Effect of amlodipine on platelet inhibition by clopidogrel in patients with ischaemic heart disease: a randomised, controlled trial.

BACKGROUND: Amlodipine inhibits cytochrome P450 (CYP) enzyme and has the potential to reduce clopidogrel bioactivation in vivo. Reports in previous retrospective studies described greater platelet reactivity in patients on amlodipine. OBJECTIVE: To evaluate the treatment effect of clopidogrel in patients on amlodipine versus not on calcium-channel blockers (CCBs). DESIGN AND SETTING: Randomised, controlled, open-label trial conducted in a regional acute hospital. PATIENTS AND INTERVENTIONS: 98 patients on clopidogrel for ischaemic heart disease were recruited consecutively and randomised to take either amlodipine or drugs with inert CYP effects as controls. The P2Y12 reaction unit (PRU) was measured using whole blood obtained at baseline and on day 28. MAIN OUTCOME MEASURES: The primary analysis involved the PRU values on day 28. The secondary analyses were percentage of platelet inhibition and poor response to clopidogrel as defined by PRU>235. RESULTS: Both groups experienced comparable day 28 PRUs (amlodipine 227±84 vs control 214±90; mean difference 12.7, 95% CI -22 to +47). Percentage of platelet inhibition (amlodipine 33% vs control 38%, mean difference -4.5%, 95% CI -14% to +5%) and those with poor response on day 28 (amlodipine 49% vs control 45%; p=0.76) did not differ significantly. CONCLUSIONS: Concomitant amlodipine has no negative impact on clopidogrel-mediated platelet inhibition in patients with ischaemic heart disease.

Attainment of normal lipid levels among patients on lipid-modifying therapy in Hong Kong.

INTRODUCTION: Although low-density lipoprotein cholesterol (LDL-C) is the primary lipid target for coronary heart disease (CHD) risk reduction, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) have also emerged as CHD risk factors. The objective of this study was to evaluate attainment of lipid goals and normal levels following lipid-modifying therapy (LMT) and its predictors in a representative sample of Chinese patients from Hong Kong. METHODS: Using longitudinal data collected from patient medical records, the study identified 706 patients who initiated LMT from January 2004 to December 2006 and had full lipid panels 12 months before and after therapy. LDL-C goals and normal levels of HDL-C and TG were defined according to the National Cholesterol Education Program Adult Treatment Panel 3 guidelines. Patients with previous CHD, diabetes, and 10-year CHD risk > 20% were classified as high risk. Multiple logistic regressions evaluated predictors of normal lipid-level attainment. RESULTS: Among 706 patients (mean age 64.6 years, 58.6% male), 71.7% had elevated LDL-C, 32.4% had low HDL-C, and 24.9% had elevated TG before LMT. Despite therapy (91.2% statins only), 22.7% had elevated LDL-C, 31.9% had low HDL-C, 12.3% had elevated TG, and 13.9% had multiple abnormal lipid levels. The strongest predictors of attaining ≥ 2 normal lipid levels included male gender (odds ratio [OR]: 2.11 [1.12 to 4.01]), diabetes (OR: 0.43 [0.23 to 0.78]), obesity (OR: 0.91 [0.86 to 0.97]), and CHD risk > 20% (OR: 0.33 [0.15 to 0.71]). CONCLUSIONS: Current approaches to lipid management in Hong Kong, primarily using statins, considerably improve attainment of LDL-C goal. However, a large proportion of patients do not achieve normal HDL-C levels and control of multiple lipid parameters remains poor. Patients could benefit from a more comprehensive approach to lipid management that treats all three lipid risk factors, as suggested in clinical guidelines.

Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction.

OBJECTIVES: Little is known about the efficacy of proton pump inhibitors compared with H(2) receptor antagonists in preventing adverse upper gastrointestinal complications in patients with acute coronary syndrome (ACS) or ST elevation myocardial infarction (STEMI) receiving aspirin, clopidogrel, and enoxaparin or thrombolytics. The objective of this study was to compare the efficacies of esomeprazole and famotidine in preventing gastrointestinal complications. METHODS: A double-blind, randomized, controlled trial was performed in patients receiving a combination of aspirin, clopidogrel, and either enoxaparin or thrombolytics. Patients received either esomeprazole (20 mg nocte) or famotidine (40 mg nocte) orally for 4-52 weeks, depending on the duration of dual antiplatelet therapy. The primary end point was upper gastrointestinal bleeding (GIB), perforation, or obstruction from ulcer/erosion (http://www.clinicaltrials.gov NCT00683111). RESULTS: In all, 311 patients were recruited, with 163 and 148 patients in the esomeprazole and famotidine groups, respectively. Mean (s.d.) follow-up was 19.2 (17.6) and 17.6 (18.0) weeks, respectively. One (0.6%) patient in the esomeprazole group and 9 (6.1%) in the famotidine group reached the primary end point (log-rank test, P=0.0052, hazard ratio=0.095, 95% confidence interval: 0.005-0.504); all had upper GIB. CONCLUSIONS: In patients with ACS or STEMI, esomeprazole is superior to famotidine in preventing upper gastrointestinal complications related to aspirin, clopidogrel, and enoxaparin or thrombolytics.

Predictive value of auricular diagnosis on coronary heart disease.

The ear has a reflexive property; therefore, various physical attributes may appear on the auricle when disorders of the internal organs or other parts of the body exist. Auricular diagnostics is an objective, painless, and noninvasive method that provides rapid access to information. Thus, the association between auricular signals and coronary heart disease (CHD) should be further investigated. A case control study was conducted to determine the predictive value of auricular signals on 100 cases of CHD (CHD+ve = 50; CHD-ve = 50) via visual inspection, electrical skin resistance measurement, and tenderness testing. The results showed that the presence of an ear lobe crease (ELC) was significantly associated with coronary heart disease. The "heart" zone of the CHD+ve group significantly exhibited higher conductivity on both ears than that of the controls. The CHD+ve group experienced significant tenderness in the "heart" region compared with those in the CHD-ve group in both acute and chronic conditions. Further studies that take into consideration the impact of age, race, and earlobe shape on ELC prevalence in a larger sample should be done.

Effect of esomeprazole versus famotidine on platelet inhibition by clopidogrel: a double-blind, randomized trial.

BACKGROUND: Previous studies showed that esomeprazole does not interfere significantly with the platelet inhibitory effect of clopidogrel. It is unknown whether famotidine, a histamine 2 receptor antagonist, interacts with clopidogrel. This double-blind, randomized study aimed to compare the influence of esomeprazole and famotidine on the platelet inhibitory effect of clopidogrel. METHODS: Patients with acute coronary syndrome or elective percutaneous coronary interventions treated with aspirin and clopidogrel cotherapy were randomized to receive esomeprazole 20 mg daily or famotidine 40 mg daily. Platelet reactivity units (PRUs) were measured at baseline and on day 28. The primary analysis involved the PRU values on day 28. RESULTS: There were 44 patients in the esomeprazole group and 44 in the famotidine group. The baseline PRUs of the 2 groups were comparable (esomeprazole vs famotidine, 229.1 ± 85.6 vs 220.4 ± 83.0, P = .63). The PRUs on day 28 were 242.6 ± 89.7 and 237.5 ± 79.2 in the groups receiving esomeprazole and famotidine, respectively (mean difference 5.1, 95% CI -30.8 to 41.0, P = .78). CONCLUSIONS: The platelet inhibitory effect of clopidogrel was not significantly different between patients receiving esomeprazole and those receiving famotidine. Neither esomeprazole nor famotidine reduced the platelet inhibitory effect of clopidogrel. (Clinicaltrial.gov Identifier NCT01062516).

Famotidine is inferior to pantoprazole in preventing recurrence of aspirin-related peptic ulcers or erosions.

BACKGROUND & AIMS: Little is known about the efficacy of H(2)-receptor antagonists in preventing recurrence of aspirin-related peptic ulcers. We compared the efficacy of high-dose famotidine with that of pantoprazole in preventing recurrent symptomatic ulcers/erosions. METHODS: We performed a randomized, double-blind, controlled trial of 160 patients with aspirin-related peptic ulcers/erosions, with or without a history of bleeding. Patients were given either famotidine (40 mg, morning and evening) or pantoprazole (20 mg in the morning and placebo in the evening). All patients continued to receive aspirin (80 mg daily). The primary end point was recurrent dyspeptic or bleeding ulcers/erosions within 48 weeks. RESULTS: A total of 130 patients (81.1%) completed the study; 13 of 65 patients in the famotidine group reached the primary end point (20.0%; 95% one-sided confidence interval [CI] for the risk difference, 0.1184-1.0) compared with 0 of 65 patients in the pantoprazole group (P < .0001, 95% one-sided CI for the risk difference, 0.1184-1.0). Gastrointestinal bleeding was significantly more common in the famotidine group than the pantoprazole group (7.7% [5/65] vs 0% [0/65]; 95% one-sided CI for the risk difference, 0.0226-1.0; P = .0289), as was recurrent dyspepsia caused by ulcers/erosions (12.3% [8/65] vs 0% [0/65]; 95% one-sided CI for the risk difference, 0.0560-1.0; P = .0031). No patients had ulcer perforation or obstruction. CONCLUSIONS: In patients with aspirin-related peptic ulcers/erosions, high-dose famotidine therapy is inferior to pantoprazole in preventing recurrent dyspeptic or bleeding ulcers/erosions.

Fatal co-infection with swine origin influenza virus A/H1N1 and community-acquired methicillin-resistant Staphylococcus aureus.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) co-infection has been described previously in association with respiratory tract infection caused by seasonal influenza A viruses, but not with swine origin influenza A (H1N1) virus (S-OIV). We report the clinical and pathological findings of the first death with fulminant co-infection by CA-MRSA. Since early empirical treatment with beta-lactam plus fluoroquinolone or macrolides is often initiated before specimen collections, bacterial co-infection in S-OIV may have been under-reported.

Upper gastrointestinal bleeding in patients with aspirin and clopidogrel co-therapy.

INTRODUCTION: The major complication of aspirin and clopidogrel (A+C) co-therapy is upper gastrointestinal bleeding (UGIB). However, data are unavailable for real-life situations. Furthermore, the treatment effect of antisecretory agents is unknown. AIM: This cohort study aimed to determine the occurrence of UGIB. The treatment effect of H2-receptor antagonist (H2RA) and proton pump inhibitor (PPI) was also analyzed. METHOD: The records of 987 consecutive patients on A+C co-therapy between January 2001 and September 2006 were analyzed. The follow-up ended on the dates of a first occurrence of UGIB, stopping A+C co-therapy, a change in the antisecretory class, death, or March 2007. RESULTS: After a follow-up of 5.8 +/- 6.5 months, UGIB occurred in 39 (4.0%) patients. PPI, H2RA and control were prescribed in 213, 287 and 487 patients respectively. After adjustment for age, dose of aspirin, previous UGIB and duration of treatment, the risk was marginally reduced by H2RA (OR = 0.43, 95% CI 0.18-0.91, p = 0.04) and significantly reduced by PPI (OR = 0.04, 95% CI 0.002-0.21, p = 0.002), as compared to control. CONCLUSION: The occurrence of UGIB associated with A+C co-therapy for a median of 5.8 months was 4.0%. Co-prescription with PPI was associated with a lower risk.

Gastrointestinal bleeding in patients receiving a combination of aspirin, clopidogrel, and enoxaparin in acute coronary syndrome.

BACKGROUND: The combination of aspirin, clopidogrel, and enoxaparin (combination therapy) is the standard treatment for acute coronary syndrome but is associated with gastrointestinal bleeding. However, information in this area is scarce. AIM: This retrospective study aimed to determine the incidence of upper gastrointestinal bleeding in a real-life situation. The effect of proton pump inhibitor (PPI) treatment was also analyzed. METHOD: From January 2002 to December 2006, all patients receiving combination therapy were analyzed. The end point was the occurrence of upper gastrointestinal bleeding during combination therapy or within 7 days of stopping enoxaparin. RESULTS: The patient group consisted of 666 patients (age 72.1 +/- 12.6 yr). Gastrointestinal bleeding occurred in 18 (2.7%) patients. The overall hospital mortality was 4.1% (27 patients). A cardiac event was the major cause (N = 24, 3.6%). Only one patient died of massive gastrointestinal bleeding (0.15%). Multiple logistic regression analysis demonstrated that previous peptic ulcer, cardiogenic shock, and the lack of PPI coprescription were significant risk factors for gastrointestinal bleeding. The age-adjusted odds ratio (95% confidence interval) for gastrointestinal bleeding was 5.07 (1.31-16.58) for previous peptic ulcer, 21.41 (2.56-146.68) for cardiogenic shock, and 0.068 (0.010-0.272) for the coprescription with a PPI. CONCLUSION: In real life, the incidence of gastrointestinal bleeding associated with the combination of aspirin, clopidogrel, and enoxaparin therapy was estimated to be 2.7%. Previous peptic ulcer disease or cardiogenic shock were significant independent risk factors. Coprescription with a PPI can significantly reduce the risk.

Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease.

CONTEXT: Colorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated. OBJECTIVES: To investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases. DESIGN, SETTING, AND PARTICIPANTS: Patients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years. MAIN OUTCOME MEASURES: The prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex. RESULTS: The prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P < .001 by chi2 test), prevalence of advanced lesions was 18.4%, 8.7%, and 5.8% (P < .001), and prevalence of cancer was 4.4%, 0.5%, and 1.4% (P = .02), respectively. Fifty percent of the cancers in CAD-positive participants were early stage. After adjusting for age and sex, an association still existed between colorectal neoplasm and presence of CAD (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.25-2.70; P = .002) and between advanced lesions and presence of CAD (OR, 2.51; 95% CI, 1.43-4.35; P = .001). The metabolic syndrome (OR, 5.99; 95% CI, 1.43-27.94; P = .02) and history of smoking (OR, 4.74; 95% CI, 1.38-18.92; P = .02) were independent factors for the association of advanced colonic lesions and CAD. CONCLUSIONS: In this study population undergoing coronary angiography, the prevalence of colorectal neoplasm was greater in patients with CAD. The association between the presence of advanced colonic lesions and CAD was stronger in persons with the metabolic syndrome and a history of smoking.

A randomized, double-blind, placebo-controlled trial of abciximab for prevention of in-stent restenosis in diabetic patients after coronary stenting: results of the ASIAD (Abciximab in Stenting Inhibits restenosis Among Diabetics) Trial.

OBJECTIVES: Coronary stenting is associated with a high incidence of restenosis in patients with diabetes mellitus. Recent data suggest that diabetic patients treated with abciximab have a lower rate of target vessel revascularization (TVR). We sought to investigate whether abciximab can reduce in-stent restenosis after coronary stenting in diabetic patients. METHODS: In this prospective double-blind trial, we randomly assigned 254 patients with type 2 diabetes mellitus undergoing nonurgent coronary stenting to receive abciximab with an initial heparin bolus of 50 U/kg (n = 128) or placebo with an initial heparin bolus of 70 U/kg (n = 126). All patients received aspirin and clopidogrel before the procedure. The primary endpoint was angiographic restenosis by quantitative coronary angiography at 6 months. The secondary endpoint was death, myocardial infarction (MI), or target lesion revascularization (TLR) at 6 months. RESULTS: The clinical, angiographic, and procedural characteristics were matched between the 2 groups. Angiographic follow-up was completed in 226 patients (90%). Angiographic restenosis occurred in 29.1% of the abciximab group, and 24% of the placebo group (p = 0.30). The rates of the secondary endpoint were similar between the 2 groups (23.4% in the abciximab group versus 22.2% in the placebo group; p = 0.88). TLR was performed on 36 (18.4%) lesions in 29 (23.4%) patients of the abciximab group, and 26 (13.6%) lesions in 23 (18.3%) patients of the placebo groups, respectively (p = 0.21 and 0.35, respectively). CONCLUSIONS: Abciximab does not reduce angiographic restenosis or TLR in type 2 diabetic patients undergoing nonurgent coronary stenting.

Stable and optimal anticoagulation is achieved with a single dose of intravenous enoxaparin in patients undergoing percutaneous coronary intervention.

This study assessed the pharmacokinetics, safety and efficacy of intravenous enoxaparin in patients undergoing percutaneous coronary intervention (PCI). Sixty consecutive patients [(age, 62 11 years; female, 16%; diabetes, 18%; hypertension, 53%; prior myocardial infarction (MI), 43%] undergoing PCI (stable angina, 89%; stent, 92%; two-vessel disease, 23%; B2/C lesions, 45%) were administered intravenous enoxaparin 1 mg/kg for procedural anticoagulation. Blood samples for anti-Xa level and activated partial thromboplastin time (aPTT) were assayed from the first 20 patients before and after enoxaparin administration at the following intervals: 5, 30, 60, 90, 120, 150, 180, 210, 240, 360 and 480 minutes. Activated clotting time was assessed 5 minutes after enoxaparin administration. Bleeding complications were classified according to Thrombolysis In Myocardial Infarction (TIMI) criteria. All patients were monitored for adverse clinical events at clinic visit 4 8 weeks after hospital discharge. No TIMI major or minor bleedings occurred during hospitalization for the PCI (median stay post-PCI = 1 day). One patient (2%) developed a non-Q wave MI after the PCI and before hospital discharge. There was no death or urgent revascularization up to clinical follow-up. The peak anti-Xa level was 1.30 0.18 IU/ml (range, 1.03 1.69 IU/ml). The minimum anti-Xa level was 0.55 IU/ml 4 hours after enoxaparin. Thus, the use of intravenous enoxaparin in patients undergoing PCI is associated with a low incidence of ischemic and bleeding complications. A stable therapeutic anticoagulant effect is provided without the need for monitoring within 4 hours of enoxaparin administration.

Comparison of perindopril versus captopril for treatment of acute myocardial infarction.

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality in patients with acute myocardial infarction (AMI), but these benefits might be limited by acute hemodynamic changes and difficulties in titrating to recommended doses. The objective of this study was to compare the hemodynamic changes and tolerability of perindopril with captopril after AMI. We randomized 212 patients to receive either captopril (n = 102) or perindopril (n = 110) within 72 hours of AMI. Captopril was given as an initial dose of 6.25 mg, and then 50 mg/day on day 1 and 100 mg/day thereafter. The corresponding doses of perindopril were 2, 4, and 8 mg/day. Acute hemodynamic changes, the percentage of patients who reached target doses, and in-hospital and 6-month cardiovascular events were monitored. Baseline clinical characteristics of the 2 groups were identical, but patients randomized to perindopril were in a higher Killip class (1.4 +/- 0.6 vs 1.2 +/- 0.5, p = 0.05). During the first 6 hours, treatment with perindopril resulted in higher minimal systolic (97 +/- 15 vs 91 +/- 14 mm Hg, p <0.01) and diastolic blood pressure (BP) (57 +/- 11 vs 54 +/- 10 mm Hg, p <0.02), later occurrence of minimal BP (3.6 +/- 0.2 vs 2.7 +/- 0.1 hour, p <0.001), and a lower incidence of persistent hypotension with systolic BP < 90 mm Hg for > or =1 hour (5% vs 16%; p < 0.01) compared with captopril. At initial administration, target doses of perindopril and captopril were attained in 97% and 82% of the patients, respectively (p < 0.01). After 6 months, there were no differences between patients treated with perindopril and captopril in mortality rates (6% vs 13%, p = 0.16) and need for revascularization (20% vs 21%, p = 0.9). Thus, in patients during AMI, perindopril treatment showed better short-term tolerance than treatment with captopril, with significantly less acute hemodynamic changes and fewer withdrawals.