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To assess the impact of secondary prevention medical therapies (statins, ACE-inhibitors/Angiotensin Receptor Blockers (ARB), beta-blockers (BB) and Dual Antiplatelet Therapy (DAPT)) on outcomes of patients with myocardial infarction with nonobstructive coronary artery disease (MINOCA). Five adjusted observational studies encompassing 10,546 were included in this meta-analysis. All-cause death was the primary endpoint, while Major Adverse Cardiovascular Events (MACE) and acute myocardial infarction (AMI) were the secondary endpoints. After 24 months of follow up, statins (tested in 8093 patients) were associated with a reduced risk of all-cause death (HR 0.60:0.45–0.81, p 〈0,001), while ACE-inhibitors/ARB (on 9666 patients) were not. Aggregate data from two studies (n = 9720, 7719 on beta-blockers, 6423 on DAPT) indicated that beta-blockers and DAPT (median follow-up 34.1 and 15.7 months, respectively) were both associated with a significant reduction of all-cause death (HR0.81:0.66–0.99, p = 0.04, and HR0.73:0.55–0.98, p = 0.03, for beta-blockers and DAPT, respectively). Among the investigated therapies, only ACE-inhibitors/ARBs entailed a reduced risk of MACE (HR0.65:0.44–0.94, p = 0.02, all CI 95%) over 36.5 months (four studies, n = 10,150). None of the investigated therapies was associated with a reduced risk of AMI. Data from adjusted observational studies suggest that beta-blockers, statins and DAPT are associated with a survival benefit among MINOCA patients. ACE-inhibitors/ARB entail a reduced risk of MACE while none of the investigated secondary prevention therapies is associated with a reduced risk of AMI. Randomized controlled trials are warranted to confirm these findings. • MINOCA are associated with a not negligible incidence of impaired prognosis and recurrent ischemic events. • There is a paucity of data investigating the impact of cardioprotective therapies on outcomes in this subset. • This meta-analysis suggests that beta-blockers, statins and DAPT are associated with a survival benefit for MINOCA patients • ACE-inhibitors/ARB provide a beneficial effect on reducing composite endpoints such as major adverse cardiovascular events. • None of the investigated therapies has a significant impact on lowering the risk of acute myocardial infarction. [ABSTRACT FROM AUTHOR]

Background/objectives The role of intravenous (IV) beta-blockers in conjunction with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) remains unclear. We therefore conducted a meta-analysis to assess their role in the acute phase of STEMI. Methods We systematically searched the Cochrane Libraries, Medline, and EMBASE for RCTs comparing IV beta-blockers with inactive controls in STEMI patients undergoing PCI. The primary outcome was left ventricular ejection fraction (LVEF). Pooling was performed using DerSimonian and Laird random-effects models. Results Four RCTs ( n = 1149) were included in our meta-analysis. All RCTs only enrolled patients with confirmed STEMI with symptoms lasting < 6 or < 12 hours, and presenting in Killip Class 1 or 2. Mean age ranged across trials from 58.5–62.5 years. Most patients were male (range: 74.8%–86.3%). Data suggest that IV beta-blockers may improve LVEF at 0–2 weeks (weighted mean difference [WMD]: 1.9%; 95% confidence interval [CI]: − 0.7%, 4.5%) and 4–6 weeks (WMD: 1.4%; 95% CI: − 3.1%, 5.9%) post-infarct, reaching statistical significance at 24 weeks (WMD: 2.6%; 95% CI: 0.6%, 4.6%). Rates of ventricular arrhythmia (risk ratio [RR]: 0.65; 95% CI: 0.33, 1.29), any arrhythmia (RR: 0.67; 95% CI: 0.36, 1.27), and cardiogenic shock (RR: 0.77; 95% CI: 0.31, 1.95) during index hospitalization were numerically lower with IV beta-blockers, but 95% CIs were wide. Conclusions In STEMI patients presenting in Killip Class 1 or 2, IV beta-blockers in conjunction with PCI are associated with improved LVEF at 24 weeks relative to PCI alone. [ABSTRACT FROM AUTHOR]

Abstract: Aims: The present study aims to investigate patterns of beta-blocker usage in a national primary care cohort. Methods and results: This is a retrospective cohort study utilising the UK General Practice Research Database from 2004 to 2008. Inclusion criteria were (i) a first diagnosis of chronic heart failure (CHF), myocardial infarction (MI) or angina, and (ii) first-ever prescription of beta-blocker on or after 1st April 2004. Outcome measures were discontinuation of beta-blockers over time, initiation dosages, titration patterns, incidence of adverse events (AEs) and associated prescribing actions. A total of 12,493 patients (68.0% male; mean age 58.0±SD 17.6years) were included. Of these, 27% had discontinued beta-blockers within 1year of initiation, increasing to 39% by 2years and 50% by 3years. Persistence appeared to be greater in the MI cohort compared with angina or CHF cohorts. Beta-blocker dose at initiation averaged approximately 33% of guideline recommended target, rising to 40% in those who continued with therapy. Dyspnoea, fatigue and dizziness were the most common incident AEs at 98, 53 and 49 per 1000 patient years, with little difference between indications. Conclusion: A quarter of patients with cardiovascular disease who are commenced on a beta-blocker are no longer taking the drug by one year. This rises to 50% by three years, a finding that is consistent irrespective of whether the prescription is for prognostic (CHF or post MI) or symptomatic (angina) benefit. There is an urgent need to understand and address the prescribing difficulties of beta-blockers in these at-risk patients. [Copyright &y& Elsevier]

Abstract: Despite being the most effective means of limiting infarct size, coronary reperfusion comes at a price and induces additional damage to the myocardium. Lethal reperfusion injury (death of myocytes that were viable at the time of reperfusion) is an increasingly acknowledged phenomenon. There are many interconnected mechanisms involved in this type of cell death. Calcium overload (generating myocyte hypercontracture), rapid recovery of physiological pH, neutrophil infiltration of the ischemic area, opening of the mitochondrial permeability-transition-pore (PTP), and apoptotic cell death are among the more important mechanisms involved in reperfusion injury. The activation of a group of proteins called reperfusion injury salvage kinases (RISK) pathway confers protection against reperfusion injury, mainly by inhibiting the opening of the mitochondrial PTP. Many interventions have been tested in human trials triggered by encouraging animal studies. In the present review we will explain in detail the main mechanism involved in reperfusion injury, as well as the various approaches (pre-clinical and human trials) performed targeting these mechanisms. Currently, no intervention has been consistently shown to reduce reperfusion injury in large randomized multicenter trials, but the research in this field is intense and the future is highly promising. [Copyright &y& Elsevier]

Abstract: Background: Myocardial infarct size is a strong predictor of cardiovascular events. Intravenous metoprolol before coronary reperfusion has been shown to reduce infarct size; however, it is unknown whether oral metoprolol initiated early after reperfusion, as clinical guidelines recommend, is similarly cardioprotective. We compared the extent of myocardial salvage associated with intravenous pre-reperfusion-metoprolol administration in comparison with oral post-reperfusion-metoprolol or placebo. We also studied the effect on suspected markers of reperfusion injury. Methods: Thirty Yorkshire-pigs underwent a reperfused myocardial infarction, being randomized to pre-reperfusion-metoprolol, post-reperfusion-metoprolol or placebo. Cardiac magnetic resonance imaging was performed in eighteen pigs at day 3 for the quantification of salvaged myocardium. The amounts of at-risk and infarcted myocardium were quantified using T2-weighted and post-contrast delayed enhancement imaging, respectively. Twelve animals were sacrificed after 24h for reperfusion injury analysis. Results: The pre-reperfusion-metoprolol group had significantly larger salvaged myocardium than the post-reperfusion-metoprolol or the placebo groups (31±4%, 13±6%, and 7±3% of myocardium at-risk respectively). Post-mortem analyses suggest lesser myocardial reperfusion injury in the pre-reperfusion-metoprolol in comparison with the other 2 groups (lower neutrophil infiltration, decreased myocardial apoptosis, and higher activation of the salvage-kinase phospho-Akt). Salvaged myocardium and reperfusion injury pair wise comparisons proved there were significant differences between the pre-reperfusion-metoprolol and the other 2 groups, but not among the latter two. Conclusions: The intravenous administration of metoprolol before coronary reperfusion results in larger myocardial salvage than its oral administration initiated early after reperfusion. If confirmed in the clinical setting, the timing and route of β-blocker initiation could be revisited. [Copyright &y& Elsevier]

Abstract: Background: After a myocardial infarction, a higher prevalence of coronary vasospastic response has been reported in the Japanese population than in the Caucasian population. Beta-blockers may exacerbate coronary vasospasm. However, beta-blockers are given to Japanese patients after an acute myocardial infarction, though the mortality benefit is unknown. Thus, we investigated the mortality benefit of beta-blockers given to Japanese patients after an acute myocardial infarction. Methods: We prospectively studied consecutive patients with a first myocardial infarction admitted to the coronary care unit of Kansai Medical University Hospital, Osaka, Japan from May 1994 through the end of 2001. Patients who died during hospitalization or who were referred for coronary artery bypass graft surgery were excluded. The association of beta-blocker use with mortality after discharge was assessed by a proportional hazards regression analysis. Results: There were 546 patients and 400 (73.3%) patients were treated with beta-blockers at the time of discharge from hospital. During a mean follow-up of 2 years, 46 (8.4%) patients died. Beta-blocker therapy was associated with a reduced mortality after adjustment for age, gender, Q wave myocardial infarction, reperfusion therapy during acute phase, Killip functional class, serum creatinine level, cardiovascular risk factors, and medications (hazard ratio=0.51, 95% confidence interval=0.27 to 0.95). Conclusions: Contrary to the concern that beta-blocker therapy might induce coronary vasospasm and reduce survival, beta-blocker therapy improved survival after discharge in Japanese patients with a first myocardial infarction. [Copyright &y& Elsevier]

Atrioventricular node blocking agents including beta-adrenergic blockers, non-dihydropyridine calcium channel blockers and digoxin are usually effective in controlling ventricular rate in atrial fibrillation and flutter. Intravenous beta-blockers and non-dihydropyridine calcium channel blockers are equally effective in rapidly controlling the ventricular rate. The addition of digoxin to the regimen causes a favorable outcome but digoxin as a single agent is generally less effective in slowing the ventricular rate in acute setting. Clonidine, magnesium, and amiodarone have also been used for acute ventricular rate control in atrial fibrillation. Limited data suggest that combination regimens provide better ventricular rate control than any agent alone. The agent of first choice is usually individualized depending upon the clinical situation. Beta-blockers are preferable in patients with myocardial ischemia, myocardial infarction and hyperthyroidism and in post-operative state, but should be avoided in patients with bronchial asthma and chronic obstructive pulmonary disease where non-dihydropyridine calcium channel blockers are preferred. Beta-blockers are preferred drugs used for acute ventricular rate control in atrial fibrillation during pregnancy. In atrial fibrillation with Wolff–Parkinson–White syndrome, beta-blockers, calcium channel blockers and digoxin should be avoided, as these drugs are selective atrioventricular node blockers without slowing conduction through the accessory pathway, which can lead to increased transmission of impulses preferentially through the accessory pathway and precipitate ventricular fibrillation. The drug of choice for atrial fibrillation in pre-excitation syndrome is procainamide but propafenone, flecainide and disopyramide have also been used. When clinical condition is unstable or patient is hemodynamically compromised, immediate electrical cardioversion is the treatment of choice, as the best measure to control ventricular rate is by conversion to sinus rhythm. Factors precipitating rapid ventricular rate should be treated as well. [Copyright &y& Elsevier]

Background: The Southwestern region of France is characterized by a low mortality rate from MI. Since screening and management of the main cardiovascular risk factors has remained stable in this region, we hypothesized that any decrease in CHD mortality would be due to a better treatment of MI cases. Methods: Analysis of all MI treatments during hospitalization and at discharge collected between 1986 and 1993 in the Toulouse-MONICA register. Results: During the acute phase and at discharge from hospital, the prescription of beta-blockers and antiplatelet drugs increased whereas the prescription of calcium channel blockers decreased in men and women, although in women most trends did not reach statistical significance. In men, angioplasty increased steadily, whereas thrombolysis showed an increase followed by a slight decrease after 1991. After multivariate analysis adjusting for age, year, blood pressure, smoking status and personal history of coronary heart disease, women received significantly less beta-blockers and angioplasty and more calcium channel blockers and diuretics than men, while no differences were found for thrombolysis. Conclusions: The prescription of the most efficient therapies against MI has increased in Southwestern France during the period studied. The reasons for a lower prescription of beta-blockers and angioplasty in women remain to be assessed. [Copyright &y& Elsevier]