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Abstract
Objective To evaluate the effects of fixed dose combination (FDC) medications on cardiovascular outcomes in different age groups in an individual participant meta-analysis of three primary prevention randomised trials.
Methods Participants at intermediate risk (17.7% mean 10-year Framingham Cardiovascular Risk Score), randomised to FDC of two or more antihypertensives and a statin with or without aspirin, or to their respective control, were followed up for 5 years. Age groups were <60, 60–65 and ≥65 years. The primary outcome was cardiovascular death, myocardial infarction, stroke or revascularisation. Cox proportional HRs and 95% CIs were computed within each age group.
Results The primary outcome risk was reduced by 37% (3.3% in FDC vs 5.2% in control (HR 0.63; 95% CI 0.54 to 0.74)) in the total population of 18 162 participants with larger benefits in older groups (HR 0.58; 95% CI 0.42 to 0.78, 60 to 65 years) and (HR 0.57; 95% CI 0.47 to 0.70, ≥65 years), as were their numbers needed to treat to avoid one primary outcome: 53 and 33, respectively. The primary outcome risk was reduced in the two oldest groups with FDC with aspirin (n=8951) by 54% and 54%, and without aspirin (n=12 061) by 34% and 38%. Dizziness, the most frequent FDC adverse effects, was higher in participants aged <65 years. Aspirin was not associated with significant bleeding excess.
Conclusions In participants with intermediate cardiovascular risk, FDCs produce larger cardiovascular benefits in older individuals, which appear greater with aspirin.
Trial registration number HOPE-3, NCT00468923; TIPS-3, NCT016464137; PolyIran, NCT01271985.
- Hypertension
- Hyperlipidemias
Data availability statement
Data are available upon reasonable request. Individual participant data will only be available to the steering committee members of the contributing trials. For individuals who have not been part of the steering committees of the three main trials, it is recommended that they write to the Population Health Research Institute Project Office. Requests that do not compete with ongoing or planned analytic efforts of members of the steering committee may be considered as long as the costs associated with the efforts and an access fee are covered.
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Data availability statement
Data are available upon reasonable request. Individual participant data will only be available to the steering committee members of the contributing trials. For individuals who have not been part of the steering committees of the three main trials, it is recommended that they write to the Population Health Research Institute Project Office. Requests that do not compete with ongoing or planned analytic efforts of members of the steering committee may be considered as long as the costs associated with the efforts and an access fee are covered.
Footnotes
Contributors GRD and PP designed the analysis plan of this report and wrote the initial drafts. PG did the statistical analyses. All authors were involved in the meta-analysis. They reviewed the data and provided comments on the different versions. All authors approved the final version of the manuscript. GRD had full responsibility for the work of the study, had access in the data and controlled the decision to publish.
Funding The meta-analysis involving HOPE-3, PolyIran and TIPS-3 trials, and this substudy were completed through the Population Health Research Institute, Hamilton, Ontario, Canada, without study-specific funding. PP was co-principal investigator for the TIPS-3 Study, and his institution received study grants from the study sponsor Cadila Pharmaceuticals, India. RM was the principal investigator for the PolyIran study that was supported by Barakat Foundation and Alborz Daru Company. SY was the principal investigator for the HOPE-3 and TIPS-3 studies and his institution received funding from the Canadian Institutes of Health Research and AstraZeneca for HOPE-3 study, and from the Wellcome Trust, Cadila Pharmaceuticals, India, Canadian Institutes of Health Research, and Heart and Stroke Foundation of Canada for TIPS-3 study. All other authors have no relationships relevant to the contents of this paper to disclose.
Competing interests PP was co-principal investigator for the TIPS-3 Study, and his institution received study grants from the study sponsor Cadila Pharmaceuticals, India. RM was the principal investigator for the PolyIran study that was supported by Barakat Foundation and Alborz Daru Company. SY was the principal investigator for the HOPE-3 and TIPS-3 studies and his institution received funding from the Canadian Institutes of Health Research and AstraZeneca for HOPE-3 study, and from the Wellcome Trust, Cadila Pharmaceuticals, India, Canadian Institutes of Health Research, and Heart and Stroke Foundation of Canada for TIPS-3 study. All other authors have no relationships relevant to the contents of this paper to disclose.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
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