Percutaneous Coronary Intervention for Left Main Coronary Disease in New Zealand: National Linkage Study of Characteristics and In-Hospital Outcomes (ANZACS-QI 38).

BACKGROUND: Approximately 5% of coronary angiographies detect LMS disease >50%. Recent randomized trials showed PCI has comparable outcomes to coronary artery bypass grafting (CABG) in low or intermediate risk candidates. In clinical practice, PCI is frequently utilized in those with prohibitive surgical risk. We reviewed contemporary national results of percutaneous coronary intervention (PCI) for left main coronary disease (LMS) disease in New Zealand. METHODS: All patients undergoing PCI for LMS disease from 01/09/2014-24/09/2017 were extracted from the All New Zealand Acute Coronary Syndrome-Quality Improvement registry with national dataset linkage, analyzing characteristics and in-hospital outcomes. RESULTS: The cohort included 469 patients, mean age 70.8 ±â€¯10.7 years, male 331 (71%), and the majority 339 (72%) were unprotected LMS. Indications include ST-elevation myocardial infarction (STEMI) 83 (18%) and NSTEMI or unstable angina 229 (49%). Compared with protected LMS, unprotected LMS were more likely to present with an acute coronary syndrome (73% versus 48%, P < 0.001), and to die in-hospital (9.4% versus 3.9%, P = 0.045). In those with unprotected LMS, in-hospital mortality after acute STEMI PCI was higher than for other indications (21.1% versus 6.1%, P < 0.001). Independent predictors of in-hospital death and major adverse cardiovascular events included STEMI, femoral access and worse renal function. CONCLUSION: Our LMS PCI cohort had high mortality rates, especially those presenting with STEMI and an unprotected LMS. This reflects the contemporary real-world practice of LMS PCI being predominantly performed in high risk patients which differs from randomized trial populations, and this should be considered before comparing with CABG outcomes.

Hyperbaric oxygen therapy for acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS), includes acute myocardial infarction and unstable angina, is common and may prove fatal. Hyperbaric oxygen therapy (HBOT) will improve oxygen supply to the threatened heart and may reduce the volume of heart muscle that perishes. The addition of HBOT to standard treatment may reduce death rate and other major adverse outcomes.This an update of a review previously published in May 2004 and June 2010. OBJECTIVES: The aim of this review was to assess the evidence for the effects of adjunctive HBOT in the treatment of ACS. We compared treatment regimens including adjunctive HBOT against similar regimens excluding HBOT. Where regimens differed significantly between studies this is clearly stated and the implications discussed. All comparisons were made using an intention to treat analysis where this was possible. Efficacy was estimated from randomised trial comparisons but no attempt was made to evaluate the likely effectiveness that might be achieved in routine clinical practice. Specifically, we addressed:Does the adjunctive administration of HBOT to people with acute coronary syndrome (unstable angina or infarction) result in a reduction in the risk of death?Does the adjunctive administration of HBOT to people with acute coronary syndrome result in a reduction in the risk of major adverse cardiac events (MACE), that is: cardiac death, myocardial infarction, and target vessel revascularization by operative or percutaneous intervention?Is the administration of HBOT safe in both the short and long term? SEARCH METHODS: We updated the search of the following sources in September 2014, but found no additional relevant citations since the previous search in June 2010 (CENTRAL), MEDLINE, EMBASE, CINAHL and DORCTHIM. Relevant journals were handsearched and researchers in the field contacted. We applied no language restrictions. SELECTION CRITERIA: Randomised studies comparing the effect on ACS of regimens that include HBOT with those that exclude HBOT. DATA COLLECTION AND ANALYSIS: Three authors independently evaluated the quality of trials using the guidelines of the Cochrane Handbook and extracted data from included trials. Binary outcomes were analysed using risk ratios (RR) and continuous outcomes using the mean difference (MD) and both are presented with 95% confidence intervals. We assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: No new trials were located in our most recent search in September 2014. Six trials with 665 participants contributed to this review. These trials were small and subject to potential bias. Only two reported randomisation procedures in detail and in only one trial was allocation concealed. While only modest numbers of participants were lost to follow-up, in general there is little information on the longer-term outcome for participants. Patients with acute coronary syndrome allocated to HBOT were associated with a reduction in the risk of death by around 42% (RR: 0.58, (95% CI 0.36 to 0.92), 5 trials, 614 participants; low quality evidence).In general, HBOT was well-tolerated. No patients were reported as suffering neurological oxygen toxicity and only a single patient was reported to have significant barotrauma to the tympanic membrane. One trial suggested a significant incidence of claustrophobia in single occupancy chambers of 15% (RR of claustrophobia with HBOT 31.6, 95% CI 1.92 to 521). AUTHORS' CONCLUSIONS: For people with ACS, there is some evidence from small trials to suggest that HBOT is associated with a reduction in the risk of death, the volume of damaged muscle, the risk of MACE and time to relief from ischaemic pain. In view of the modest number of patients, methodological shortcomings and poor reporting, this result should be interpreted cautiously, and an appropriately powered trial of high methodological rigour is justified to define those patients (if any) who can be expected to derive most benefit from HBOT. The routine application of HBOT to these patients cannot be justified from this review.

Patient access and 1-year outcomes of percutaneous coronary intervention facilities with and without on-site cardiothoracic surgery: insights from the Veterans Affairs (VA) Clinical Assessment, Reporting, and Tracking (CART) program.

BACKGROUND: The safety of percutaneous coronary intervention (PCI) at medical facilities without on-site cardiothoracic (CT) surgery has been established in clinical trials. However, the comparative effectiveness of this strategy in real-world practice, including impact on patient access and outcomes, is uncertain. The Veterans Affairs (VA) health care system has used this strategy, with strict quality oversight, since 2005, and can provide insight into this question. METHODS AND RESULTS: Among 24,387 patients receiving PCI at VA facilities between October 2007 and September 2010, 6616 (27.1%) patients underwent PCI at facilities (n=18) without on-site CT surgery. Patient drive time (as a proxy for access), procedural complications, 1-year mortality, myocardial infarction, and rates of subsequent revascularization procedures were compared by facility. Results were stratified by procedural indication (ST-segment-elevation myocardial infarction versus non-ST-segment-elevation myocardial infarction/unstable angina versus elective) and PCI volume. With the inclusion of PCI facilities without on-site CT surgery, median drive time for patients treated at those facilities decreased by 90.8 minutes (P<0.001). Procedural need for emergent coronary artery bypass graft and mortality rates were low and similar between facilities. Adjusted 1-year mortality and myocardial infarction rates were similar between facilities (hazard ratio in PCI facilities without relative to those with on-site CT surgery, 1.02; 95% confidence interval, 0.87-1.2), and not modified by either PCI indication or PCI volume. Subsequent revascularization rates were higher at sites without on-site CT surgery facilities (hazard ratio, 1.21; 95% confidence interval, 1.03-1.42). CONCLUSIONS: This study suggests that providing PCI facilities without on-site CT surgery in an integrated health care system with quality oversight improves patient access without compromising procedural or 1-year outcomes.

Efficacy of folic acid supplementation in cardiovascular disease prevention: an updated meta-analysis of randomized controlled trials.

BACKGROUND: In observational studies, lower serum homocysteine levels are associated with a lower incidence of cardiovascular disease (CVD). However, individual randomized controlled trials (RCTs) have yielded mixed findings regarding the efficacy of therapeutic homocysteine in lowering cardiovascular risk. Our aim was to perform an updated meta-analysis of relevant RCTs to assess the efficacy of folic acid supplementation in the prevention of CVD, coronary heart disease (CHD), and stroke. METHODS: We performed systematic search to identify RCTs reported at least one of the CVD, CHD, or stroke as outcomes. Relative risk (RR) with 95% confidence interval was used as a measure of the association between folic acid supplementation and risk of CVD, CHD, stroke, and all-cause mortality. The analysis was further stratified by factors that could affect the treatment effects. RESULTS: The systematic search identified 26 RCTs enrolling 58,804 participants. Pooling the RRs showed that folic acid supplementation was not associated with any significant change in the risk of CVD (RR 0.98, 0.95 to 1.02; p=0.36), CHD (RR 1.03, 0.98 to 1.08; p=0.23), and all-cause mortality (RR 1.00, 0.96 to 1.04; p=0.92), but was linked to a decreasing trend in stroke risk (RR 0.93, 0.86 to 1.00; p=0.05). In stratified analyses, the only heterogeneity was found for stroke risk reduction among groups with (RR 1.07, 0.92 to 1.25) vs. without (RR 0.88, 0.81 to 0.96) mandatory grain fortification (P for heterogeneity=0.03). CONCLUSIONS: This meta-analysis suggests that there might be a potentially modest benefit of folic acid supplementation in stroke prevention.

Hyperbaric oxygen therapy for acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS), includes acute myocardial infarction and unstable angina, is common and may prove fatal. Hyperbaric oxygen therapy (HBOT) will improve oxygen supply to the threatened heart and may reduce the volume of heart muscle that perishes. The addition of HBOT to standard treatment may reduce death rate and other major adverse outcomes. OBJECTIVES: To assess the benefits and harms of adjunctive HBOT for treating ACS. SEARCH STRATEGY: We updated the search of the following sources in June 2010, finding one further trial: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, DORCTHIM, LILACS and checked the references from selected articles. Relevant journals were handsearched and researchers in the field contacted. No language restrictions were applied. SELECTION CRITERIA: Randomised studies comparing the effect on ACS of regimens that include HBOT with those that exclude HBOT. DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of trials using the guidelines of the Cochrane Handbook and extracted data from included trials. MAIN RESULTS: Six trials with 665 participants contributed to this review. There was a significant decrease in the risk of death with HBOT (risk ratio (RR) 0.58, 95% CI 0.36 to 0.92, P = 0.02). The extent of heart muscle damage was lower following HBOT, as shown by a lesser rise in muscle enzyme in the blood (mean difference (MD) 493 IU, P = 0.005) and a better LVEF (MD 5.5%, P = 0.001). There was evidence from individual trials of reductions in the risk of major adverse coronary events (MACE) (RR 0.12, P = 0.03); re-infarction (RR 0.28, P = 0.04) and dysrhythmias following HBOT (RR 0.59, P = 0.01, and the time to relief of pain was reduced with HBOT (MD 353 minutes shorter, P < 0.00001). One trial suggested a significant incidence of claustrophobia in single occupancy chambers of 15% (RR of claustrophobia with HBOT 31.6, P = 0.02). AUTHORS' CONCLUSIONS: For people with ACS, there is some evidence from small trials to suggest that HBOT is associated with a reduction in the risk of death, the volume of damaged muscle, the risk of MACE and time to relief from ischaemic pain. In view of the modest number of patients, methodological shortcomings and poor reporting, this result should be interpreted cautiously, and an appropriately powered trial of high methodological rigour is justified to define those patients (if any) who can be expected to derive most benefit from HBOT. The routine application of HBOT to these patients cannot be justified from this review.

Effects of loading dose of atorvastatin before percutaneous coronary intervention on periprocedural myocardial injury.

OBJECTIVES: To investigate the effects of loading dose of atorvastatin on periprocedural myocardial injury and inflammatory reaction in patients with non-ST segment elevation (NSTE) acute coronary syndromes (unstable angina or NSTE acute myocardial infarction). METHODS: A total of 81 patients with NSTE-acute coronary syndromes were randomly divided into the pretreatment with atorvastatin group [80 mg 12 h before percutaneous coronary intervention (PCI), with a further 40 mg preprocedure dose] (n=41) or the placebo group (n=40). The main end point was a 30-day incidence of major adverse cardiac events (cardiac death, nonfatal acute myocardial infarction, or revascularization with either PCI or coronary artery bypass grafting). Creatine kinase-MB, cardiac troponin I, and high-sensitivity C-reactive protein levels were measured at the baseline and at 8 and 24 h after the procedure. RESULTS: Major adverse cardiac events occurred in 2.4% of patients in the atorvastatin group and 22.5% of those in the placebo group (P=0.0161). This difference was mostly because of reduction in the incidence of myocardial infarction (2.4 vs. 20.0%; P=0.0307). Markers of the two groups were elevated after PCI; however, the higher values of creatine kinase-MB, cardiac troponin I, and high-sensitivity C-reactive protein in the atorvastatin treatment group were significantly lower than those in the placebo group (P<0.01). CONCLUSION: Short-term pretreatment with a high dose of atorvastatin significantly reduces procedural myocardial injury in early PCI.

Contemporary treatment of unstable angina and non-ST-segment-elevation myocardial infarction (part 2).

In Part 1 of this review, we discussed how plaque rupture is the most common underlying cause of most cases of unstable angina/non-ST-segment-elevation myocardial infarction (UA/NSTEMI) and how early risk stratification is vital for the timely diagnosis and treatment of acute coronary syndromes (ACS). Now, in Part 2, we focus on the medical therapies and treatment strategies (early conservative vs early invasive) used for UA/NSTEMI. We also discuss results from various large randomized controlled trials that have led to the contemporary standards of practice for, and reduced morbidity and death from, UA/NSTEMI. In summary, ACS involving UA/NSTEMI is associated with high rates of adverse cardiovascular events, despite recent therapeutic advances. Plaque composition and inflammation are more important in the pathogenesis of ACS than is the actual degree of arterial stenosis. As results from new trials challenge our current practices and help us develop the optimal treatment strategy for UA/NSTEMI patients, the cornerstones of contemporary treatment remain early risk stratification and aggressive medical therapy, supplemented by coronary angiography in appropriately selected patients. An early-invasive-treatment strategy is of most benefit to high-risk patients, whereas an early-conservative strategy is recommended for low-risk patients. Adjunctive medical therapy with acetylsalicylic acid, clopidogrel or another adenosine diphosphate antagonist, glycoprotein IIb/IIIa inhibitors, and either low-molecular-weight heparin or unfractionated heparin, in the appropriate setting, further reduces the risk of ischemic events secondary to thrombosis. Short- and long-term inhibition of platelet aggregation should be achieved by appropriately evaluating the risk of bleeding complications in these patients.

Updated Strategies and Therapies for Reducing Ischemic and Vascular Events (STRIVE) ST-segment elevation myocardial infarction critical pathway toolkit.

The Strategies and Therapies for Reducing Ischemic and Vascular Events (STRIVE) acute coronary syndromes critical pathway toolkit has been revised again based on the 2007 focused update of the American College of Cardiology/American Heart (ACC/AHA) Association guidelines for the management of patients with ST-segment elevation myocardial infarction (STEMI). A previous update of the toolkit incorporated the 2007 ACC/AHA guidelines for unstable angina/non-ST-segment elevation myocardial infarction. This review highlights the major revisions to the STEMI guidelines, and illustrates and describes the revised STRIVE critical pathway tools for STEMI, which include pathway flowcharts, standing orders, pocket cards, and posters. The updated STEMI tools are available to clinicians online on the STRIVE Website.

Updated Strategies and Therapies for Reducing Ischemic and Vascular Events (STRIVE) unstable angina/non-ST elevation myocardial infarction critical pathway toolkit.

The Strategies and Therapies for Reducing Ischemic and Vascular Events (STRIVE) acute coronary syndromes (ACS) critical pathway toolkit, developed in 2002, has been revised and updated. The updated toolkit is based on the American College of Cardiology/American Heart Association 2007 guidelines for the management of patients with unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMI). This review highlights the major revisions to the UA/NSTEMI guidelines and illustrates and describes the revised STRIVE critical pathway tools, which include pathway flowcharts, standing orders, pocket cards, posters, and form letters. These materials are being made available online to help physicians, nurses, and hospitals implement the new guidelines and thus improve the quality of care and outcomes for patients with ACS.

Effect of intensive lipid-lowering therapy on mortality after acute coronary syndrome (a patient-level analysis of the Aggrastat to Zocor and Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trials).

Compared with moderate lipid lowering with standard-dose statin therapy, intensive lipid lowering with high-dose statin therapy after acute coronary syndromes (ACS) significantly reduces cardiovascular events. However, the 2 trials of high-dose versus standard-dose statin therapy in patients with ACS, Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE-IT-TIMI 22), were not individually powered to evaluate the impact on mortality alone. In this study, a pooled, patient-level analysis of these trials of 8,658 post-ACS patients was performed to provide a more robust estimate of the impact of intensive statin therapy on mortality. By 8 months, achieved low-density lipoprotein levels were lower in the group with intensive statin therapy (median 64 mg/dl, interquartile range 51 to 81) than in the group with moderate statin therapy (median 87 mg/dl, interquartile range 71 to 107) (p <0.001). All-cause mortality was significantly reduced in the group with intensive statin therapy compared with the group with moderate statin therapy (3.6% vs 4.9%, hazard ratio 0.77, 95% confidence interval 0.63 to 0.95, p = 0.015), without significant interaction by trial (interaction p = 0.63). The reduction in all-cause mortality with intensive statin therapy was consistent across key subgroups. In conclusion, in this analysis of >8,600 patients, intensive lipid lowering with high-dose statin therapy after ACS was associated with reduced mortality compared with moderate lipid lowering with standard-dose statin therapy. On the basis of these findings, 1 death was prevented for every 95 patients treated with high-dose statin therapy for 2 years. The results of this pooled analysis provide further evidence for early intensive statin therapy after ACS.

In-hospital initiation of statin therapy in acute coronary syndromes: maximizing the early and long-term benefits.

Patients with acute coronary syndrome (ACS) are at high risk for recurrent coronary events, sudden death, and all-cause mortality. Conventional revascularization therapies reduce the risk of further ischemia but do not affect the underlying atherosclerotic disease. Statins have a proven record in the secondary prevention of coronary heart disease. Furthermore, statins have been shown to exert varying degrees of pleiotropic effects, which may stabilize vulnerable atherosclerotic plaques. A compelling body of evidence from randomized controlled trials demonstrates that high-dose, potent statin therapy initiated immediately after an acute coronary event can significantly reduce early as well as longer-term morbidity and mortality. Furthermore, high-dose, potent statin therapy displays a reasonable safety profile. National guidelines now recommend that in patients with ACS, statin therapy should be initiated in hospital prior to discharge, irrespective of baseline low-density lipoprotein cholesterol levels, to improve clinical outcomes. Every effort should be made to ensure all eligible patients with ACS are initiated and maintained on statin therapy.

Hyperbaric oxygen therapy for acute coronary syndrome.

BACKGROUND: Acute coronary syndrome (ACS) includes acute myocardial infarction and unstable angina. ACS is common and may prove fatal. Hyperbaric oxygen therapy (HBOT) will improve oxygen supply to the threatened heart and may reduce the volume of heart muscle that will perish. The addition of HBOT to the standard treatment may reduce death rate and other major adverse outcomes. OBJECTIVES: To assess the benefits and harms of adjunctive HBOT for treating ACS. SEARCH STRATEGY: We searched the following from inception to November 2004: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTHIM, and references from selected articles. Relevant journals were handsearched and researchers in the field contacted. SELECTION CRITERIA: Randomised studies comparing the effect on ACS of regimens that include HBOT with those that exclude HBOT. DATA COLLECTION AND ANALYSIS: Three reviewers independently evaluated the quality of trials using the guidelines of the Cochrane Handbook and extracted data from included trials. MAIN RESULTS: Four trials with 462 participants contributed to this review. There was a trend towards, but no significant decrease in, the risk of death with HBOT (relative risk (RR) 0.64, 95% CI 0.38 to 1.06, P=0.08). There was evidence from individual trials of reductions in the risk of major adverse coronary events [MACE] (RR 0.12, 95% CI 0.02 to 0.85, P=0.03; NNT 4, 95% CI 3 to 10) and some dysrhythmias following HBOT (RR 0.59, 95% CI 0.39 to 0.89, P=0.01; NNT 6, 95% CI 3 to 24), particularly complete heart block (RR 0.32, 95%CI 0.12 to 0.84, P=0.02), and that the time to relief of pain was reduced with HBOT (Weighted Mean Difference [WMD] 353 minutes shorter, 95% CI 219 to 488, P<0.0001). One trial suggested a significant incidence of claustrophobia in single occupancy chambers of 15% (RR of claustrophobia with HBOT 31.6, 95%CI 1.92 to 521, P=0.02). AUTHORS' CONCLUSIONS: For people with ACS, individual small trials suggest the addition of HBOT reduced the risk of Major Adverse Cardiac Events, some dysrrhythmias, and reduced the time to relief from ischaemic pain, but did not reduce mortality. In view of the modest number of patients, methodological shortcomings and poor reporting, this result should be interpreted cautiously, and an appropriately powered trial of high methodological rigour is justified to define those patients (if any) who can be expected to derive most benefit from HBOT. The routine application of HBOT to these patients cannot be justified from this review.

Low-molecular-weight heparin and platelet glycoprotein IIb/IIIa receptor blockade in the treatment of acute coronary syndromes: complementary or competing therapies?

Clinical trials have reported the beneficial effects of platelet glycoprotein (GP) IIb/IIIa receptor antagonists and low-molecular-weight heparins in patients presenting with unstable angina or non-ST elevation myocardial infarction. In an overview of all trials comparing GP IIb/IIIa antagonists with control treatment (i.e., heparin or placebo on a background of aspirin therapy), the incidence of death/myocardial infarction at 30 days was reduced by 11%, from 13% to 11.7% (p = 0.008).Overall, the trials of low-molecular-weight heparin have shown a non-significant 10% reduction in the incidence of death/myocardial infarction at 30 days (4.8% versus 5.5% with unfractionated heparin; p = 0.2). There has been no evidence of heterogeneity (p = 0.1) in these trials. In contrast to the examination of all the low-molecular-weight heparins, when the results of the two trials of enoxaparin were combined, there was an 18% reduction in death/myocardial infarction at 43 days (7.1% versus 8.6%; p = 0.02). Given the differing mechanisms of action of GP IIb/IIIa antagonists and low-molecular-weight heparins, and these encouraging trial results, the use of both agents was tested in a small pilot study of patients randomized to receive tirofiban plus either unfractionated heparin or enoxaparin. There was a trend for greater inhibition of platelet aggregation and shorter bleeding times in those who had received tirofiban plus enoxaparin. These data support the theoretical potential of this combination for the treatment of patients with acute coronary syndromes, but prospective randomized trials will need to be conducted to assess efficacy and safety.

Angina inestable: los calcibloqueantes sin betabloqueantes no previenen la recurrencia de la angina, los procedimientos intervencionistas, ni la insuficiencia cardíaca / Calcium channel bloquer agentes, not associated to betabloquers, do not prevent recurrent angina, further invasive procedures or pump failure in patients hospitalized for unstable angina

Antecentes. Los calciantagonistas (CA) deberían ser eficaces en reducir la mortalidad y el infarto (IAM) no fatal en la angina inestable (AI). Se ha demostrado que los CA proporcionan alivio sintomático y mejor evolución. Objetivo. Investigar si los CA en la AI disminuyen la muerte y el IAM no fatal, previenen la recurrencia de la angina y mejoran la evolución. Material y métodos. Análisis en la base de datos del estudio ENAI (Enalapril en la Angina Inestable) que sigue durante 7 días a 1022 pacientes con AI. Indicación de betabloqueantes (BB) y CA a criterio de los participantes. Resultados. La angina recurrente y los procedimientos invasivos no son diferentes en la AI previamente tratada con CA (RR 1,02; IC95 0,74 - 1,40; P 0,8958). En 1022 pacientes los eventos secundarios aumentan en los no tratados (53,3 por ciento en 629) en relación a los tratados con CA cuando se asocian a los BB (46,7 por ciento en 392; RR 1,39; IC95 1,19 - 1,62; P 0,00003) Para Diltiazem-BB los eventos secundarios disminuyen desde un 61,3 por ciento al 38,7 por ciento (RR 1,74; ; IC95 1,39 - 2,18; P 0,0000), similar con otros CA-BB. Reducen los eventos secundarios del 66 por ciento al 34 por ciento en el grupo con SD del ST/ST normal (RR del 1,92; IC95 1,05 - 3,51; P 0,0335). Conclusiones. La indicación de CA sin BB en AI no disminuye los eventos isquémicos secundarios ni el desarrollo de insuficiencia cardíaca. Indicados en AI con SD del ST.

Angina inestable: los calcibloqueantes sin betabloqueantes no previenen la recurrencia de la angina, los procedimientos intervencionistas, ni la insuficiencia cardíaca / Calcium channel bloquer agentes, not associated to betabloquers, do not prevent recurrent angina, further invasive procedures or pump failure in patients hospitalized for unstable angina

Antecentes. Los calciantagonistas (CA) deberían ser eficaces en reducir la mortalidad y el infarto (IAM) no fatal en la angina inestable (AI). Se ha demostrado que los CA proporcionan alivio sintomático y mejor evolución. Objetivo. Investigar si los CA en la AI disminuyen la muerte y el IAM no fatal, previenen la recurrencia de la angina y mejoran la evolución. Material y métodos. Análisis en la base de datos del estudio ENAI (Enalapril en la Angina Inestable) que sigue durante 7 días a 1022 pacientes con AI. Indicación de betabloqueantes (BB) y CA a criterio de los participantes. Resultados. La angina recurrente y los procedimientos invasivos no son diferentes en la AI previamente tratada con CA (RR 1,02; IC95 0,74 - 1,40; P 0,8958). En 1022 pacientes los eventos secundarios aumentan en los no tratados (53,3 por ciento en 629) en relación a los tratados con CA cuando se asocian a los BB (46,7 por ciento en 392; RR 1,39; IC95 1,19 - 1,62; P 0,00003) Para Diltiazem-BB los eventos secundarios disminuyen desde un 61,3 por ciento al 38,7 por ciento (RR 1,74; ; IC95 1,39 - 2,18; P 0,0000), similar con otros CA-BB. Reducen los eventos secundarios del 66 por ciento al 34 por ciento en el grupo con SD del ST/ST normal (RR del 1,92; IC95 1,05 - 3,51; P 0,0335). Conclusiones. La indicación de CA sin BB en AI no disminuye los eventos isquémicos secundarios ni el desarrollo de insuficiencia cardíaca. Indicados en AI con SD del ST. (AU)

Incorporating platelet glycoprotein IIb/IIIa inhibition in critical pathways: unstable angina/non-ST-segment elevation myocardial infarction.

Platelet glycoprotein (GP) IIb/IIIa inhibitors have been shown to be effective in reducing thrombotic events in patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI) and when used as medical therapy in patients with unstable angina/non-ST-segment elevation myocardial infarction (MI). Recent findings include dramatic preventive benefits in the setting of coronary stent deployment and a significant long-term preventive effect on mortality. The benefits of GP IIb/IIIa receptor inhibition suggest the utility of adopting routine use of these agents in critical pathways of unstable angina/non-ST-segment elevation MI and PCI. Because cost constraints may limit use of these agents, however, targeting treatment based on patient risk assessment may be warranted.

International, randomized, controlled trial of lamifiban (a platelet glycoprotein IIb/IIIa inhibitor), heparin, or both in unstable angina. The PARAGON Investigators. Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network.

BACKGROUND: Unstable angina and non-Q-wave myocardial infarction involve coronary arterial plaque rupture, platelet activation, and thrombus formation. This study tested the benefit of different doses of lamifiban (a platelet IIb/IIIa antagonist) alone and in combination with heparin in patients with these conditions to select the most promising lamifiban regimen for subsequent evaluation. METHODS AND RESULTS: At 273 hospitals in 20 countries, 2282 patients were randomly assigned to lamifiban (2x2 factorial design: low-dose [1 microg/min] with and without heparin versus high-dose [5 microg/min] with and without heparin) or to standard therapy (placebo and heparin). All patients received aspirin. The composite primary end point of death or nonfatal myocardial infarction at 30 days occurred in 11.7% of those receiving standard therapy, 10.6% receiving low-dose lamifiban, and 12.0% receiving high-dose lamifiban (P=0.668). By 6 months, this composite was lowest for those assigned to low-dose lamifiban (P=0.027) and intermediate for those assigned to high-dose lamifiban (P=0.450) compared with control (13.7%, 16.4%, and 17.9%, respectively). Compared with control, the combination of high-dose lamifiban and heparin resulted in more intermediate or major bleeding (12.1% versus 5.5%; P=0.002) and a similar rate of ischemic events. Conversely, low-dose lamifiban and heparin yielded similar bleeding rates as in the control group but fewer ischemic events at 6 months (12.6% versus 17.9%; P=0.025). CONCLUSION: In unstable angina and non-Q-wave infarction, platelet IIb/IIIa antagonism with lamifiban reduces adverse ischemic events at 6 months beyond that of aspirin and heparin therapy. The role of conjunctive heparin remains uncertain but appears more favorable with low-dose IIb/IIIa antagonism. Larger-scale study is needed to more reliably estimate these effects.

A low molecular weight, selective thrombin inhibitor, inogatran, vs heparin, in unstable coronary artery disease in 1209 patients. A double-blind, randomized, dose-finding study. Thrombin inhibition in Myocardial Ischaemia (TRIM) study group.

BACKGROUND: Unstable coronary artery disease, i.e. unstable angina or non-Q wave myocardial infarction, is caused by rupture of atheromatous plaques initiating thrombus formation. Thrombin is thought to be pivotal in platelet activation and thrombus growth. The aim of the present study was to compare the effect of three different doses of a novel, low molecular weight, selective thrombin inhibitor (inogatran) with that of heparin in unstable coronary artery disease. The composite primary end-point was death, incidence of myocardial infarction, refractory angina or recurrent angina after 7 days. Secondary end-points were the same after 3 and 30 days, as were death and myocardial infarction with or without refractory angina on all three occasions. METHODS: Patients (n = 1209) admitted with suspected unstable angina, or non-Q wave myocardial infarction, were randomly assigned to double-blind treatment with inogatran or heparin bolus doses. This was followed by a 3 day infusion with a low (LDI), medium (MDI), or high (HDI) dose of inogatran, aiming at plasma concentrations of 0.15, 0.4 or 0.8 micromol.l-1, or heparin initiated at 1200 U.h-1. FINDINGS: Treatment with inogatran resulted in median activated partial thromboplastin times after 24 h of 36, 44 and 53 s in the low, medium and high dose inogatran groups, respectively, as compared to 54 s in the heparin group (ns). At the end of the infusion, after 3 days, heparin-treated patients had fewer composite events (29.5%) than inogatran-treated patients (LDI = 39.4%, MDI = 37.6%, HDI = 36.1%; P = 0.01). The event rate after 7 days with respect to the primary end-point, however, did not differ between the groups (heparin = 41.0%, LDI = 45.7% MDI = 45.9%, HDI = 45.5%; ns). Death and myocardial infarction occurred less frequently in the heparin group (0.7%) than in the three inogatran groups (LDI = 3.6%, MDI = 2.0%, HDI = 4.0%; P < 0.05) after 3 days. After 7 days, this difference was attenuated (heparin = 2.6% vs LDI = 4.0%, MDI = 4.3%, HDI = 6.7%; P = 0.10). After 30 days there were no significant differences in event rates between the four groups. Major bleeding occurred in 1.1% of the patients within 7 days, with no differences between the groups. CONCLUSIONS: During study drug infusion the event rate was very low in the heparin group, and none of the inogatran dosages were better than heparin in preventing ischaemic events. Furthermore, there was no relationship between event rate and inogatran dosage. Thus, this study does not indicate that the efficacy of inogatran would improve with higher doses, despite a clear dose-effect as regards the prolongation of activated partial thromboplastin time. After cessation of heparin or inogatran there was an increase in event rates, suggestive of a rebound phenomenon.

Long-term survival and risk stratification in patients with angina at rest undergoing medical treatment.

In order to determine those factors which influence long-term prognosis in patients with angina at rest associated with transient ST-segment changes, 217 patients undergoing medical treatment were followed for a mean of 39 months. All patients underwent coronary arteriography. Univariate analysis identified 12 variables significantly related to prognosis. These were disease of the left main coronary artery; the number of diseased vessels; left ventricular end-diastolic pressure; ejection fraction; baseline electrocardiogram; presence of prior myocardial infarction; ST-segment depression and ventricular arrhythmias during pain; disease of the proximal anterior descending coronary artery; crescendo angina; hypertension; and age. Use of the Cox regression model for survival analysis revealed only 3 variables which were independent predictors of prognosis. They were disease of the left main coronary artery; the number of diseased vessels and left ventricular end-diastolic pressure. The model allowed stratification of patients into 3 groups. Survival at 3 years was 98% in the low risk group; 82% in the intermediate risk group; and 58% in the high risk group. These data indicate that disease of the left main coronary artery, the number of diseased vessels and left ventricular end-diastolic pressure are the independent predictors of prognosis in angina at rest. These variables may allow stratification of patients into groups having different long-term survivals.