Two episodes of major bleeding occurred in group B. Silent myocardial ischemia was present in 38%, 41% and 25% of patients in groups A, B and C, respectively, and was significantly less frequent in group C than group B (odds ratio 2.12, 95% CI 0.97 to 4.69, p = 0.04). Minor bleeding was detected in 10 patients in group B, 1 patient in group C (B vs. C, p = 0.01) and no patient in group A (A vs. B, p = 0.003). CONCLUSIONS In this study, treatment with aspirin plus a high dose of low molecular weight heparin during the acute phase of unstable angina was significantly better than treatment with aspirin alone or aspirin plus regular heparin.

Influenza Vaccine Pilot Study in Acute Coronary Syndromes and Planned Percutaneous Coronary Interventions

Background— Recent reports have detected an increase in the number of patients with acute coronary syndromes during the flu season. In addition, the World Health Organization recommended vaccination against influenza infection for the Southern hemisphere in the winter of 2001.We evaluated the preventive impact of vaccination on subsequent ischemic events in myocardial infarction patients and in subjects undergoing planned percutaneous coronary angioplasty. Methods and Results— We included 200 myocardial infarction patients admitted in the first 72 hours and 101 planned angioplasty/stent (PCI) patients without unstable coronary artery disease, prior bypass surgery, angioplasty, or tissue necrosis, in a prospective, multicenter log during the winter season. Infarct patients received a standard therapy and were then randomly allocated in a single-blind manner to either a unique intramuscular influenza vaccination or a control group. Similarly, PCI patients were allocated to either vaccination or control grou...

Serum neopterin levels and the angiographic extent of coronary arterial narrowing in unstable angina pectoris and in non–Q-wave acute myocardial infarction

Systemic serum markers of inflammation are elevated in diseases due to atherosclerosis, but have not been associated with the extent of atherosclerotic disease. We examined the role of neopterin, a byproduct of activated macrophage metabolism, in patients with unstable angina. Baseline neopterin samples and clinical histories were obtained in 52 patients admitted with unstable angina pectoris. Coronary angiograms of 27 patients were reviewed using Sullivans method to assess the total atherosclerotic burden in the coronary arteries. Twenty-six of the 52 patients were eventually diagnosed with a non-Q-wave acute myocardial infarction (AMI) and had higher neopterin levels (10.1 +/- 6.7 vs 7.2 +/- 4.0 nmol/L, p = 0.06) than patients with a final diagnosis of unstable angina. Patients with neopterin >8.7 were more likely to be diagnosed with a non-Q-wave AMI (75% vs 39%, p = 0.035) and were more likely to have significantly more severe and extensive angiographically determined atherosclerosis than patients with low neopterin levels. Neopterin levels correlated with the score of atherosclerotic extension (Spearmans rank correlation coefficient 0.4807, p = 0.034). This study demonstrates a correlation between immune cell activation and the extent of angiographically determined atherosclerosis and the degree of myocardial ischemia.

Time significance of acute thrombotic reactant markers in patients with and without silent myocardial ischemia and overt unstable angina pectoris

Ischemic electrocardiographic changes were recorded within 2 hours of admission using a 12-lead electrocardiographic continuous monitor with a 20-second scanning interval and an alarm mode for asymptomatic events. Blood samples were obtained at admission and at the moment of asymptomatic events (group A). In the other patients who did not develop ischemia, a second blood sample was taken 12 hours later (group B). We determined prothrombin time, activated partial thromboplastin time, clotting factor VIII activity, tissue plasminogen activator activity, tissue plasminogen activator inhibitor-1, cross-linked fibrin degradation product, and thrombin-antithrombin III complexes. There was a statistically significant difference between group A and B patients when the basal samples were analyzed for thrombin-antithrombin III (p = 0.046) and d-Dimer (p = 0.005). Prothrombin fragment 1 + 2 were significantly reduced, and d-Dimer was elevated when basal blood samples were compared with the second sample in patients who developed silent events (p = 0.008 and 0.055, respectively). A plasma concentration of thrombin-antithrombin III complex was also significantly decreased when sample 2 was compared with the basal blood sample (p = 0.039). Five recurrent episodes of angina and 2 nonfatal infarctions occurred, and 4 urgent revascularization procedures were performed in group A. In group B, there was only 1 nonfatal infarction (p = 0.01). The results of the present study suggest that a time-dependent thrombotic process is detectable in the blood stream as a cyclic movement. Further studies are needed to determine if some other factors, such as intensive shear stress in the vessel wall, may activate plaque instability during asymptomatic episodes.

Socio economic crisis and mortality. Epidemiological testimony of the financial collapse of Argentina.

BackgroundNatural disasters, war, and terrorist attacks, have been linked to cardiac mortality. We sought to investigate whether a major financial crisis may impact on the medical management and outcomes of acute coronary syndromes.MethodsWe analyzed the Argentine cohort of the international multicenter Global Registry of Acute Coronary Events (GRACE). The primary objective was to estimate if there was an association between the financial crisis period (April 1999 to December 2002) and in- hospital cardiovascular mortality, with the post-crisis period (January 2003 to September 2004) as the referent. Each period was defined according to the evolution of the Gross Domestic Product. We investigated the demographic characteristics, diagnostic and therapeutic procedures, morbidity and mortality.ResultsWe analyzed data from 3220 patients, 2246 (69.8%) patients in the crisis period and 974 (30.2%) in the post-crisis frame. The distribution of demographic and clinical baseline characteristics were not significantly different between both periods. During the crisis period the incidence of in-hospital myocardial infarction was higher (6.9% Vs 2.9%; p value < 0.0001), as well as congestive heart failure (16% Vs 11%; p value < 0.0001). Time to intervention with angioplasty was longer during the crisis, especially among public sites (median 190 min Vs 27 min). The incidence proportion of mortality during hospitalization was 6.2% Vs 5.1% after crisis. The crude OR for mortality was 1.2 (95% C.I. 0.87, 1.7). The odds for mortality were higher among private institutions {1.9 (95% C.I. 0.9, 3.8)} than for public centers {1.2 (95% C.I. 0.83, 1.79)}. We did not observe a significant interaction between type of hospital and crisis.ConclusionOur findings suggest that the financial crisis may have had a negative impact on cardiovascular mortality during hospitalization, and higher incidence of medical complications.

Premature ventricular beats: Experimental study

Abstract This study was undertaken as an attempt to establish the reliability of the ECG diagnosis of the site of origin of premature ventricular beats in the light of a new understanding of heart activation given by the description of hemiblocks. Following anesthesia with intravenous pentobarbital, 60 dogs were submitted to left thoracotomy and copper electrodes were placed subepicardially in the anterior and posterior walls of both ventricles. The electrodes were stimulated by a Grass S4 device. Standard and several precordial leads were simultaneously registered. Morphology and electrical axis of the ventricular complexes registered before and during stimulation are analyzed. Principal findings are: 1. 1. Stimulation of the anterior wall of the left ventricle showed a QRS pattern of right bundle branch block with left posterior hemiblock. 2. 2. Stimulation of the left ventricular posterior wall gave rise to a right bundle branch block with left anterior hemiblock pattern. 3. 3. By stimulating anterior and posterior right ventricular walls, left bundle branch block was achieved. 4. 4. Neither morphologic nor axis difference between base and apex stimulation of the same ventricular wall were registered, except for the left anterior ventricular wall, whose apex had a left posterior ventricular wall-like response.

Vacunación antigripal en pacientes con síndromes coronarios agudos: beneficio del tratamiento en diferentes subgrupos

Background. The first prospective clinical Flu Vaccination in Acute Coronary Syndromes (FLUVACS) Trial has provided some evidence that flu vaccination together with standard therapy may be useful during the winter season to reduce the risk of death and major cardiac events in patients with acute myocardial infarction. Patients and method. Information available in the FLUVACS database was analyzed to evaluate the efficacy of flu vaccination in different subgroups. Logistic regression was used to identify features related with better therapeutic results. Results. Flu vaccination was effective in reducing the incidence of the composite endpoint (death, nonfatal myocardial reinfarction or recurrent angina prompting urgent revascularization) in most subgroups at 6 months after inclusion. The regression model showed a greater benefit of flu vaccination in patients with no ST-segment elevation or older than 65 years, nonsmokers and patients with a TIMI risk score higher than 6. Conclusions. Our data suggest that vaccination for secondary prevention of flu during the acute phase of myocardial infarction may be effective in a broad range of patients with acute coronary artery disease, regardless of their initial clinical risk.

Rationale for the Management of Coronary Syndromes With Low-Molecular-Weight Heparins

The well-documented disadvantages of unfractionated heparin in the management of coronary syndromes, such as unpredictable bioavailability and maintenance of therapeutic range, has prompted several studies into the benefits of low-molecular-weight heparins (LMWHs). The favorable pharmacologic properties of LMWHs include a binding affinity for antithrombin III, anti-factor IIa activity, excellent bioavailability, minimal protein binding, predictable anticoagulant response, and clinical tolerance by patients. LMWHs are also characterized by having a specific anti-factor Xa effect and inducing only a small prolongation in general clotting tests-i.e., activated partial thromboplastin time, prothrombin time, and antithrombin activity-when used in high doses. Several studies have recently demonstrated that LMWHs are superior to placebo and are at least equal or superior to standard heparin when added to aspirin for the treatment of unstable angina and following non-Q-wave myocardial infarction. These studies, which include Thrombolysis in Myocardial Infarction (TIMI) 11A and Efficacy and Safety of Subcutaneous Enoxaparin versus intravenous unfractionated heparin in Non-Q-wave Coronary Events (ESSENCE), will be reviewed and discussed.

Prevención secundaria de la cardiopatía isquémica con la vacuna antigripal. Nueva evidencia sobre el papel de la infección y los síndromes coronarios agudos

Recent reports have detected an increase in the number of patients with acute coronary syndromes during the flu season. More recently, case-control studies of patients with prior infarction have shown that flu vaccination significantly reduces the risk of myocardial necrosis and strokes. The World Health Organization recommended flu vaccination for the Southern Hemisphere in the winter of 2001. We evaluated the preventive impact of flu vaccination on subsequent ischemic events in myocardial infarction patients and in subjects undergoing scheduled percutaneous coronary angioplasty. In the first study we included 200 myocardial infarction patients admitted in the first 72 hours and 100 patients scheduled for angioplasty/stent (PCI) without unstable coronary artery disease, prior bypass surgery, angioplasty or tissue necrosis, were included in a prospective, multicenter registry, during the winter season. Infarction patients received standard therapy, and then were randomly allocated in a single-blind manner as a unique intramuscular Influenza vaccination or as controls. Similarly, PCI patients were allocated to either vaccination or control. The first primary outcome ‐cardiovascular death‐ occurred within 6 months in 2% of the patients in the vaccinnated group vs 8% of controls (RR: 0.25; 95% CI, 0.07-0.86; p = 0.01). The triple composite end point occurred in 11% of the patients in the vaccinnated group vs 23% of controls (p = 0.009) at 6 months. Although our study is the first to demonstrate lower rates of cardiovascular ischemic events in patients vaccinated against Influenza during the flu season, the modification of flu vaccination recommendations in patients admitted for cardiovascular events merits further study before being considered. Key word: Influenza. Atherosclerosis. Immune system. Prevencion secundaria de la cardiopatia isquemica con la vacuna antigripal. Nueva evidencia sobre el papel de la infeccion y los sindromes coronarios agudos