New drug beats heart disease by reducing inflammation

How much would this help in preventing stroke?
Hopefully you can use this off-label.  They would rather pay for your heart attack or stroke. 

New drug beats heart disease by reducing inflammation 

By Dr. Manny Alvarez, Fox News

About every 40 seconds, an American has a heart attack, and almost 15 percent of those heart attacks are fatal. As the leading cause of death in the U.S., heart disease has been the subject of thousands of studies in the last several decades, and breakthroughs in the last 50 years have been significant.

First, diet, exercise, and smoking cessation were all proven to play an enormous role in heart health, helping physicians guide patients to less risky lifestyle choices.

Then, in the 1980s, the first commercial statin was approved by the FDA, ushering in an era in which medication could be used alongside lifestyle changes to lower cholesterol levels, potentially reducing heart attack risk by over a third for some high risk patients.
STDS HIT RECORD HIGH IN US, 2M CASES REPORTED IN 2016
Despite these gains and the fact that statins are one of the most frequently prescribed drugs, heart disease is still the number one killer of Americans, but researchers are excited about the results of a study published last month in the New England Journal of Medicine that investigates the impact of a new drug on cardiovascular risk.
The trial is the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), and the drug, called Canakinumab, may be able to bring heart attack risk to an all-time low by targeting inflammation.
This study is the first in which a systemic anti-inflammatory, a drug that reduces inflammation throughout the body, has been shown to lower heart attack risk independent of cholesterol-lowering medications.
The purpose of the trial was to see whether reducing inflammation could reduce the risk of recurring cardiovascular events among people who had already had a heart attack and who had elevated levels of high sensitivity C-reactive protein (hsCRP), an indication of systemic inflammation.
The study was the culmination of more than 25 years of research. By treating all patients in the trial with standard care (high doses of statins) and then dividing them into groups that would receive either 50, 150, or 300 mg of Canakinumab (or a placebo), the researchers were able to accurately assess the impact of the new drug. More than 10,000 patients took part in the trial, some of whom were monitored for up to four years.

The results showed a 15 percent reduction in heart attacks and strokes for patients taking either 150 or 300 mg of the of Canakinumab, proving for the first time that inflammation plays a role in heart disease risk independent of cholesterol levels.
This discovery may change therapeutic practice for patients at high risk of heart attack or stroke. More studies are underway to establish the best strategies for using Canakinumab – which patients benefit most and how the drug can be used in combination with other therapies.
“These findings represent the end game of more than two decades of research, stemming from a critical observation: Half of heart attacks occur in people who do not have high cholesterol," Paul M. Ridker, M.D., the study's lead author, said. "For the first time, we’ve been able to definitively show that lowering inflammation independent of cholesterol reduces cardiovascular risk. This has far-reaching implications. It tells us that by leveraging an entirely new way to treat patients — targeting inflammation — we may be able to significantly improve outcomes for certain very high-risk populations.”
The need for invasive and expensive interventions, like bypass surgery and angioplasty, were reduced by more than 30 percent in patients taking Canakinumab, a far greater reduction than is usually found with the use of statins alone.

ESC: At Long Last, Inflammatory Hypothesis Confirmed in CVD by CANTOS Residual major CV event risk reduced by 15%

Since this is an orphan drug you better start saving your pennies, your insurance likely won't pay for it. They would rather pay for your heart attack or stroke. 
https://www.medpagetoday.com/MeetingCoverage/ESC/67529?xid=nl_mpt_DHE_2017-08-28&

• by Peggy Peck, Editor-in-Chief, MedPage Today August 27, 2017
• This article is a collaboration between MedPage Today® and:
  

Action Points

• Note that this large randomized trial demonstrated that the anti-IL-1 therapy canakinumab reduces the rate of myocardial infarction among those with prior MI and an elevated CRP.
• Be aware that deaths from infection were significantly more common in the canakinumab arm.

BARCELONA -- Long-awaited evidence that targeting an inflammatory pathway can reduce heart attacks and stroke independent of lipids is now in hand -- canakinumab (Ilaris) reduced events by 15% compared with placebo.
But there is a two-fold catch: Because canakinumab is an immunotherapy, the drug carries a high price tag and use was associated with an increased risk of fatal infections.
Canakinumab is a human monoclonal antibody that targets the interleukin-1beta innate immunity pathway and it is currently approved as an orphan drug for treatment of two rare pediatric conditions -- systemic juvenile idiopathic arthritis and cryopyrin-associated periodic syndromes for which it is administered monthly and carries an annual price tag of $200,000.
Thus, the reception was mixed: Anthony DeMaria, MD, of the University of California San Diego School of Medicine, called the results "really big because it is a totally new mechanism." But while Stanford cardiologist Robert Harrington, MD, agreed that CANTOS provides evidence to validate the inflammation hypothesis, he suggested it is too soon to strike up the band.
In the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), 150 mg of canakinumab every 3 months reduced high-sensitivity C-reactive protein (hs-CRP) levels by an average of 37% compared with placebo and achieved a 15% reduction in cardiovascular events -- mostly MIs -- compared with placebo, Paul Ridker, MD, reported here at the European Society of Cardiology 2017 congress.
The CANTOS findings were simultaneously published online by the New England Journal of Medicine.
After a median follow-up of 3.7 years, the event rate was 4.5 per 100 person-years in the placebo group versus 3.86 events per 100 person-years in the canakinumab 150 mg group. Two other arms -- canakinumab 50 mg and 300 mg -- also achieved reductions in events (4.11 and 3.90 per 100 person-years, respectively) but only the 150-mg dose achieved a statistically significant reduction. There was no reduction in mortality.
The trial recruited patients who had a history of MI and a hs-CRP level of 2.0 mg/L or higher.
Reflecting on the finding, Ridker told MedPage Today that he had spent roughly 25 years investigating "one fundamental question: Why do half of all heart attacks and strokes occur in people with no known risks?"
Click here for video comments from study authors of the ESC late-breaking trials, and discussions by leading cardiologists from around the world.
His timeline for proving the inflammation hypothesis began more than 20 years ago, "when we published the first paper that said if you checked an inflammatory marker, what we now call CRP, you could identify people at high risk for heart attacks ... 19 years ago we published a paper showing that statins reduced inflammation, and about 8 0r 9 years ago we published a paper that showed if you had high CRP and low LDL, you had better be on a statin.
And through that whole process the fundamental question we asked remained: Can we lower event rates by reducing inflammation?"
The answer, based on CANTOS, is yes, Ridker concluded.
Moreover, he noted that, although there was no cardiovascular mortality benefit, there was 30% reduction in need for bypass surgery, angioplasty, and heart failure -- all of which means a significant improvement in quality of life. And treatment was also associated with a reduction in gout, rheumatoid arthritis, and osteoarthritis, he said.
Interestingly, the treatment had no effect on lipids, which suggests that the benefit was all attributable to the anti-inflammatory activity. But Ridker added that the inflammatory hypothesis in no way competes with the lipid hypothesis. "I think statins are the miracle drugs of the century, and all of these patients [in CANTOS] were on aggressive statin therapy."
Cancer Benefit
And canakinumab treatment had yet another benefit: There was an apparent decrease in risk of cancer, a finding that was elucidated in a Lancet paper also published today. In the cancer analysis, also authored by Ridker, total cancer mortality was lower only in the 300-mg group, but "[i]ncident lung cancer (n=129) was significantly less frequent in the 150 mg (HR 0.61 [95% CI 0.39–0.97]; P=0.034) and 300 mg groups (HR 0.33 [95% CI 0.18–0.59] P<0.0001."
And now the bad: Canakinumab was associated with a higher incidence of fatal infection than placebo -- the rate was 0.18 in the 3,344 patient placebo group versus 0.32 among the 6,717 patients who received any dose of the drug, which worked out to 23 deaths vs 78 deaths (P=0.02).
There was no significant difference in all-cause mortality (HR for all canakinumab doses vs placebo, 0.94; 95% CI 0.83-1.06; P=0.31).
"Despite the scientific and clinical excitement associated with having a new mechanism of action to attack in the treatment of coronary artery disease," Harrington wrote, "a better understanding of the risks and benefits of this form of therapy is needed. Given that there was no observed effect on cardiovascular mortality in this trial, more information about the details of the myocardial infarctions (infarct size, Q-wave vs. non–Q-wave, and spontaneous or procedure-related) is needed to better assess the clinical benefit of canakinumab. We also need additional information about the fatal infections encountered in CANTOS. Furthermore, any discussion of the use of canakinumab in patients with a previous myocardial infarction must consider cost. Given monthly for approved indications, canakinumab is priced at approximately $200,000 per year in the United States. Such pricing may be suitable for rare diseases, but not for a common indication such as coronary artery disease, even if given every 3 months."
Price vs Benefit
Harrington is not the first to point out this difficulty with CANTOS -- on June 28 heart failure specialist Milton Packer, MD, wrote this in his MedPage Today blog: "My prediction: [canakinumab] may cost $64,000 for a 15-20% reduction in the risk of a major cardiovascular event, without decreasing cardiovascular death by itself.
"Is it worth it? If there was push back from payers for [evolocumab] Repatha, I can just imagine what will happen if Ilaris receives a cardiovascular indication."
Repatha is a PCSK9 inhibitor that aggressively lowers lipids and is approved for patients who fail statin therapy, including patients with heterozygous or homozygous familial hypercholesterolemia. But while the lipid reductions with the PCSK9 therapy are impressive, and the FOURIER trial found a 15% reduction in events with treatment, neither evolocumab nor alirocumab (Praluent), a PCSK9 inhibitor from Sanofi/Regeneron have achieved wide uptake as payers balk at the high price tags for the drugs.
Speaking at an ESC press briefing, Ridker said, "This is what personalized predictive medicine is all about." Once a patient has experienced an MI, there is always residual risk of recurrence. Thus, he suggested that residual risk can be divided into residual lipid-driven risk and residual inflammatory-driven risk.
Co-investigator, Peter Libby, MD, of Massachusetts General Hospital, put it this way: 30 days after an MI, when a patient is on statin therapy and stable, physicians could check LDL and then initiate more aggessive statin therapy if it is not well-controlled. Similarly, physicians should check hs-CRP, and if it is elevated -- 2.0 mg/L or higher -- initiating anti-inflammatory therapy targeting interleukin-1 beta would be an option.
That said, Libby noted that he was not recommending off-label use of canakinumab. "We need to wait for guideline committees to assess the evidence."
Ridker told MedPage Today he believed canakinumab might prove to be most useful if it were given to an identified high-responder group. He noted that after a single injection responders have a significant reduction in highly sensitive-CRP and it is those patients who would benefit from continuing on treatment. At that point, "I believe the benefit would outweigh the toxicity risk," he said.
"Maybe that first dose could be free," Ridker added.
And while canakinumab is the first anti-inflammatory agent to demontrate benefit, there may be others, Ridker said. For example, "we have a [National Heart, Lung, and Blood Institute] trial of methotrexate that is on-going. If that proves to be effective, it would be only pennies per treatment." At the press conference, Ridker said the methotrexate trial has "randomized about 4,000 patients, and we will need to get to 7,000 so it will be a few years before we have results."
Novartis, which developed canakinumab, may be sympathetic to that approach. Novartis Global Head Drug Development and Chief Medical Officer Vas Narasimhan, MD, and Jay Bradner, MD, president of the company's Institutes for BioMedical Research, told reporters that the company planned to go ahead with a filing with the FDA as early as October.
"We plan to move ahead with a cardiovascular filing" based on the CANTOS results, Narasimhan said. And while the filing will be based on the total results, "we plan to bring the findings in the hs-CRP responders to our meeting with the FDA." The company also plans to proceed with a phase III trial in non-small cell lung cancer in the first quarter of 2018.
Narasimhan said that, in CANTOS, patients whose hs-CRP declined to 1.8 mg/L or less had a much more robust response. In that subgroup, the number needed to treat to prevent a primary endpoint event was 50 at 2 years and 30 at 3.7 years.