In patients with acute coronary syndromes, early invasive intervention (coronary angiography at a median of 14 hours) was compared with delayed intervention (angiography at a median of 50 hours). ...There was no difference in outcomes between the two groups overall, but high-risk patients had better outcomes with the early strategy and in particular had less risk of refractory ischemia.
There was no difference in outcomes between the two groups overall, but high-risk patients had better outcomes with the early strategy and in particular had less risk of refractory ischemia.
Randomized trials have shown that a routine invasive strategy is beneficial in high-risk patients with acute coronary syndromes.
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In patients with myocardial infarction with ST-segment elevation, in which the infarct-related artery is usually occluded and there is ongoing transmural ischemia, it is well established that the earlier primary percutaneous coronary intervention (PCI) can be performed, the lower the mortality.
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By contrast, in patients with acute coronary syndromes without ST-segment elevation (including unstable angina and myocardial infarction), the culprit artery is often patent, there is usually no ongoing transmural ischemia, and the patient often has a good response to . . .
Patients with known cardiovascular disease who have not had a recent acute event are often referred to as having stable coronary artery disease (CAD). The concept of 'stable' CAD is misleading for ...two important reasons: the continuing risks of cardiovascular events over the longer term and the diverse spectrum of powerful risk characteristics. The risks of cardiovascular events are frequently underestimated and continue to exist, despite current standards of care for secondary prevention, including lifestyle changes, optimal medical therapy, myocardial revascularization and the use of antiplatelet agents to limit thrombosis. In dispelling the myth of 'stable' CAD, we explore the pathophysiology of the disease and the relative contribution of plaque and systemic factors to cardiovascular events. A broader concept of the vulnerable patient, not just the vulnerable plaque, takes into account the diversity and future risks of atherothrombotic events. We also evaluate new and ongoing research into medical therapies aimed at further reducing the risks of cardiovascular events in patients with chronic - but not stable - atherothrombotic disease.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Advances in antiplatelet therapies for patients with cardiovascular disease have improved patient outcomes over time, but the challenge of balancing the risks of ischaemia and bleeding remains ...substantial. Moreover, many patients with cardiovascular disease have a residual risk of ischaemic events despite receiving antiplatelet therapy. Therefore, novel strategies are needed to prevent clinical events through mechanisms beyond platelet inhibition and with an acceptable associated risk of bleeding. The advent of non-vitamin K antagonist oral anticoagulants, which attenuate fibrin formation by selective inhibition of factor Xa or thrombin, has renewed the interest in dual-pathway inhibition strategies that combine an antiplatelet agent with an anticoagulant drug. In this Review, we highlight the emerging pharmacological rationale and clinical development of dual-pathway inhibition strategies for the prevention of atherothrombotic events in patients with different manifestations of cardiovascular disease, such as coronary artery disease, cerebrovascular disease and peripheral artery disease.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this trial, 14,264 patients with atrial fibrillation were randomly assigned to receive either rivaroxaban or warfarin. In a per-protocol, as-treated analysis, rivaroxaban was noninferior to ...warfarin with respect to the primary end point of stroke or systemic embolism.
Atrial fibrillation is associated with an increase in the risk of ischemic stroke by a factor of four to five
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and accounts for up to 15% of strokes in persons of all ages and 30% in persons over the age of 80 years.
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The use of vitamin K antagonists is highly effective for stroke prevention in patients with nonvalvular atrial fibrillation and is recommended for persons at increased risk.
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However, food and drug interactions necessitate frequent coagulation monitoring and dose adjustments, requirements that make it difficult for many patients to use such drugs in clinical practice.
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Rivaroxaban is . . .
Clopidogrel must be metabolized to an active form to be effective. Cytochrome P-450 variants resulting in slow metabolism may reduce clinical efficacy. This study in patients with acute coronary ...syndromes or atrial fibrillation did not confirm diminished efficacy in those with slow metabolism.
Clopidogrel, when added to aspirin, reduces the rate of major vascular events among patients with acute coronary syndromes and atrial fibrillation.
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Recent reports suggest that certain common genetic variants, involving the hepatic cytochrome P-450 system, that are involved in the conversion of clopidogrel to its active metabolite are associated with an increased rate of recurrent cardiovascular events, implying that the benefits of clopidogrel may be attenuated in patients with these genetic variants. Specifically, in patients who are carriers of a loss-of-function
CYP2C19
allele (including the *2 and *3 alleles), the conversion of clopidogrel to its active metabolite may be . . .
In patients with acute coronary syndromes, low doses of rivaroxaban were effective in reducing the primary end point of death from cardiovascular causes, myocardial infarction, or stroke. Rivaroxaban ...also reduced overall mortality, although there was more bleeding.
After an acute coronary syndrome, patients remain at risk for recurrent cardiovascular events despite standard medical therapy, including long-term antiplatelet therapy with aspirin and an adenosine diphosphate–receptor inhibitor. This risk may be related in part to excess thrombin generation that persists beyond the acute presentation in such patients.
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As a result, there has been interest in evaluating the role of oral anticoagulants after an acute coronary syndrome. Improved cardiovascular outcomes were reported for patients who were treated with the anticoagulant warfarin in addition to aspirin.
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However, widespread use of long-term warfarin in such patients has been limited by challenges associated . . .
There is limited knowledge of the scale and impact of multimorbidity for patients who have had an acute myocardial infarction (AMI). Therefore, this study aimed to determine the extent to which ...multimorbidity is associated with long-term survival following AMI.
This national observational study included 693,388 patients (median age 70.7 years, 452,896 65.5% male) from the Myocardial Ischaemia National Audit Project (England and Wales) who were admitted with AMI between 1 January 2003 and 30 June 2013. There were 412,809 (59.5%) patients with multimorbidity at the time of admission with AMI, i.e., having at least 1 of the following long-term health conditions: diabetes, chronic obstructive pulmonary disease or asthma, heart failure, renal failure, cerebrovascular disease, peripheral vascular disease, or hypertension. Those with heart failure, renal failure, or cerebrovascular disease had the worst outcomes (39.5 95% CI 39.0-40.0, 38.2 27.7-26.8, and 26.6 25.2-26.4 deaths per 100 person-years, respectively). Latent class analysis revealed 3 multimorbidity phenotype clusters: (1) a high multimorbidity class, with concomitant heart failure, peripheral vascular disease, and hypertension, (2) a medium multimorbidity class, with peripheral vascular disease and hypertension, and (3) a low multimorbidity class. Patients in class 1 were less likely to receive pharmacological therapies compared with class 2 and 3 patients (including aspirin, 83.8% versus 87.3% and 87.2%, respectively; β-blockers, 74.0% versus 80.9% and 81.4%; and statins, 80.6% versus 85.9% and 85.2%). Flexible parametric survival modelling indicated that patients in class 1 and class 2 had a 2.4-fold (95% CI 2.3-2.5) and 1.5-fold (95% CI 1.4-1.5) increased risk of death and a loss in life expectancy of 2.89 and 1.52 years, respectively, compared with those in class 3 over the 8.4-year follow-up period. The study was limited to all-cause mortality due to the lack of available cause-specific mortality data. However, we isolated the disease-specific association with mortality by providing the loss in life expectancy following AMI according to multimorbidity phenotype cluster compared with the general age-, sex-, and year-matched population.
Multimorbidity among patients with AMI was common, and conferred an accumulative increased risk of death. Three multimorbidity phenotype clusters that were significantly associated with loss in life expectancy were identified and should be a concomitant treatment target to improve cardiovascular outcomes.
ClinicalTrials.gov NCT03037255.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In a randomized trial involving patients with high-risk vascular disease, the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers but was ...not associated with a lower rate of cardiovascular events than placebo.
Pharmacologic reduction of the low-density lipoprotein (LDL) cholesterol level with statins substantially decreases the risks of death and complications from cardiovascular causes.
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Considerable interest has focused on the identification of approaches that might further reduce cardiovascular-event rates among high-risk patients.
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Epidemiologic studies have shown inverse associations between high-density lipoprotein (HDL) cholesterol levels and cardiovascular outcomes,
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a correlation that persists despite treatment with statins.
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Nevertheless, therapeutic interventions that raise the HDL cholesterol level have not been shown to reduce cardiovascular risk.
Cholesteryl ester transfer protein (CETP) modulates the transfer of esterified cholesterol from HDL to apolipoprotein B–containing lipoproteins.
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Aims
Patients with non-valvular atrial fibrillation (AF) and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation. Rivaroxaban, an oral, direct factor Xa ...inhibitor metabolized predominantly by the liver, preserves the benefit of warfarin for stroke prevention while causing fewer intracranial and fatal haemorrhages.
Methods and results
We randomized 14 264 patients with AF in a double-blind trial to rivaroxaban 20 mg/day 15 mg/day if creatinine clearance (CrCl) 30-49 mL/min or dose-adjusted warfarin (target international normalized ratio 2.0-3.0). Compared with patients with CrCl >50 mL/min (mean age 73 years), the 2950 (20.7%) patients with CrCl 30-49 mL/min were older (79 years) and had higher event rates irrespective of study treatment. Among those with CrCl 30-49 mL/min, the primary endpoint of stroke or systemic embolism occurred in 2.32 per 100 patient-years with rivaroxaban 15 mg/day vs. 2.77 per 100 patient-years with warfarin hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.57-1.23 in the per-protocol population. Intention-to-treat analysis yielded similar results (HR 0.86; 95% CI 0.63-1.17) to the per-protocol results. Rates of the principal safety endpoint (major and clinically relevant non-major bleeding: 17.82 vs. 18.28 per 100 patient-years; P = 0.76) and intracranial bleeding (0.71 vs. 0.88 per 100 patient-years; P = 0.54) were similar with rivaroxaban or warfarin. Fatal bleeding (0.28 vs. 0.74% per 100 patient-years; P = 0.047) occurred less often with rivaroxaban.
Conclusion
Patients with AF and moderate renal insufficiency have higher rates of stroke and bleeding than those with normal renal function. There was no evidence of heterogeneity in treatment effect across dosing groups. Dose adjustment in ROCKET-AF yielded results consistent with the overall trial in comparison with dose-adjusted warfarin.
CONTEXT Although troponin assays have become increasingly more sensitive, it is unclear whether further reductions in the threshold of detection for plasma troponin concentrations will improve ...clinical outcomes in patients with suspected acute coronary syndrome (ACS). OBJECTIVE To determine whether lowering the diagnostic threshold for myocardial infarction (MI) with a sensitive troponin assay could improve clinical outcomes. DESIGN, SETTING, AND PATIENTS All consecutive patients admitted with suspected ACS to the Royal Infirmary of Edinburgh, Edinburgh, Scotland, before (n = 1038; February 1-July 31, 2008, during the validation phase) and after (n = 1054; February 1-July 31, 2009, during the implementation phase) lowering the threshold of detection for myocardial necrosis from 0.20 to 0.05 ng/mL with a sensitive troponin I assay were stratified into 3 groups (<0.05 ng/mL, 0.05-0.19 ng/mL, and ≥0.20 ng/mL). During the validation phase, only concentrations above the original diagnostic threshold of 0.20 ng/mL were reported to clinicians. MAIN OUTCOME MEASURE Event-free survival (recurrent MI and death) at 1 year in patients grouped by plasma troponin concentrations. RESULTS Plasma troponin concentrations were less than 0.05 ng/mL in 1340 patients (64%), 0.05 to 0.19 ng/mL in 170 patients (8%), and 0.20 ng/mL or more in 582 patients (28%). During the validation phase, 39% of patients with plasma troponin concentrations of 0.05 to 0.19 ng/mL were dead or had recurrent MI at 1 year compared with 7% and 24% of those patients with troponin concentrations of less than 0.05 ng/mL (P < .001) or 0.20 ng/mL or more (P = .007), respectively. During the implementation phase, lowering the diagnostic threshold to 0.05 ng/mL was associated with a lower risk of death and recurrent MI (from 39% to 21%) in patients with troponin concentrations of 0.05 to 0.19 ng/mL (odds ratio, 0.42; 95% confidence interval, 0.24-0.84; P = .01). CONCLUSIONS In patients with suspected ACS, implementation of a sensitive troponin assay increased the diagnosis of MI and identified patients at high risk of recurrent MI and death. Lowering the diagnostic threshold of plasma troponin was associated with major reductions in morbidity and mortality.
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