ICDs are designed to counter arrhythmias, electrical malfunctions that throw the heart out of rhythm and are a major cause of sudden cardiac death (SCD) in 450,000 Americans each year. Many confuse SCD with heart attack, a crisis brought on when a blocked artery damages heart muscle. The two problems come together when scar tissue left behind by a heart attack interferes with the heart's electrical system, bringing on arrhythmia.
Beta blockers in combination with ACE-inhibitors and statins are the treatment of choice for heart attack survivors, but fail to reduce risk of arrhythmia in many cases. ICDs have been gaining ground since the 2002 MADIT II study (Multicenter Automatic Defibrillator Implantation Trial II) found that the devices could reduce mortality by 31 percent in patients who had a heart attack. Led out of the University of Rochester Medical Center, the landmark study changed medical guidelines nationwide and made a hundred thousand heart attack survivors eligible for ICD therapy.
Some experts have since questioned, however, whether the ICD benefit extends to women, who were underrepresented in past studies and continue to be undertreated for heart disease in general, according to the American Heart Association. Until now, little data has been available to either support or debunk their use specifically in women. To address the gap, researchers at the University of Rochester Medical Center re-analyzed the MADIT II data, pulling out the data on women comparing the effects of ICD therapy in women and men.
The analysis found that women have similar risk of both overall mortality and SCD following heart attack as men. The study also found that both genders get a similar benefit from ICD therapy, which reduced mortality risk in women by an estimated 43 percent, and in men by 34 percent.
"Studies show that women received just 9,000 of 46,000 ICDs implanted in 2001," said Wojciech Zareba, M.D., Ph.D., lead author on the study and associate professor of Medicine (Cardiology) within the Cardiology Unit at the medical center. "Some physicians may be biased, perceiving that women have a lower cardiac mortality rate. Our study provides evidence that this perception needs to change if we are to better prevent sudden death in women after their heart attack."
In the current MADIT II re-analysis, researchers evaluated the risk of cardiac events and effects of ICD therapy in women as compared to men enrolled in MADIT II. Specifically, data has been limited until now regarding ICD therapy in women whose heart attack has left them with severe injury to their left ventricle, the chamber of the heart that contracts to force oxygen-filled blood into the aorta and out to the rest of the body. Left-ventricular ejection fraction, a measure of the left ventricle's pumping capacity and efficiency, is often reduced by damage to the heart's walls.
When published in 2002, the MADIT II trial led to a change in the treatment guidelines published by a joint committee of the American College of Cardiology, the American Heart Association and the North American Society of Pacing and Electrophyiology. The guideline states that heart attack survivors with an ejection fraction of less than 30 percent are recommended for an ICD implant for primary prevention of sudden cardiac death (SCD). About 10 percent to 15 percent of the 1 million annual U.S. heart attack survivors meet the MADIT II criteria, making them candidates for an implant.
Among 1,232 patients enrolled in the original MADIT II trial, 192 (16 percent) were women and 1,040 (84 percent) men. All patients had had at least one heart attack more than one month prior to enrollment and an ejection fraction less than 30 percent. Those with existing ICD indications, heart attack within the past month or coronary revascularization (e.g. stent implant) within the past three months were excluded.
Enrolled patients were randomly assigned to receive either an ICD (n = 742) or conventional medical therapy (n = 490), which consisted of administering beta-blockers, ACE-inhibitors, and statins in most of the patients. Clinical and demographic data collected included information on gender.
The primary endpoint of MADIT II was all-cause mortality. Secondary endpoints for this analysis included sudden cardiac death, categorized patients randomized to conventional therapy, and appropriate therapy for ventricular fibrillation (VF) in patients randomized to ICD therapy. Ventricular fibrillation is a frequently fatal form of arrhythmia characterized by rapid twitching of the ventricles, resulting in a loss of pulse.
The two-year cumulative mortality in patients randomized to non-ICD conventional therapy was 30 percent in women and 20 percent in men, but those figures were not statistically significant (P = 0.19). Hazard ratios, statistical measures of difference in survival rate when comparing patients with versus without ICDs, were similar in women (0.57; 95% CI=0.28-1.18; P=0.132) and in men (0.66; 95% CI=0.48-0.91; P = 0.011), according to the new analysis.
The difference between hazard ratios was not statistically significant (P=0.72) indicating similar effectiveness of ICD therapy in men and women. In the ICD treatment arm, the two-year mortality rate was found to be 16 percent in both men and women and the risk of life-threatening arrhythmias was also similar in men and women (28% and 21%, respectively).