RESUMO

BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI), percutaneous coronary intervention (PCI) of the culprit lesion reduces the risk of cardiovascular death or myocardial infarction. Whether PCI of nonculprit lesions further reduces the risk of such events is unclear. METHODS: We randomly assigned patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion PCI to a strategy of either complete revascularization with PCI of angiographically significant nonculprit lesions or no further revascularization. Randomization was stratified according to the intended timing of nonculprit-lesion PCI (either during or after the index hospitalization). The first coprimary outcome was the composite of cardiovascular death or myocardial infarction; the second coprimary outcome was the composite of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. RESULTS: At a median follow-up of 3 years, the first coprimary outcome had occurred in 158 of the 2016 patients (7.8%) in the complete-revascularization group as compared with 213 of the 2025 patients (10.5%) in the culprit-lesion-only PCI group (hazard ratio, 0.74; 95% confidence interval [CI], 0.60 to 0.91; P=0.004). The second coprimary outcome had occurred in 179 patients (8.9%) in the complete-revascularization group as compared with 339 patients (16.7%) in the culprit-lesion-only PCI group (hazard ratio, 0.51; 95% CI, 0.43 to 0.61; P=0.62 and P=0.27 for interaction for the first and second coprimary outcomes, respectively). CONCLUSIONS: Among patients with STEMI and multivessel coronary artery disease, complete revascularization was superior to culprit-lesion-only PCI in reducing the risk of cardiovascular death or myocardial infarction, as well as the risk of cardiovascular death, myocardial infarction, or ischemia-driven revascularization. (Funded by the Canadian Institutes of Health Research and others; COMPLETE ClinicalTrials.gov number, NCT01740479.). (AU)

Assuntos

RESUMO

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials. (AU)

Assuntos

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 x 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. (AU)

Assuntos

Assuntos

RESUMO

BACKGROUND: REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding. METHODS: We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions...

Assuntos

RESUMO

BACKGROUND: Atherothrombosis is becoming the leading cause of chronic morbidity in developing countries. This epidemiological transition will represent an unbearable socioeconomic burden in the near future. We investigated factors associated with 4-year all-cause mortality in a Latin American population at high risk. HYPOTHESIS: Largely modifiable risk factors as well as polyvascular disease are the main predictors of 4-year all-cause and cardiovascular mortality in this Latin American cohort. METHODS: We analyzed 1816 Latin American stable outpatients (62.3% men, mean age 67 years) with symptomatic atherothrombosis (87.1%) or with multiple risk factors only (12.9%), in the Reduction of Atherothrombosis for Continued Health registry. RESULTS: Of patients with symptomatic atherothrombosis, 57.3% had coronary artery disease, 32% cerebrovascular disease, and 11.7% peripheral artery disease at baseline (9.1% polyvascular). The main risk factors were hypertension (76%), hypercholesterolemia (60%), and smoking (52.3%) in patients with established atherothrombosis; and hypertension (89.7%), diabetes (80.8%), and hypercholesterolemia (73.9%) in those with risk factors only. Four-year all-cause mortality steeply increased with none (6.8%), 1 (9.2%), 2 (15.5%), and 3 (29.2%) symptomatic arterial disease locations. In patients with only 1 location, cardiovascular mortality was significantly higher with peripheral artery disease (11.3%) than with cerebrovascular disease (6%) or coronary artery disease (5.1%). Significant baseline predictors of 4-year all-cause mortality were congestive heart failure (hazard ratio [HR]: 3.81), body mass index <20 (HR: 2.32), hypertension (HR: 1.84), polyvascular disease (HR: 1.69), and age ≥ 65 years (HR: 1.47), whereas statin use (HR: 0.49) and body mass index ≥ 30 (HR: 0.58) were associated with a reduced risk. CONCLUSIONS: Hypertension was the main modifiable risk factor for atherothrombosis and all-cause mortality in this Latin American cohort. Nearly one-third of the population with 3 symptomatic vascular-disease locations died at 4-year follow-up.

Assuntos

RESUMO

Patients with end-stage renal disease commonly develop acute coronary syndromes (ACS). Little is known about the natural history of ACS in patients receiving dialysis. We evaluated the presentation, management, and outcomes of patients with ACS who were receiving dialysis before presentation for an ACS and were enrolled in the Global Registry of Acute Coronary Events (GRACE) at 123 hospitals in 14 countries from 1999 to 2007. Of 55,189 patients, 579 were required dialysis at presentation. Non-ST-segment elevation myocardial infarction was the most common ACS presentation in patients receiving dialysis, occurring in 50% (290 of 579) of patients versus 33% (17,955 of 54,610) of those not receiving dialysis. Patients receiving dialysis had greater in-hospital mortality rates (12% vs 4.8%; p <0.0001) and, among those who survived to discharge, greater 6-month mortality rates (13% vs 4.2%; p <0.0001), recurrent myocardial infarction (7.6% vs 2.9%; p <0.0001), and unplanned rehospitalization (31% vs 18%; p <0.0001). The outcome in patients receiving dialysis was worse than that predicted by their calculated GRACE risk score for in-hospital mortality (7.8% predicted vs 12% observed; p <0.05), 6-month mortality/myocardial infarction (10% predicted vs 21% observed; p <0.05). In conclusion, in the present large multinational study, approximately 1% of patients with ACS were receiving dialysis. They were more likely to present with non-ST-segment elevation myocardial infarction, and had markedly greater in-hospital and 6-month mortality. The GRACE risk score underestimated the risk of major events in patients receiving dialysis.

Assuntos

RESUMO

BACKGROUND: The time course of events after acute coronary syndromes might influence the timing and duration of therapeutic interventions. We investigated the impact of risk status and ST-segment category at presentation. METHODS: The timing of death, reinfarction, stroke and major bleeding within 6 months of acute coronary syndromes was determined in 46,829 patients enrolled in the Global Registry of Acute Coronary Events (GRACE). Acute coronary syndromes were classified by elevation (n = 17,668), depression (n = 8,542), or neither (n = 20,619) in the ST segment. GRACE risk scores and hazard ratios (HR) were determined for three time periods: 0-4, 5-15 and 16-180 days. RESULTS: ST-segment elevation was associated with a higher early risk of death than was ST-segment depression (0-4 days, HR 1.89, 95% CI 1.60-2.24 versus 5-15 days, HR 1.26, 95% CI 1.05-1.50), but after 15 days the risk was reversed (16-180 days, HR 0.85, 95% CI 0.75-0.97). Throughout the study, patients with ST-segment deviation had a higher mortality risk than those without. Within each ST category, the highest GRACE risk scores were associated with a 10-40-fold greater risk of death than the lowest scores (all categories P <0.0001). Most deaths occurred after day 4 (57%, 74%, and 78% for ST-segment elevation, depression and neither, respectively). CONCLUSION: The timing of events after acute coronary syndromes was affected by ST category and influenced by GRACE risk score within each electrocardiographic category of acute coronary syndromes. Risk stratification should, therefore, include multiple risk factors rather than ST shift alone.

Assuntos