A controlled study of the effects of carvedilol on clinical events, left ventricular function and proinflammatory cytokines levels in patients with dilated cardiomyopathy.
BACKGROUND
Carvedilol is known to decrease the severity of ventricular dysfunction, to increase the left ventricular ejection fraction (LVEF), and, consequently, to reduce morbidity and mortality in patients with dilated cardiomyopathy. There is accumulating evidence that inflammatory cytokines have an important role in the pathogenesis of heart failure.


OBJECTIVE
To establish whether the addition of carvedilol has an additive beneficial effect on cytokines in patients with dilated cardiomyopathy who are already receiving treatment with angiotensin-converting enzyme (ACE) inhibitors, digoxin and diuretics.


RESULTS
In this single-centre, prospective, randomized study, 60 patients with dilated cardiomyopathy with an LVEF less than 40% and already receiving digoxin, ACE inhibitors and diuretics for six months as the standard therapy were randomly assigned to receive either carvedilol (n=30) or placebo (n=30). Patients received an initial dosage of 3.125 mg carvedilol or placebo twice daily for two weeks, which was then increased at two-week intervals (if tolerated), first to 6.25 mg, then to 12.5 mg, and, finally, to a target dosage of 25 mg twice daily. Clinical examinations, radionuclide studies, and determinations of plasma levels of tumour necrosis factor-alpha (TNF-a), interleukin (IL)-2 and IL-6 were performed at baseline and repeated four months after random assignment. Primary end points were New York Heart Association functional class, LV function and plasma cytokines levels. Eight patients died (seven in the placebo group, P=0.05). Patients treated with carvedilol had a significant improvement in functional class compared with the baseline values (P=0.001), with a decrease in the levels of cytokines (IL-6 [P=0.001] and TNF-a [P=0.001]). LVEF increased from 22.14+/-7.85% to 27.85+/-11.80% (P=0.002), but diastolic function did not change in the carvedilol group.


CONCLUSIONS
In patients with dilated cardiomyopathy, the addition of carvedilol to treatment with digoxin, ACE inhibitors and diuretics is associated with a significant improvement in symptoms and in LV function, and suppression of inflammatory cytokines.
Tatli
Ersan
E
Department of Cardiology, School of Medicine, Trakya University, Gullapoglu Yerleskesi, Edirne, Turkey.
Kurum
Turhan
T
D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D002227:Carbazoles / Q000627:therapeutic use*; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000077261:Carvedilol; D004359:Drug Therapy, Combination; D005260:Female; D015637:Gated Blood-Pool Imaging; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011412:Propanolamines / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D018836:Inflammation Mediators; D007376:Interleukin-2; D015850:Interleukin-6; D011412:Propanolamines; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D000077261:Carvedilol