Up-titration to high-intensity statins early on in the course of treatment was found to be associated with a lower risk for cardiovascular (CV) events compared with no up-titration in patients at very high risk for CV disease, according to a study published in the European Heart Journal – Quality Care and Clinical Outcomes.

The data of 192,435 patients (ages, ≥18 years; mean age, 68 years) from a Swedish national population-based registry database were retrospectively examined. Patients in this cohort were at very high risk for atherosclerotic CV disease — according to European Society of Cardiology guideline definitions — and had initiated moderate-intensity stating therapy between 2006 and 2013.

The study’s main outcomes of interest were titration to high-intensity statin therapy and a composite major adverse cardiovascular events (MACE) of myocardial infarction, ischemic stroke, or CV death. The cumulative incidence of the MACE outcome was examined by titration status 1 year after statin therapy initiation in patients who adhered to treatment during this period. Early up-titration was defined as an up-titration occurring in the 12 weeks following treatment initiation.

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Of the patients who had initiated statin therapy, 75.1% were taking treatment for ≥80% of the days during the period examined and were still alive at the end of this exposure period. Of these 144,498 patients, 1.8% had an early up-titration to high-intensity statins, 2.8% had a late up-titration, and 95.4% had no up-titration.

Up-titration (early or late) was found to be associated with a lower MACE risk compared with no titration (hazard ratio, [HR], 0.83, 95% CI, 0.74–0.93). Early — but not late — vs no up-titration was associated with a lower MACE risk in the 2 years after treatment initiation (early: HR, 0.76; 95% CI, 0.62–0.92; P <.01; late: HR, 0.88; 95% CI, 0.76-1.02; P =.08).

Study limitations include the lack of data on low-density lipoprotein cholesterol and other lipid levels, as well as limited information on patients’ smoking habits.

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“Despite the higher risk associated with no up-titration, few patients at very high CV risk who started treatment on moderate-intensity up-titrated to high-intensity treatment, indicating a potential need for more aggressive lipid management of these patients in clinical practice,” noted the study authors.


Banefelt J, Lindh M, Svensson MK, Eliasson B, Tai M. Statin dose titration patterns and subsequent major cardiovascular events in very high-risk patients – estimates from Swedish population-based registry data [published online April 1, 2020]. Eur Heart J Qual Care Clin Outcomes. doi:10.1093/ehjqcco/qcaa023