Fixed-dose combination therapies reduce risk of CV outcomes in a primary prevention setting

Introduction and methods

This individual participant data meta-analysis of three large RCTs assessed whether fixed-dose combination treatment strategies in a primary prevention setting reduced CVD risk compared with a control strategy.

Data from in total 18 162 participants with no known vascular disease from TIPS-3, HOPE-3 and PolyIran were included in this analysis [1-3]. These trials tested a fixed-dose combination strategy consisting of at least two blood pressure lowering agents plus a statin, with or without aspirin, versus placebo or usual care in the primary prevention of CVD. The primary composite outcome of this meta-analysis was time to first occurrence of CV death, MI, stroke, or arterial revascularization. Median follow-up was 5 years (IQR 4.8-5.6).

Main results

• After a mean follow-up of 2.1 years, mean LDL-c was 22.6 mg/dL (0.58 mmol/L) lower in participants receiving fixed-dose combination therapy, compared to those in the control group (P<0.0001). After a median follow-up of 5 years, mean SBP was 4.7 mmHg lower in the fixed-dose combination therapy group compared with the control group (P<0.001).
• During follow-up, the primary outcome occurred in 3.0% of participants receiving fixed-dose combination therapy with or without aspirin and in 4.9% of participants in the control group (HR 0.62, 95%CI 0.53-0.73, P<0.001). The corresponding 5-year NNT was 52. Proportional risk reductions with the fixed-dose combination strategy were apparent after 1 year (HR 0.73, 95%CI 0.50-1.06) and increased to more than 3 years after randomization (HR 0.58, 95%CI 0.46-0.72).
• In the analysis of fixed-dose combination therapy with aspirin compared to control, the primary outcome occurred in 2.6% of participants in the treatment group and in 4.8% in the control group (HR 0.53, 95%CI 0.41-0.67, P<0.0001). The corresponding 5-year NNT was 37.
• In the analysis of fixed-dose combination therapy without aspirin compared to control, the primary outcome occurred in 3.3% of participants in the treatment group and in 4.9% in the control group (HR 0.68, 95%CI 0.57-0.81, P<0.0001). The 5-year NNT was 66.
• Dizziness was the only side-effect which was reported more frequently in the fixed-dose combination therapy group compared to the control group (11.7% vs 9.2%, P<0.0001). A higher number of gastrointestinal bleed were reported in the fixed-dose combination therapy group compared to the control group (19 [0.4%] vs 11 [0.2%]), but this difference was not statistically significant.

Conclusion

References

Find this article online at The Lancet.