ACE inhibitor benefits persist 12 years in CHF. (Follow-up of Patients in Solvd Trails).

BERLIN -- The true benefits of ACE inhibitors in patients with heart failure are likely to be significantly greater than have been reported in the landmark clinical trials, Dr. Salim Yusuf said at the 24th Congress of the European Society of Cardiology.

He and his colleague Dr. Philip Jong presented the results of the Extended Studies of Left Ventricular Dysfunction (XSOLVD), an unprecedented 12-year follow-up study of participants in the landmark SOLVD prevention and treatment trials.

The original SOLVD trials randomized nearly 7,000 Americans, Canadians, and Belgians with congestive heart failure (CHF) or asymptomatic left ventricular dysfunction to enalapril or placebo, then followed them for a mean of 3.3 years.

In XSOLVD, 99.8% of the original SOLVD participants were tracked down 12 years after the studies had formally ended to learn how the patients had subsequently fared.

At the conclusion of the SOLVD prevention trial, patients with asymptomatic left ventricular dysfunction who received enalapril had significantly lower rates of MI and hospitalization than those who received placebo. But the overall survival rates at that time were not significantly different: 86% in the enalapril arm and 84% in controls.

XSOLVD revealed a continued divergence in survival over the next dozen years. At 5 years, the absolute difference had grown from 2% to 4%-77% survival in the enalapril arm and 73% in controls. At 12 years the margin had grown still further: 47% survival in the enalapril group and 41% in controls, a highly significant difference, Dr. Jong noted.

At the end of the SOLVD treatment trial, patients with CHE in the enalapril arm had a significant survival advantage: 64%, vs. 60% among controls. This absolute 4% survival advantage was sustained for 5 years after the study's end. Thereafter the rates began to converge, and the 12-year XSOLVD data showed that the overall survival rate was 21% in the enalapril arm and 20% in controls.

Even so, XSOLVD probably underestimates the true benefits of lifelong ACE inhibitor therapy That's because for much of the 12-year follow-up, most participants in the original control group were actually on an ACE inhibitor, which in the aftermath of the SOLVD trials had become the standard of care, observed Dr. Yusuf, professor of medicine and director of the division of cardiology at McMaster University Hamilton, Ont.

Enalapril extended median life expectancy by 9.2 months in the SOLVD Prevention trial and by 8.6 months in the SOLVD Treatment trial, Dr. Yusuf commented.

The survival benefits of ACE inhibitor therapy that were documented in XSOLVD were seen in every patient subgroup examined: men and women, older and younger patients, hypertensive and normotensive, white and nonwhite, severe CHF and mild, diabetic and normoglycemic.

The fact that equal benefit was observed in hypertensive and nonhypertensive patients in XSOLVD suggests that the benefits of ACE inhibitor therapy are nor primarily related to the lowering of blood pressure. Only about half of the late survival benefit documented in the 12 years after conclusion of the SOLVD prevention trial appeared to be due to a reduction in rates of acute MI and CHF during the course of the study; the other half involved other mechanisms, perhaps including left ventricular and vascular remodeling, Dr. Yusuf said.

The original SOLVD trials were sponsored by the National Heart, Lung, and Blood Institute. XSOLVD was funded by Merck & Co.