Achievement of Low-Density Lipoprotein Cholesterol Targets in CKD.

INTRODUCTION: We describe the characteristics of patients with moderate/advanced chronic kidney disease (CKD) according to receipt of lipid-lowering therapy (LLT), and whether they achieved low-density lipoprotein cholesterol (LDL-C) targets for high- and very high-risk patients. METHODS: CKD-REIN (NCT03381950), a prospective cohort study conducted in 40 nephrology clinics in France, enrolled 3033 patients with moderate (stage G3) or advanced (stage G4/G5) CKD (2013-2016) who had not been on chronic dialysis or undergone kidney transplantation. Data were collected from patients' interviews and medical records. Patients were followed up at 1 year. RESULTS: Among 2542 patients (mean [SD] age 67 [13] years, 34% women) with LDL-C measurements at baseline (mean [SD] LDL-C 2.7 [1.1] mmol/l; cholesterol 4.8 [1.3] mmol/l), 63% were on LLT; 24% were at high (CKD stage G3, no cardiovascular disease [CVD] or diabetes) and 74% at very high (CKD stage G3 with diabetes or CVD, or CKD stage G4/5) cardiovascular risk. Among high-risk patients, 45% of those on statin and/or ezetimibe achieved the LDL-C treatment target (<2.6 mmol/l). Among very high-risk patients, the percentage at goal (<1.8 mmol/l) was 38% for CKD stage G3 and 29% for stage G4/5. There was a trend toward higher achievement of LDL-C targets with increasing LLT intensity (adjusted odds ratios for moderate vs. low intensity 1.20; 95% confidence interval 0.92-1.56; high vs. low intensity 1.46; 1.02-2.09; Ptrend = 0.036). CONCLUSION: Many patients with CKD stage G3-G5 who are eligible for LLT are not treated, and those on LLT rarely achieve LDL-C targets.

Use of guideline-recommended management in established coronary heart disease in the observational DYSIS II study.

BACKGROUND: Guidelines recommend lifestyle modification and medications to control risk factors in coronary heart disease (CHD). Using data from the observational DYSIS II study, we sought to evaluate the use of guideline-recommended treatments at discharge for acute coronary syndromes (ACS) or in the chronic phase for CHD, and participation in rehabilitation/secondary prevention programs. METHODS AND RESULTS: Between 2013 and 2014, 10,661 patients (3867 with ACS, 6794 with stable CHD) were enrolled in 332 primary and secondary care centers in 18 countries (Asia, Europe, Middle East). Patients with incident ACS were younger and more likely to be smokers than patients with recurrent ACS or stable CHD (both p < 0.0001). Sedentary lifestyle was common (44.4% of ACS patients; 44.2% of stable CHD patients); 22.8% of ACS patients and 24.3% of stable CHD patients were obese. Prevalence of low high-density lipoprotein cholesterol (<40 mg/dL in men/50 mg/dL in women) was 46.9% in chronic CHD and 55.0% in ACS. Rates of secondary prevention medications were lower among CHD versus ACS (all p < 0.0001): antiplatelet 94.3% vs 98.0%, beta-blocker 72.0% vs 80.0%, lipid-lowering therapy 94.7 vs 97.5%, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers 69.4% vs 73.7%, respectively. Attendance at cardiac rehabilitation (16.8% of patients with a first ACS, 10.8% with recurrent ACS) or a secondary prevention program (3.7% of ACS and 11.7% of stable CHD patients) was infrequent. CONCLUSIONS: The high prevalence of risk factors in all CHD patients and reduced rates of secondary prevention medications in stable CHD offer areas for improvement. TRANSLATIONAL ASPECTS: The findings of DYSIS II may reinforce the importance of adopting a healthy lifestyle and prescribing (by clinicians) and adhering (by patients) to evidence-based medications in the management of CHD, not only during the short term but also over the longer term after a cardiac ischemic event. The results may help to increase the proportion of ACS patients who are referred to cardiac rehabilitation centres.

New strategies for the development of lipid-lowering therapies to reduce cardiovascular risk.

The very high occurrence of cardiovascular events presents a major public health issue, because treatment remains suboptimal. Lowering LDL cholesterol (LDL-C) with statins or ezetimibe in combination with a statin reduces major adverse cardiovascular events. The cardiovascular risk reduction in relation to the absolute LDL-C reduction is linear for most interventions without evidence of attenuation or increase in risk at low LDL-C levels. Opportunities for innovation in dyslipidaemia treatment should address the substantial risk of lipid-associated cardiovascular events among patients optimally treated per guidelines but who cannot achieve LDL-C goals and who could benefit from additional LDL-C-lowering therapy or experience side effects of statins. Fresh approaches are needed to identify promising drug targets early and develop them efficiently. The Cardiovascular Round Table of the European Society of Cardiology (ESC) convened a workshop to discuss new lipid-lowering strategies for cardiovascular risk reduction. Opportunities to improve treatment approaches and the efficient study of new therapies were explored. Circulating biomarkers may not be fully reliable proxy indicators of the relationship between treatment effect and clinical outcome. Mendelian randomization studies may better inform development strategies and refine treatment targets before Phase 3. Trials should match the drug to appropriate lipid and patient profile, and guidelines may move towards a precision-based approach to individual patient management. Stakeholder collaboration is needed to ensure continued innovation and better international coordination of both regulatory aspects and guidelines. It should be noted that risk may also be addressed through increased attention to other risk factors such as smoking, hypertension, overweight, and inactivity.