A meta-analysis of 3 large primary prevention trials revealed that fixed-dose combination treatments are successful to prevent cardiovascular (CV) death, myocardial infarction (MI), stroke, or revascularisation. Benefits are most pronounced in the elderly.
About 80% of cardiovascular disease (CVD) events occur in individuals without prior vascular disease. “Therefore, strategies that avoid a high proportion of first CVD events are critical to reducing global CVD burden,” said Prof. Philip Joseph (McMaster University; Hamilton Health Services, Canada) . Fixed-dose combination (FDC) treatment could substantially reduce CVD risk, but more data are needed to quantify efficacy.
The so-called polypill in a single formulation usually contains 2+ blood pressure-lowering agents, a statin, and eventually aspirin. In their meta-analysis of long-term, randomised controlled trials (each including >1,000 participants >2 years follow-up), the researchers tested different FDC strategies versus controls for primary prevention. The primary objective was the prevention of a composite of CV death, MI, stroke, or revascularisation. In addition, the impact on individual CV outcomes and the difference between regimens with and without aspirin were evaluated.
Data from 3 large RCTs of FDC in primary prevention could be included in the analysis: the TIPS-3 trial (NCT01646437), the HOPE-3 trial (NCT00468923), and the Polylran trial (NCT01271985). With 18,162 included patients from these trials, the meta-analysis is the largest study to date showing the effect of polypill therapy in CVD prevention.
“There was a large difference in the primary outcome: with FDC, we saw a 38% reduction [versus control]. This became apparent within 1 year of follow-up and the curves continued to diverge,” Prof. Joseph said. Likewise, single events were markedly reduced. The polypill led to a marked reduction of systolic blood pressure and LDL cholesterol. “The largest effects were seen in combinations that included aspirin, but the others were still very important,” Prof. Joseph said. A subgroup analysis revealed that the benefit of FDC was most prevalent in the elderly (> 66 years).
Regarding safety, there was no significantly elevated risk of haemorrhagic stroke or fatal bleeding, but a numerically increasing risk of gastrointestinal bleedings was seen that failed to achieve statistical significance. Thus, Prof. Joseph advocated FDC treatment as a key strategy in primary CVD prevention.
1. Joseph Ph. Fixed dose combination therapies with and without aspirin in primary CVD prevention. Late-breaking trials in prevention, ESC Congress 2021, 27–30 August.