Incidence and characteristics of arterial thromboemboli in patients with COVID-19

Background Studies have reported COVID-19 as an independent risk factor for arterial thromboemboli. Methods From a cross-sectional sample, we determined the incidence and location of arterial thromboemboli (myocardial infarction, ischemic stroke, peripheral artery), stratified by COVID-19 status, in the RECOVER database, which included data on patients at 45 United States medical centers in 22 states. Epidemiological factors, clinical characteristics and outcomes were collected through a combination of individual chart review and automatic electronic query and recorded in REDCap®. We investigated the association of baseline comorbidities on the development of arterial thromboemboli and analyzed results based on the presence or absence of concomitant COVID-19 infection, testing this association with Chi-squared. We also described use of anticoagulants and statins. Results Data were collected on 26,974 patients, of which 13,803 (51.17%) tested positive for COVID-19. Incidence of arterial thromboemboli during hospitalization was 0.13% in patients who tested positive for COVID-19 and 0.19% in patients who tested negative. Arterial thromboemboli tended to be more common in extremities than in core organs (heart, kidney, lung, liver) in patients with COVID-19, odds ratio 2.04 (95% CI 0.707 – 5.85). Patients with COVID-19 were less likely to develop an arterial thrombus when on baseline statin medication (p=0.014). Presence of metabolic syndrome predicted presence of core arterial thrombus (p=0.001) and extremity arterial thrombus (p=0.010) in those with COVID-19. Arterial thromboemboli were less common in patients with COVID-19 than in those who tested negative for COVID-19. Conclusions Presence of a composite metabolic syndrome profile may be associated with arterial clot formation in patients with COVID-19 infection.

PCSK9 Levels and Metabolic Profiles in Elderly Subjects with Different Glucose Tolerance under Statin Therapy

Proprotein convertase subtilisin/kexin type 9 (PCSK9) degrades low-density lipoprotein cholesterol (LDL-C) receptors, and thus regulates the LDL-C levels in the circulation. Type 2 diabetics often have elevated LDL-C levels. However, the functions of PCSK9 in patients with alterations of glu-cose metabolism and statin therapy are still unclear. Method: we investigated a large cohort of 608 subjects, born in 1945 in Oulu, Finland (Oulu Cohort 1945). We studied the effects of PSCK9 lev-els with different glucose tolerances (normal glucose tolerance (NGT), prediabetes (PreDM) or type 2 diabetes (T2D)) with and without statin medication, and analyzed clinical data, NMR metabolomics and PCSK9 plasma levels. Results: PCSK9 plasma levels did not significantly differ between the three groups. Statin therapy significantly increased the PCSK9 levels in NGT, PreDM and T2D groups compared with subjects with no statins. In the NGT group, negative associations between PCSK9 and LDL-C, intermediate-density lipoprotein cholesterol (IDL-C), very low-density lipoprotein cholesterol (VLDL-C), total cholesterol and LDL and IDL triglycerides were observed under statin medication. In contrast, in the PreDM and T2D groups, these associa-tions were lost. Conclusions: our data suggest that in subjects with abnormal glucose metabolism and statin therapy, the significant PCSK9-mediated effects on the lipid metabolites are lost com-pared to NGT subjects, but statins reduced the LDL-C and VLDL-C levels.

Associations Between Regularity of General Practitioner Contacts and Adherence to Statin Therapy

IntroductionResearch has demonstrated continuity and regularity of general practitioner (GP) contacts to be associated with reduced hospitalisations and emergency department (ED) presentations. Opportunities for improved medication management are often cited as a potential causal mechanism, but little research has directly addressed this. Objectives and ApproachTo determine associations between continuity of primary care and adherence with statin medications amongst individuals at risk of cardiovascular disease outcomes, taking statins through the exposure period of July 2011 - June 2012. We used self-report and administrative data from 267,153 participants of the 45 and Up Study conducted in New South Wales, Australia from 2006-2009. Medicare Benefits Schedule and Pharmaceutical Benefits Scheme data, from the Australian Government Department of Human Services, were linked to survey, hospital and death data by the NSW Centre for Health Record Linkage. Exposures were the Usual Provider of Care (UPC) index, i.e. the proportion of visits made to the usual GP; and a regularity index assessing whether patients were visiting the GP on a regular basis. Cox regression estimated associations between these exposures and time to cessation of statin medication, defined as a 30-day period without supply. ResultsPreliminary findings amongst a cohort of approximately 48,000 indicated that increases in both regularity and continuity of primary care were associated with reduced likelihood of statin cessation. After controlling for socio-demographic and health status indicators the hazard ratio for cessation in the most regular quintile (baseline least) was 0.84 (95%CI 0.80 – 0.87) and in the highest continuity quintile was 0.93 (95%CI 0.89 – 0.96). Conclusion / ImplicationsPrevious work assessed relationships between continuity of care and downstream hospital and ED outcomes. This work complements existing literature by assessing intermediate outcomes, aiding understanding of potential causal pathways. These findings are relevant given adherence to statin medication is often sub-optimal.

Statin adherence is lower in primary than secondary prevention: A national follow-up study of new users

Background Maintaining adherence to statins reduces the risk of an initial cardiovascular disease (CVD) event in high-risk individuals (primary prevention) and additional CVD events following the first event (secondary prevention). The effectiveness of statin therapy is limited by the level of adherence maintained by the patient. We undertook a nationwide study to compare adherence and discontinuation in primary and secondary prevention patients. Methods Dispensing data from New Zealand community pharmacies were used to identify patients who received their first statin dispensing between 2006 and 2011. The Medication Possession Ratio (MPR) and proportion who discontinued statin medication was calculated for the year following first statin dispensing for patients with a minimum of two dispensings. Adherence was defined as an MPR ≥ 0.8. Previous CVD was identified using hospital discharge records. Multivariable logistic regression was used to control for demographic and statin characteristics. Results Between 2006 and 2011 289,666 new statin users were identified with 238,855 (82.5%) receiving the statin for primary prevention compared to 50,811 (17.5%) who received it for secondary prevention. The secondary prevention group was 1.55 (95% CI 1.51–1.59) times as likely to be adherent and 0.67 (95% CI 0.65–0.69) times as likely to discontinue statin treatment than the primary prevention group. An early gap in statin coverage increased the odds of discontinuing statin treatment. Conclusion Adherence to statin medication is higher in secondary prevention than primary prevention. Within each group, a range of demographic and treatment factors further influences adherence.

Increased risk of 2-year death in patients who discontinued their use of statins

Objective This study examined the association between statin usage (discontinued, reduced or continued) and two-year death following a 21% increase in the Pharmaceutical Benefits Scheme (PBS) consumer co-payment in Western Australia. Methods A retrospective observational study in Western Australia using linked administrative Commonwealth PBS data and State hospital inpatient and death data (n = 207,066) was undertaken. We explored the two-year all-cause and ischemic heart disease(IHD)/stroke-specific-death in individuals who discontinued, reduced or continued statin medication following the January 2005 PBS co-payment increase, overall, by beneficiary status (general population vs. social security recipients) and by a history of admission for ischemic heart disease or stroke. Non-cardiovascular (CVD)-related death was also considered. Results In the first six months of 2005, 3.3% discontinued, 12.5% reduced and 84.2% continued statin therapy. We found those who discontinued statins were also likely to discontinue at least two other medicines compared to those who continued therapy. There were 4,607 all-cause deaths. For IHD/stroke-specific death, there were 1,317. For all non-CVD-related death, there were 2,808 deaths during the 2-year follow-up period. Cox regression models, adjusted for demographic and clinical characteristics, showed a 39%-61% increase in the risk of all-cause death for individuals who reduced or discontinued statin medication compared to those who continued their statin medication (Discontinued: Adj HR = 1.61, 95% CI 1.40–1.85; Reduced: Adj HR = 1.39, 95% CI 1.28–1.51). For IHD/stroke-specific death, there was an increased risk of death by 28–76% (Discontinued: Adj sHR = 1.76, 95% CI 1.37–2.27; Reduced: Adj sHR = 1.28, 95% CI 1.10–1.49), and for non-CVD-related death, there was an increased risk of death by 44–57% (Discontinued: Adj sHR = 1.57, 95% CI 1.31–1.88; Reduced: Adj sHR = 1.44, 95% CI 1.30–1.60), for individuals who discontinued or reduced their statin medication compared to those who continued. Conclusions Patients who discontinued their statin therapy had a significantly increased risk of IHD and stroke death. Health professionals should be aware that large co-payment changes may be associated with patients discontinuing or reducing medicines to their health detriment. Factors that lead to such changes in patient medication-taking behaviour need to be considered and addressed at the clinical and policy levels.