Antiinflammatory cuts risk of heart attack

first_imgA targeted anti-inflammatory drug can reduce the risk of heart attacks or strokes, often brought on by narrowed coronary arteries (pictured), in high-risk patients. Sign up for our daily newsletter Get more great content like this delivered right to you! Country Email CANTOS grew out of years of ups and downs in the heart disease field, as scientists tried to trace the role of inflammation, a complex cascade of immune signals and various white blood cells that occurs in response to wounds, infections, and more. One detective was cardiologist Peter Libby at Brigham and Women’s Hospital in Boston, who determined that various molecules recruit macrophages and other immune cells to blood vessels. That leads to inflammation and eventually, arterial plaques.Back in the 1980s, when Libby’s work began, “I was a lonely voice” advocating a connection, he says. Now, researchers believe “the whole atherosclerosis process begins as an inflammatory event,” explains Mark Creager, director of the heart and vascular center at Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, who wasn’t involved in the study. But was inflammation relevant to the triggering of actual heart attack—which often occurs when an arterial plaque ruptures and blocks an artery—not just the long process leading up to it? While Libby worked away in his lab, another cardiologist at Brigham and Women’s, Paul Ridker, began testing this premise in people.  Ridker showed that high levels of inflammation molecules in a person’s blood can help predict a heart attack. One such marker is called c-reactive protein (CRP). In patients, Ridker found that statin drugs, widely known to prevent heart attacks by lowering cholesterol, lower CRP levels, too, suggesting they blunt inflammation—something Libby had seen in animals. But neither physician could promise that this anti-inflammatory power had anything to do with statins’ heart protection.Meanwhile, results from these and other animal and observational studies appeared to clash with how anti-inflammatory drugs affected human hearts. In 2004, a large clinical trial of arthritis sufferers taking the nonsteroidal anti-inflammatory drug (NSAID) Vioxx for their condition were found to have double the normal risk of a heart attack, and the drug was yanked from the market. Steroids, which are potent anti-inflammatory drugs, also didn’t prevent heart attacks or strokes in people taking them for other reasons, several studies showed.Ridker and Libby speculated that for an anti-inflammatory to work, it needed to be much more specific; NSAIDs and steroids have broad effects all over the body, and NSAIDs can spur inflammation along with blunting it. The pair focused on the monoclonal antibody canakinumab, already approved for juvenile arthritis, because it selectively targets a molecule called IL-1β, which is part of the pathway driving atherosclerosis. Together, they persuaded Novartis to support a study.The heart attack patients who enrolled all had high CRP levels and were given the best treatments available, including aggressive statin therapy. Half also received four infusions of canakinumab each year, at one of three different doses.  And in the end, those infusions made a difference, if a modest one. People receiving the placebo had about a 4.5% risk of a second cardiovascular event after a year versus 3.86% for those on the medium dose of the drug. This meant they were about 15% less likely to suffer a heart attack or stroke or die from cardiovascular disease. Over about 3.5 years, 535 of 3344 people in the placebo group suffered such an “event,” compared with 642 of 4547 getting the medium and high doses. Participants were also about 30% less likely to need a stent or cardiac bypass surgery if they got canakinumab, suggesting that damping down inflammation helps arteries stay healthy.Ridker and others say that even a 15% reduction is exciting, because it came on top of the already significant benefits from the best standard treatment. They’re especially happy with the larger drop in invasive treatments. “I’m pinching myself,” Ridker says. This is “exactly what we had hoped for the last 30 years that we’d get. … It makes absolutely clear that if you lower inflammation, you lower risk.”The results were presented this morning at the European Society of Cardiology meeting in Barcelona, Spain, with the heart data appearing simultaneously in The New England Journal of Medicine and the cancer analysis in The Lancet.Where to go from here is complicated. For one, canakinumab is expensive, at about $16,000 per infusion. Cardiologists agree that Novartis will have to lower the drug’s price to make it more competitive with existing heart treatments. Doctors will also need to carefully balance the risks with benefits. About 1% of those on canakinumab died from an infection during the multiyear trial, nearly double the rate of infection deaths on placebo; those who died were often older and had diabetes. Asked whether he’d offer this therapy to people with high CRP who’ve never had a heart attack, Ridker was unequivocal: No way. “I think this is going to be a therapy for very high risk patients,” he says.More information may come from another large trial Ridker is running. This one is federally funded and is testing the much cheaper but less targeted anti-inflammatory methotrexate in a similar population. Results will be available in a couple of years.The lung cancer piece is murkier, if provocative. “There needs to be more work in this area,” says Colin Baigent, an epidemiologist at the University of Oxford in the United Kingdom, who sees the observation as fodder for a future trial. “It’s not convincing on its own.”Baigent is most excited that CANTOS firmly backs the notion that blocking inflammation can prevent heart disease. This first salvo is now sure to be followed by many more, he and others say. “It’s a gateway to a very wide variety of therapies that are going to be developed,” says Steven Nissen, a cardiologist at the Cleveland Clinic in Ohio who has long sided with Ridker. “This is as big as anything we’ve seen in a while.” Zephyr/Science Source Anti-inflammatory cuts risk of heart attackcenter_img By Jennifer Couzin-FrankelAug. 27, 2017 , 5:00 AM Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Click to view the privacy policy. Required fields are indicated by an asterisk (*) A clinical trial of more than 10,000 heart attack patients reported today supports a novel way to protect them from a stroke or a second attack: with drugs that stop inflammation. The approach has been advanced by some scientists for years, but this is the first trial to conclusively show that it works. Cardiologists hailed it as vindication for the heart attack–inflammation link, which hadn’t been proved in people.The effect on future heart attacks is modest, but even skeptics were swayed. “I have to congratulate” those running this trial, says Terje Pedersen, a cardiologist at Oslo University who had been skeptical in the past.Called the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) and funded by the drug giant Novartis, the trial also found fewer cases of lung cancer in those on the treatment, rekindling basic research findings hinting that the same inflammatory pathway may initiate or spur the growth of such tumors. Nearly 2% of people in the placebo group were diagnosed with lung cancer during the study compared with 1% on the treatment. The actual disparity in number of cases between the two groups was small, with 129 lung cancers in all, and the trial wasn’t set up to study that disease.last_img