https://www.nejm.org/doi/full/10.1056/NEJMoa2309002
In this placebo-controlled trial, postexposure prophylaxis with nirmatrelvir–ritonavir for 5 or 10 days did not significantly reduce the risk of symptomatic SARS-CoV-2 infection.


https://www.nejm.org/doi/full/10.1056/NEJMoa2309003

https://www.nejm.org/doi/full/10.1056/NEJMoa2118542


Pfizer has some serious problems! #pfizer

this paper out in JAMA makes you think this is an issue but likely just too much noise with only 17 patietns and didnt control for confounders

https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2820255

Be careful, most observational data have a large amount of confounders not accounted for and even when accounted for you can never account for all the confounders

https://www.ahajournals.org/doi/10.1161/CIR.0000000000001251.

Diagnosis:

• To establish a PAD diagnosis, the resting ankle–brachial index (ABI) remains the initial test of choice in patients with suggestive history or exam findings. The ABI result should be reported as normal (1–1.4), borderline (0.91–0.99), abnormal (≤0.9) or noncompressible (>1.4).

TREATMET

• Low-dose rivaroxaban 2.5mg BID, in addition to daily aspirin, is now recommended to decrease the risk for major adverse cardiovascular events (MACEs) and major adverse limb events in patients with symptomatic PAD who are not at increased bleeding risk. This is based on the COMPASS trial Cardiovascular Outcomes for People Using Anticoagulation Strategies - American College of Cardiology (acc.org) and as a reminder inclusion criteria was “Atherosclerosis in ≥2 vascular beds or two additional risk factors (current smoking, diabetes, renal insufficiency, heart failure, or nonlacunar ischemic stroke ≥1 month)”

• In pts with symptomatic PAD—single antiplatelet with clopidogrel 75mg daily (NOT ASPIRIN) to lower risk of MACE. If the patient can’t get clopidogrel then aspirin will work but clopidogrel preferred!

• In patients with PAD and type 2 diabetes, the use of glucagon-like peptide-1 (GLP-1) agonists and sodium–glucose cotransporter-2 (SGLT-2) inhibitors are effective to reduce MACE.

https://jamanetwork.com/journals/jama/article-abstract/2818624

Conclusion--

“Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.”

For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277)

So this paper is saying look “Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality.”

Not wrong these labs improve outcomes but when you look at the c stats we go from 0.81 to 0.82… remember as we talked about yesterday

C-statistic gives the probability a randomly selected patient who experienced an event (e.g. a disease or condition) had a higher risk score than a patient who had not experienced the event.

A score of 1 is perfect. A score of 0.5 is a coin flip. A score of .8 is pretty good but the question we have to ask ourselves “is there a difference between 0.81 and 0.82. If you are getting a grade in school is there a real difference in the knowledge between someone that gets 81% and gets 82%.

Bottom line-

Authors might say something is beneficial and great but if they give you the c statistics you will know weather it is actually beneficial because now you know cstatics and how to use it within a study.

What are c statistics

C-statistic gives the probability a randomly selected patient who experienced an event (e.g. a disease or condition) had a higher risk score than a patient who had not experienced the event.

Obviously there are people with low scores that still have events and people with high scores that never have events but the goal is the decision score gives us an idea of who is most likely.

· The idea or educated estimate can be turned into a C score- and c scores are kind of like grades== a score of 1 is absolue perfect model it means the model perfectly predicts those group members who will experience a certain outcome and those who will not.

· But we know in medicine that isn’t possible

IF

· A value of 0.5 means that the model is no better than predicting an outcome than random chance.

· Values over 0.7 indicate a good model.

· Values over 0.8 indicate a strong model.

https://pubmed.ncbi.nlm.nih.gov/38598573/

In fully vaccinated adults with a risk factor or unvaccinated patients without a risk factor who have symptomatic COVID-19, does paxlovid--nirmatrelvir-ritonavir reduce the duration of symptoms or the likelihood of hospitalization?

Nirmatrelvir-ritonavir (Paxlovid) was shown in its initial randomized trial to reduce hospitalization and death in unvaccinated adults with at least one risk factor for severe disease when the ancestral variant of SARS-CoV-2 was predominant.

But it is important that drugs be evaluated in the correct target population patients who have been vaccinated or have the Omicron variant.

This industry-sponsored study enrolled 2 groups of patients: (1) fully vaccinated adults with symptomatic, confirmed infection with SARS-CoV-2 and at least one risk factor for severe disease,

(2) unvaccinated adults with a symptomatic infection but no risk factors

The onset of symptoms was within the past 5 days. Patients (N = 1296) were randomized to receive the standard 5-day course of nirmatrelvir-ritonavir or matching placebo.

the 1440 participants who were initially randomized There was no difference in duration of symptoms between groups, and no significant difference in the likelihood of hospitalization or death (0.8% vs 1.6% for placebo; difference -0.8%; 95% CI -2.0 to 0.4).

https://www.nejm.org/doi/10.1056/NEJMoa2314063

Randomized trials have shown the benefit of endovascular thrombectomy in patients with acute stroke due to large-artery occlusion in the anterior circulation and a large baseline infarct (core) In these trials,1-5 a large core was defined by an ASPECTS value of 5 or less, but because of concerns about the deleterious effects associated with the reperfusion of large infarcts,8 patients with the largest infarcts (ASPECTS value, 0 or 1) were excluded from enrollment

Now, researchers have compared EVT plus medical therapy to medical therapy alone in patients who could be treated within 6.5 hours of stroke onset and had a large amount of ischemic tissue

The primary outcome was the modified Rankin scale (mRS) score and the major safety outcome was all-cause mortality, both at 90 days.

a 3-year period, 333 patients cerebral vessel occlusion in the anterior circulation

The median NIH Stroke Scale score was 21, and the median baseline infarct volume was 135 mL;

Median time to randomization was 270 minutes after symptom onset. The EVT group had a lower median mRS score at 90 days than the medical-therapy group (4 vs. 6) and also lower mortality (36% vs. 56%).

The overall rate of death or dependency (mRS score ≥4) at 90 days was high in both groups but lower with thrombectomy (67% vs. 88%). NNT of 5

Symptomatic intracranial hemorrhage was more common with EVT (9.6% vs. 5.7%).—NNH of 25