Lunesta Cardiovascular Impact Long-Term: What the Evidence Actually Shows

What the 6-month and 12-month studies measured

Krystal and colleagues randomized 788 adults aged 21 to 69 with primary insomnia to eszopiclone 3 mg (n=593) or placebo (n=195) nightly for 6 months [1]. The endpoints were patient-reported sleep latency, total sleep time, wake time after sleep onset and sleep quality; eszopiclone was significantly better than placebo on each sleep measure (P <= 0.003), with no evidence of tolerance [1].

The open-label extension followed patients to 12 months: 360 sustained their gains, 111 who had been randomized to placebo improved after switching, and no tolerance appeared on any measure; the extension had no placebo arm [2].

What this means for heart questions

Both reports give sleep and daytime-function outcomes rather than cardiovascular results [1][2]. The label says ECGs were assessed in the broader premarketing program, but that does not establish whether nightly eszopiclone over months or years changes blood pressure or heart rhythm [3].

What the label says about caution

The label's warnings summary says to use Lunesta with caution in patients with hepatic impairment, impaired respiratory function, impaired drug metabolism or hemodynamic responses [3]. It also says that because Lunesta can cause drowsiness and a decreased level of consciousness, patients, particularly the elderly, are at higher risk of falls [3].

Drug interactions in the label

CYP3A4 is a major elimination pathway for eszopiclone [3]. Ketoconazole raised eszopiclone exposure, and the label says dose reduction is needed with potent CYP3A4 inhibitors, with a maximum of 2 mg; it expects itraconazole, clarithromycin, nefazodone and ritonavir to behave similarly [3]. Rifampicin reduced exposure to racemic zopiclone by 80%, with a similar effect expected for eszopiclone [3]. Ethanol adds to psychomotor impairment, and olanzapine decreased DSST scores through a pharmacodynamic interaction [3].