EXTEND: More Evidence of Clot Dissolving Therapy Benefit 9 Hours After Paralysis

Treat the brain and not the time. Extending the time window for clot dissolving thrombolytic therapy to 9 hours for patients selected using automated computed tomography perfusion imaging can result in excellent functional outcomes. The study, EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND), was presented here during the International Stroke Conference (ISC) 2019.

Earlier the WAKE-UP trial showed that tPA was safe and effective in patients with wake-up stroke that had occurred more than 4.5 hours before treatment, but that study used magnetic resonance imaging (MRI), not CT perfusion, for patient selection. In most stroke centers, CT perfusion imaging is much more available than MRI.

The current guideline for thrombolysis in acute ischemic stroke is administration within 4.5 hours of stroke onset, but advanced neuroimaging studies suggest that the ischemic penumbra can exist for up to 24 hours and salvaging tissue can lead to improved clinical outcome.

EXTEND was a phase 3, multicenter, double-blind trial in which patients were randomized to receive either intravenous (IV) tissue plasminogen activator (tPA) at 0.9 mg/kg, or to placebo. Researchers stratified patients into 3 groups according to time of randomization after stroke: 4.5 to 6 hours; more than 6 to 9 hours; and "wake up" stroke, where the precise time of the stroke is unknown.

CT perfusion or MR perfusion imaging was used with RAPID software for automated image processing. The software interprets images and indicates whether a patient has a small infarct core and a large area of salvageable brain. This information can be used to decide if a particular patient might benefit from thrombolysis.

Never get lipid profile done without hsCRP

Eur Heart J. 2018;39(46):4109-4111: Heart attack, stroke, and atherothrombotic cardiovascular deaths are characterized by chronic hyperlipidaemia in the setting of a persistent pro-inflammatory response, often exacerbated by hypertension and behavioural factors such as smoking.

Yet, most cardiologists measure cholesterol and blood pressure in virtually all of their patients but very few measure high sensitivity C-reactive protein (hsCRP), a validated measure of cardiovascular inflammation.

The risk associated with a 1 SD increase in hsCRP is at least as great, if not greater, than that associated with a comparable 1 SD increase in cholesterol or blood pressure, even after adjustment for a wide range of additional factors.

The JUPITER trial—published more than a decade ago—made it clear that individuals with levels of hsCRP >2 mg/L benefit from statin therapy even in the absence of overt hyperlipidaemia.

More than 40 studies published since 1995 in prominent journals have demonstrated that elevated levels of hsCRP are a major independent determinant of vascular risk in a wide range of settings, including following acute coronary ischaemia, in stable secondary prevention, post-percutaneous coronary intervention (PCI), post-bypass surgery, and in multiple high-risk patient groups such as those with moderate to severe chronic kidney disease and diabetes.

In this issue of the European Heart Journal, Kalkman and colleagues present yet more evidence supporting hsCRP use in secondary prevention.

Among 7026 PCI patients with serial hsCRP measures treated at the Mount Sinai Hospital in New York between 2009 and 2016, a total of 38% had persistently high residual inflammatory risk (hsCRP >2 mg/L) despite high quality care, and another 10% developed residual inflammatory risk over time.

Kalkman and colleagues followed these patients over 12 months and found that rates of recurrent myocardial infarction were 7.5% for those with hsCRP persistently above 2 mg/L as compared with 4.3% for those with persistently lower hsCRP.

Rates for all-cause mortality were 2.6% and 0.7%, respectively, for those with and without residual inflammatory risk. In subgroups analyses, adverse outcomes associated with elevated hsCRP were present among women as well as men, and among those with LDL cholesterol levels above and below 70 mg/dL.

These results demonstrate that persistent high residual inflammatory risk is observed frequently in patients undergoing PCI with significantly higher all-cause mortality and myocardial infarction rates at 1-year follow-up.

Following exercise, diet, and smoking cessation, statins should be initiated in primary and secondary cardiovascular prevention to lower both LDL-C and hsCRP.

How long the knee replacement will last?

The majority of knee and hip replacements can be expected to last 25 years, according to two new studies. Jonathan T. Evans, MRCS, Bristol Medical School, Southmead Hospital, United Kingdom, and colleagues conducted both studies. Their findings were published online February 14 in the Lancet.

82% of primary total knee replacements (TKRs) last 25 years, as do 70% of unicondylar knee replacements (UKRs) and approximately 58% of hip replacements. For each study, Evans and colleagues conducted a systematic review and meta-analysis, evaluating data from multiple sources, including national joint replacement registries and published reports. They provided simple and generalizable estimates of survival for knee and hip replacements.

In the knee replacement study, they included articles reporting at least 15-year survival rates of TKRs, UKRs, and patellofemoral replacements in patients with osteoarthritis. Their analysis included 33 case series that reported all-cause survival for 6490 TKRs and 742 UKRs. A registry search identified 47 series reporting 299,291 TKRs and 7714 UKRs. On the basis of these data, the estimated 25-year survival of TKRs (14 registries) was 82.3%; for UKRs (four registries), it was 69.8%.

Similarly, in the hip replacement study, the researchers included articles reporting at least 15-year survival of primary, conventional total hip replacement constructs for patients with osteoarthritis. Their analysis included 44 case series reporting 13,212 total hip replacements. The registry search identified 92 series reporting 215,676 total hip replacements. The estimated 25-year survival of hip replacements was 77.6% and On the basis of registry data, it was 57.9% (Medscape).