Antihypertensives and Statin Therapy for Primary Stroke Prevention: A Secondary Analysis of the HOPE-3 Trial

BACKGROUND AND PURPOSE: The HOPE-3 trial (Heart Outcomes Prevention Evaluation­3) found that antihypertensive therapy combined with a statin reduced first stroke among people at intermediate cardiovascular risk. We report secondary analyses of stroke outcomes by stroke subtype, predictors, treatment effects in key subgroups. METHODS: Using a 2-by-2 factorial design, 12 705 participants from 21 countries with vascular risk factors but without overt cardiovascular disease were randomized to candesartan 16 mg plus hydrochlorothiazide 12.5 mg daily or placebo and to rosuvastatin 10 mg daily or placebo. The effect of the interventions on stroke subtypes was assessed. RESULTS: Participants were 66 years old and 46% were women. Baseline blood pressure (138/82 mm Hg) was reduced by 6.0/3.0 mm Hg and LDL-C (low-density lipoprotein cholesterol; 3.3 mmol/L) was reduced by 0.90 mmol/L on active treatment. During 5.6 years of follow-up, 169 strokes occurred (117 ischemic, 29 hemorrhagic, 23 undetermined). Blood pressure lowering did not significantly reduce stroke (hazard ratio [HR], 0.80 [95% CI, 0.59­1.08]), ischemic stroke (HR, 0.80 [95% CI, 0.55­1.15]), hemorrhagic stroke (HR, 0.71 [95% CI, 0.34­1.48]), or strokes of undetermined origin (HR, 0.92 [95% CI, 0.41­2.08]). Rosuvastatin significantly reduced strokes (HR, 0.70 [95% CI, 0.52­0.95]), with reductions mainly in ischemic stroke (HR, 0.53 [95% CI, 0.37­0.78]) but did not significantly affect hemorrhagic (HR, 1.22 [95% CI, 0.59­2.54]) or strokes of undetermined origin (HR, 1.29 [95% CI, 0.57­2.95]). The combination of both interventions compared with double placebo substantially and significantly reduced strokes (HR, 0.56 [95% CI, 0.36­0.87]) and ischemic strokes (HR, 0.41 [95% CI, 0.23­0.72]). CONCLUSIONS: Among people at intermediate cardiovascular risk but without overt cardiovascular disease, rosuvastatin 10 mg daily significantly reduced first stroke. Blood pressure lowering combined with rosuvastatin reduced ischemic stroke by 59%. Both therapies are safe and generally well tolerated.

Five-year outcomes after off-pump or on-pump coronary-artery bypass grafting

BACKGROUND: We previously reported that there was no significant difference at 30 days or at 1 year in the rate of the composite outcome of death, stroke, myocardial infarction, or renal failure between patients who underwent coronary-artery bypass grafting (CABG) performed with a beating-heart technique (off-pump) and those who underwent CABG performed with cardiopulmonary bypass (on-pump). We now report the results at 5 years (the end of the trial). METHODS: A total of 4752 patients (from 19 countries) who had coronary artery disease were randomly assigned to undergo off-pump or on-pump CABG. For this report, we analyzed a composite outcome of death, stroke, myocardial infarction, renal failure, or repeat coronary revascularization (either CABG or percutaneous coronary intervention). The mean follow-up period was 4.8 years. RESULTS: There were no significant differences between the off-pump group and the on-pump group in the rate of the composite outcome (23.1% and 23.6%, respectively; hazard ratio with off-pump CABG, 0.98; 95% confidence interval [CI], 0.87 to 1.10; P=0.72) or in the rates of the components of the outcome, including repeat coronary revascularization, which was performed in 2.8% of the patients in the off-pump group and in 2.3% of the patients in the on-pump group (hazard ratio, 1.21; 95% CI, 0.85 to 1.73; P=0.29)...

Outcomes after thrombus aspiration for ST elevation myocardial infarction: 1-year follow-up of the prospective randomised TOTAL trial

BackgroundTwo large trials have reported contradictory results at 1 year after thrombus aspiration in ST elevation myocardial infarction (STEMI). In a 1-year follow-up of the largest randomised trial of thrombus aspiration, we aimed to clarify the longer-term benefits, to help guide clinical practice.MethodsThe trial of routine aspiration ThrOmbecTomy with PCI versus PCI ALone in Patients with STEMI (TOTAL) was a prospective, randomised, investigator-initiated trial of routine manual thrombectomy versus percutaneous coronary intervention (PCI) alone in 10 732 patients with STEMI. Eligible adult patients (aged ≥18 years) from 87 hospitals in 20 countries were enrolled and randomly assigned (1:1) within 12 h of symptom onset to receive routine manual thrombectomy with PCI or PCI alone. Permuted block randomisation (with variable block size) was done by a 24 h computerised central system, and was stratified by centre. Participants and investigators were not masked to treatment assignment. The trial did not show a difference at 180 days in the primary outcome of cardiovascular death, myocardial infarction, cardiogenic shock, or heart failure. However, the results showed improvements in the surrogate outcomes of ST segment resolution and distal embolisation, but whether or not this finding would translate into a longer term benefit remained unclear...

Relationship between healthy diet and risk of cardiovascular disease among patients on drug therapies for secondary prevention: a prospective cohort study of 31 546 high-risk individuals from 40 countries

Background—Diet quality is strongly related to cardiovascular disease (CVD) incidence, but little is known about itsimpact on CVD events in older people at high risk of CVD and receiving effective drugs for secondary prevention. Thisstudy assessed the association between diet quality and CVD events in a large population of subjects from 40 countrieswith CVD or diabetes mellitus with end-organ damage receiving proven medications.Methods and Results—Overall, 31 546 women and men 66.5 6.2 years of age enrolled in 2 randomized trials, theOngoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) and theTelmisartan Randomized Assessment Study in ACEI Intolerant Subjects With Cardiovascular Disease (TRANSCEND),were studied. We used 2 dietary indexes: the modified Alternative Healthy Eating Index and the Diet Risk Score. The association between diet quality and the primary composite outcome of CV death, myocardial infarction, stroke, or congestive heart failure was assessed with Cox proportional hazard regression with adjustment for age, sex, trial enrollment allocation, region, and other known confounders. During the 56-month follow-up, there were 5190 events. Patients in the healthier quintiles of modified Alternative Healthy Eating Index scores had asignificantly lower risk of CVD (hazard ratio, 0.78; 95% confidence interval, 0.71– 0.87, top versus lowest quintileof modified Alternative Healthy Eating Index). The reductions in risk for CV death, myocardial infarction, andstroke were 35%, 14%, and 19%, respectively. The protective association was consistent regardless of whetherpatients were receiving proven drugs.Conclusions—A higher-quality diet was associated with a lower risk of recurrent CVD events among people 55 yearsof age with CVD or diabetes mellitus. Highlighting the importance of healthy eating by health professionals wouldsubstantially reduce CVD recurrence and save lives globally.

Influenza vaccination and major adverse vascular events in high-risk patients

Background—We sought to determine the association between influenza vaccination and major adverse vascular events because the association remains uncertain.Methods and Results—A total of 31 546 participants were enrolled from 40 countries. Eligibility included age 55 years and known vascular disease. The primary outcome was a composite of death resulting from cardiovascular causes, myocardial infarction, or stroke during 4 influenza seasons (2003–2007). Influenza vaccination was associated with a lower risk of the outcome during 3 influenza seasons (defined using World Health Organization FluNet reports): 2004to 2005 (adjusted odds ratio [OR], 0.62; 95% confidence interval [CI], 0.50–0.77), 2005 to 2006 (adjusted OR, 0.69; 95% CI, 0.53– 0.91), and 2006 to 2007 (adjusted OR, 0.52; 95% CI, 0.42– 0.65), the same years that circulating influenza matched the vaccine antigen. In 2003 to 2004, there was an incomplete match between circulating influenza and the vaccine antigen, and there was no association between influenza vaccination and the outcome (adjusted OR, 0.96; 95% CI, 0.73–1.27). However, tests of potential biases in the analyses revealed associations between influenza vaccination and outcome during noninfluenza seasons except 2003 to 2004. The summary ORs in the influenza season (OR, 0.65; 95% CI, 0.58–0.74]) and noninfluenza season (OR, 0.66; 95% CI, 0.57– 0.76) were almost identical. The reduction in risk of noncardiovascular death associated with the influenza vaccine ranged from 73% to 79%.Conclusion—Although initial analyses suggest that influenza vaccination was associated with reduced risk of majoradverse vascular events during influenza seasons when the influenza vaccine matched the circulating virus, sensitivity analyses revealed that risk of bias remained. A randomized trial is needed to definitively address this question.

Radial versus femoral access for coronary angiography and intervention in patients with acute coronary syndromes (RIVAL): a randomised, parallel group, multicentre trial

Background Small trials have suggested that radial access for percutaneous coronary intervention (PCI) reducesvascular complications and bleeding compared with femoral access. We aimed to assess whether radial access was superior to femoral access in patients with acute coronary syndromes (ACS) who were undergoing coronaryangiography with possible intervention.Methods The RadIal Vs femorAL access for coronary intervention (RIVAL) trial was a randomised, parallel group,multicentre trial. Patients with ACS were randomly assigned (1:1) by a 24 h computerised central automated voiceresponse system to radial or femoral artery access. The primary outcome was a composite of death, myocardialinfarction, stroke, or non-coronary artery bypass graft (non-CABG)-related major bleeding at 30 days. Key secondary outcomes were death, myocardial infarction, or stroke; and non-CABG-related major bleeding at 30 days. A masked central committee adjudicated the primary outcome, components of the primary outcome, and stent thrombosis. All other outcomes were as reported by the investigators. Patients and investigators were not masked to treatment allocation. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, NCT01014273. Findings Between June 6, 2006, and Nov 3, 2010, 7021 patients were enrolled from 158 hospitals in 32 countries.3507 patients were randomly assigned to radial access and 3514 to femoral access. The primary outcome occurred in128 (3·7%) of 3507 patients in the radial access group compared with 139 (4·0%) of 3514 in the femoral access group (hazard ratio [HR] 0·92, 95% CI 0·72–1·17; p=0·50). Of the six prespecifi ed subgroups, there was a signifi cant interaction for the primary outcome with benefi t for radial access in highest tertile volume radial centres (HR 0·49, 95% CI 0·28–0·87; p=0·015)...