Major Adverse Cardiovascular Events End Research Articles

ADCY9 Genetic Variants and Cardiovascular Outcomes With Evacetrapib in Patients With High-Risk Vascular Disease

A pharmacogenetic analysis of dalcetrapib, a cholesteryl ester transfer protein inhibitor, reported an association between a single-nucleotide polymorphism (SNP) in the ADCY9 gene (rs1967309) and reduction in major adverse cardiovascular events despite a neutral result for the overall trial. To determine whether the association between the SNP in the ADCY9 gene and a reduction in major adverse cardiovascular events could be replicated for another cholesteryl ester transfer protein inhibitor, evacetrapib, in patients with high-risk vascular disease. A nested case-control study examining the rs1967309 SNP in 1427 cases and 1532 matched controls selected from the 12 092-patient Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition with Evacetrapib in Patients at a High Risk for Vascular Outcomes (ACCELERATE) trial, a randomized, double-blind, placebo-controlled phase 3 trial conducted in patients with high-risk vascular disease randomized from October 2012 through December 2013. The genotyping was conducted from January 2017 to March 2017, and the data analyses were conducted from July 2017 to November 2017. Evacetrapib, 130 mg, or matching placebo. The primary analyses used a conditional logistic regression model to assess the odds ratio (OR) for major adverse cardiovascular events for evacetrapib compared with placebo for each genotype. The basic model included adjustment for age, sex, and the top 5 principal components. An additional model included cardiovascular risk factors to adjust for potential bias in selecting control patients. The primary major adverse cardiovascular event end point was the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. For patients with the AA genotype reported to demonstrate a beneficial effect from dalcetrapib, the OR for evacetrapib compared with placebo was 0.88 (95% CI, 0.69-1.12). For patients with the AG genotype, the OR was 1.04 (95% CI, 0.90-1.21). For patients with the GG genotype reported to show evidence for a harmful effect from dalcetrapib, the OR for evacetrapib was 1.18 (95% CI, 0.98-1.41). The interaction P value among the 3 genotypes was P = .17 and the trend P value was P = .06. When adjusted for cardiovascular risk factors, the OR for evacetrapib was 0.93 (95% CI, 0.73-1.19) for the AA genotype, 1.05 (95% CI, 0.91-1.22) for the AG genotype, and 1.02 (95% CI 0.85-1.24) for the GG genotype; interaction P = .71 and trend P = .59. Pharmacogenetic analysis did not show a significant association between the ADCY9 SNP (rs1967309) and cardiovascular benefit or harm for the cholesteryl ester transfer protein inhibitor evacetrapib.

Comparing Inverse Probability of Treatment Weighting and Instrumental Variable Methods for the Evaluation of Adenosine Diphosphate Receptor Inhibitors After Percutaneous Coronary Intervention.

There is increasing interest in performing comparative effectiveness analyses in large observational databases, yet these analyses must adjust for treatment selection issues. To conduct comparative safety and efficacy analyses of prasugrel vs clopidogrel bisulfate after percutaneous coronary intervention and to evaluate inverse probability of treatment weighting (a propensity score method) and instrumental variable methods. This study used data from the Treatment With Adenosine Diphosphate Receptor Inhibitors-Longitudinal Assessment of Treatment Patterns and Events After Acute Coronary Syndrome (TRANSLATE-ACS) study. Included in the study were patients undergoing percutaneous coronary intervention for myocardial infarction, 26.0% of whom received prasugrel. The study dates were April 4, 2010, to October 31, 2012. Choice of initial antiplatelet agent (prasugrel or clopidogrel). Safety and efficacy outcomes included 1-year composite major adverse cardiovascular events, moderate to severe bleeding, and stent thrombosis. Hospitalizations for pneumonia, bone fractures, and planned percutaneous coronary intervention were used as the falsification end points. The study cohort comprised 11 784 participants (mean [SD] age, 60.0 [11.6] years, and 28.0% were female). Using inverse probability of treatment weighting adjustment, prasugrel and clopidogrel had similar major adverse cardiovascular events (hazard ratio [HR], 0.98; 95% CI, 0.83-1.16) and bleeding outcomes (1.18; 0.77-1.80), but prasugrel had a lower rate of stent thrombosis (0.51; 0.31-0.85). Using instrumental variable methods, prasugrel use was associated with a lower rate of the major adverse cardiovascular event end point (HR, 0.68; 95% CI, 0.47-1.00) but nonsignificant differences in the rates of bleeding (0.95; 0.41-2.08) and stent thrombosis (0.67; 0.16-2.00). There was no significant treatment difference noted in any of the falsification end-point rates when analyses were performed using inverse probability of treatment weighting, although the bone fracture end point approached statistical significance. Nevertheless, a lower rate of pneumonia-related hospitalizations was noted in the prasugrel-treated patients when analyses were performed using instrumental variable methods. Conclusions regarding the safety and efficacy of antiplatelet therapy varied depending on analytic technique, and none were concordant with the results from randomized trials. In addition, both statistical strategies demonstrated concerning associations when tested in the falsification analyses. A high level of scrutiny and careful attention to assumptions and validity are required when interpreting complex analyses of observational data.

Impact of Carotid Atherosclerosis on the Risk of Adverse Cardiac Events in Patients With and Without Coronary Disease

Carotid atherosclerosis (CA) is reportedly a strong predictor of imminent cardiac events even in the absence of established coronary artery disease (CAD). We examined the differential impact of CA on the risk of major adverse cardiovascular events in patients with and without CAD diagnosed angiographically. We conducted a follow-up survey of 1391 patients who underwent clinically driven coronary angiography and a same-day carotid ultrasound and Doppler study. Definitions of CAD, CA, and carotid artery stenosis were in accordance with current practice guidelines. Of 1391 patients, angiographic CAD was present in 1105 (79%) patients. Mean and median follow-up was 1574 and 1702 days, respectively. Rates of the primary composite major adverse cardiovascular event end point were higher among patients with CAD compared with those without CAD (48% versus 20%; P<0.001), whereas the rates of all-cause mortality (10% versus 9%; P=0.81) and stroke (7% versus 5%; P=0.3) did not differ significantly between both groups. Carotid artery stenosis and CA were associated with an increased risk of the composite major adverse cardiovascular event end point among patients without CAD (hazard ratio=3.17 [95% confidence interval, 1.52-6.60]; P<0.01; and hazard ratio=1.69 [0.95-3.01]; P=0.07, respectively) though not in patients with CAD. Carotid artery stenosis was associated with an increased risk of all-cause mortality among patients without CAD (hazard ratio=2.93 [1.09-7.87]; P=0.03]) though not among those with CAD. CA and carotid artery stenosis are independent predictors of major adverse cardiovascular event in patients undergoing coronary angiography. The prognostic implications of carotid disease are imparted predominantly in patients without pre-existent CAD.

Cost effectiveness of titanium nitride-coated bioactive coronary stents compared to BMS and DES

BackgroundThe Medical Devices Commission of United Hospitals of Ancona (UHA) was asked to authorise a coronary stent made of steel, coated with bioactive titanium nitride (TITAN 2).PurposeTo consider whether Titan...

Effect of Coronary Collaterals on Long-Term Prognosis in Patients Undergoing Primary Angioplasty for Acute ST-Elevation Myocardial Infarction

The aim of this study was to examine the effect of coronary collateral flow before reperfusion on long-term clinical prognosis in patients with acute ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. We studied 235 patients with STEMI within 12 hours after symptom onset. All patients had Thrombolysis In Myocardial Infarction grade < or =1 flow before percutaneous coronary intervention. Collateral flow was graded according to the Rentrop classification. Patients were categorized as having absent or poor collateral flow to the infarct-related artery (group A) or significant flow (group B). In 166 patients there was absent or weak collateral flow (group A), whereas 69 had significant flow (group B). Long-term follow-up was available in 227 patients (97%) at a median of 797 days. Overall, 25 patients died during the follow-up period, 22 patients (13.8%) in group A and 3 patients (4.4%) in group B (p = 0.04). A total of 12 (7.5%) nonfatal recurrent myocardial infarctions occurred in group A compared to 2 (2.9%) in group B (p = 0.18). The combined major adverse cardiovascular event end point (death or nonfatal reinfarction) showed a significantly lower event rate in group B (p = 0.02). Extensive collateral flow at baseline was a significant predictor for a favorable long-term clinical outcome on multivariable analysis after adjustment for established prognostic markers. In conclusion, the presence of a well-developed collateral network before mechanical reperfusion in patients with STEMI is associated with improved long-term survival and lower major adverse cardiovascular event rates.