Low-Dose Methotrexate for the Prevention of Atherosclerotic Events.

BACKGROUND: Inflammation is causally related to atherothrombosis. Treatment with canakinumab, a monoclonal antibody that inhibits inflammation by neutralizing interleukin-1ß, resulted in a lower rate of cardiovascular events than placebo in a previous randomized trial. We sought to determine whether an alternative approach to inflammation inhibition with low-dose methotrexate might provide similar benefit. METHODS: We conducted a randomized, double-blind trial of low-dose methotrexate (at a target dose of 15 to 20 mg weekly) or matching placebo in 4786 patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome. All participants received 1 mg of folate daily. The primary end point at the onset of the trial was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. Near the conclusion of the trial, but before unblinding, hospitalization for unstable angina that led to urgent revascularization was added to the primary end point. RESULTS: The trial was stopped after a median follow-up of 2.3 years. Methotrexate did not result in lower interleukin-1ß, interleukin-6, or C-reactive protein levels than placebo. The final primary end point occurred in 201 patients in the methotrexate group and in 207 in the placebo group (incidence rate, 4.13 vs. 4.31 per 100 person-years; hazard ratio, 0.96; 95% confidence interval [CI], 0.79 to 1.16). The original primary end point occurred in 170 patients in the methotrexate group and in 167 in the placebo group (incidence rate, 3.46 vs. 3.43 per 100 person-years; hazard ratio, 1.01; 95% CI, 0.82 to 1.25). Methotrexate was associated with elevations in liver-enzyme levels, reductions in leukocyte counts and hematocrit levels, and a higher incidence of non-basal-cell skin cancers than placebo. CONCLUSIONS: Among patients with stable atherosclerosis, low-dose methotrexate did not reduce levels of interleukin-1ß, interleukin-6, or C-reactive protein and did not result in fewer cardiovascular events than placebo. (Funded by the National Heart, Lung, and Blood Institute; CIRT ClinicalTrials.gov number, NCT01594333.).

Variability in healthcare delivery: It is never a good thing.

In medicine, wide variations in healthcare delivery or outcomes are a sign of missing information and beg for more information in a timely resolution. While differences in patient selection for intervention in out-of-hospital-cardiac-arrest in Wales and England might seem regional, there is little reason to assume this is not true across many other geographical areas.

Radial artery intervention: Facile for you is best for me, too.

If you have transitioned to the radial artery as the preferred approach, congratulations. If you are in training or currently transitioning, good for you, too. Your patient satisfaction scores are going to rise, and complications will be less frequent. If you are still a femoral first, you are as old or older than me, and you should master this approach soon before you retire. Left radial approach is pretty much just like femoral, but with fewer complications.

Revascularization for multivessel disease: Getting closer, but .

In a registry, it is all about any differences. PCI and CABG for multivessel disease are comparable with regard to risk of death/MI/stroke, but PCI has a significantly higher risk of return to Cath Lab for PCI or even CABG in follow-up.

No Option? Maybe just a matter of time, as in No Option for now?

The No Option coronary patient may have options after all. Rethinking the state of the No Option patient at follow-up may be more fruitful than expected. Reviewing videos by more experienced interventionalists AND surgeons may also yield more options.

Great report, food for thought, or wait a second?

In this retrospective report, earlier intervention in NSTEMI reduced the composite outcome and mortality at 1 year. However, earlier intervention did not significantly reduce the composite outcome or mortality at 30 days. Reminder: retrospective (even propensity-matched) trials may suggest differences that prospective randomized trials may or may not support.

Hey, American College of Cardiology interventionalists: What are you thinking?

There is large variation in the utilization of the appropriate Use-Criteria (AUC). There has been a significant decrease in the number of Percutaneous coronary intervention (PCI) cases deemed rarely appropriate. The value of the AUC remains a questionable tool for many clinicians.

Another tool for the fork-in-the-road toolbox.

A provisional stent strategy for bifurcation disease is a good rule of thumb. The Tryton bifurcation stent is an additional potential useful tool for use in complex coronary disease. If and when this device has a drug-eluting side branch, its true role may be clearer.

I do not want to go to the hospital again.

Readmission after myocardial infarction is not uncommon. The likely readmission patient is by and large predictable. Coronary interventions appear to reduce the rate of readmissions.

Unstable presentation: One Stent trumps two.

This report was a retrospective look at a large registry database. A one-stent strategy trumps a two-stent approach in patients with acute coronary syndromes in this large registry. The primary endpoint and target lesion revascularization was half the rate if a one-stent strategy was used. The incidence of stent thrombosis was more than three-fold as high using a planned two-stent strategy.

KISS for in-stent restenosis.

We treat ISR primarily with new DES implantation. DES therapy appears to provide the best protection from TVR and possibly death, as well. Be mindful of occult or other evidence of incomplete stent expansion of the original stent.

If not now, why are you waiting?

There is some surrogate outcome data supporting deferring PCI in STEMI No hard data to support deferring PCI in STEMI No hard data to refute deferring PCI in STEMI Current national quality measures do not offer a method to adequately document appropriateness of deferring PCI.

One arterial puncture: Radial, please; if two? Make one radial, please.

There is less bleeding with a radial approach There is less bleeding with a radial approach See above.

Low Gradient, "Dismal" Outcome TAVR: Should We?

Low gradient (<40 mm) aortic valve stenosis (AVA < 1.0 cm2 ) outcomes with TAVR are worse than when gradients are > 40 mm Hg. Concomitant coronary disease, older age, presence of diabetes, and lower ejection fraction in patients with low gradient aortic valve stenosis account for the poorer outcome after TAVR. Historically, similar results have been seen with surgical AVR.

Percutaneous coronary intervention after a surgeon says, "no way".

The rate of surgical turndowns (1.5-2.5%) in this report that went on to PCI is relatively consistent across centers. Unprotected left main intervention in patients turned down for surgery has high hospital mortality. With certain caveats, the HEART Team approach to these unique patients may be the answer.

Ready, set, pull, ow!

The BADFORM technique is a novel technique in getting devices across otherwise uncrossable lesions It is critical to perform the pulling parallel to the vessel The technique and its success has only been described in the 10 cases reported so caution is advised.

Our aspirations still disappoint.

Routine thrombectomy during coronary intervention for STEMI is not supported by two large prospective randomized trials. Occasional case-specific clot removal, while appealing, remains an unproven adjunct to primary stenting during STEMI therapy. While early MACE events may be lower, during follow-up, there is a higher risk of stroke in patients who undergo thrombectomy.

In early returns scoring scores big.

A scoring or cutting balloon is always useful in preventing slippage during therapy of in-stent restenosis. A drug-coated scoring balloon for in-stent restenosis may be an alternative to a drug-coated balloon Definitive comparison trials are needed and likely to help define their exact role in patients with in-stent restenosis.