Plasma concentration of atorvastatin metabolites correlates with low-density lipoprotein cholesterol reduction in patients with coronary heart disease.

In this exploratory study from a randomized double-blinded crossover trial including 70 patients with coronary heart disease and self-perceived muscular side effects of statins, we aimed to determine the relationship between low-density lipoprotein cholesterol (LDL-C) reduction and atorvastatin metabolite plasma concentrations. All patients underwent a 7 weeks treatment period with atorvastatin 40 mg/day and a 7 weeks placebo period in random order. Nonlinear regression with a three-parameter equation explored the relationship between percentage LDL-C reduction (statin vs. placebo) and the pharmacokinetic variables. Mean LDL-C reduction was 49% (range 12% to 71%). The sum of 4-OH-atorvastatin acid and lactone correlated moderately with the LDL-C response (Spearman ρ 0.27, 95% confidence interval [CI]: 0.03 to 0.48). Accordingly, nonlinear regression showed R2 of 0.14 (95% CI: 0.03 to 0.37, R2 adjusted equaled 0.11). Even a perfect underlying correlation of 1.0 showed R2 = 0.32 by simulation, using historical intra-individual LDL-C variation (8.5%). The 90% inhibitory concentration was 2.1 nmol/L, and the 4-OH-metabolite sum exceeded this threshold in 34% of the patients. In conclusion, trough plasma concentrations of 4-OH-atorvastatin metabolites correlated moderately to the LDL-C reduction. A plateau LDL-C response was observed above a pharmacokinetic threshold, below which the response was highly variable. The usefulness of monitoring concentrations of atorvastatin metabolites to optimize the individual dosage have limitations, but its supportive potential may be pursued in relevant patient subsets to achieve adequate efficacy at the lowest possible dose. The results add knowledge to the overall understanding of the variable LDL-C response mediated by atorvastatin.

Challenges in coronary heart disease prevention - experiences from a long-term follow-up study in Norway.

Objective. To determine longitudinal changes in lifestyle behaviour and lipid management in a chronic coronary heart disease (CHD) population. Design. A multi-centre cohort study consecutively included 1127 patients at baseline in 2014-2015, on average 16 months after a CHD event. Data were collected from hospital records, a questionnaire and clinical examination. Seven hundred and seven of 1021 eligible patients participated in a questionnaire-based follow-up in 2019. Data were analysed with univariate statistics. Results. After a mean follow-up of 4.7 years (SD 0.4) from baseline, the percentage of current smokers (15% versus 16%), obesity (23% versus 25%) and clinically significant symptoms of anxiety (21% versus 17%) and depression (13% versus 14%) remained unchanged, whereas the proportion with low physical activity increased from 53% to 58% (p < .001). The proportions with reduced physical activity level were similar in patients over and under 70 years of age. Most patients were still taking statins (94% versus 92%) and more patients used high-intensity statin (49% versus 54%, p < .001) and ezetimibe (5% versus 15%, p < .001) at follow-up. 73% reported ≥1 primary-care consultation(s) for CHD during the last year while 27% reported no such follow-up. There were more smokers among participants not attending primary-care consultations compared to those attending (19% versus 14%, p = .026). No differences were found for other risk factors. Conclusions. We found persistent suboptimal risk factor control in coronary outpatients during long-term follow-up. Closer follow-up and intensified risk management including lifestyle and psychological health are needed to improved secondary prevention and outcome of CHD. Trial registration: Registered at ClinicalTrials.gov: NCT02309255.Registered at 5 December 2014, registered retrospectively.

Preventable clinical and psychosocial factors predicted two out of three recurrent cardiovascular events in a coronary population.

BACKGROUND: The relative importance of lifestyle, medical and psychosocial factors on the risk of recurrent major cardiovascular (CV) events (MACE) in coronary patients' needs to be identified. The main objective of this study is to estimate the association between potentially preventable factors on MACE in an outpatient coronary population from routine clinical practice. METHODS: This prospective follow-up study of recurrent MACE, determine the predictive impact of risk factors and a wide range of relevant co-factors recorded at baseline. The baseline study included 1127 consecutive patients 2-36 months after myocardial infarction (MI) and/or revascularization procedure. The primary composite endpoint of recurrent MACE defined as CV death, hospitalization due to MI, revascularization, stroke/transitory ischemic attacks or heart failure was obtained from hospital records. Data were analysed using cox proportional hazard regression, stratified by prior coronary events before the index event. RESULTS: During a mean follow-up of 4.2 years from study inclusion (mean time from index event to end of study 5.7 years), 364 MACE occurred in 240 patients (21, 95% confidence interval: 19 to 24%), of which 39 were CV deaths. In multi-adjusted analyses, the strongest predictor of MACE was not taking statins (Relative risk [RR] 2.13), succeeded by physical inactivity (RR 1.73), peripheral artery disease (RR 1.73), chronic kidney failure (RR 1.52), former smoking (RR 1.46) and higher Hospital Anxiety and Depression Scale-Depression subscale score (RR 1.04 per unit increase). Preventable and potentially modifiable factors addressed accounted for 66% (95% confidence interval: 49 to 77%) of the risk for recurrent events. The major contributions were smoking, low physical activity, not taking statins, not participating in cardiac rehabilitation and diabetes. CONCLUSIONS: Coronary patients were at high risk of recurrent MACE. Potentially preventable clinical and psychosocial factors predicted two out of three MACE, which is why these factors should be targeted in coronary populations. TRIAL REGISTRATION: Registered at ClinicalTrials.gov: NCT02309255. Registered at December 5th, 2014, registered retrospectively.