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.

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.

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).

Chronic hepatitis C genotype 6 responds better to pegylated interferon and ribavirin combination therapy than genotype 1.

BACKGROUND AND AIMS: Chronic hepatitis C genotype 6 is common in Hong Kong, especially among i.v. drug abusers. Responses of these patients to combination of pegylated interferon and ribavirin treatment were inconsistent and the numbers of patients involved in previous studies were small. We performed a retrospective study to compare the therapeutic responses of this regimen in patients infected with genotype 6 and genotype 1. METHODS: Seventy patients with either genotype 6 or genotype 1 were recruited. Both groups received 800-1200 mg of ribavirin daily plus either 180 mg of pegylated alpha-interferon-2a or 1.5 mg/kg pegylated alpha-interferon-2b weekly for 48 weeks. Their responses to treatments were compared. RESULTS: The early virological response to combination therapy of patients with genotype 6 was significantly better than that of genotype 1 (88.6% vs 74.3%, P = 0.03). Significant difference was also identified in the end of treatment response of the two genotypes (60% vs 81.4% for genotype 1 and 6, respectively; P = 0.005). The sustained virological response (SVR) to treatment in patients with genotype 6 was also significantly superior to that of patients with genotype 1 (75.7% vs 57.1%, P = 0.02). Multiple logistic regression analysis demonstrated that age of 55 years or less, genotypes of hepatitis C virus, liver biopsy staging and baseline hepatitis C virus RNA of 200,000 IU/mL or less were independent predictors for better SVR in this cohort. CONCLUSION: Patients with chronic hepatitis C genotype 6 respond better to pegylated interferon and ribavirin combination treatment than patients with genotype 1.

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.

Management and outcome of peptic ulcers or erosions in patients receiving a combination of aspirin plus clopidogrel.

BACKGROUND: This multicenter retrospective study investigated the management and outcome of patients with peptic ulcer/erosion-related aspirin and clopidogrel (A + C) cotherapy. METHODS: From January 2002 to September 2006, patients with endoscopically proven peptic ulcers/erosions after receiving A + C cotherapy were analyzed. RESULTS: This group consisted of 106 patients (age, 69.3 +/- 11.7 years). Ulcers/erosions developed in 27 patients during hospitalization for cardiac events and in 79 patients after hospital discharge. Of 27 patients hospitalized for acute cardiac events, gastrointestinal (GI) bleeding and dyspepsia occurred in 24 and three, respectively. The most common lesion was gastric ulcer. Of 79 discharged patients, GI bleeding and dyspepsia occurred in 64 and 15, respectively. The most common bleeding and dyspeptic lesions were gastric ulcer and gastritis, respectively. Overall, 17 patients underwent endoscopic hemostasis all successfully. A + C cotherapy was continued in 57 patients for a median (interquartile range) of 3.0 (6.2) months. Most were coprescribed a proton pump inhibitor (PPI) (53, 93%). No recurrent GI bleeding was observed. CONCLUSIONS: After A + C cotherapy, gastric ulcer or gastritis were the most common endoscopic lesions. The combination of a PPI and endoscopic treatment for ulcer bleeding was highly successful. After patient stabilization, continuation of A + C cotherapy with a PPI appears to be safe.

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.

Evaluation of two stool antigen tests for the detection of Helicobacter pylori infection in the Chinese population.

BACKGROUND AND AIM: The stool antigen test, the HpSA test, has been validated mainly in Western countries, but not properly in the Chinese population. Recently, another stool antigen test, the Apollo test, was developed, but its accuracy has rarely been validated. The aim of this study is to compare the accuracy of these two tests in the diagnosis of Helicobacter pylori infection in the Chinese population. METHODS: Consecutive dyspeptic patients referred for upper endoscopy were recruited. During endoscopy, biopsies were taken for the rapid urease test and histological examination as the gold standard. Stool specimens were collected and used for the HpSA and Apollo tests. RESULTS: Overall, 86 patients (39 males and 47 females, with a mean age of 55.8 years) were recruited. Helicobacter pylori infection was present in 44 (51%) patients as determined by the gold standard. The sensitivity, specificity and accuracy were 86.4, 100, and 93.0%, respectively, for the HpSA, and 90.9, 97.6, and 94.2%, respectively, for the Apollo test when cases with equivocal results were considered as positive. In addition, agreement was achieved in 81 (94.2%) cases between the two tests, with a Kappa value of 0.887. CONCLUSION: Both the HpSA and Apollo tests achieve acceptable sensitivity and excellent specificity, with accuracies of over 90% for the detection of H. pylori infection in the Chinese population.

[13C]-urea breath test without prior fasting and without test meal is accurate for the detection of Helicobacter pylori infection in Chinese.

BACKGROUND AND AIM: Conventional [13C]-urea breath test ([13C]-UBT) requires prior fasting and a test meal, which theoretically improves the accuracy of the test. However, recent studies have suggested that prior fasting and test meal may not be essential. We aimed to determine the accuracy of a new [13C]-UBT protocol without fasting in Chinese. METHODS: Dyspeptic patients referred for upper endoscopy were recruited. The gold standard for Helicobacter pylori infection was the combination of Campylobacter-like organism (CLO) test and histology. Group I (n = 213) patients underwent [13C]-UBT with prior fasting and with citrate acid test meal. Group II (n = 123) patients underwent [13C]-UBT without prior fasting but with test meal. Group III (n = 90) patients underwent [13C]-UBT without prior fasting and without test meal. RESULTS: The highest accuracy for groups I, II and III was 96.7, 95.1 and 95.5% using a cut-off value of 5.0, 5.5 and 3.5, respectively. The sensitivities and specificities were 97.4 and 95.8% in group I, 93.3 and 96.8% in group II, and 96.5 and 93.9% in group III, respectively. CONCLUSION: The [13C]-UBT protocols without prior fasting and either with or without test meal produce highly accurate and reliable results in the Chinese population.