Date Published: January 18, 2019
Publisher: Public Library of Science
Author(s): Tian-Tian Ma, Ian C. K. Wong, Kenneth K. C. Man, Yang Chen, Thomas Crake, Muhiddin A. Ozkor, Ling-Qing Ding, Zi-Xuan Wang, Lin Zhang, Li Wei, Katriina Aalto-Setala.
The combination pharmacotherapy of antiplatelet agents, lipid-modifiers, ACE inhibitors/ARBs and beta-blockers are recommended by international guidelines. However, data on effectiveness of the evidence-based combination pharmacotherapy (EBCP) is limited.
To determine the effect of EBCP on mortality and Cardiovascular events in patients with Coronary Heart Disease (CHD) or cerebrovascular disease.
Publications in EMBASE and Medline up to October 2018 were searched for cohort and case-control studies on EBCP for the secondary prevention of cardiovascular disease. The main outcomes were all-cause mortality and major cardiovascular events. Meta-analyses were performed based on random effects models.
21 studies were included. Comparing EBCP to either monotherapy or no therapy, the pooled risk ratios were 0.60 (95% confidence interval 0.55 to 0.66) for all-cause mortality, 0.70 (0.62 to 0.79) for vascular mortality, 0.73 (0.64 to 0.83) for myocardial infarction and 0.79 (0.68 to 0.91) for cerebrovascular events. Optimal EBCP (all 4 classes of drug prescribed) had a risk ratio for all-cause mortality of 0.50 (0.40 to 0.64). This benefit became more dilute as the number of different classes of drug comprising EBCP was decreased—for 3 classes of drug prescribed the risk ratio was 0.58 (0.49 to 0.69) and for 2 classes, the risk ratio was 0.67 (0.60 to 0.76).
EBCP reduces the risk of all-cause mortality and cardiovascular events in patients with CHD or cerebrovascular disease. The different classes of drugs comprising EBCP work in an additive manner, with optimal EBCP conferring the greatest benefit.
Cardiovascular disease (CVD) is the leading cause of mortality and morbidity worldwide. Based on statistics from The World Health Organization (WHO), coronary heart disease (also known as ischaemic heart disease) and stroke are the top two causes of death globally . Pharmacological therapy plays a key role in the secondary prevention of CVD. Large evidence supports drugs conferring mortality benefit from several different classes: antiplatelet agents, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), beta blockers and lipid-lowering drugs [2–4]. These are recommended by the WHO  and guideline bodies including the National Institute for Health and Care Excellence (NICE) [6,7], the European Society of Cariology (ECS) , the American College of Cardiology/American Heart Association (ACC/AHA)  and American Heart Association/American Stroke Association (AHA/ASA) .
The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was used to guide the reporting of the methods and findings.[18,19]. A completed PRISMA checklist is provided as an additional file (S1 Appendix). The study protocol was registered in the International Prospective Register of Systematic Reviews database (PROSPERO: CRD42018078069).
Our meta-analysis of observational studies assessed the effects of EBCP with antiplatelet drugs, ACEIs/ARBs, beta-blockers, and lipid-modifiers on mortality and major cardiovascular events in CVD patients. The results show a benefit for EBCP, suggesting an overall decrease in the risk of all-cause mortality (approximately by 40%) and cardiovascular events (25%-30%) compared to either monotherapy or no therapy.
In conclusion, our systematic review and meta-analysis suggest that in patients with CVD, EBCP can reduce the risk of all-cause mortality by approximately 40% and major cardiovascular events by 25%-30%. Antiplatelet agents, beta-blockers and statins could be considered as stable components of combination therapy in secondary prevention of CHD.