Statins cut risk of stroke, heart attack in study
Reported November 10, 2008
Boston researchers reported yesterday they have developed a strategy that dramatically reduces the risk of heart attacks, strokes, and even death among older adults who don’t have the traditional warning signs of perilously clogged arteries.
Using a test they pioneered, scientists from Brigham and Women’s Hospital screened patients for evidence of cardiovascular disease missed by conventional cholesterol tests and then gave them preventive doses of a type of drug known as a statin.
The result: Heart attacks and strokes were cut by roughly 50 percent among patients who received the pill as part of a sprawling medical study that spanned 26 countries and included nearly 18,000 people. And the patients who got the medication rosuvastatin, marketed under the brand name Crestor, suffered only one side effect potentially linked to the pill, according to the study, which was paid for by the drug’s maker, AstraZeneca.
A half-dozen specialists not involved in the research predicted that the findings, presented in New Orleans at an American Heart Association convention that attracts thousands of cardiologists, will spawn a seismic shift in heart disease prevention.
Describing the study as a landmark, the doctors said millions of patients who previously would not have been considered candidates for statins now appear destined to receive some form of the medication widely used to lower cholesterol.
“The extent of reduction in death, heart attacks, and stroke is larger than we’ve seen in any trial I can remember,” said Dr. Steven Nissen, a prominent Cleveland Clinic cardiologist. “I don’t know how you get much bigger than that.”
The National Heart, Lung, and Blood Institute will take the findings under “strong consideration” as it revises guidelines on preventing and treating heart disease next year, said Dr. Elizabeth Nabel, the agency’s director. That could translate into widespread use of the Brigham test among men over 50 and women over 60 – and more prescriptions for drugs.
Still, reflecting persistent controversy over how best to detect and treat heart disease, a cardiovascular researcher at Stanford University sounded a cautionary note about rushing to prescribe statins, already the top-selling drugs in America, to millions of additional patients.
Scientists need to better identify those patients who stand to benefit the most from a medication designed to prevent, not treat, an illness, because all drugs carry medical risks and financial costs, warned Dr. Mark A. Hlatky, who penned a critical editorial published online with the study in The New England Journal of Medicine.
“You and I have all seen drugs that everybody thought were wonderful and safe, but after a few years you say, ‘Uh-oh,’ ” he said. “The reason I’m cautious about this is because of that history.”
Every year, nearly 900,000 Americans die from cardiovascular disease, the nation’s number one killer. But half of people who suffer heart attacks or strokes had no warning signs, such as previous episodes of chest pain or elevated levels of bad cholesterol, which gums up arteries.
“And that’s what this study is all about,” said Dr. Paul Ridker, the Brigham specialist who presided over the research. “It’s about the guy who goes running and does not come back, and the doctor and the spouse are shocked because this is someone who was thin and seemingly in good health and with a good cholesterol level.”
So years ago Ridker invented a blood test to identify some of these people by detecting C-reactive protein, or CRP, a measurement of inflammation in arteries that suggests patients are prone to catastrophic blood clots. Because Brigham holds patents on the high-sensitivity CRP test, both the hospital and Ridker stand to profit handsomely from royalties if it becomes as common as a cholesterol screening.
Some doctors have been reluctant, however, to use the test, which typically costs less than $100 and is sometimes covered by insurance.
“We’ve known that CRP has been an indicator of risk, but never had the data to suggest that once you’ve identified patients with the risk factor, if you were to treat them, would it make a difference?” said Dr. W. Douglas Weaver, president of the American College of Cardiology.
Ridker’s study was crafted to answer that question.
People were eligible to participate if they had a high CRP result but healthy cholesterol readings. Patients are generally advised to keep their total cholesterol levels below 200; more specifically, a reading lower than 130 is recommended for the bad form of cholesterol, known as LDL.
The study participants, on average, were 66 years old and overweight, but not obese.
Half received a 20 milligram dose of rosuvastatin each day while the others received a placebo. The study was supposed to last for five years, but a board monitoring the safety of the trial stopped it early because the results were so overwhelmingly positive.
“They said, ‘Dr. Ridker, we think it’s unethical to continue giving anyone in your trial a placebo,’ ” the Brigham doctor recalled. “We were just stunned by the result.”
LDL cholesterol and CRP levels plunged, and patients who received the drug suffered considerably fewer health emergencies, with 31 heart attacks and 33 strokes, compared with 68 heart attacks and 64 strokes among people who took the placebo. Deaths also fell, by 20 percent.
The only indication of a serious side effect was that patients taking the medication were more likely to be diagnosed with diabetes, a concern previously identified with the drugs.
Statins – with $18.4 billion in US sales in 2007, according to consulting company IMS Health – have generated their fair share of criticism. Some doctors complained the drugs had not been tested sufficiently in women, and others were concerned that pharmaceutical companies underreported side effects.
Dr. Gregg Fonarow, a heart specialist at the University of California, Los Angeles, said that because of the sheer size of the study and the significant percentages of women, African-Americans, and Hispanics included, lingering concerns about statins should be silenced.
“This really changes everything,” said Fonarow, who was not involved in the study but has received consulting and other payments from statin makers. Now, he said, when doctors encounter patients in their 50s, 60s, or older, they should “make sure there are absolutely no risk factors present and no elevation of CRP before deciding it’s safe for that person to leave without a statin prescription.”
Specialists said it remained unclear how many additional patients would be eligible to receive statins if the findings from the Brigham study were widely implemented, with Ridker estimating at least 6 million Americans while other specialists forecast tens of millions. Worldwide, 13 million patients already take rosuvastatin; in his editorial, Hlatky pegged the monthly cost at about $100 a patient.
By one standard measurement used to evaluate whether it makes sense to give a drug to big groups of people, rosuvastatin fared quite well. The researchers found that 25 people would need to take the statin for five years to prevent one serious cardiovascular episode.
“As expensive as this might be to give this drug to all these people, it might still save money if you take into account” costs associated with the complications of heart attacks and strokes, said Dr. James E. Muller, chief executive of InfraReDx, a Burlington biotech company that makes a system to detect fatty deposits embedded in arteries.