Joseph P, Roshandel G, Gao P, et al. - A substantial reduction in cardiovascular disease, myocardial infarction, stroke, revascularization, and cardiovascular death in primary cardiovascular disease prevention occurred in correlation with implementing fixed-dose combination treatment strategies.

• An individual participant data meta-analysis was conducted including large randomized controlled trials (each with ≥ 1000 participants and ≥ 2 years of follow-up) of a fixed-dose combination treatment strategy vs control in a primary cardiovascular disease prevention population.

• A total of three large randomized trials (TIPS-3, HOPE-3, and PolyIran) with a total of 18,162 participants were included.

• In the included trials, comparison of fixed-dose combination strategy of at least two blood pressure lowering agents plus a statin (with or without aspirin) was done with a control strategy (either placebo or usual care).

• The analyses of fixed-dose combination strategies with and without aspirin revealed significant reductions in the primary outcome (time to first occurrence of a composite of cardiovascular death, myocardial infarction, stroke, or arterial revascularization) and its components; greater reductions appeared for strategies including aspirin.

• There were similar treatment effects at different lipid and blood pressure levels, and in the presence or absence of diabetes, smoking, or obesity.

• Although uncommon, gastrointestinal bleeding occurred slightly more frequently in correlation with the fixed-dose combination strategy with aspirin group vs control.

• The groups had low and did not differ significantly in frequencies of hemorrhagic stroke (10 [0·2%] vs 15 [0·3%]), fatal bleeding (two [< 0·1%] vs four [0·1%]), and peptic ulcer disease (32 [0·7%] vs 34 [0·8%]).

• Fixed-dose combination treatment more frequently linked with experiencing dizziness (1,060 [11·7%] vs 834 [9·2%]).