Cognitive dysfunction and poor health literacy are common in veterans presenting with acute coronary syndrome: insights from the MEDICATION study

Lucas N Marzec,1 Evan P Carey,1 Anne C Lambert-Kerzner,1 Eric J Del Giacco,2 Stephanie D Melnyk,3 Chris L Bryson,4 Ibrahim E Fahdi,2 Hayden B Bosworth,3 Fran Fiocchi,5 P Michael Ho11Division of Cardiology, Denver VA Medical Center, Denver, CO, USA; 2Department of Medicine, Little Rock VA Medical Center, Little Rock, AR, USA; 3Department of Medicine, Durham VA Medical Center, Durham, NC, USA; 4Department of Medicine, Puget Sound VA Medical Center, Seattle, WA, USA; 5American College of Cardiology, Washington, DC, USABackground: Patient nonadherence to cardiac medications following acute coronary syndrome (ACS) is associated with increased risk of recurrent events. However, the prevalence of cognitive dysfunction and poor health literacy among ACS patients and their association with medication nonadherence are poorly understood.Methods: We assessed rates of cognitive dysfunction and poor health literacy among participants of a clinical trial that tested the effectiveness of an intervention to improve medication adherence in patients hospitalized with ACS. Of 254 patients, 249 completed the Rapid Estimate of Adult Literacy in Medicine, Revised (REALM-R) survey, an assessment of risk for poor literacy, and the St Louis University Mental Status (SLUMS) exam, a tool assessing for neurocognitive deficits, during ACS hospitalization. We assessed if SLUMS or REALM-R scores were associated with medication adherence.Results: Based on SLUMS score, 14% of patients were categorized as having dementia, and 52% with mild neurocognitive disorder (MNCD). Based on REALM-R score of ≤6, 34% of patients were categorized as at risk for poor health literacy. There was no association between poor health literacy and medication nonadherence. Of those with MNCD, 35.5% were nonadherent, compared to 17.5% with normal cognitive function and 6.7% with dementia. In multivariable analysis, cognitive dysfunction was associated with medication nonadherence (P=0.007), mainly due to an association between MNCD and nonadherence (odds ratio =12.2, 95% confidence interval =1.9 to 243; P=0.007). Cognitive status was not associated with adherence in patients randomized to the intervention.Conclusion: Cognitive dysfunction and risk for poor health literacy are common in patients hospitalized with ACS. We found an association between MNCD and medication nonadherence in the usual care group but not in the intervention group. These findings suggest efforts to screen for MNCD are needed during ACS hospitalization to identify patients at risk for nonadherence and who may benefit from an adherence intervention.Keyword: medication adherenc

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients