Quantification of survival gain from cardiac resynchronization therapy: nonlinear growth with time, and greater gain in low-risk patients, make raw trial data an underestimate of real-world behavior.

Abstract:

OBJECTIVES:The goal of this study was to examine the impact of calculation-window duration on lifespan gain (as observed in trials) and on who gains most. BACKGROUND:The landmark trials of biventricular pacing (cardiac resynchronization therapy [CRT]) typically ran for <1 device battery life, and they may therefore underestimate lifespan benefit over longer durations. METHODS:We conducted a meta-analysis of biventricular pacing trials to calculate lifespan gained: first, within the duration of randomized controlled trial data up to 2 years; second, over a 5-year typical battery life; and third, over >1 battery life. Importantly, we applied the Gompertz method for age-related increase in mortality from non-CRT-preventable causes. RESULTS:Five landmark trials (COMPANION [Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure], CARE-HF (CArdiac REsynchronization-Heart Failure), MADIT-CRT [Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy], REVERSE [Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction], RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure)) provided data for 2 years (6,561 patients), with an average hazard ratio of 0.71. Lifespan gained across all trials increased nonlinearly with time from 0.1 month at 1 year, to 0.5 month at 2 years, and a projected 6.5 months at 5 years (65 times more than at 1 year). After multiple devices, it reached 14 months, involving on average 1.6 devices (i.e., 8.8 months per device implanted). Moreover, while over a short window (e.g., 2 years), lower-mortality patients may gain less than higher-mortality patients (1.4 vs. 2.3 months), their positions reverse by 15 years (16.0 vs. 13.7 months). CONCLUSIONS:Lifespan gain from biventricular pacing rises nonlinearly with time. Early on, higher-risk patients exhibit more gain, but later, lower-risk patients exhibit more gain. Quantifying gain over less than a patient's lifetime underestimates lifespan gain. Over the first 1 or 2 years, lower-risk patients may seem to gain less, although they may ultimately be the ones who gain the most.

journal_name

J Am Coll Cardiol

authors

Finegold JA,Raphael CE,Levy WC,Whinnett Z,Francis DP

doi

10.1016/j.jacc.2013.07.080

subject

Has Abstract

pub_date

2013-12-24 00:00:00

pages

2406-2413

issue

25

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(13)04008-4

journal_volume

62

pub_type

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