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October 6, 2009 (Oakland, California)— High-risk individuals who took a "bundle" of fixed doses of two generic cardioprotective drugs for two years had a lower risk of cardiovascular (CV) events the following year, in an observational study [1].
The study subjects were members of a health insurance plan who lived in California and had coronary artery disease (CAD) and/or were over age 55 and diabetic.
Those who took the drug bundle--a statin and an angiotensin-converting enzyme (ACE) inhibitor--less than half the time had a 60% lower risk of myocardial infarction (MI) or stroke, and those who took it more than half of the time had an 80% lower risk, lead author Dr Robert James Dudl (Care Management Institute, Kaiser Permanente, Oakland, CA) told heartwire.
"We think all patients with diabetes who are over age 55 and/or patients with heart disease--whether they have hypertension or high cholesterol or not--should be on these pills," he said.
The study is published in the October 2009 issue of the American Journal of Managed Care.
"Weak Study," Too Early to Advocate Drug Bundle
Others, however, caution that it is still way too early to recommend widespread use of this drug bundle, which is like the cardioprotective "polypill" in the The Indian Polycap Study (TIPS), although that drug is a single pill that also includes aspirin and two other antihypertensives.
"This study [by Dudl et al] was very weak, and the conclusions are not scientifically acceptable," Dr Steven Nissen (Cleveland Clinic, OH) told heartwire. The authors did not correct for the many baseline confounding variables, and the manuscript was published in a low-impact journal, he noted. "Given the flawed methodology, no reasonable scientific conclusions are possible," he said.
On the other hand, Dr Christopher Cannon (Brigham and Women's Hospital, Boston, MA), told heartwire that although this was not a randomized trial, this study does suggest that this simple strategy can be effective, even in high-risk patients, with access to these therapies.
The high-risk patients in this study should have already been on these two key preventive medications, he noted, but, as is often the case, only a third of them were taking lipid treatment and a quarter of them were taking the ACE inhibitor.
Keep It Simple, Increase Compliance
Based on the Archimedes model, Kaiser Permanente researchers projected that an aspirin, lisinopril, and lipid-lowering medication (ALL) patient-care program would reduce CV outcomes in high-risk patients.
To investigate this, they looked at data from 170 024 high-risk individuals who were members of this healthcare plan, lived in California, and were over age 55 and diabetic (78%) and/or had CAD (32%).
They examined use of a two-drug bundle--typically lovastatin (40 mg/day) with lisinopril (20 mg/day), or, if clinically indicated, with an angiotensin receptor blocker. An estimated 75% of these individuals also took aspirin, but complete data on aspirin use were not available.
During the two-year study period, 28% of the individuals took the drug bundle less than half the time, 12% took it more than half the time, and 60% did not take both drugs. Taking the drug bundle more often was associated with a greater reduction in risk of subsequent MI or stroke.
"Good Starting Point," Potential Broad Implications
The strategy was designed to be simple (three pills a day) and affordable (about $12 a month), with a middle dose meant to attain desired outcomes without undue side effects, Dudl said. Adverse effects--such as cough with lisinopril and muscle aches with statins--were not greater than typical rates associated with these drugs, he added.
The medication bundle is meant to complement, not replace, a healthy lifestyle, he added, and physicians who would like patients to reach target cholesterol or blood-pressure goals can increase the medication doses.
According to Dudl, this strategy is designed to avoid "therapeutic inertia," where treatment stops due to lack of follow-up to titrate a patient's medicine dose.
The ongoing, randomized TIPS trial--which compares a cardioprotective polypill strategy and usual care--should provide stronger evidence about the merits of this treatment strategy, Cannon said.
A two-drug bundle or a polypill strategy "could be a good starting point, or stepping stone, if it brings many people onto some therapy, of whom some go on to receive optimal therapy," Cannon added. "It would have broad implications, because we know that there are tens of millions of people in the United States and worldwide who are at risk and not taking these basic therapies that we know they should be taking."
The authors report having no conflict of interest with the subject matter of this article.
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