Join Dr. Mehta and Dr. Connolly as they review data from late-breaking trials presented at ESC.17.
The experts will review the most talked about late-breaking sessions and cutting-edge research, and discuss the clinical impact for Canadian cardiologists.
The majority of patients (88%) received clopidogrel and only 12% received ticagrelor. There was no significant interaction according to type of P2Y12 inhibitor received.
Canakinumab reduced the primary outcome of MACE by 15% vs. placebo. Looked at another way, 167 patients would need to be treated with canakinumab to prevent one MACE event.
These results are exciting in that they support the rationale for targeting inflammation as in the secondary prevention of atherosclerosis. Many other targets in the inflammatory cascade could potentially be targets for treatment, such as IL-6, IL-12p40, tumour necrosis factor-alpha (TNF-), triggering receptor expressed on myeloid cells 1 (TREM-1), xanthine oxidase, C-C chemokine receptor type 2 (CCR2), p38 mitogen-activated protein kinase (MAPK), NADPH oxidase subunit (Nox), and others; many of these are in preclinical and clinical stages of investigation.
Recent evidence suggests that achieving ultra-low LDL levels is beneficial in high-risk patients, and that there may not be a “floor effect” for LDL reduction. An analysis of the FOURIER trial of the PCSK9 inhibitor, evolocumab, plus statin therapy suggests that the risk for CV events progressively declines as LDL levels decrease, even below 0.5 mmol/L. This is well below current LDL treatment targets. Ultra-low LDL reduction was not associated with a higher risk of adverse events in this trial.
The Cardiovascular Inflammation Reduction Trial (CIRT) is evaluating the efficacy and safety of low-dose methotrexate, a disease-modifying anti-rheumatic drug commonly used to treat various forms of inflammatory arthritis, in patients with stable CAD with persistent elevations in hsCRP. The rationale is that MTX inhibits inflammation without impacting other components of the atherothrombotic process, and has been associated with reduced vascular event rates in patients with inflammatory arthritis. Although MTX is inexpensive, it is not without toxicity; potential adverse effects with this agent include hepatic, GI, respiratory, hematologic, infectious, mucocutaneous, oncologic, renal, neurologic, and musculoskeletal outcomes. A separate substudy of CIRT has the goal of comprehensively evaluating these potential toxicities when low-dose MTX is administered for secondary prevention of cardiovascular disease.
The secondary endpoint of all-cause mortality was 13.4% in the catheter ablation arm vs. 25% in the conventional treatment arm (HR 0.53, 95% CI 0.32-0.86; p=0.011). The rate of hospitalization for heart failure was 20.7% vs. 35.9%, respectively (HR 0.56, 95% CI 0.37-0.83; p=0.004).
Change in LVEF is an a priori secondary endpoint of the CASTLE-AF trial. The absolute change in LVEF from baseline favoured the ablation vs. conventional arm at 12 months (p=0.001) and at 60 months (p=0.005); at 36 months, the difference was not statistically significant (p=0.055).
Nearly a third of patients were receiving an antiarrhythmic drug (32% in the ablation group, 30% in the conventional treatment group); most commonly, this was amiodarone (97% and 85%, respectively).
Stroke was considered a serious adverse event in this trial. Rates of stroke or TIA were 3.9% in the ablation arm vs. 6.7% in the conventional group.
Although the rate difference for MI did not reach statistical significance in the COMPASS trial (p=0.14), the trend was in the right direction (14% relative risk reduction for rivaroxaban + aspirin vs. aspirin alone). It’s possible that with a longer duration of follow-up, the difference will become statistically significant.
It should also be noted that the two trials evaluated different populations; notably, 26% of patients in ATLAS had a prior MI whereas 62% of patients in COMPASS had a prior MI (an average of 6.5 years prior). ATLAS had a relatively large contribution from Eastern Europe (~40%) whereas most patients in COMPASS were from Western Europe (31%) and South America (22%).