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Adherence to Placebo Regimen Predicts Outcome

December 9, 2005

Adhering to the directions on drug-labels appears to be good for heart patients, according to a new study-even when the "drug" is a placebo.

In the Candesartan in Heart Failure: Assessment of Reduction in Mortality and morbidity (CHARM) trial, which included 7,599 participants, those with chronic heart failure improved if they strictly adhered to the study drug, even if they were in the placebo group.

Results of the CHARM trial were published in the 10 December issue of The Lancet (online on 7 December) and by MedPage Today on 7 December 2005.

In their article, the CHARM researchers wrote that, compared with participants who patients who had poor medication adherence, "good adherence was associated with lower all-cause mortality in all patients (p<0.0001)."

Patients receiving Atacand (candesartan) had a 34% lower mortality risk, while patients in the placebo arm had a 36% lower mortality risk(P<0.0001 for both), compared with less compliant participants in the matched arm, according to wrote lead author Bradi D Granger, PhD, of Duke University Medical Center and Duke University School of Nursing, and colleagues.

Moreover, participants who adhered to the placebo regimen had a 10% lower mortality risk compared with participants who did not adhere to the active treatment.

Clinical Trial

The CHARM study included 7,599 participants patients with congestive heart failure randomized to receive Atacand or placebo in addition to standard treatment for congestive heart failure. Beta-blockers, diuretics, aspirin and statins were background medications, based on physician discretion. Median follow-up was 38 months.

In total, 53% of participants had a history of myocardial infarction, 55% had hypertension, 28% had diabetes, 27% had atrial fibrillation, and 24% had a history of angina. Most participants were taking 3-6 different drugs.

Researchers assessed adherence to the study-drug regimen at each follow-up, and categorized participants into three groups, based on adherence: less than 20%, 20-80%, and >80%. Good adherence was defined as > 80%, while 80% or lower was considered poor adherence.

"Overall, 6,763 (89%) of the patients were at least 80% adherent," the researchers wrote.

According to the researchers, these findings suggest that adherence to a study-drug regimen "is possibly a marker of good adherence to other beneficial medications known to improve outcome."

In a commentary (published in the same issue of The Lancet), Harvey D White, MD, of the Green Lane Cardiovascular Service at Auckland City Hospital in New Zealand, wrote that poor adherence is "common in congestive heart failure and results in poor outcomes and increased costs."

However, improving adherence may have a disadvantage, according to Dr.White, who wrote that "the frequency of adverse events may also increase and the risk-benefit ratio may be different than in trials." However, he concluded that the evidence strongly supports developing novel strategies to improve adherence to both "pharmacological and lifestyle measures."

Posted: December 2005