Ticagrelor and aspirin for the prevention of cardiovascular events after coronary artery bypass graft surgery.

BACKGROUND: Ticagrelor was shown to reduce mortality in patients who underwent coronary artery bypass grafting (CABG), but its effect on graft patency is unknown. METHODS: We performed a prospective, randomised, double-blind, placebo-controlled trial, comparing ticagrelor 90 mg twice daily versus placebo for 3 months added to aspirin 81 mg/day, following isolated CABG. Aspirin was started within 12 h, and study medication within 72 h after CABG. Primary outcome was graft occlusion on CT angiography (CTA) performed 3 months post CABG. Patients were followed to 12 months for death, myocardial infarction, stroke, repeat revascularisation and bleeding. RESULTS: The study was terminated prematurely after randomising 70 patients between September 2011 and August 2014 because of slow recruitment. CTA was performed in 56 patients who completed >1 month of study drug. Graft occlusion occurred in 7/25 (28.0%) patients on ticagrelor and 17/31 (48.3%) on placebo, p=0.044. Of 207 analysable grafts, graft occlusion occurred in 9/87 (10.3%) with ticagrelor and 22/120 (18.3%) with placebo, p=0.112. Graft occlusion or stenosis ≥50% occurred in 10/87 (11.5%) ticagrelor vs 32/120 (26.7%) placebo, p=0.007. There was no major bleeding, but minor bleeding was higher with ticagrelor (31.4% vs 2.9%, p=0.003). In univariate analysis, ticagrelor use reduced graft occlusion (OR 0.32, 95% CI 0.10 to 0.97, p=0.047), which remained significant on multivariable analysis (OR 0.25, 95% CI 0.073 to 0.873, p=0.03). CONCLUSIONS: Ticagrelor added to aspirin after CABG reduced the proportion of patients with graft occlusion, and was a significant univariate and multivariable predictor of graft occlusion. These results are hypothesis-generating and should be confirmed in larger studies. TRIAL REGISTRATION NUMBER: NCT01373411: Results.

Prophylactic intravenous magnesium sulphate in addition to oral {beta}-blockade does not prevent atrial arrhythmias after coronary artery or valvular heart surgery: a randomized, controlled trial.

BACKGROUND: Atrial arrhythmias (AA) are an important cause of morbidity after cardiac surgery. Efforts at prevention of postoperative AA have been suboptimal. Perioperative beta-blocker administration is the standard of care at many centers. Although prophylactic administration of magnesium sulfate (MgSO(4)) has been recommended, review of all previously published trials of MgSO(4) reveals conflicting results. This study was designed to address methodological shortcomings from previous studies and is the largest randomized, placebo-controlled trial of intravenous (IV) MgSO(4) for the prevention of AA after coronary artery bypass grafting or cardiac valvular surgery. METHODS AND RESULTS: A total of 927 nonemergent cardiac surgery patients were stratified into 2 groups: isolated coronary artery bypass grafting (n=694), or valve surgery with or without coronary artery bypass grafting (n=233), and randomized to receive either 5g IV MgSO(4) or placebo on removal of the cross-clamp, followed by daily 4-hour infusions, from postoperative day 1 until postoperative day 4. All patients were treated according to an established oral beta-blocker protocol. Postoperative serum Mg levels were checked and standard of care was to administer IV MgSO(4) for low serum levels. The primary end point was AA lasting > or =30 minutes or requiring treatment for hemodynamic compromise. There were no differences in the incidence of AA between patients who received IV MgSO(4) or placebo (26.4% versus 24.3%, respectively). The results were similar when broken down according to stratified groups. CONCLUSIONS: In patients treated with a protocol for postoperative oral beta-blocker after nonemergent cardiac surgery, the addition of prophylactic IV MgSO(4) did not reduce the incidence of AA.

Antecedent hypertension and the effect of captopril on the risk of adverse cardiovascular outcomes after acute myocardial infarction with left ventricular systolic dysfunction: Insights from the Survival and Ventricular Enlargement Trial.

BACKGROUND: Hypertension is a well-established risk factor for myocardial infarction (MI), but its prognostic importance in survivors of an acute MI is less clear. METHODS: We used Cox proportional hazards models to examine the risk of any major cardiovascular event (cardiovascular death, heart failure, recurrent MI, or stroke)-combined or individual components-and all-cause death and evaluate the efficacy of captopril in 906 patients with hypertension and 1325 patients without hypertension in the Survival and Ventricular Enlargement (SAVE) clinical trial. All patients had survived an acute MI with resultant left ventricular (LV) systolic dysfunction, but without overt heart failure, and were randomized within 3 to 16 days after the index MI to receive either captopril or placebo. The mean (+/- SD) follow-up period was 42 +/- 10 months. RESULTS: After adjustment for known risk factors, medication use at enrollment, and baseline systolic blood pressure, patients with hypertension had a significant increase in the risk of experiencing a combined cardiovascular event (47.7% vs 31.3%; hazard ratio [HR], 1.49; 95% CI, 1.28-1.74), cardiovascular death (23.4% vs 15.9%; HR, 1.40; 95% CI, 1.12-1.74), heart failure (27.7% vs 15.5%; HR, 1.64; 95% CI, 1.34-2.02), and all-cause death (27.4 vs 19.3%; HR, 1.25; 95% CI, 1.02-1.53), and a similar but statistically non-significant increase in the risk of non-fatal or fatal recurrent MI (17.4% vs 10.9%; HR, 1.27; 95% CI, 0.98-1.65), and non-fatal or fatal stroke (5.0% vs 3.6%; HR, 1.31; 95% CI, 0.81-2.09). Captopril resulted in similar benefits for both patients with and patients without hypertension. The number of combined cardiovascular events prevented for every 100 patients treated with captopril was 7.0 (95% CI, 0.5-13.5) in patients with hypertension and 7.5 (95% CI, 2.6-12.5) in patients without hypertension. CONCLUSIONS: In survivors of an acute MI with LV systolic dysfunction, antecedent hypertension was associated with a greater risk of subsequent adverse cardiovascular events, not directly explained by elevated blood pressure levels. Captopril use was beneficial in both patients with and patients without hypertension.

Effect of long-term therapy with ramipril in high-risk women.

OBJECTIVES: We evaluated the effects of long-term therapy with the angiotensin-converting enzyme (ACE) inhibitor ramipril on major cardiovascular (CV) outcomes in high-risk women. BACKGROUND: The effect of long-term ACE inhibitor therapy in high-risk women without heart failure and with preserved left ventricular (LV) systolic function has not been previously reported. METHODS: The Heart Outcomes Prevention Evaluation (HOPE) trial is a large, randomized clinical trial that evaluated ramipril and vitamin E in high-risk patients. We present the preplanned analysis of the effects of ramipril in women in the HOPE study. The study randomized 2,480 women aged >or=55 years with vascular disease or diabetes and at least one additional CV risk factor and without heart failure or a known low LV ejection fraction to ramipril (10 mg/day) or placebo. The primary outcome was the composite of myocardial infarction, stroke or CV death. Average follow-up was 4.5 years. RESULTS: Treatment with ramipril resulted in reduced primary end point rates (11.3% vs. 14.9% in the placebo arm; relative risk [RR] 0.77, 95% confidence interval [CI] 0.62 to 0.96; p = 0.019), fewer strokes (3.1% vs. 4.8%; RR 0.64, 95% CI 0.43 to 0.96; p = 0.029) and fewer CV deaths (4.2% vs. 6.9%; RR 0.62, 95% CI 0.44 to 0.88; p = 0.0068). There were trends toward reduced rates of myocardial infarction, heart failure and all-cause death. The beneficial effect of ramipril was similar in women and men. CONCLUSIONS: Treatment with ramipril reduces the CV risk in high-risk women without heart failure and with preserved LV systolic function.