Repatha Jump-Starts LDL Lowering In-Hospital

Adding a PCSK9 inhibitor to high-intensity statin treatment early after an acute coronary syndrome (ACS) -- before hospital discharge -- was safe and more effectively lowered LDL levels, the phase III EVOPACS trial found.
By week 8, the evolocumab (Repatha) cohort experienced a 77.1% reduction from baseline in mean LDL versus a 35.4% reduction for the statin plus placebo group (P<0.001), Konstantinos Koskinas, MD, MSc, of Bern University Hospital in Switzerland, reported here at the European Society of Cardiology (ESC) congress.

 

Furthermore, while only 37.6% of patients on placebo reached an LDL of <1.8 mmol/L (70 mg/dL) at this time point, nearly all patients in the evolocumab group (95.7%) hit that target.
"In this first randomized trial assessing a PCSK9 antibody in the very high-risk acute setting of ACS, evolocumab added to high-intensity statin therapy resulted in substantial reduction in LDL-C levels without raising safety concerns," Koskinas said.
A similar proportion of patients in the placebo and investigational groups (50.7% vs 50.3%) experienced any adverse event (AE), or any serious AE (7.2% vs 7.7%). And no AEs of special interest were significantly different between the placebo and evolocumab groups, respectively, including:

• Musculoskeletal pain: 2.6% vs 5.8%
• Local injection site reaction: 2.0% vs 3.2%
• Diarrhea: 2.0% vs 3.9%
• Nasopharyngitis: 2.0% vs 2.6%
• Elevated liver enzymes: 1.3% for each

Drug discontinuation due to toxicity occurred in 2.0% of placebo patients and 1.3% of evolocumab patients. Notably, two deaths were reported in the evolocumab cohort, but were deemed unrelated to treatment.
Koskinas noted that a dedicated cardiovascular outcomes trial is needed to assess the clinical impact of early LDL lowering with evolocumab in the acute setting of ACS.

 

Results of the randomized, double-blind, placebo-controlled trial were simultaneously published in the Journal of the American College of Cardiology.
In an interview with MedPage Today, session chair Alaide Chieffo, MD, of San Raffaele Scientific Institute in Milan, Italy, explained that most of the prior literature has focused on stable patients rather than addressing ACS at the time of onset.
Newly released joint guidelines from ESC and the European Atherosclerosis Society suggest that ACS patients already on ezetimibe (Zetia) and a maximally tolerated dose of statins, but with LDL levels not at the desired level, should also receive a PCSK9 inhibitor as soon as possible.
Researchers for EVOPACS randomized 308 patients 1:1 to high-intensity statins plus either placebo or evolocumab. The cohort had a mean age of 60.8 years and were mostly men (82.5%). All participants were hospitalized for ACS with elevated LDL of at least 3.2 mmol/L (124 mg/dL) for those on no stable statin dose, 2.3 mmol/L (89 mg/dL) or more for those on a low- or moderate-intensity statin, and 1.8 mmol/L (70 mg/dL) or more for those on a high-intensity statin for at least 4 weeks.
On top of 40 mg of atorvastatin (Lipitor), patients were subcutaneously given either 420 mg evolocumab or placebo, which was administered in-hospital and after 4 weeks.

 

 

Findings showed that for the primary endpoint, average LDL declined from 3.42 mmol/L at baseline to 2.06 mmol/L at week 8 in the placebo cohort, and from 3.61 to 0.79 mmol/L in the evolocumab group.
As for inflammatory biomarkers, average levels of high sensitivity C-reactive protein declined from 6.6 mg/L to 2.5 mg/L at 8 weeks, but no significant differences were seen between the cohorts. Likewise, there were no differences in the change for IL-6 and IL-1β levels.
Limitations of the study included having a short duration and modest sample size. Further, the primary endpoint could only be assessed in 90% of the cohort, though the researchers noted that directly measuring LDL in cases of very low LDL or very high triglycerides demonstrated consistent results. Another limitation cited was that they were unable to capture evolocumab's effects prior to week 4, even though the therapy lowers LDL within days.

 

The study was funded by Amgen.
Koskinas disclosed relationships with Sanofi and Amgen.

• Primary Source

  Journal of the American College of Cardiology

  Source Reference: Koskinas KC, et al "Evolocumab for early reduction of LDL-cholesterol levels in patients with acute coronary syndromes (EVOPACS)" J Am Coll Cardiol 2019; DOI: 10.1016/j.jacc.2018.08.541.

https://www.medpagetoday.com/meetingcoverage/esc/81920

Drive LDL as Low as Possible: Euro Cardiology Society

LDL cholesterol levels should be driven as low as possible, especially in high-risk patients, according to new European guidelines that tighten down treatment targets.
"[T]here is no longer an 'LDL-C hypothesis', but established facts that increased LDL-C values are causally related to ASCVD [atherosclerotic cardiovascular disease], and that lowering LDL particles and other ApoB-containing lipoproteins as much as possible reduces CV events," the European Society of Cardiology (ESC) and European Atherosclerosis Society guideline stated.

 

"What's changing is the mindset, the idea that when you get down to 1.8 [70 mg/dL] you still go further, you push it down lower because there's clear evidence you can still benefit even at that low level," said guideline writing committee co-chair Colin Baigent, MD, of Oxford University in England.
Revised recommendations in the document, appearing in the European Heart Journal and slated for presentation at the ESC meeting here, included:

• For secondary prevention in "very-high-risk" patients, cut LDL by at least 50% from baseline and to under 55 mg/dL (previously the goal was 70 mg/dL)
• For very-high-risk patients on maximally tolerated statin therapy with a second vascular event within 2 years (regardless of type), an LDL goal under 40 mg/dL may be considered
• Primary prevention for people with a risk factor other than familial hypercholesterolemia, at least halve LDL from baseline and reach less than 55 mg/dL
• For patients at high risk, the target was below 50% of baseline and less than 70 mg/dL (previous goal was 100 mg/dL)
• For individuals at moderate risk (calculated 10-year risk of 1% to less than 5%) or young diabetes patients without other risk factors, the goal to consider is under 100 mg/dL (previously 115 mg/dL)
• For those with a 10-year risk score under 1%, an LDL goal under 116 mg/dL should be considered

High and very-high risk was delineated by ASCVD, diabetes, chronic kidney disease, familial hypercholesterolemia, and very high levels of triglycerides or other individual risk factors. Risk stratification using the newly tweaked Systematic Coronary Risk Estimation (SCORE) charts was otherwise recommended.
There's no lower limit for LDL or J-curve effect for efficacy, and "studies of the clinical safety of these very low achieved LDL-C values have proved reassuring," the document added.
As with the 2018 American Heart Association/American College of Cardiology (AHA/ACC) lipid guidelines, ESC upgraded PCSK9 inhibitor use from "may be considered" to "is recommended" for certain high-risk groups.

 

It also, in parallel with the AHA/ACC, added a recommendation that coronary artery calcium score is reasonable to assess as a cardiovascular risk modifier for asymptomatic individuals at low or moderate risk along with a recommendation to consider icosapent ethyl (Vascepa) for higher risk patients with triglycerides that remain high despite statins.
But unlike the AHA/ACC guideline, ESC suggested considering measurement of Lp(a) at least once for adults to catch inherited levels over 180 mg/dL, which may confer lifetime ASCVD risk on par with heterozygous familial hypercholesterolemia.
"Because it's stable over a lifetime, there's no need to keep redoing it," Baigent noted.
However, he cautioned that the impact of these guidelines really will depend upon the extent to which PCSK9 inhibitors are available to patients.
"Many patients will achieve their goals just using what's already available and cheap," he said. "However, where people do remain at very high risk despite being on a high-dose statin and ezetimibe [Zetia], we think that the evidence supports further reduction in LDL cholesterol, and that can only be achieved currently with PCSK9 inhibitors. We know that they are expensive, we know that there are many parts of Europe they won't be affordable, but we believe that we should reflect the available evidence in the guidelines."
The ESC also released a slate of other guidelines, including those on diabetes and pre-diabetes, acute pulmonary embolism, supraventricular tachycardia, and stable coronary artery disease -- now renamed to chronic coronary syndromes.

 

Baigent reported institutional research funding from Novartis, Pfizer, and Boehringer Ingelheim. Declarations of interest for the full guideline writing committee can be found here.

• Primary Source

  European Heart Journal

  Source Reference: Mach F, et al "2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk" Eur Heart J 2019; DOI: 10.1093/eurheartj/ehz455.

https://www.medpagetoday.com/meetingcoverage/esc/81919

1/Day Netarsudil Lowers Pressure in Glaucoma, Ocular Hypertension

Netarsudil ophthalmic solution (0.02 percent; once daily) significantly reduced mean intraocular pressure (IOP) among patients with open-angle glaucoma or ocular hypertension, according to a study published in the August issue of the American Journal of Ophthalmology.
In a double-masked, randomized, phase 3, noninferiority study, Albert S. Khouri, M.D., from the Rutgers New Jersey School of Medicine in Newark, and colleagues randomly assigned patients with open-angle glaucoma or ocular hypertension (unmedicated baseline IOP >20 to <30 mm Hg at 8:00 a.m.) to either netarsudil ophthalmic solution 0.02 percent once daily (186 patients) or timolol ophthalmic solution 0.5 percent twice daily (186 patients).
The researchers found that daily netarsudil was noninferior to twice-daily timolol, with a mean treated IOP range from 16.3 to 17.9 mm Hg for netarsudil and 16.7 to 17.6 mm Hg for timolol (mean reductions from baseline of 3.9 to 4.7 mm Hg and 3.8 to 5.2 mm Hg, respectively). Netarsudil demonstrated noninferiority to timolol in patients with baseline IOP <27 mm Hg and <30 mm Hg in prespecified secondary analyses. For netarsudil, the IOP-lowering effects were sustained during six months of treatment. Neither drug had treatment-related serious adverse events. For timolol, there were statistically significant reductions in mean heart rate at all study visits. Among netarsudil-treated patients, the most frequent ocular adverse event was conjunctival hyperemia (47.9 percent), which was mostly mild.
"In conclusion, netarsudil [once daily] is effective at lowering IOP in patients with open-angle glaucoma or ocular hypertension, with tolerable ocular adverse events," the authors write.
Several authors disclosed financial ties to pharmaceutical companies, including Aerie Pharmaceuticals, which manufactures netarsudil and funded the study.
Abstract/Full Text
https://www.physiciansbriefing.com/ophthalmology-13/glaucoma-news-335/netarsudil-lowers-iop-in-glaucoma-ocular-hypertension-749751.html

Interest in Marijuana, Cannabinoids for Pain Rising Rapidly

There is rapidly growing interest in the use of marijuana and cannabinoids for pain, according to a survey commissioned by the American Society of Anesthesiologists (ASA).
The five-question CARAVAN Survey was conducted online by Engine during Aug. 5 to 7, 2019; 1,005 U.S. adults (503 men and 502 women) were surveyed. The survey was released in time for September's Pain Awareness Month.
The results of the survey indicate that overall, more than two-thirds of respondents have used or would consider using marijuana or cannabinoid compounds, including cannabidiol (CBD) and tetrahydrocannabinol, to manage pain. Among millennials, nearly three-quarters would consider using marijuana or cannabinoid compounds for pain compared with two-thirds of Gen Xers and baby boomers. However, some of the results demonstrate significant misunderstanding among those surveyed. For instance, 62 percent believe marijuana or cannabinoid compounds are safer than opioids and 57 percent believe they have fewer side effects than other medications. More than one-third of respondents do not think they need to discuss use of these products with their doctor. Nearly half of respondents think they know what they are getting with marijuana or cannabinoids, while 40 percent believe cannabidiol sold at grocery stores, truck stops, health food stores, or medical marijuana dispensaries is approved by the U.S. Food and Drug Administration.

 

"As experts in managing pain, physician anesthesiologists are concerned about the lack of research regarding the safety and effectiveness of marijuana and cannabinoids," Linda J. Mason, M.D., president of the ASA, said in a statement.
More Information
https://www.physiciansbriefing.com/pain-management-31/marijuana-news-759/interest-in-marijuana-cannabinoids-for-pain-rising-rapidly-749671.html

FTC probes marketing practices of e-cigarette maker Juul

The Federal Trade Commission is investigating the marketing practices of e-cigarette maker Juul Labs Inc sending shares of tobacco stocks down, a person briefed on the matter said Thursday.

 

Shares of Altria Group Inc (MO.N), which has a 35% stake in Juul, fell 4.1% to $43.96 in afternoon trading after the Wall Street Journal earlier reported the probe.
Juul has already come under scrutiny for its marketing efforts, including its use of social media influencers to promote its vaping devices, which have become extremely popular among teens.

 

The U.S. House of Representatives and some state attorneys general have also launched separate investigations into the company’s promotion practices. Last year, the Food and Drug Administration conducted a surprise inspection at Juul’s San Francisco headquarter and seized documents.
“Without commenting on any specific investigation, we fully cooperate and are transparent with any government agency or regulator who have interest in our category,” a Juul spokesman said.
The company “never marketed to youth” but has changed its advertising to feature adult smokers aged 35 and above, and has stopped promoting on social media, the spokesman added.

 

A May 2019 court filing from lawyers, who filed a proposed class action lawsuit against Juul on behalf of customers, disclosed that an unnamed government agency was investigating the company’s marketing practices.
The group is seeking refunds for purchases of Juul products and an injunction to prevent the company from continuing to market to children and non-smokers.
The filing said that while Juul had not turned over documents about its marketing practices to the lawyers, it “has presumably already gathered and produced many of these documents in response to investigatory demands from the FDA, (REDACTED), and Attorneys General for California, Massachusetts, and Washington, as well as the Los Angeles District Attorney.”
FTC investigators are examining Juul’s involvement in deceptive marketing, including by targeting minors or using influencers, and is also determining whether to seek monetary damages, according to the Wall Street Journal report.

 

Altria did not immediately respond to Reuters’ request for comment, while an FTC spokesman declined to comment.
Shares of Philip Morris International Inc (PM.N), which is in talks to merge with Altria, fell 2.7%.
Separately on Thursday, Juul said it was giving over $100 million of incentives to retailers to install new age-verification systems at stores, part of efforts to curb sales of e-cigarettes to minors.
https://www.reuters.com/article/us-juul-probe/ftc-probes-marketing-practices-of-e-cigarette-maker-juul-source-idUSKCN1VJ26B

Democrats' Medicare for All must consider union-won plans: AFL-CIO

Democratic White House hopefuls should ensure their Medicare for All proposals honor union-negotiated private insurance, AFL-CIO President Richard Trumka, head of the largest federation of U.S. labor unions, said on Thursday.

 

 

How to best extend health coverage to millions of uninsured or under-insured Americans has been one of the early issues defining the Democratic nominating contest to take on Republican President Donald Trump in November 2020.
The issue is increasingly cropping up on the campaign trail as the 20 candidates still vying to become the Democratic nominee compete for support from unionized workers and official endorsements that can lead to critical on-the-ground resources.
“There’s no question that ultimately we need to establish a single-payer system, but there has to be a role for those hard, hard-fought-for, high-quality plans that we’ve negotiated,” Trumka told reporters at an event hosted by the Christian Science Monitor.
“You can’t ask the American worker, who sacrificed wages and everything, to simply say: ‘Okay, I’ll accept this plan here,’” Trumka added, noting that some union plans likely provide more benefits than Medicare.
Progressive U.S. Senators Bernie Sanders and Elizabeth Warren have favored a Medicare for All approach that would extend the existing, government-run Medicare health insurance program to all Americans, largely eliminating a role for private insurance. Medicare currently serves Americans aged 65 and older.
Moderate candidates such as former Vice President Joe Biden and U.S. Senator Michael Bennet prefer taking a more incremental approach that would create a so-called “public option” allowing people to enroll in a government healthcare plan that would exist alongside private insurance.

 

Still others, including U.S. Senators Kamala Harris and Cory Booker, have modified their healthcare proposals, after backing Sanders’ Medicare for All bill in the Senate, to preserve some role for private insurance, even if for a limited time.
Candidates have invoked union-negotiated health insurance as one reason why a public option is preferable to the Medicare for All proposals offered by their rivals.
“If you have a generous union-backed plan and you have given up union wages to get that plan, you can keep it,” Biden said last week at Dartmouth College in Hanover, New Hampshire.
Most national unions, including the AFL-CIO, which is a federation of more than 50 unions that collectively represent more than 12 million workers, have yet to back a candidate.
Sanders won his first national endorsement this week from the 35,000-member United Electrical, Radio and Machine Workers of America. Biden in April secured an endorsement from the International Association of Firefighters, which has more than 300,000 members.
Sanders, after speaking to the Iowa Federation of Labor last week, updated his campaign website to show that his Medicare for All legislation would allow unions to renegotiate their contracts in a government-overseen process and seek plans for additional services not covered by Medicare.
His “Workplace Democracy” proposal now states that there will be a “fair transition to Medicare for All” that will “require that resulting healthcare savings from union-negotiated plans result in wage increases and additional benefits for workers during the transition.”

Trumka called it a “positive sign” that candidates seem to be listening to union workers and are integrating their feedback into policy proposals.
“It’s going to generate huge savings for employers,” Trumka said of transitioning to a single-payer system. “The question will be: What happens to the savings?”
“What we’re saying is our plans, we’ve negotiated hard ... there has to be a way for us to recoup that.”
https://www.reuters.com/article/us-usa-election-healthcare/democrats-medicare-for-all-must-consider-union-won-plans-afl-cio-idUSKCN1VJ268

Okla. hospital used dirty gastroscopes on almost 1,000; no infections reported

An unnamed hospital in Oklahoma used contaminated gastroscopes in procedures performed on nearly a thousand patients in recent months, device maker Pentax Medical told U.S. regulators last month, putting the patients at risk of exposure to bacteria that can cause infections.
In a July 22 report here that only recently became public and was reviewed by Reuters, Pentax told the Food and Drug Administration that a hospital used up to four gastroscopes contaminated with bacteria in 998 procedures performed sometime last year through June 2019, when the problem was discovered. Pentax, a unit of Tokyo-based Hoya Corp, said it was not aware of any patient infections thus far.
Gastroscopes are inserted in the mouth and used to examine the stomach, conduct biopsies and perform other procedures.
The FDA redacts the names of hospitals from device injury reports before releasing them publicly. “Per FDA regulation, we are not permitted to disclose the facility identity publicly,” agency spokeswoman Alison Hunt said.
Neither Pentax nor the Oklahoma State Department of Health would name the hospital involved.
In a statement to Reuters, Pentax described the incident as a “failure by the facility reprocessing personnel to completely follow” the company’s cleaning instructions for gastroscopes.
The company said the “hospital has notified all potentially affected patients of their options for post-exposure medical screening.”
The FDA echoed Pentax’s assessment and said regulators “have determined that the manufacturer’s reprocessing instructions were not followed.” The agency said it is continuing to discuss the incident with Pentax and the hospital to learn more details.
Gastroscopes, like other endoscopes, are brushed and washed with disinfectants in preparation for the next patient. Despite those efforts, contamination can persist and patients can be exposed to drug-resistant bacteria and develop infections that are difficult or even impossible to treat.
They are not required to be sterilized, a process that for many manufacturers would require design changes to enable complex scopes to withstand gas or chemicals.

DESIGN HINDERS CLEANING

U.S. Senator Patty Murray of Washington state, who led a Senate investigation into duodenoscope infections following an outbreak at a Seattle hospital several years ago, expressed concern about the persistent lapses in patient safety related to endoscopy despite years of scrutiny by regulators and lawmakers.

Duodenoscopes are another type of endoscope.
Murray told Reuters that families “should be confident the medical equipment they rely on for critical procedures is safe. But I’m still very concerned about the risks here and I’m going to keep pushing for more transparency, more accountability and stronger protections for patients.”
Researchers say the intricate design of many endoscopes, with narrow channels and tiny crevices, hinders cleaning and those problems are compounded when health workers skip steps or ignore basic protocols in a rush to get scopes ready for the next patient.
In a study published last year in the American Journal of Infection Control, 71% of reusable scopes deemed ready for use on patients tested positive for bacteria at three U.S. hospitals. The study found problems with gastroscopes, colonoscopes and bronchoscopes, among others.
“Scopes get highly contaminated every time they’re used,” said Cori Ofstead, the study’s author and an epidemiologist in St. Paul, Minnesota. In the latest incident involving gastroscopes, she said, “It appears the institution continued to use damaged scopes, and inadequate cleaning allowed potential pathogens to remain on the scopes.”
In its filing to the FDA, Pentax said the “forward water jet channel” was not properly cleaned on three of the gastroscopes and a “foreign liquid was evacuated from at least one of the devices upon flushing” that channel. After discovering the problem, the hospital took the scopes out of service and returned them to Pentax.
Some infection-control experts have urged manufacturers and regulators to move toward sterilization for scopes, which would be a step above the current U.S. requirement for high-level disinfection.
Some companies are selling single-use scopes as a safer alternative, but reusable devices continue to be used widely.
In 2015, the FDA ordered Pentax and two other scope manufacturers – Olympus Corp and Fujifilm Holdings Corp – to conduct surveillance studies after the spread of antibiotic-resistant “superbugs” at U.S. and European hospitals from contaminated duodenoscopes. Those gastrointestinal scopes are put down a patient’s throat to diagnose and treat problems such as gallstones, cancers and blockages in the bile duct.

In April, the FDA said 5.4% of duodenoscopes tested positive during those industry studies for “high concern” organisms such as E. coli, even after being disinfected. The FDA said that contaminated duodenoscopes were linked to three deaths last year and 45 reports of patient infection from October 2018 to March 31.
This week, FDA urged hospitals and device makers to adopt newer models of duodenoscopes that have disposable parts that can aid cleaning and reduce the risk of infection.
“We recognize that a full transition away from conventional duodenoscopes to innovative models will take time and immediate transition is not possible for all health care facilities due to cost and market availability,” Dr. Jeff Shuren, director of the FDA’s Center for Devices and Radiological Health, said in a statement Thursday.
https://www.reuters.com/article/us-hoya-pentax-scopes/oklahoma-hospital-used-dirty-gastroscopes-on-almost-1000-patients-no-infections-reported-idUSKCN1VK2OK