Larger statin dosages urged for many with cholesterol, heart risks

UPI

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1 of 2 | Dr. Charles Hennekens, a medical school professor and heart disease researcher at Florida Atlantic University in Boca Raton, Fla., says too many patients at high risk of heart attacks and stroke are being "underdosed" with beneficial statin drugs. Photo by Alex Dolce, Florida Atlantic University
ST. PAUL, Minn., July 31 (UPI) -- Doctors are routinely "underdosing" statins for patients at risk for heart attacks and strokes due to elevated levels of "bad" cholesterol, even though the drugs have proven safe and effective, a top U.S. researcher maintains.
At a time when an estimated 40% of U.S. adults have metabolic syndrome -- a combination of heart risk factors including obesity, hypertension, dyslipidemia and insulin resistance -- doctors usually don't start them off with the maximum dosage of statins, even though they can quickly lower levels of LDL cholesterol, according to an opinion published this month in the medical journal Trends in Cardiovascular Medicine.
Co-author Dr. Charles Hennekens, the Sir Richard Doll Professor of Medicine and Preventive Medicine at Florida Atlantic University's Charles E. Schmidt College of Medicine in Boca Raton, says his analysis of several major clinical studies of the new generation of highly potent statins, such as rosuvastatin and atorvastatin, shows that maximal doses are safe and sorely needed, but aren't being prescribed.
Those with metabolic syndrome have cardiovascular risks equivalent to those with prior heart attacks or strokes, yet many are "undertreated" by starting their statin regimens at low or moderate dosages, Hennekens told UPI.
"The data indicate that over half of people who were put on a statin remain on the initial dose they're given, so even though the intent may be to titrate it up, it's not done in the majority of instances," he said. "So, you get on a low dose of statin and you stay on it."
But this "flies at the face of the data" showing that statins "have the strongest and most consistent body of evidence supporting their prescription in treatment and prevention in both men and women including older adults," he said. "There's no threshold for LDL below which you don't see incremental benefits."
The studies demonstrate newer statins can lower LDL, or bad cholesterol, in as quickly as a month and can provide related benefits, such as stabilizing the build-up of harmful plaque on the cells that line the interior surface of blood vessels, Hennekens said.
Therefore, he urges cardiologists who initiate drug therapies for those with metabolic syndrome to start statins at maximal tolerated levels.
"Everything points to getting on the highest dose of evidence-based statin," he noted. "The goal of LDL in the high-risk secondary patients is less than 50 [milligrams per deciliter], and we have a lot to do to achieve that goal because there are lots of forces in society, especially in American society, that are making that more difficult.
"For example, in the United States today, in middle-age people gain 7 to 10 pounds of body weight every 10 years, so we have a society that's fatter, but only about 21% of Americans reach the daily minimum recommendation for daily physical activity, Hennekens said.
"We have a nation that would benefit enormously from therapeutic lifestyle changes, but in the end, we have such high absolute risk that many are going to require adjunctive therapy."
And if so, "we make a strong case that the first one you should consider is a statin, and that every other adjunctive therapy should be viewed in the context of residual risk after the statin is given with maximal doses," Hennekens added.
Other experts on the use of statins to control LDL cholesterol contacted by UPI generally agreed with the premise that dosages should start at maximum levels for those at high risk of heart disease.
Dr. Laurence Sperling, the Katz Professor in Preventive Cardiology at the Emory University School of Medicine in Atlanta, noted it's already on a list of guidelines developed in 2018 by an American College of Cardiology/American Heart Association joint task force.
"In patients with clinical atherosclerotic cardiovascular disease, [the guidelines say] reduce LDL cholesterol with high-intensity statin therapy or maximally tolerated statin therapy," he said. "The more LDL cholesterol is reduced on statin therapy, the greater will be subsequent risk reduction."
Sperling said he agreed with the recommendation to use "a maximally tolerated statin to lower LDL-C levels by 50%."
Joseph Saseen, a researcher and professor of clinical pharmacy at the University of Colorado's Skaggs School of Pharmacy and Pharmaceutical Sciences in Boulder, told UPI one reason for the low-dosage prescriptions is that cardiologists overestimate the chances of possible side effects, such as muscle aches and digestive problems.
"While dose-related side effects can occur, they do not justify the routine underdosing of statins in high-risk populations," Saseen said. "Clinicians too often initiate therapy at suboptimal doses, particularly in patients with elevated [cardiovascular] risk. Evidence-based guidelines recommend starting high-intensity statin therapy, especially very high-risk secondary prevention patients."
Clinical data have shown, for instance, that initiating atorvastatin at as much as 80 mg. daily "is both safe and effective in reducing cardiovascular events among secondary prevention patients," Saseen said. "Similarly, rosuvastatin at 20 mg. has been shown to be a safe and effective starting dose in primary prevention patients with elevated [high-sensitivity C-reactive protein]."
Also agreeing with Hennekens' conclusion is Dr. Paul Heidenreich, a practicing cardiologist, professor at the Stanford University School of Medicine and chief of medicine at the Palo Alto, Calif., Veterans Affairs clinic.
"When high intensity statins are indicated, one can recommend starting with the high intensity or beginning with moderate intensity followed by up-titration," he said.
He noted some cardiologists are concerned that if patients can't tolerate a high-intensity statin, they may subsequently refuse all statins, in which case it may be better to start off with a moderate dose.
"However, I feel it is rare that the patient will refuse to try a lower dose," Heidenreich said. "As the authors note, titration to a higher intensity is not as frequent as it should be, with patients staying on the initial intensity. Thus, patients are likely better off starting with the recommended high-intensity statin."
The clinical data also showed that the rate of intolerance with a placebo "was surprisingly high, suggesting that patients are on the lookout for any new symptom that occurs following initiation of a new medication. It is important to stress that the vast majority of patients tolerate statins medications without side effects," he said.