METHODS: A systematic review and meta-analysis was performed in accordance with the PRISMA statement. MEDLINE, EMBASE and Cochrane Library were searched for completed manuscripts until May 2019 on TIA/ischaemic stroke patients, ≥ 18 years, treated with commonly-prescribed antiplatelet therapy, who had platelet function/reactivity testing and prospective follow-up data on recurrent stroke/TIA, myocardial infarction, vascular death or other cerebrovascular outcomes. Data were pooled using random-effects meta-analysis. Primary outcome was the composite risk of recurrent stroke/TIA, myocardial infarction or vascular death. Secondary outcomes were recurrent stroke/TIA, severe stroke (NIHSS > 16) or disability/impairment (modified Rankin scale ≥ 3) during follow-up.
RESULTS: Antiplatelet-HTPR prevalence was 3-65% with aspirin, 8-56% with clopidogrel and 1.8-35% with aspirin-clopidogrel therapy. Twenty studies (4989 patients) were included in our meta-analysis. There was a higher risk of the composite primary outcome (OR 2.93, 95% CI 1.90-4.51) and recurrent ischaemic stroke/TIA (OR 2.43, 95% CI 1.51-3.91) in patients with vs. those without 'antiplatelet-HTPR' on any antiplatelet regimen. These risks were also more than twofold higher in patients with vs. those without 'aspirin-HTPR' and 'dual antiplatelet-HTPR', respectively. Clopidogrel-HTPR status did not significantly predict outcomes, but the number of eligible studies was small. The risk of severe stroke was higher in those with vs. without antiplatelet-HTPR (OR 2.65, 95% CI 1.00-7.01).
DISCUSSION: Antiplatelet-HTPR may predict risks of recurrent vascular events/outcomes in CVD patients. Given the heterogeneity between studies, further prospective, multi-centre studies are warranted.
MATERIALS AND METHODS: We searched electronic databases. All available randomized controlled trials (RCTs) were included, and we considered the scientific novelty of the study, the reliability of the reported study results; the high methodological level of the study of non-statin therapy in patients with dyslipidemia and high residual platelet reactivity, with no language or date restrictions. We did separate random-effects meta-analyses for LDL-С, HRRP on their effects on LDL-С levels and outcomes, taking into account the reliability of the reported study results and the high methodological level of the study. The challenge of achieving target LDL-С levels, their impact on high residual platelet reactivity, and the choice of optimal antiplatelet and lipid-lowering therapy remains unresolved.
RESULTS: The integration of newer therapies, such as inclisiran and PCSK9 inhibitors, may play a critical role in achieving optimal outcomes for patients at high cardiovascular risk.
CONCLUSION: The necessity of applying an individual multidisciplinary approach in order to determine the best regimen of antiplatelet and lipid-lowering therapy in patients with coronary heart disease, including after revascularization, is shown. This approach will reduce the risk of recurrent cardiovascular events. Few studies on the relationship between LDL-С and HRPR dictate the need for more detailed research in this area.
OBJECTIVES: This study across 17 high-, middle- and low-income countries described variations in secondary CVD prevention medication use over a median follow-up of 12 years.
METHODS: In the multinational PURE (Prospective Urban Rural Epidemiology) cohort study, we conducted a repeated cross-sectional analysis to examine temporal variations in the use of secondary prevention medications in participants with CVD. In participants with coronary artery disease, we focused on antiplatelet agents, statins, renin-angiotensin system (RAS) inhibitors, and β-blockers. In participants with stroke, we focused on antiplatelet agents, statins, RAS inhibitors, and other blood pressure-lowering drugs. Medications were collected at baseline and on 4 subsequent follow-up visits.
RESULTS: The analysis included 7,409 participants with a diagnosis of CVD at the baseline visit, 8,792 at the second visit, 9,236 at the third visit, 11,082 at the fourth visit, and 11,677 at the last visit. The median age at baseline was 58.0 years, and 52.9% of the participants were female. The median follow-up was 12 years, with the median year of the baseline visit in 2007 and the fifth visit in 2019. Over this period, use of 1 or more classes of medications for secondary CVD prevention was 41.3% (95% CI: 40.2%-42.4%) at baseline, peaked at 43.1% (95% CI: 42.0%-44.1%), and then decreased to 31.3% (95% CI: 30.4%-32.1%) by the last study visit. In high-income countries, this use decreased from 88.8% (95% CI: 86.6%-91.0%) to 77.3% (95% CI: 74.9%-79.6%). In upper-middle-income countries, this use increased from 55.0% (95% CI: 52.8%-57.3%) to 61.1% (95% CI: 59.1%-63.1%). In lower-middle-income countries, use of at least 1 class of medications was 29.5% (95% CI: 28.1%-30.9%) at baseline, peaked at 31.7% (95% CI: 30.4%-33.1%), and then decreased to 13.4% (95% CI: 12.5%-14.2%) by the last visit. In low-income countries, use of at least 1 class of medications was 20.8% (95% CI: 18.1%-23.5%) at baseline, peaked at 47.3% (95% CI: 44.8%-49.9%), and then decreased to 27.5% (95% CI: 25.2%-29.9%) by the last study visit.
CONCLUSIONS: Globally and in most country income-level groups, the use of medications for secondary CVD prevention has been low, with little improvement over time.
METHODS: We used a matched case-control design using the Virtual International Stroke Trials Archive (VISTA). Cases were patients who had an acute coronary syndrome, recurrent stroke or transient ischaemic attack within 90 days post-stroke and were matched for age ± 10 years and sex with up to four controls. Antiplatelet use was categorized as persistent (used for >3 days and continued up to day 90), early cessation (used antiplatelet <3 days) or stopped/interrupted users (used for >3 days but stopped prior to day 90). These categories were compared in cases and controls using a conditional logistic regression model that adjusted for potential confounders.
RESULTS: A total of 970 patients were included, of whom 194 were cases and 776 were matched controls. At 90 days, 10 cases (5.2%) and 58 controls (7.5%) stopped/interrupted their antiplatelet. The risk of cardiovascular event was not different in stopped/interrupted users (adjusted odds ratio 0.70, 95% confidence interval 0.33, 1.48; P = 0.352) and early cessations (adjusted odds ratio 1.04, 95% confidence interval 0.62, 1.74; P = 0.876) when compared to persistent users.
CONCLUSION: We found no increased risk in patients who stopped and interrupted antiplatelets early after stroke but the study was limited by a small sample size and further research is needed.