Statin is mildly protective against atrial fib in heart failure.
GISSI-Heart Failure (GISSI-HF) was a double-blind, placebo-controlled trial that randomized 4,574 patients with New York Heart Association (NYHA) class II-IV heart failure to fish oil capsules and/or rosuvastatin at 10 mg/day. The primary outcomes were reported last year (Lancet 2008;372:1223-30, 1231-9).
The new post hoc analysis involved the 3,690 participants without atrial fibrillation (AF) on their baseline ECG. The study showed that during a median 3.7 years of follow-up, 16.0% of the placebo group and 13.9% on rosuvastatin (Crestor) developed AF.
This absolute 2.1% difference translated into a 13% relative risk reduction in the incidence of AF in rosuvastatin-treated patients, which achieved narrowly statistical significance after adjustment for potential con-founders, Dr. Aldo P. Maggioni said at the annual congress of the European Society of Cardiology.
On the basis of the GISSI-HF results, 47 patients with moderate to severe heart failure would have to receive rosuvastatin for nearly 4 years to prevent one case of AF.
However, the observed "modest" beneficial effect may underestimate the true benefit to be derived from longer treatment, since the event curves for rosuvastatin and placebo diverged progressively over the course of the study, noted Dr. Maggioni of the GISSI-HF Coordinating Center in Florence, Italy.
The mild preventive effect was consistently seen in all prespecified subgroups regardless of patient age, ejection fraction, heart failure etiology, renal function, NYHA class, or the presence of diabetes.
In search of the mechanism of benefit, Dr. Maggioni and coinvestigators analyzed the relationship between extent of LDL cholesterol lowering and AF risk. The two proved unrelated, meaning the protective effect involved some statin property other than lipid lowering.
"The effect of rosuvastatin was not overwhelming," observed discussant Dr. Harry J.G.M. Crijns. "Statins are not very effective in my mind for preventing atrial fibrillation in patients with class II-IV heart failure."
He called AF and heart failure "an insufferable odd couple." Patients with heart failure have an increased likelihood of developing AF. When they do, it worsens their heart failure and causes strokes. Antiarrhythmic agents are contraindicated in the setting of heart failure, so there is a great need for drugs that will work "upstream"--that is, on the aberrant substrate that gives rise to AF.
The most plausible mechanism by which statins prevent AF is by reducing atrial fibrosis. Statins have been shown to do so in animal studies. But statin therapy that is delayed until patients have advanced heart failure, as in GISSI-HF, is likely too late to have a robust effect because the atrial remodeling is too extensive.
If this hypothesis is correct, starting statin therapy further upstream, when patients have only a short history of heart failure and limited atrial remodeling, should result in a greater anti-atrial fibrillation benefit than seen in GISSI-HF, said Dr. Crijns of Maastricht (the Netherlands) University.
He added that the primary outcome of future studies of statins for prevention of AF in heart failure should be the total AF burden--that is, the cumulative time patients spend in AF--rather than the incidence of the arrhythmia. There is evidence to suggest total burden is more important from the standpoint of stroke risk.
It's also important to recognize that it has never actually been established that prevention of AF in patients with heart failure will improve their cardiovascular morbidity and mortality, Dr. Crijns added. That's widely assumed to be the case, but it's entirely possible that AF in these patients is simply a marker for a worse prognosis, and that suppressing the arrhythmia may kill the messenger without squelching the associated risks.
Dr. Maggioni disclosed receiving research support and honoraria from AstraZeneca, which funded GISSI-HF. Dr. Crijns did not disclose any industry relationships.
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|Title Annotation:||CARDIOVASCULAR MEDICINE; atrial fibrillation|
|Publication:||Internal Medicine News|
|Date:||Oct 1, 2009|
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