Randomized comparison of new dual-antiplatelet therapy (aspirin,prasugrel) and triple-antiplatelet therapy (aspirin,clopidogrel, cilostazol) using P2Y12 point-of-care assay in patients with STEMI undergoing primary PCI

Background

Both new dual antiplatelet therapy (DAT; aspirin and prasugrel) and triple antiplatelet therapy (TAT; aspirin, clopidogrel and cilostazol) are more potent than classic DAT (aspirin and clopidogrel). We compared the antiplatelet efficacy between new DAT and TAT in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary coronary percutaneous coronary intervention (PCI).

Methods

Forty patients who were eligible for primary PCI were prospectively randomized to DAT group (n = 20) or TAT group (n = 20) immediately after hospital arrival. The primary end point was P2Y12 reaction unit (PRU) determined with the VerifyNow P2Y12 point-of-care assay at the time of discharge.

Results

PRU value at discharge was significantly lower in patients receiving DAT compared with that of TAT (84.5 ± 44.7 vs. 128.4 ± 74.9, p = 0.032). Percent platelet inhibition was significantly higher for DAT compared with TAT at discharge (72.1 ± 12.2 vs. 57.5 ± 23.5, p = 0.020). Inter-patient variability of PRU values at discharge was significantly smaller in patient taking DAT compared with TAT (p = 0.026).

Conclusion

A new DAT is more potent antiplatelet therapy than TAT in patients with STEMI undergoing primary PCI.     

24-hour antiplatelet effect of aspirin in patients with previous definite stent thrombosis

Objective

Once-daily aspirin is standard treatment, but recent studies point towards increased platelet function at the end of the dosing interval. Stent thrombosis (ST) has been linked with reduced antiplatelet effect of aspirin, so we investigated if platelet inhibition by aspirin declines through 24 h in patients with previous definite ST. Furthermore, we explored whether increased levels of immature platelets and thrombopoietin are associated with a particularly rapid recovery of platelet function.

Methods

This case–control study included 50 patients with previous definite ST matched with 100 patients with stable coronary artery disease and 50 healthy volunteers. All participants were on aspirin 75 mg/day mono antiplatelet therapy. Platelet aggregation was measured 1 and 24 h after aspirin intake using platelet aggregometry (Multiplate^® Analyzer). Cyclooxygenase-1 activity, platelet activation, immature platelets, and thrombopoietin were measured.

Results

Platelet aggregation increased by 109 ± 150 (arachidonic acid) and 47 ± 155 (collagen) aggregation units per minute from 1 to 24 h after aspirin intake (p-values < 0.0001) with corresponding increases in thromboxane B₂ (5.6 ± 5.1 ng/ml, p < 0.0001) and soluble P-selectin (6.2 ± 15.5 ng/ml, p < 0.0001). Platelet aggregation increased equally in all groups, but patients with previous ST displayed the highest levels of platelet aggregation at 24 h (p-values ≤ 0.05) and the highest levels of immature platelets (p < 0.01) and thrombopoietin (p < 0.0001).

Conclusions

Platelet inhibition declined significantly during the 24-hour dosing interval in aspirin-treated patients with previous definite ST or stable coronary artery disease and in healthy individuals. Increased levels of immature platelets and thrombopoietin were observed in patients with previous definite ST.     

Low‐dose naproxen interferes with the antiplatelet effects of aspirin in healthy subjects: Recommendations to minimize the functional consequences

Objective

To investigate whether low‐dose naproxen sodium (220 mg twice a day) interferes with aspirin's antiplatelet effect in healthy subjects.

Methods

We performed a crossover, open‐label study in 9 healthy volunteers. They received for 6 days 3 different treatments separated by 14 days of washout: 1) naproxen 2 hours before aspirin, 2) aspirin 2 hours before naproxen, and 3) aspirin alone. The primary end point was the assessment of serum thromboxane B₂ (TXB₂) 24 hours after the administration of naproxen 2 hours before aspirin on day 6 of treatment. In 5 volunteers, the rate of recovery of TXB₂ generation (up to 72 hours after drug discontinuation) was assessed in serum and in platelet‐rich plasma stimulated with arachidonic acid (AA) or collagen.

Results

Twenty‐four hours after the last dosing on day 6 in volunteers receiving aspirin alone or aspirin before naproxen, serum TXB₂ was almost completely inhibited (median [range] 99.1% [97.4–99.4%] and 99.1% [98.0–99.7%], respectively). Naproxen given before aspirin caused a slightly lower inhibition of serum TXB₂ (median [range] 98.0% [90.6–99.4%]) than aspirin alone (P = 0.0007) or aspirin before naproxen (P = 0.0045). All treatments produced a maximal inhibition of AA‐induced platelet aggregation. At 24 hours, compared with baseline, collagen‐induced platelet aggregation was still inhibited by aspirin alone (P = 0.0003), but not by aspirin given 2 hours before or after naproxen. Compared with administration of aspirin alone, the sequential administration of naproxen and aspirin caused a significant parallel upward shift of the regression lines describing the recovery of platelet TXB₂.

Conclusion

Sequential administration of 220 mg naproxen twice a day and low‐dose aspirin interferes with the irreversible inhibition of platelet cyclooxygenase 1 afforded by aspirin. The interaction was smaller when giving naproxen 2 hours after aspirin. The clinical consequences of these 2 schedules of administration of aspirin with naproxen remain to be studied in randomized clinical trials.

     

Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials

Purpose

We performed a systematic review to define the relative and absolute risk of clinically relevant adverse events with the antiplatelet agents, aspirin and clopidogrel.

Materials and methods

Databases were searched for randomized controlled trials of low-dose aspirin (75-325 mg/dayay) or clopidogrel administered for cardiovascular prophylaxis. Relative risks (RR) were determined by meta-analysis of 22 trials for aspirin versus placebo and from single studies for aspirin versus clopidogrel, aspirin versus aspirin/clopidogrel, and clopidogrel versus aspirin/clopidogrel. Absolute risk increase was calculated by multiplying RR increase by the pooled weighted incidence of the control.

Results

Aspirin increased the risk of major bleeding (RR = 1.71; 95% confidence interval [CI], 1.41-2.08), major gastrointestinal (GI) bleeding (RR = 2.07; 95% CI, 1.61-2.66), and intracranial bleeding (RR = 1.65; 95% CI, 1.06-5.99) versus placebo. No difference between 75-162.5 mg/day and >162.5-325 mg/day aspirin versus placebo was seen. The absolute annual increases attributable to aspirin were major bleeding: 0.13% (95% CI, 0.08-0.20); major GI bleeding: 0.12% (95% CI, 0.07-0.19), intracranial bleeding: 0.03% (95% CI, 0.01-0.08). No study compared clopidogrel with placebo. One study showed increased major GI bleeding (but not non-GI bleeding endpoints) with aspirin versus clopidogrel (RR = 1.45; 95% CI, 1.00-2.10). The absolute annual increase was 0.12% (95% CI, 0.00-0.28).

Conclusions

Low-dose aspirin increases the risk of major bleeding by ∼70%, but the absolute increase is modest: 769 patients (95% CI, 500-1250) need to be treated with aspirin to cause one additional major bleeding episode annually. Compared with clopidogrel, aspirin increases the risk of GI bleeding but not other bleeding; however, 883 patients (95% CI, 357-∞) would need to be treated with clopidogrel versus aspirin to prevent one major GI bleeding episode annually at a cost of over 1 million dollars.     

Imbalance between pro-angiogenic and anti-angiogenic factors in rheumatic and mixomatous mitral valves

Background

A balance between angiogenic and anti-angiogenic factors is critical in tissue development, tissue repair and homeostasis. Aberrant angiogenesis has been implicated in several pathologic conditions, including valvular heart disease. The aim of this study was to ascertain the pathogenetic role of angiogenesis in rheumatic and mixomatous mitral valve diseases.

Methods

Leaflets from mixomatous (n = 20) and rheumatic (n = 20) mitral valves removed from surgical patients, and normal mitral valve (n = 6) obtained at autopsy were collected. Immunohistochemical studies were performed on sequential valve sections, evaluating CD31, CD34, α smooth muscle actin (α-SMA), vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR1), VEGF receptor-2 (VEGFR-2), and chondromodulin-I (Chm-I).

Results

Immunohistochemistry revealed significant differences among groups in CD31 (p = 0.001), CD34 (p < 0.001), α-SMA (p < 0.001), VEGF (p < 0.001), VEGFR1 (p = 0.007), VEGFR2 (p = 0.011), and Chm-I (p < 0.001) expressions. Rheumatic valves demonstrated a severe up-regulation and down-regulation in pro-angiogenic and anti-angiogenic factors, respectively, compared with mixomatous and normal mitral valves. On the contrary, mixomatous valves showed a significant up-regulation of anti-angiogenic factors with respect to rheumatic and normal valves.

Conclusions

These findings provide evidence that an imbalance between pro-angiogenic and anti-angiogenic factors is implicated in mitral valve disease. Pro-angiogenic factors are up-regulated in rheumatic disease, while anti-angiogenic ones in mixomatous mitral valves.     

Pathophysiology of coronary blood flow in congenital heart disease

Objectives

The aim was to investigate the effects of volume and pressure overload and increased coronary perfusion pressure on coronary flow (CF) in congenital heart disease (CHD) patients.

Background

The effects of CHD on CF are poorly mapped.

Methods

A total of 65 patients with acyanotic CHD and 49 age-matched healthy controls were examined by transthoracic Doppler echocardiography. Posterior descending artery flow was measured in patients with pulmonary valve stenosis (PS) and atrial septal defects (ASDs) i.e. in lesions with right ventricular pressure or volume overload, and left anterior descending artery flow in patients with coarctation of the aorta (CoA) and ventricular septal defect (VSD), in lesions with left ventricular pressure or volume overload. The CF data in each patient group were expressed as the percent of the median for healthy controls from the same age group.

Results

The CF values were in VSD 172%, ASD 185%, PS 233%, and CoA 773% patients. In CoA patients body surface area (r = 0.90, p < 0.0001), systolic blood pressure (r = 0.72, p < 0.0001), diastolic blood pressure (r = 0.77, p < 0.0001), systolic wall tension (r = −0.77, p = 0.004), and signs of inflammation (log CRP, r = −0.75, p = 0.007) correlated with CF.

Conclusions

The increase in CF and velocity was most significant in patients with CoA. In newborns, increased coronary perfusion pressure seems to be the most important factor for increased CF, even if the pressure is not assumed to cause a significant increase in flow over the auto-regulatory range of 70-130 mm Hg. We also showed that inflammation decreases CF.     

Low-level environmental exposure to lead and progressive chronic kidney diseases

Purpose

To determine whether low-normal body lead burden (BLB) accelerates progressive renal insufficiency in nondiabetic patients with chronic kidney diseases (CKD).

Methods

One hundred eight CKD patients (serum creatinine between 1.5 and 2.9 mg/dL) with low-normal BLB (<80 μg) and no lead exposure history were observed for 24 months. Following the observation, 32 patients with low-normal BLB (≥20 μg and <80 μg) were randomly assigned to chelation and control groups. The chelation group patients were given edetate calcium disodium (EDTA) chelation therapy for 3 months and repeated chelation therapy during the following 24 months to maintain their BLB below 20 μg, while the control group patients underwent placebo therapy. The primary endpoint was an increased serum creatinine level to 1.25 times the baseline value. The secondary endpoint was temporal changes in renal function.

Results

The primary endpoint occurred in 14 patients in the observation period. Baseline BLB was the important risk factor in determining progressive renal insufficiency. The mean glomerular filtration rate (GFR) change in the chelation group patients was 6.6 ± 10.7 mL/min/1.73m², compared with −4.6 ± 4.3 mL/min/1.73m² in control group patients (P <.001) at the end of the intervention period. The mean decrease in GFR per year of chelation group patients was lower than that of control group patients during the repeated chelation period.

Conclusion

Environmental exposure to lead, even at low level, may accelerate progressive renal insufficiency of nondiabetic patients with CKD.     

Abnormal hyperventilation in patients with hepatic cirrhosis: Role of enhanced chemosensitivity to carbon dioxide

Background

Patients with hepatic cirrhosis frequently show idiopathic hyperventilation at rest, despite no concomitant cardiopulmonary disease. The aim of the study was to determine whether altered chemosensitivity either to hypoxia or hypercapnia could underlie inappropriate hyperventilation in cirrhotic patients.

Methods

We consecutively recruited 30 biopsy proven cirrhotic patients equally distributed in the three Child's classes A, B and C (age 54 ± 8 years, mean ± SD). All patients underwent evaluation of chemosensitivity to hypoxia and to hypercapnia and blood sampling for brain natriuretic peptide, norepinephrine and progesterone, besides full clinical characterization. We also recruited 10 age- and gender-matched healthy controls (age 55 ± 7 years).

Results

Overall, 18 patients (60%) showed an increased chemosensitivity to carbon dioxide (CO₂), while 8 patients (27%) showed enhanced chemosensitivity to hypoxia. Child's class C patients had lower arterial partial pressure of CO₂ (PaCO₂), higher rest ventilation, increased chemosensitivity to hypercapnia, plasma level of norepinephrine and serum progesterone levels when compared to class A patients and controls (all p < 0.05). Rest ventilation was positively related to pH (R = 0.41, p = 0.023), chemosensitivity to hypercapnia (R = 0.54, p = 0.002), and progesterone (R = 0.53, p = 0.016) and negatively to PaCO₂ (R = 0.61, p < 0.001), but not to hemoglobin level and chemosensitivity to hypoxia. Chemosensitivity to hypercapnia was positively related to PaCO₂ (R = 0.74, p < 0.001), serum progesterone (R = 0.50, p = 0.016), and to plasma norepinephrine (R = 0.57, p = 0.004).

Conclusions

Enhanced chemosensitivity to hypercapnia was found in more decompensated cirrhotic patients and was associated with sympathetic overactivity and elevated serum progesterone, likely representing a key mechanism underlying the “unexplained” hyperventilation observed in such patients.     

New-onset diabetes and cardiovascular events in essential hypertensives: A 6-year follow-up study

Background

Controversy still exists regarding the impact of new-onset diabetes (NOD) on CV outcomes among patients with hypertension. Our aim was to determine the incidence of NOD in essential hypertensives and to evaluate its association with major cardiovascular (CV) events.

Methods

We followed-up for a mean period of 6 years 1572 essential hypertensives (mean age 54.3 years, 696 males) for the incidence of NOD, as well as of fatal and non-fatal coronary artery disease and stroke. Based on the development of NOD, the cohort was divided into patients with pre-existing diabetes (10%), patients with NOD (10%) and those who remained free from diabetes.

Results

During the follow-up period, new or recurrent cases of coronary artery disease and stroke events occurred at a rate of 5.6% (n = 88) and 4.65% (n = 73). The independent predictors for NOD were age (OR = 1.026, p = 0.041), waist circumference (OR = 1.044, p < 0.001), family history of diabetes (OR = 2.173, p = 0.003) and systolic BP at follow-up (OR 1.022, p = 0.044). The presence of NOD was independently associated with greater incidence of stroke (HR 2.404, p = 0.046), along with age (HR 1.078, p < 0.001), duration of hypertension (HR 1.039, p = 0.017) and office systolic blood pressure at follow-up (HR 1.022, p = 0.026), whereas development of NOD had no relationship with the incidence of coronary artery disease.

Conclusions

Our findings indicate the high incidence of NOD and its close association with stroke in essential hypertension. Poorer control of hypertension appears to be a common denominator of both NOD and stroke in this setting.     

Platelet Activation Is Associated With Myocardial Infarction in Patients With Pneumonia

Background

Troponins may be elevated in patients with pneumonia, but associations with myocardial infarction (MI) and with platelet activation are still undefined.

Objectives

The aim of this study was to investigate the relationship between troponin elevation and in vivo markers of platelet activation in the early phase of hospitalization of patients affected by community-acquired pneumonia.

Methods

A total of 278 consecutive patients hospitalized for community-acquired pneumonia, who were followed up until discharge, were included. At admission, platelet activation markers such as plasma soluble P-selectin, soluble CD40 ligand, and serum thromboxane B₂ (TxB₂) were measured. Serum high-sensitivity cardiac troponin T levels and electrocardiograms were obtained every 12 and 24 h, respectively.

Results

Among 144 patients with elevated high-sensitivity cardiac troponin T, 31 had signs of MI and 113 did not. Baseline plasma levels of soluble P-selectin and soluble CD40 ligand and serum TxB₂ were significantly higher in patients who developed signs of MI. Logistic regression analysis showed plasma soluble CD40 ligand (p < 0.001) and soluble P-selectin (p < 0.001), serum TxB₂ (p = 0.030), mean platelet volume (p = 0.037), Pneumonia Severity Index score (p = 0.030), and ejection fraction (p = 0.001) to be independent predictors of MI. There were no significant differences in MI rate between the 123 patients (45%) taking aspirin (100 mg/day) and those who were not aspirin treated (12% vs. 10%; p = 0.649). Aspirin-treated patients with MIs had higher serum TxB₂ compared with those without MIs (p = 0.005).

Conclusions

MI is an early complication of pneumonia and is associated with in vivo platelet activation and serum TxB₂ overproduction; aspirin 100 mg/day seems insufficient to inhibit thromboxane biosynthesis. (MACCE in Hospitalized Patients With Community-acquired Pneumonia; NCT01773863)     

Cardiovascular risk in obesity: Different activation of inflammation and immune system between obese and morbidly obese subjects

Background

Both inflammation and immunity are involved in the development and progression of atherosclerosis. Obesity is considered a major modifiable cardiovascular risk factor, however, the correlation between increasing degrees of obesity and cardiovascular risk is not clear yet. Aim of our study was to investigate how different degrees of obesity are associated with inflammation and immune system responses.

Methods

One-hundred healthy individuals were divided into 3 groups according to body mass index (BMI): 22 overweight (OW), 26 obese (O) and 52 morbidly obese (MO). High-sensitivity C-Reactive Protein (hs-CRP, immunonephelometry), leptin (radio-immunoassay) and CD4⁺CD28^nullT-lymphocytes (flow-cytometry), a particular subset of T-lymphocytes with pro-atherogenic and plaque-destabilizing properties, were assessed.

Results

hs-CRP levels were significantly higher in O vs OW (p = 0.036), in MO vs OW (p < 0.001) and in MO vs O (p = 0.012). Similarly, leptin levels were higher in O vs OW (p = 0.02), in MO vs OW (p < 0.001) and in MO vs O (p < 0.001). CD4⁺CD28^nullT-lymphocytes were higher in O vs OW (p < 0.001), in O vs MO (p = 0.03) and in MO vs OW (p = 0.01). hs-CRP and leptin levels significantly correlated each other (r = 0.39; p < 0.001) and with waist circumference (r = 0.52; p < 0.001; r = 0.64; p < 0.001) and BMI (r = 0.60; p < 0.001; r = 0.74; p < 0.001).

Conclusions

Our study demonstrates that, notwithstanding higher levels of inflammation, MO are characterized by less detrimental immune activation, as shown by the reduced CD4⁺CD28^nullT-cells expansion as compared to OW and O, which might translate in less immune vascular injury. These findings suggest that MO might represent a particular population, in which different pathophysiological mechanisms take part if compared with “classic” obesity.     

Local persistent hypercoagulability after sirolimus-eluting stent implantation in patients with stable angina

Background

Late stent thrombosis (LST) after sirolimus-eluting stent (SES) implantation has been demonstrated previously. Although incomplete neointimal coverage after SES implantation has been reported, local long-term hypercoagulability remains unknown.

Methods

We evaluated the local persistent coagulative response in eighty-three consecutive patients with stable angina, treated with either SES (n = 51) or BMS (n = 32) implantation for isolated de novo left anterior descending (LAD) stenosis. We measured prothrombin fragment F1 + 2 (frF1 + 2) and D-dimer levels sampled in the coronary sinus (CS) and sinus of Valsalva (V). The transcardiac gradient (Δ) was defined as the CS level minus V level.

Results

The ΔfrF1 + 2 and ΔD-dimer were significantly greater in the SES group than in the BMS group (0.50 ± 0.35 vs −0.14 ± 0.15 nmol/l, p = 0.009 and 0.24 ± 0.21 vs −0.05 ± 0.16 μg/ml, p = 0.041, respectively). We selected the hypocoagulative [ΔfrF1 + 2 < 0.15 (mean value − SD) nmol/l, n = 21] and hypercoagulative [ΔfrF1 + 2 > 0.85 (mean value + SD) nmol/l, n = 14] groups out of the SES patients. Multivariate analysis was performed to identify independent predictors of local hypercoagulability. Total SES length was the only independent predictor of local hypercoagulability. There was a significant positive correlation between the ΔfrF1 + 2 and total stent length in the SES group (r = 0.57, p < 0.05).

Conclusions

An increased local coagulative response was observed in the convalescent phase after SES implantation as compared to BMS. Careful long-term follow-up of patients after longer SES implantation is recommended in order to avoid LST.     

Flow-induced changes in pial artery compliance registered with a non-invasive method in rabbits

Aim

This study was performed: 1) to assess the relationship between blood flow velocity in the internal carotid artery (CBF_ICA) and pial artery pulsation (cc-TQ) and 2) to evaluate flow-induced changes in pial artery compliance.

Methods

Experiments were performed on 10 crossbred male rabbits. Heart rate (HR), blood pressure (BP), left ventricle ejection fraction (LVEF), CBF_ICA, the systolic-diastolic blood volume fraction in the brain circulation (CBF_SDF) and cc-TQ were recorded after glucagon and acetazolamide administration. cc-TQ was measured with near-infrared transillumination back scattering sounding (NIR-T/BSS), LVEF and CBF_SDF with gated scintigraphy and BP and CBF_ICA with electromagnetic pressure and flow transducers, respectively. Doses of drugs were chosen to exert a haemodynamic effect but not change BP or intracranial pressure.

Results

Acetazolamide and glucagon evoked significant increases in cc-TQ, CBF_SDF, CBF_ICA, LVEF and HR. The following interdependencies were found: 1) changes after acetazolamide administration compared to baseline: CBF_SDF vs. LVEF (r = 0.73, p < 0.05), cc-TQ vs. CBF_SDF (r = − 0.67, p < 0.05), cc-TQ vs. LVEF (r = − 0.76, p < 0.05), 2) changes after glucagon administration compared to baseline: CBF_ICA vs. BP (r = 0.73, p < 0.05), CBF_SDF vs. LVEF (r = 0.87, p < 0.05), cc-TQ vs. HR (r = 0.85, p < 0.05), cc-TQ vs. CBF_ICA (r = − 0.74, p < 0.05).

Conclusion

In the absence of systemic BP changes, pial arteries are significantly affected by changes in CBF_ICA. Pial arteries counteract changes in CBF_ICA and CBF_SDF. The ability of pial arteries to stabilise CBF_ICA is impaired after acetazolamide administration. Changes in cardiac output directly affect the brain's microcirculation. NIR-T/BSS recordings allow for non-invasive assessment of changes in pial artery compliance.     

Myocardial iron overload assessed by magnetic resonance imaging (MRI)T2* in multi-transfused patients with thalassemia and acquired anemias

Background

Cardiac complications secondary to iron overload remain a significant matter in patients with transfusion dependent anemias.

Patients and methods

To evaluate cardiac siderosis, Magnetic resonance imaging T2* (MRI T2*) was performed in 3 cohorts of transfusion dependent patients: 99 with thalassemia major (TM), 20 with thalassemia intermedia (TI), and 10 with acquired anemias (AA). Serum ferritin was measured and all patients underwent echocardiographic evaluation.

Results

In TM patients cardiac T2* pathologic values (below 20 ms) were found in 37 patients. Serum ferritin was negatively associated with age (r = −0.32, p = 0.001) and weakly with T2* values (r = −0.19, p = 0.057). A positive correlation was found between T2* and LVEF (r = 0.27, p = 0.006). Out of 37 patients with T2* < 20 ms, 18 (48%) had serum ferritin values < 1000 ng/ml. In TI cohort, 3 patients had cardiac T2* pathologic values. In AA cohort, pathologic T2* values were found in 2 patients, who received 234 and 199 PRBC units, respectively, and were both on chelation therapy (in one patient ferritin value was 399 ng/ml). T2* values were negatively associated, but not significantly, with the number of PRBC transfused (r = −0.53, p = 0.07).

Conclusion

In our experience, 37% of TM patients had a myocardial iron overload assessed by MRI T2*; this value is higher than in TI patients. Serum ferritin measurement was a poor predictor of myocardial siderosis. In patients with AA, more than 200 PRBC units transfused were required to induce cardiac hemosiderosis, in spite of chelation therapy and, in one patient, of normal ferritin values.     

Aspirin resistance and adverse clinical events in patients with coronary artery disease

Purpose

We sought to determine the clinical significance of aspirin resistance measured by a point-of-care assay in stable patients with coronary artery disease (CAD).

Methods

We used the VerifyNow Aspirin (Accumetrics Inc, San Diego, Calif) to determine aspirin responsiveness of 468 stable CAD patients on aspirin 80 to 325 mg daily for ≥4 weeks. Aspirin resistance was defined as an Aspirin Reaction Unit ≥550. The primary outcome was the composite of cardiovascular death, myocardial infarction (MI), unstable angina requiring hospitalization, stroke, and transient ischemic attack.

Results

Aspirin resistance was noted in 128 (27.4%) patients. After a mean follow-up of 379 ± 200 days, patients with aspirin resistance were at increased risk of the composite outcome compared to patients who were aspirin-sensitive (15.6% vs 5.3%, hazard ratio [HR] 3.12, 95% confidence intervals [CI], 1.65-5.91, P < .001). Cox proportional hazard regression modeling identified aspirin resistance, diabetes, prior MI, and a low hemoglobin to be independently associated with major adverse long-term outcomes (HR for aspirin resistance 2.46, 95% CI, 1.27-4.76, P = .007).

Conclusions

Aspirin resistance, defined by an aggregation-based rapid platelet function assay, is associated with an increased risk of adverse clinical outcomes in stable patients with CAD.     

Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis

Objective

Many recommendations for aspirin in stable cardiovascular disease are based on analyses of all antiplatelet therapies at all dosages and in both stable and unstable patients. Our objective was to evaluate the benefit and risk of low-dose aspirin (50-325 mg/d) in patients with stable cardiovascular disease.

Methods

Secondary prevention trials of low-dose aspirin in patients with stable cardiovascular disease were identified by searches of the MEDLINE database from 1966 to 2006. Six randomized trials were identified that enrolled patients with a prior myocardial infarction (MI) (n = 1), stable angina (n = 1), or stroke/transient ischemic attack (n = 4). A random effects model was used to combine results from individual trials.

Results

Six studies randomized 9853 patients. Aspirin therapy was associated with a significant 21% reduction in the risk of cardiovascular events (nonfatal MI, nonfatal stroke, and cardiovascular death) (95% confidence interval [CI], 0.72-0.88), 26% reduction in the risk of nonfatal MI (95% CI, 0.60-0.91), 25% reduction in the risk of stroke (95% CI, 0.65-0.87), and 13% reduction in the risk of all-cause mortality (95% CI, 0.76-0.98). Patients treated with aspirin were significantly more likely to experience severe bleeding (odds ratio 2.2, 95% CI, 1.4-3.4). Treatment of 1000 patients for an average of 33 months would prevent 33 cardiovascular events, 12 nonfatal MIs, 25 nonfatal strokes, and 14 deaths, and cause 9 major bleeding events. Among those with ischemic heart disease, aspirin was most effective at reducing the risk of nonfatal MI and all-cause mortality; however, among those with cerebrovascular disease, aspirin was most effective at reducing the risk of stroke.

Conclusion

In patients with stable cardiovascular disease, low-dose aspirin therapy reduces the incidence of adverse cardiovascular events and all-cause mortality, and increases the risk of severe bleeding.     

Short-term prevention of thromboembolic complications in patients with atrial fibrillation with aspirin plus clopidogrel: the Clopidogrel-Aspirin Atrial Fibrillation (CLAAF) pilot study

Background

We evaluated the short-term safety and efficacy of aspirin-plus-clopidogrel as antithrombotic therapy in nonvalvular atrial fibrillation (AF).

Methods and results

Thirty patients (11 women, 45 to 75 years of age) with non-high-risk permanent (n = 12) or persistent AF awaiting cardioversion (n = 18) underwent transesophageal echocardiography to exclude left heart thrombi and were then randomly assigned to receive warfarin (international normalized ratio, 2 to 3 for 3 weeks) or aspirin (100 mg/d alone for 1 week)-plus-clopidogrel (75 mg/d added to aspirin for 3 weeks). Bleeding time and serum thromboxane B2 were measured at entry and at 3 weeks. Bleeding time, not affected by warfarin, was prolonged by 71% by aspirin (P < .05) and further, by 144%, by adding clopidogrel (P < .01 vs aspirin alone; +319%, P < .01, vs baseline). Thromboxane B2, not affected by warfarin, was reduced by aspirin (−98%, P < .01) but not further by clopidogrel. No thrombi or dense spontaneous echo-contrast were found at the 3-week transesophageal echocardiography. Seven of 9 patients receiving warfarin and 7 of 9 patients receiving aspirin-plus-clopidogrel, undergoing electrical cardioversion, achieved sinus rhythm. No thromboembolic or hemorrhagic events occurred in both arms throughout the 3-week treatment and a further 3-month follow-up.

Conclusions

Aspirin-plus-clopidogrel and warfarin were equally safe and effective in preventing thromboembolism in this small group of patients with non-high-risk AF.     

Targeting dietary fat or glycemic load in the treatment of obesity and type 2 diabetes: a randomized controlled trial

Aims

To compare the effects of lifestyle modification programs that prescribe low-glycemic load (GL) vs. low-fat diets in a randomized trial.

Methods

Seventy-nine obese adults with type 2 diabetes received low-fat or low-GL dietary instruction, delivered in 40-week lifestyle modification programs with identical goals for calorie intake and physical activity. Changes in weight, HbA_1c, and other metabolic parameters were compared at weeks 20 and 40.

Results

Weight loss did not differ between groups at week 20 (low-fat: −5.7 ± 3.7%; low-GL: −6.7 ± 4.4%, p = .26) or week 40 (low-fat: −4.5 ± 7.5%; low-GL: −6.4 ± 8.2%, p = .28). Adjusting for changes in antidiabetic medications, subjects on the low-GL diet had larger reductions in HbA_1c than those on the low-fat diet at week 20 (low-fat: −0.3 ± 0.6%; low-GL: −0.7 ± 0.6%, p = .01), and week 40 (low-fat: −0.1 ± 1.2%; low-GL: −0.8 ± 1.3%; p = .01). Groups did not differ significantly on any other metabolic outcomes (p ≥ .06).

Conclusions

Results suggest that targeting GL, rather than dietary fat, in a low-calorie diet can significantly enhance the effect of weight loss on HbA_1c in patients with type 2 diabetes.     

Abnormal heart rate recovery on exercise in ankylosing spondylitis

Objectives

This study evaluated the heart rate recovery response in ankylosing spondylitis (AS) patients and control subjects.

Background

Delayed heart rate recovery after exercise reflects AD and independently predicts adverse cardiac outcome.

Methods

Fifty-one patients with AS and 50 age- and matched controls received electrocardiography, echocardiography, and treadmill exercise testing. The heart rate recovery (HRR) index was calculated as the reduction in heart rate from the rate at peak exercise to the rate at the 1st (HRR₁), 2nd (HRR₂), 3rd (HRR₃) and 5th (HRR₅) minute after the cessation of exercise stress testing.

Results

There were significant differences in HRR₁ and HRR₂ indices between patients and controls (24.8 ± 12.1 vs 34.9 ± 11.0; p < 0.001 and 41.2 ± 14.2 vs 54.3 ± 11.8; p < 0.001, beats/min, respectively). Similarly, HRR₃ and HRR₅ indices were lower in patients than controls (51.3 ± 15.1 vs 65.2 ± 14.0; p < 0.001 and 61.0 ± 14.2 vs 76.1 ± 14.8; p < 0.001). In addition, exercise capacity was markedly lower (8.1 ± 2.0 vs 10.5 ± 2.5 METs; p < 0.001) in AS than controls.

Conclusion

The HRR index is impaired in AS patients, implying the occurrence of autonomic dysfunction even without active joint disease or frank cardiac involvement.     

Evaluación de la musculatura respiratoria en la predicción del resultado de la extubación de pacientes con ictus

Background

Patients with cerebral infarction often present impaired consciousness and unsatisfactory extubation. We aimed to assess the respiratory mechanics components that might be associated with the success of extubation in stroke patients.

Methods

Twenty consecutive patients with stroke who needed mechanical ventilation support were enrolled. The maximal inspiratory pressure, gastric and the esophageal pressure (Pdi/Pdimax), minute volume, respiratory rate, static compliance, airway resistance, rapid and superficial respiration index (RSRI), inspiratory time/total respiratory cycle (Ti/Ttot), and PaO₂/FiO₂ were measured.

Results

The group who presented success to the extubation process presented 12.5 ± 2.2 = days in mechan-ical ventilation and the group who failed presented 13.1 ± 2 = days. The mean Ti/Ttot and Pdi/Pdimax for the failure group was 0.4 ± 0.08 (0.36-0.44) and 0.5 ± 0.7 (0.43-0.56), respectively. The Ti/Ttot ratio was 0.37 ± 0.05 (0.34-0.41; p = 0.0008) and the Pdi/Pdimax was 0.25 ± 0.05 for the success group (0.21-0.28; p < 0.0001). A correlation was found between Pdi/Pdimax ratio and the RSRI (r = 0.55; p = 0.009) and PaO₂/FiO₂ (r = −0.59; p = 0.005). Patients who presented a high RSRI (OR, 3.66; p = 0.004) and Pdi (OR, 7.3; p = 0.002), and low PaO₂/FIO₂ (OR, 4.09; p = 0.007), Pdi/Pdimax (OR, 4.12; p = 0.002) and RAW (OR, 3.0; p = 0.02) developed mechanical ventilation extubation failure.

Conclusion

Muscular fatigue index is an important predicting variable to the extubation process in prolonged mechanical ventilation of stroke patients.