Faculty Bibliography

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist is the standard of care in acute coronary syndromes. Additionally, novel P2Y12 receptor antagonists such as prasugrel and ticagrelor are even recommended over clopidogrel in certain clinical guidelines. Despite the fact that clopidogrel is fraught with significant variability in on-treatment platelet reactivity, the novel P2Y12 receptor antagonists come at the price of increased side effects and cost. Therefore, alternative or supplementary antiplatelet therapies are needed. Cilostazol, a phosphodiesterase III inhibitor, has been shown to significantly improve high on-treatment platelet reactivity in patients receiving both aspirin and clopidogrel and has antiproliferative effects (inhibiting neointimal hyperplasia and smooth muscle proliferation), thus reducing the risk of restenosis after coronary stent implantation. Further, cilostazol in addition to aspirin and clopidogrel versus DAPT in patients undergoing percutaneous coronary intervention showed that triple antiplatelet therapy (TAPT) was associated with a significantly greater platelet inhibition, reduced major adverse cardiovascular events, target lesion revascularization, and target vessel revascularization with no increased risk for a hemorrhagic event. Moving forward, larger randomized controlled trials are required comparing TAPT versus DAPT (clopidogrel, prasugrel or ticagrelor on top of aspirin). (c) 2013 S. Karger AG, Basel.

OBJECTIVE: Limited studies suggest that blood pressure variability over time is a risk factor of long-term cardiovascular outcomes. However, most of these were in populations with pre-existing cardiovascular diseases (CVD) and studies in general population are lacking. METHODS: The study included 11,153 participants in a population-based, prospective cohort study in Araihazar, Bangladesh. Resting blood pressure was measured at baseline and every two years thereafter. Participants were followed up for an average of 6.5years (2002-2009). RESULTS: Male gender, older age, baseline systolic blood pressure (SBP), and absence of betel leaf use were independently positively associated with greater SBP variability over time. There was a significant association between SBP variability and the risk of death from overall CVD, especially from major CVD events. The positive association with the risk of death from any cause and stroke in age- and sex-adjusted models was attenuated in fully-adjusted models. In addition, the hazard ratio (HR) of stroke mortality was greater for individuals with both high baseline and high SBP variability. Similar patterns of HRs were observed for all-cause and CVD mortalities. CONCLUSION: In this rural Bangladeshi population, variability in SBP contributes to the risk of death from CVD and may further potentiate the increased mortality risk associated with high SBP.

BACKGROUND: In randomized clinical trials, procedural myocardial infarction (MI) or spontaneous MI is often weighted equally as a component of a composite clinical end point. An underlying assumption of this approach is that procedural and spontaneous MIs have similar prognostic impact. Our aim was to evaluate the prognostic impact of procedural vs spontaneous MI in patients undergoing percutaneous coronary intervention (PCI). METHODS: We used data from the EVENT registry to examine the relative prognostic impact of procedural vs spontaneous MI. For the purposes of this study, patients undergoing initial PCI were stratified into 3 groups-no MI, procedural MI, or spontaneous MI-based on standard definitions applied at the time of the index procedure and followed for 1 year for outcomes of all-cause mortality and cardiovascular mortality. Multiple propensity score adjustment analysis was used to adjust for differences in baseline covariates among the 3 groups. RESULTS: Among 7,380 patients included in this analysis, 4,568 (62%) patients had no MI, 580 (8%) patients had procedural MI at the time of their index procedure, and 2,232 (30%) patients presented with a spontaneous MI before PCI. In unadjusted analyses, there was a graded increase in risk of 1-year mortality (1.9% vs 3.1% vs 3.9%; P < .0001) and cardiovascular death (0.5% vs 1.0% vs 1.7%; P < .0001) across the 3 groups. After adjusting for propensity scores, spontaneous MI (adjusted hazard ratio [HR] 1.62, 95% CI 1.11-2.37, P = .01) but not procedural MI (adjusted HR 1.51, 95% CI 0.89-2.54, P = .12) was independently associated with death at 12 months when compared with the no-MI group. Findings were similar when the analysis was limited to cardiovascular death (adjusted HRs 3.14 [95% CI 1.68-5.90, P < .001] and 1.74 [95% CI 0.69-4.40, P = .24], respectively). CONCLUSIONS: Among patients undergoing PCI, spontaneous but not procedural MI was independently associated with death and cardiovascular death at 1 year. These finding suggest that the prognostic impact of procedural MI may be less than that of spontaneous MI and should be considered in designing end points for future studies of coronary revascularization.

OBJECTIVE: To compare the efficacy and safety of biodegradable polymer drug eluting stents with those of bare metal stents and durable polymer drug eluting stents. DESIGN: Mixed treatment comparison meta-analysis of 258 544 patient years of follow-up from randomized trials. DATA SOURCES AND STUDY SELECTION: PubMed, Embase, and Central were searched for randomized trials comparing any of the Food and Drug Administration approved durable polymer drug eluting stents (sirolimus eluting, paclitaxel eluting, cobalt chromium everolimus eluting, platinum chromium everolimus eluting, zotarolimus eluting-Endeavor, and zotarolimus eluting-Resolute) or biodegradable polymer drug eluting stents, with each other or against bare metal stents. OUTCOMES: Long term efficacy (target vessel revascularization, target lesion revascularization) and safety (death, myocardial infarction, stent thrombosis). Landmark analysis at more than one year was evaluated to assess the potential late benefit of biodegradable polymer drug eluting stents. RESULTS: From 126 randomized trials and 258 544 patient years of follow-up, for long term efficacy (target vessel revascularization), biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.66, 95% credibility interval 0.57 to 0.78) and zotarolimus eluting stent-Endeavor (0.69, 0.56 to 0.84) but not to newer generation durable polymer drug eluting stents (for example: 1.03, 0.89 to 1.21 versus cobalt chromium everolimus eluting stents). Similarly, biodegradable polymer drug eluting stents were superior to paclitaxel eluting stents (rate ratio 0.61, 0.37 to 0.89) but inferior to cobalt chromium everolimus eluting stents (2.04, 1.27 to 3.35) for long term safety (definite stent thrombosis). In the landmark analysis after one year, biodegradable polymer drug eluting stents were superior to sirolimus eluting stents for definite stent thrombosis (rate ratio 0.29, 0.10 to 0.82) but were associated with increased mortality compared with cobalt chromium everolimus eluting stents (1.52, 1.02 to 2.22). Overall, among all stent types, the newer generation durable polymer drug eluting stents (zotarolimus eluting stent-Resolute, cobalt chromium everolimus eluting stents, and platinum chromium everolimus eluting stents) were the most efficacious (lowest target vessel revascularization rate) stents, and cobalt chromium everolimus eluting stents were the safest with significant reductions in definite stent thrombosis (rate ratio 0.35, 0.21 to 0.53), myocardial infarction (0.65, 0.55 to 0.75), and death (0.72, 0.58 to 0.90) compared with bare metal stents. CONCLUSIONS: Biodegradable polymer drug eluting stents are superior to first generation durable polymer drug eluting stents but not to newer generation durable polymer stents in reducing target vessel revascularization. Newer generation durable polymer stents, and especially cobalt chromium everolimus eluting stents, have the best combination of efficacy and safety. The utility of biodegradable polymer stents in the context of excellent clinical outcomes with newer generation durable polymer stents needs to be proven.