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Cardiac resynchronization therapy might benefit asymptomatic, mildly symptomatic patients with HF, according to 12-month REVERSE trial data

Friday, April 04 2008 | Comments
Evidence Grade 0 What's This?
By Courtneay Parsons

Although cardiac resynchronization therapy (CRT) did not demonstrate a statistically significant benefit in the REVERSE trial's primary endpoint, other data from the trial suggest CRT reverses left ventricular remodeling and reduces the risk of hospitalization for heart failure in asymptomatic or mildly symptomatic patients.

The trial investigators evaluated the benefits of CRT in patients with asymptomatic or mildly symptomatic HF and ventricular dyssynchrony (with or without an implantable cardioverter defibrillator). They enrolled 684 patients, all of whom met criteria for New York Heart Association class I or II (class II, >80%) and had a QRS duration ≥120 msec, an LV ejection fraction ≤40%, and an LV end-diastolic dimension ≥55 mm.

There were 642 implant attempts, 621 (97%) of which were successful. A total of 610 patients were randomized to have the device turned on (CRT-ON; n=191) or off (CRT-OFF; n=419) during follow-up.

Overall, 594 of 598 patients completed 12 months of follow-up; there were 12 deaths during the trial (2%). Of the randomized patients, >80% had an ICD. Dr. Cecilia Linde, lead investigator of the trial, noted that the group as a whole exhibited generally poor LV function in spite of optimal medical therapy.

The primary endpoint of the analysis was the HF clinical composite response, which was based on all-cause mortality, HF hospitalizations, crossover due to worsening HF, NYHA class, and patient global assessments. Using this endpoint, the authors compared the proportion of patients who worsened in each group.

Overall, 21% worsened in the CRT-OFF group as compared with 16% in the CRT-ON group (P=.10). However, Dr. Linde noted, in a more conventional analysis that compared the distribution of patients whose status worsened, remained unchanged (39% vs 30%, respectively), or improved (40% vs 54%), the authors observed a significant between-group difference favoring active treatment (P=.004).

The prospectively powered secondary endpoint of the trial, the LV end-systolic volume index (LVESVi), also suggested a benefit with active treatment. Specifically, the LVESVi declined 18.4 mL/m2 in the CRT-ON group compared with 1.3 mL/m2 in the CRT-OFF group (P<.0001). This improvement, coupled with similarly significant improvements in the LV end-diastolic volume index (-20.5 mL/m2 in the CRT-ON group vs -1.4 mL/m2 in the CRT-OFF group; P<.0001) translated into a significant improvement in LVEF in the CRT-ON group (+3.8%) relative to the CRT-OFF group (+0.6%; P<.0001).

Active CRT therapy did not have a statistically significant effect on quality of life or symptomatic improvement, assessed with the Minnesota Living With Heart Failure Questionnaire and the 6-minute walk test (secondary endpoints; P=.26 for each). However, Dr. Linde suggested that the lack of significance in these outcome measures could be at least partially attributed to a placebo effect.

Her research team also observed a trend toward improvement in NYHA class with active therapy when they compared the proportions of patients in each group who worsened, remained unchanged, or improved (P=.06).

The mortality rate was low and equally distributed between the 2 groups, but the CRT-ON group was significantly less likely to experience HF-related hospitalizations during follow-up (HR, 0.47; P=.03). When asked about the difference in risk between the 2 groups for total hospitalizations for cardiovascular causes (including those related to complications), Dr. Linde noted that she and her colleagues are currently evaluating this data, but they believe the benefit of receiving the device still outweighs the risk.

Regarding the safety of the procedure, Dr. Linde pointed to the high implant success rate in the trial and noted that the excess risk linked to CRT therapy was 9.5%; there were 66 LV lead-related complications that occurred in 59 of 621 patients with successful implants. (Presentation 412-9.)

This information concerns a use that has not been approved by the Food and Drug Administration.

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