Reduction in cardiovascular risk using proactive multifactorial intervention versus usual care in younger (<65 years) and older (≥65 years) patients in the CRUCIAL trial

Abstract

Objective:

To compare the reduction in calculated Framingham 10 year coronary heart disease (CHD) risk after 52 weeks’ intervention with a proactive multifactorial intervention (PMI) strategy (based on single-pill amlodipine/atorvastatin [SPAA]) versus continuing usual care (UC) (based on investigators' best clinical judgment) among younger (<65 years) and older (≥65 years) patients.

Research design and methods:

Sub-analysis of the Cluster Randomized Usual Care versus Caduet Investigation Assessing Long-term risk (CRUCIAL) trial. Eligible patients had hypertension and ≥3 cardiovascular risk factors.

Main outcome measure:

Treatment-related reduction in calculated Framingham 10 year CHD risk between baseline and Week 52 in younger and older patients.

Results:

Nine hundred patients (63.5%) were <65 years (mean age 54.2 years, 57.4% men) and 517 patients (36.5%) were ≥65 years (mean age 70.5 years, 42.7% men). Younger patients had lower mean baseline CHD risk versus older patients (17.1% vs. 22.6%). A greater reduction in calculated CHD risk at Week 52 was observed in the PMI versus the UC arm in both younger (−33.2% vs. −2.9%, p < 0.001) and older (−32.7% vs. −5.7%, p < 0.001) patients. Least-squares mean treatment differences (PMI vs. UC) in percentage change from baseline in calculated CHD risk were similar in younger and older patients (−26.3% vs. −25.7%, age interaction p = 0.887). CHD risk reduction was slightly greater among younger men than younger women (−29.3 vs. −23.9, gender interaction p = 0.062). A low proportion of patients discontinued the PMI strategy due to adverse events in both age groups (5.8% vs. 6.1%, respectively). Study limitations included ad-hoc (not pre-specified) sub-group analysis and short duration of follow-up.

Conclusions:

The PMI strategy based on the inclusion of SPAA in the treatment regimen is more effective than UC in reducing calculated CHD risk. This strategy may be considered as the treatment of choice in younger and older hypertensive patients with additional cardiovascular risk factors.

Keywords::

• Age
• Cardiovascular risk
• Hypertension
• Lipid-lowering therapy

Transparency

Declaration of funding

This study was sponsored by Pfizer Inc.

Declaration of financial/other relationships

J.-H.K., J.Z., S.E., A.P. and A.A.-K. have served as consultants or received travel expenses, payment for speaking at meetings or funding for research from one or more pharmaceutical companies (including Pfizer Inc., who sponsored this study) that market blood-pressure-lowering or lipid-lowering drugs. S.S. and C.Y. are employees of Pfizer Inc.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgments

Medical writing support was provided by Sarah Partridge, PhD, and Penny Gorringe, MSc, of UBC Scientific Solutions and funded by Pfizer Inc.