Inflammation: Is It the New Cholesterol?

In scientific circles, the hypothesis that reducing inflammation can lower the risk of heart disease has been gaining ground. Last weekend, that hypothesis may have finally become fact, with far-reaching implications.

At the European Society of Cardiology meetings in Barcelona, the Novartis-sponsored CANTOS trial demonstrated that an anti-inflammation drug (albeit one that is currently reported to be priced at about $200,000 a year) could reduce the risk of the combination of heart attacks, stroke and death from cardiovascular disease in people who had previously had a heart attack and a blood test that indicated the presence of inflammation. And it did so without affecting cholesterol levels.

The effect on patient care will not be immediate, but the study is transformative in moving inflammation into the category of a modifiable risk factor for heart disease.

What is inflammation? The body’s immune system protects us from foreign invaders, like viruses and bacteria.

Inflammation is the body’s response, with the activation of white blood cells and other substances. Most often, that response helps us. In cancer, scientists have been using our own immune systems to target disease.

However, sometimes, our immune systems can actually attack our own body and cause disease; these are called autoimmune diseases, like rheumatoid arthritis.

Now people are looking at inflammation as contributing to the risk of common conditions, like heart disease.

Paul Ridker, the principal investigator of the CANTOS trial and a cardiologist at Harvard, is the leading proponent of this inflammation hypothesis. [Disclosure: Paul is married to my sister (and I want to disclose that) and so I have had a front row seat in these developments over the last two decades.] His work and that of other scientists carefully and methodically laid the groundwork for the idea that giving people treatment that would quiet their immune systems would reduce their risk of heart disease.

As basic scientists were revealing that inflammation played a role in the biology of the causes of heart disease, clinical scientists were showing that blood tests of inflammation could indicate levels of risk.

People who had a more revved-up immune system had a higher risk of heart disease. And this risk was in addition to what was indicated by traditional risk factors like smoking and high cholesterol levels.

They found that statin drugs, which are highly effective in reducing heart disease risk, actually not only lowered cholesterol, but also calmed inflammation.

And so many speculated that the benefit of statins may also derive from what they do to the immune system.

But the question persisted – could an intervention that targeted the immune system without affecting lipid levels reduce heart disease risk? CANTOS used canakinumab, an expensive drug that is approved for use in some autoimmune diseases, like juvenile arthritis. It targets a particular part of the immune system and can reduce inflammation.

In the study of about 10,000 people who were randomized to receive canakinumab or placebo and followed for 4 years, there was a benefit. For every 1000 people treated with canakinumab, there were about 6 fewer deaths from heart attacks, stroke, or heart disease.

There was also a higher risk of an infection causing death.

There was no difference in deaths from any cause (though the study was not designed to detect a difference in overall deaths).

For patients, this trial is not likely to make canakinumab a household name.

 The benefits were modest, there were some risks, and the price tag, at least now, is in the stratosphere.

But make no mistake, this trial heralds the beginning of a new era in cardiology. It signals that the manipulation of the immune system is likely to be another avenue of reducing cardiovascular risk – and there are many possibilities with new drugs and old ones that could be repurposed.

In fact, the NIH has supported Dr. Ridker to investigate the possibility that methotrexate, an old and inexpensive drug with anti-inflammatory effects, could reduce the risk of heart disease – and that trial, theCardiovascular Inflammation Reduction Trial, according to ClinicalTrials.gov is still recruiting.

And there is something more. In an exploratory analysis that ultimately may or may not turn out to be important, the CANTOS investigators reported that lung cancer rates and deaths were much lower in the canakinumab.

Could such drugs reduce the risk of cancer and heart disease? Could an even safer and less expensive drug do the same thing? This trial should open the gates to an abundance of future research.

The idea that inflammation is important in heart disease is not new and is supported by a mountain of science.

But now we may be at the beginning of translating that science into strategies and interventions. Healthy behaviors continue to be the best way to combat heart disease – but it will be nice to have more tools available and to see this potential unfold in the years ahead.

Source        forbes

Prostate Cancer Trial Stuns Researchers

'It's a once in a career feeling'

Study with ‘powerful results’ finds that combining two existing therapies could extend the life of men with advanced, high-risk prostate cancer by 37%

Combining two existing prostate cancer therapies could extend the life of men with advanced, high-risk prostate cancer by 37%, according to a study presented at the world’s largest cancer conference. The new findings could change how doctors first approach treatment of prostate cancer.

“These are the most powerful results I’ve seen from a prostate cancer trial,” said Nicholas James, the lead author of the abstract presented as the American Society of Clinical Oncology. “It’s a once in a career feeling. This is one of the biggest reductions in death I’ve seen in any clinical trial for adult cancers.”

Researchers combined standard hormone therapy with a drug called abiraterone , which is typically used only for cancer patients whose disease has stopped responding to standard hormone therapy. The research was conducted as part of the Stampede trial, an ongoing randomized trial conducted in the UK and Switzerland.

“Abiraterone not only prolonged life, but also lowered the chance of relapse by 70% and reduced the chance of serious bone complications by 50%,” James said. “Based on the magnitude of clinical benefit, we believe the upfront care for patients newly diagnosed with advanced prostate cancer should change.”

The study looked at a group of 2,000 men. Patients who received both abiraterone and normal hormone therapy were significantly less likely to die, compared to patients who received only hormone therapy.

Comparatively, 83% of men assigned abiraterone therapy survived versus 76% of men on standard hormone therapy. Researchers also found that patients who received both medications had slightly stronger side effects, especially cardiovascular and liver problems.

One patient who participated in the trial, Alfred Samuels, 59, was diagnosed with advanced prostate cancer in January 2012. “It felt like my world fell apart overnight,” Samuels said. “The doctors explained that surgery wasn’t an option for me because the cancer had spread beyond my prostate.”

“As part of the trial, I started taking abiraterone four times a day and had a hormone injection every eight weeks,” he said. “During the first six months, tests showed that the treatment was working. I’m still on the trial, which I find reassuring and, fortunately, my cancer is being managed well.”

More than 27,000 men in the US and 11,000 men in the UK die of prostate cancer each year, according to the US Centers for Disease Control and Prostate Cancer UK. In the US, aside from skin cancer, it is the most common cancer in men.

“The potential benefits of giving some men abiraterone alongside hormone therapy are clearly impressive and we will be working with all relevant bodies to make sure this treatment becomes an option available for these men via the NHS,” said Dr Iain Frame, director of research at Prostate Cancer UK.

Source:      The Guardian