Effect of statin dose on incidence of atrial fibrillation: data from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) and Aggrastat to Zocor (A to Z) trials.
BACKGROUND
Inflammation has been suggested as a factor in the initiation and maintenance of atrial fibrillation (AF). Several observational studies have suggested that statins, presumably through their anti-inflammatory properties, decrease the risk of AF.


METHODS
We analyzed 2 large, randomized trials, PROVE IT-TIMI 22 and phase Z of the A to Z trial, which compared lower- versus higher-intensity statin therapy to evaluate whether higher-intensity statin therapy lowered the risk of AF onset during the 2 years of follow-up. We hypothesized that higher-intensity statin therapy would decrease the risk of AF when compared to lower-intensity statin therapy. From each trial, patients experiencing the onset of AF during follow-up were identified from the adverse event reports.


RESULTS
Neither study showed a decreased AF risk with higher-dose statin. In PROVE IT-TIMI 22, 2.9% versus 3.3% in the high- versus standard-dose statin therapy, respectively, experienced the onset of AF over 2 years (OR 0.86, 95% CI 0.61-1.23, P = .41). In A to Z, rates were 1.6% versus 0.99%, respectively (OR 1.58, 95% CI 0.92-2.70, P = .096). In both trials, C-reactive protein levels (plasma or serum) tended to be higher among patients experiencing the onset of AF.


CONCLUSIONS
Our randomized comparison among 8659 patients found that higher-dose statin therapy did not reduce the short term incidence of AF among patients after acute coronary syndromes when compared with standard dose statin treatment.
McLean
Dalton S
DS
Cardiovascular Division, Department of Medicine, Thrombolysis in Myocardial Infarction Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Ravid
Shmuel
S
Blazing
Michael
M
Gersh
Bernard
B
Shui
Amy
A
Cannon
Christopher P
CP
D054058:Acute Coronary Syndrome / Q000150:complications; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000209:etiology / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D017035:Pravastatin; D011758:Pyrroles / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000627:therapeutic use
D000893:Anti-Inflammatory Agents; D005343:Fibrinolytic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D014443:Tyrosine; D000069059:Atorvastatin; D000077466:Tirofiban; D017035:Pravastatin