Archive for November, 2016

AHA 2016: Some Heart Failure Presentations

  • EFFECT-HF: randomized clinical trial of patients with heart failure and iron deficiency comparing ferric carboxymaltose versus standard of care effect on exercise capacity. VO2 max improved.
  • IRONOUT: oral iron polysaccharide versus placebo in patients with heart failure with reduced ejection fraction. VO2 max primary end-point. Negative study.
  • REDUCELAPHF: 1 year outcome data of use of interatrial shunt device used in patients with heart failure and preserved ejection fraction and abnormal exercise pulmonary capillary wedge pressure (supine exercise). Symptomatic, exercise time, quality of life benefit and improved exercise capacity for given left atrial size.
  • ATHENA-HF: spironolactone (100 mg per day x 96 hours in acute heart failure) did not reduce NT proBNP compared with usual care
  • MOMENTUM-3: HEARTMATE 3 in advanced heart failure (compared to HEARTMATE II). The full paper is here


Nichols et al report on the GLAGOV trial. GLAGOV was a randomized placebo controlled clinical trial of evolocumab to assess progression of coronary atheroma as assessed by serial intravascular ultrasound assessment. Evolocumab was associated with marked absolute reduction in LDL-C (similar to other PCSK-9 inhibitors). Evolocumab was associated was greater reduction in percent atheroma volume compared with placebo.



Reducing levels of low-density lipoprotein cholesterol (LDL-C) with intensive statin therapy reduces progression of coronary atherosclerosis in proportion to achieved LDL-C levels. Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors produce incremental LDL-C lowering in statin-treated patients; however, the effects of these drugs on
coronary atherosclerosis have not been evaluated.


To determine the effects of PCSK9 inhibition with evolocumab on progression of coronary atherosclerosis in statin-treated patients.


The GLAGOV multicenter, double-blind, placebo-controlled, randomized clinical trial (enrollment May 3, 2013, to January 12, 2015) conducted at 197 academic and community hospitals in North America, Europe, South America, Asia, Australia,
and South Africa and enrolling 968 patients presenting for coronary angiography.


Participants with angiographic coronary disease were randomized to receive monthly evolocumab (420mg) (n = 484) or placebo (n = 484) via subcutaneous injection for 76 weeks, in addition to statins.


The primary efficacy measure was the nominal change in percent atheroma volume (PAV) from baseline to week 78, measured by serial intravascular ultrasonography (IVUS) imaging. Secondary efficacy measures were nominal change in
normalized total atheroma volume (TAV) and percentage of patients demonstrating plaque regression. Safety and tolerability were also evaluated.


Among the 968 treated patients (mean age, 59.8 years [SD, 9.2]; 269 [27.8%] women; mean LDL-C level, 92.5mg/dL [SD, 27.2]), 846 had evaluable imaging at follow-up. Compared with placebo, the evolocumab group achieved lower mean, time-weighted LDL-C levels (93.0 vs 36.6mg/dL; difference, −56.5mg/dL [95%CI, −59.7 to −53.4]; P < .001). The primary efficacy parameter, PAV, increased 0.05%with placebo and decreased 0.95% with evolocumab (difference, −1.0% [95%CI, −1.8%to −0.64%]; P < .001). The secondary efficacy parameter, normalized TAV, decreased 0.9mm3 with placebo and 5.8mm3 with evolocumab (difference, −4.9mm3 [95%CI, −7.3 to −2.5]; P < .001). Evolocumab induced plaque regression in a greater percentage of patients than placebo (64.3%vs 47.3%; difference, 17.0%[95%CI, 10.4%to 23.6%]; P < .001 for PAV and 61.5%vs 48.9%; difference, 12.5% [95%CI, 5.9% to 19.2%]; P < .001 for TAV).


Among patients with angiographic coronary disease treated with statins, addition of evolocumab, compared with placebo, resulted in a greater decrease in PAV after 76 weeks of treatment. Further studies are needed to assess the effects of
PCSK9 inhibition on clinical outcomes.


AHA 2016: Presentations

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November 15, 2016 1 comment

Gibson et al reports the results of the PIONEER AF-PCI trial. This trial was a randomized clinical trial of three antiplatelet/anticoagulation regimens for patients with atrial fibrillation undergoing coronary stent implantation. The treatment groups:

  • rivaroxaban 15 mg per day + clopidogrel/ticagrelor/prasugrel [1,6,12 months pre-specified durations]
  • rivaroxaban 2.5 mg bd + low dose aspirin + clopidogrel/ticagrelor/prasugrel [DAPT 1,6,12 months pre-specified durations]
  • vitamin K antagonist (INR 2-3) + clopidogrel/ticagrelor/prasugrel [1,6,12 months pre-specified durations]

The safety end-points were lower with rivaroxaban. The efficacy end-points were similar but the authors advise caution in regard to the confidence of no type I error.



In patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) with placement of stents, standard anticoagulation with a vitamin K antagonist plus dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor and aspirin reduces the risk of thrombosis and stroke but increases the risk of bleeding. The effectiveness and safety of anticoagulation with rivaroxaban plus either one or two antiplatelet agents are uncertain.


We randomly assigned 2124 participants with nonvalvular atrial fibrillation who had undergone PCI with stenting to receive, in a 1:1:1 ratio, low-dose rivaroxaban (15 mg once daily) plus a P2Y12 inhibitor for 12 months (group 1), very-low-dose rivaroxaban (2.5 mg twice daily) plus DAPT for 1, 6, or 12 months (group 2), or standard therapy
with a dose-adjusted vitamin K antagonist (once daily) plus DAPT for 1, 6, or 12 months (group 3). The primary safety outcome was clinically significant bleeding (a composite of major bleeding or minor bleeding according to Thrombolysis in
Myocardial Infarction [TIMI] criteria or bleeding requiring medical attention).


The rates of clinically significant bleeding were lower in the two groups receiving rivaroxaban than in the group receiving standard therapy (16.8% in group 1, 18.0% in group 2, and 26.7% in group 3; hazard ratio for group 1 vs. group 3, 0.59; 95% confidence interval [CI], 0.47 to 0.76; P<0.001; hazard ratio for group 2 vs. group 3, 0.63; 95% CI, 0.50 to 0.80; P<0.001). The rates of death from cardiovascular causes, myocardial infarction, or stroke were similar in the three groups (Kaplan– Meier estimates, 6.5% in group 1, 5.6% in group 2, and 6.0% in group 3; P values
for all comparisons were nonsignificant).


In participants with atrial fibrillation undergoing PCI with placement of stents, the administration of either low-dose rivaroxaban plus a P2Y12 inhibitor for 12 months or very-low-dose rivaroxaban plus DAPT for 1, 6, or 12 months was associated with a lower rate of clinically significant bleeding than was standard therapy with a vitamin
K antagonist plus DAPT for 1, 6, or 12 months. The three groups had similar efficacy rates, although the observed broad confidence intervals diminish the surety of any conclusions regarding efficacy.





A substudy of re-hospitalization is very interesting. Graphics from this substudy follow:





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United States Preventive Services Taskforce Statement on Statins for Primary Prevention



The recommendations are available here. The summary of the evidence is available here.

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AHA 2016: Initial Look

ACEI and ARB Prior to Non-cardiac surgery

Roshanov et al report on the VISION prospective cohort study. The study examined the relationship between continuation/discontinuation of antihypertensive medication prior to non-cardiac surgery and post operative cardiovascular events. The focus of this study relates to ACE inhibitors and angiotensin receptor blockers. The continuation of these drugs was associated with a higher rate of adverse events.



The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown.


In this international prospective cohort study, the authors analyzed data from 14,687 patients (including 4,802 angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users) at least 45 yr old who had in-patient noncardiac surgery from 2007 to 2011. Using multivariable regression models, the authors studied the relationship between withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and a primary composite outcome of
all-cause death, stroke, or myocardial injury after noncardiac surgery at 30 days, with intraoperative and postoperative clinically important hypotension as secondary outcomes.


Compared to patients who continued their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, the 1,245 (26%) angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users who withheld their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the 24 h before surgery were less likely to suffer the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P = 0.01) and intraoperative hypotension (adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001). The risk of postoperative hypotension was similar between the two groups (adjusted relative risk,
0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the range of preoperative blood pressures. The practice of withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was only modestly correlated with patient characteristics and the type and timing of surgery.


Withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers before major noncardiac surgery was associated with a lower risk of death and postoperative vascular events. A large randomized trial is needed to confirm this finding. In the interim, clinicians should consider recommending that patients withhold angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 24 h before surgery.