Bleeding risk following percutaneous coronary intervention in patients with diabetes prescribed dual anti-platelet therapy

doi:10.1016/j.ahj.2016.09.010

American Heart Journal

Volume 182, December 2016, Pages 111-118

https://doi.org/10.1016/j.ahj.2016.09.010 Get rights and content

Background

Patients with diabetes mellitus (DM) experience higher rates of in-stent restenosis and greater benefit from drug-eluting stents implant at the time of percutaneous coronary intervention (PCI), necessitating prolonged dual anti-platelet therapy (DAPT). While DAPT reduces risk of ischemic events post-PCI, it also increases risk of bleeding. Whether bleeding rates differ among patients with and without DM, receiving long-term DAPT is unknown.

Methods

Among patients who underwent PCI and were maintained on DAPT for 1 year in a multicenter US registry, we assessed patient-reported bleeding over one year following PCI in patients with and without DM. Multivariable, hierarchical Poisson regression was used to evaluate the association of DM with bleeding during follow-up.

Results

Among 2334 PCI patients from 10 US hospitals (mean age 64, 54% ACS), 32.6% had DM. In unadjusted analyses, patients with DM had fewer bleeding events over the year following PCI (DM vs no DM: BARC = 1: 78.0% vs 87.7%, P < .001; BARC ≥2: 4.3% vs 5.3%, P = .33). Following adjustment, patients with (vs without DM) had a lower risk of BARC ≥1 bleeding during follow-up (relative risk [RR] 0.89, 95% CI 0.83–0.96). This decreased bleeding risk persisted after removing bruising from the endpoint definition.

Conclusions

In a real-world PCI registry, patients with DM experienced lower risk of bleeding risk on DAPT. As patients with DM also derive greater ischemic benefit from drug-eluting stents, which requires prolonged DAPT, our findings suggest that the balance between benefit and risk of this therapeutic approach may be even more favorable in patients with DM than previously considered.

Section snippets

Study design and participants

Details regarding the OPS (Outcomes of PCI Study) and PRISM (Patient Risk Information Services Manager) prospective observational registries have been previously described.12., 13. From April 2009 to October 2011, consecutive PCI patients from 10 U.S. hospitals were prospectively approached for enrollment in OPS/PRISM (6 hospitals in PRISM, 3 hospitals in OPS, and 1 hospital with concurrent data collection [Saint Luke's Mid America Heart Institute]). The 2 registries had identical enrollment

Study participants

Of 3299 patients from 10 US sites enrolled in the OPS-PRISM registry, we excluded 135 (4.1%) patients who were not discharged on a thienopyridine or aspirin. We also excluded 218 patients (6.9%) who did not have available bleeding data during any follow-up assessment. Patients who were missing outcomes data were more likely to be younger, non-white race, smokers, and lower socioeconomic status compared with those in the analytic cohort (Supplemental Table II). In addition, patients with missing

Discussion

In this multicenter, contemporary PCI registry, we found that patients with DM experienced lower risk of BARC ≥1 bleeding over the year following PCI compared with patients who did not have DM. Importantly, these results persisted after adjustment for multiple potential confounders and in multiple sensitivity analyses. Collectively, these data reinforce the preferential use of DES over BMS in patients with DM by supplementing the well-known greater absolute risk reduction in restenosis in

Disclosures

Dr. Deepak L. Bhatt discloses the following relationships - Advisory Board: Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care; Chair: American Heart Association Get With The Guidelines Steering Committee; Data Monitoring Committees: Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, Population Health Research Institute; Honoraria: American

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Cited by (17)

Fatal, ischemic and bleeding risk of patients meeting the selection criteria of the TWILIGHT trial: Insights from a large PCI registry
2023, American Heart Journal
The TWILIGHT trial (NCT02270242) demonstrated that in selected high-risk patients undergoing percutaneous coronary intervention (PCI) ticagrelor monotherapy significantly reduced bleeding complications without ischemic harm as compared to ticagrelor plus aspirin after 3-month of dual antiplatelet therapy. The aim of this analysis was to assess the applicability of the findings TWILIGHT trial to a real-world population.
Patients undergoing PCI at a tertiary center between 2012 and 2019 and not meeting any TWILIGHT exclusion criterion (oral anticoagulation treatment, ST-segment elevation myocardial infarction [MI], cardiogenic shock, dialysis, prior stroke, or thrombocytopenia) were included. Patients were stratified into 2 groups based on whether they fulfilled the TWILIGHT inclusion criteria (high-risk) or not (low-risk). The primary outcome was all-cause death; the key secondary outcomes were MI and major bleeding at 1 year after PCI.
Out of 13,136 included patients, 11,018 (83%) were at high risk. At 1-year, these patients had an approximately 3 folds greater hazard of death (1.4% vs 0.4%, HR 3.63, 95% CI 1.70-7.77) and MI (1.8% vs 0.6%, HR 2.81, 95% CI 1.56-5.04) and a nearly 2 folds higher risk of major bleeding (3.3% vs 1.8%, HR 1.86, 95% CI 1.32-2.62) as compared to low-risk patients.
Among patients not meeting the TWILIGHT exclusion criteria from a large PCI registry, the high-risk inclusion criteria of the TWILIGHT trial were met by the majority of patients and were associated with an increased risk of mortality and MI and a moderately elevated risk of bleeding.
Questions and answers on the use of aspirin for primary prevention of cardiovascular disease in diabetes
2022, Diabetes Research and Clinical Practice
Citation Excerpt :
Conversely, several data from secondary prevention cohorts have been published. The study by Grodzinsky et al. including 2,946 patients undergoing percutaneous coronary intervention, 33% of whom affected by diabetes, reported that hemorrhagic events at 12 months of follow-up classified as BARC (Bleeding Academic Research Consortium) 1 (i.e. bleedings that do not require medical intervention and/or hospitalization) were even lower in diabetic subjects than in non-diabetics (78.0% vs. 87.7%, p < 0.001) [9]. Instead, for bleeding events classified as BARC ≥ 2 (i.e. bleedings that require medical intervention or hospitalization) no significant differences among the two groups were noticed (respectively, 4.3% in patients with diabetes vs. 5.3% in patients without diabetes, p = 0.33) [9].
Patients with diabetes have a prothrombotic state and a 2 to 4 times higher risk of cardiovascular events than those without diabetes. Aspirin is the cornerstone of treatment in patients with cardiovascular disease, irrespective of diabetes status, being able to confer a 19% relative risk reduction per year in serious vascular events compared with placebo at long-term follow-up (6.7% vs 8.2% per year, p < 0.0001). Data regarding the benefit-risk ratio of aspirin prescribed to patients with diabetes without established cardiovascular disease are less convincing, especially when compared to other preventive strategies. Of note, in primary prevention trials, aspirin allocation yielded a significant 12% proportional reduction in serious vascular events, irrespective of diabetes status, corresponding to a small annual absolute risk reduction (0.06% per year). However, in everyday clinical practice aspirin is still largely prescribed by both diabetologists and cardiologists. In this article, we provide eight questions and answers corroborated by available evidence on the use of aspirin for primary prevention of cardiovascular disease in diabetes.
Association Between Platelet Reactivity and Long-Term Bleeding Complications After Percutaneous Coronary Intervention According to Diabetes Status
2022, American Journal of Cardiology
The relation between diabetes mellitus (DM) and bleeding complications after percutaneous coronary intervention (PCI) is controversial. This study investigates the role of low platelet reactivity (LPR) in the bleeding risk stratification of patients who underwent PCI according to DM status. A total of 472 patients who underwent PCI on aspirin and clopidogrel were included retrospectively. Platelet reactivity was assessed using the VerifyNow P2Y(12) assay. LPR was defined as platelet reactivity unit ≤178. The primary end point was the occurrence of any bleeding at 5 years stratified by DM status and LPR. DM was present in 30.5% of patients. LPR was less frequent in patients with DM (p = 0.077). Overall, 11.9% of patients experienced a bleeding complication at 5 years. The incidence of bleeding did not differ in subjects with and without DM (p = 0.24). LPR had a similar value for stratifying the increased bleeding risk in patients with and without DM (interaction p between DM and LPR 0.69). A stepwise increase in the crude rates of bleeding complications was observed across patients with and without LPR and DM (log-rank p = 0.004), with those affected by both conditions having the highest crude incidence rate. In conclusion, on top of aspirin, approximately 1/3 of patients who underwent PCI on clopidogrel have LPR. Assessment of LPR provides a significant incremental value for predicting bleeding irrespective of DM status. Although the presence of DM per se does not increase the incidence of hemorrhagic complications, the coexistence of DM and LPR identifies the subgroup with the highest bleeding risk.
Adherence and persistence analysis in patients treated with double antiplatelet therapy (DAPT) at two years in real life
2021, Patient Education and Counseling
Citation Excerpt :
Unplanned interruption due to non-adherence to therapy can be more harmful than the interruption planned by the clinician according to treatment regulations and guidelines [38]. Causes of non-persistence can also be due to bleeding, in this case the interruption of the therapy is correct and in line with current guidelines [39]. As such it becomes essential to investigate the causes of non-persistence.
Double antiplatelet therapy (DAPT) is indicated for the treatment of coronary artery diseases (CAD). The optimal duration of therapy with DAPT continues to be a subject of debate in the scientific community. To improve adherence to DAPT, the FDC (fixed dose combination) of Acetylsalicylic acid (ASA) and clopidogrel was developed into a single pill instead of two separate pills thus facilitating the dosage and administration of the therapy and increasing compliance. The aim of this study was to assess adherence and persistence over a period of two years in patients treated with DAPT composed of: ASA/clopidogrel, ASA/prasugrel, ASA/ticagrelor and FDC with ASA and clopidogrel in real life and to assess whether the use of ASA and clopidogrel FDC is associated with improved adherence.
In the following retrospective pharmacological-observational non-interventional study, all patients treated with DAPT in the Hospital of Pescara from January 2010 to October 2019 were considered. Persistence to treatment is defined as the duration of time from initiation to discontinuation of treatment. Adherence was calculated as the ratio between Received Daily Dose (RDD) and Prescribed Daily Dose (PDD).
277 patients treated with ASA/clopidogrel, 77 patients treated with ASA/prasugrel, 57 patients treated with ASA/ticagrelor and 108 patients treated with FDC of ASA/clopidogrel were analysed. Persistence curves at two years showed a statistically significant difference (p < 0.001). Adherence to therapy was optimal with an absolute value at two years of 0.96. Adherence was better in patients treated with ASA/prasugrel with a value of 0.98 and with 97 % of patients with an adherence value greater than or equal to 0.8, while, it was worse in patients treated with FDC ASA/clopidogrel with an absolute value of 0.94 and with 88 % of patients with an optimal adherence value. No statistically significant difference was found between the ASA/clopidogrel FDC in comparison to each component taken as a separate pill (p = 0.0752).
DAPT along with ASA/clopidogrel showed a statistically significant better persistence than ASA/ticagrelor and ASA/prasugrel. Whereas, to our knowledge and as per the current literature no statistically significant differences were found, in terms of adherence in real life, between the use of ASA/Clopidogrel FDC and the use of two different pills.
Association of diabetes with outcomes in patients undergoing contemporary percutaneous coronary intervention: Pre-specified subgroup analysis from the randomized GLOBAL LEADERS study
2020, Atherosclerosis
Citation Excerpt :
A large individual patient data meta-analysis of 11,473 patients studying the outcomes between short- or long-term DAPT after DES implantation according to the diabetic status showed similar bleeding risk between diabetic and non-diabetic patients [29]. Diabetic patients even experienced lower bleeding risk than non-diabetic patients after PCI in a multicenter US registry of consecutive PCI patients [34]. Nonetheless, most of the patients in these studies received clopidogrel as the P2Y12 inhibitor.
Diabetes has been well recognized as a strong predictor for adverse outcomes after percutaneous coronary intervention (PCI), however, studies in the era of drug-eluting stent and potent P2Y12 inhibitors have shown conflicting results. We aimed to assess ischemic and bleeding outcomes after contemporary PCI according to diabetic status.
We studied 15,957 patients undergoing PCI for stable or acute coronary syndrome in the GLOBAL LEADERS study with known baseline diabetic status. The primary endpoint was all-cause death or new Q-wave myocardial infarction at 2 years. The secondary safety endpoint was major bleeding defined as bleeding academic research consortium (BARC) type 3 or 5.
A quarter of the study cohort were diabetic (4038/15,957), and these patients had a significantly higher risk of primary endpoint at 2 years compared to non-diabetics (adjusted hazard ratio [HR] 1.38; 95% confidence interval [CI] 1.17–1.63). The difference was driven by a significantly higher risk of all-cause mortality at 2 years in diabetics (adjusted HR 1.47, 95% CI 1.22–1.78). The risk of BARC 3 or 5 bleeding was comparable between the two groups (adjusted HR 1.09, 95% CI 0.86–1.39). The antiplatelet strategy (experimental versus reference strategy) had no significant effect on the rates of primary endpoint and secondary safety endpoint at 2 years in patients with and without diabetes.
Diabetic patients had higher risk of ischemic events after PCI than non-diabetic patients, whilst bleeding risk was comparable. The outcomes of diabetic patients following PCI were not affected by the two different antiplatelet strategies.
Use of prasugrel vs clopidogrel and outcomes in patients with and without diabetes mellitus presenting with acute coronary syndrome undergoing percutaneous coronary intervention
2019, International Journal of Cardiology
Citation Excerpt :
Importantly, we also described a higher rate of major bleeding events in diabetics. This finding is in contrast with prior reports which showed comparable 1-year rates of bleeding events in patients with and without diabetes [16]. The increased risk of bleeding in our study population became evident at 1 year follow up.
Clinical trial data studies suggest superiority of prasugrel over clopidogrel in patients with diabetes. However, the use, safety and efficacy profile of prasugrel in unselected diabetic patients presenting with acute coronary syndromes (ACS) remain unclear.
PROMETHEUS was a prospective multicenter observational study of 19,919 ACS PCI patients enrolled between 2010 and 2013. The primary endpoint was 90-day major adverse cardiovascular events (MACE), comprising all-cause death, myocardial infarction, stroke or unplanned revascularization. The safety endpoint was bleeding requiring hospitalization.
We identified 7580 (38%) subjects with and 12,329 (62%) without diabetes. Diabetic patients were older and had significantly higher rates of cardiovascular risk factors. However, they were less likely to receive prasugrel (18.2% vs. 21.7%). Use of prasugrel did not increase with the severity of clinical presentation in diabetics, whereas, among non-diabetics, prescription of prasugrel was higher in NSTEMI and STEMI compared to unstable angina. The 90-day and 1-year adjusted risk of MACE was greater in diabetics (at 1 year: 22.7% vs. 16.5%; HR 1.22 [1.14–1.33], p < 0.001). At 1 year, the risk of bleeding was also higher in diabetics (4.9% vs. 4.1%, HR 1.19 [1.01–1.39], p = 0.035). After multivariable adjustment, use of prasugrel was associated with a lower risk of death in diabetic patients both at 90 days and 1 year.
Use of prasugrel in diabetic patients with PCI-treated ACS was lower than in non-diabetics despite their high-risk profile and the severity of their clinical presentation. In diabetics, prasugrel was associated with a lower adjusted risk of 90-day death compared with clopidogrel.

View all citing articles on Scopus

: Funding source: The Outcomes of PCI Study (OPS) was supported by an American Heart Association Outcomes Research Center grant (0875149N) and the Personalized Risk Information Services Manager™ (PRISM) study was supported by a grant from the National Heart Lung and Blood Institute (R01-HL096624). Dr. Grodzinsky is supported by a T32 training grant from the NHLBI (HL110837). The funding agencies had no role in data collection, analysis, interpretation or the decision to submit the results. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

: Warren J. Cantor, MD served as guest editor for this article.

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Clinical InvestigationBleeding risk following percutaneous coronary intervention in patients with diabetes prescribed dual anti-platelet therapy

Background

Methods

Results

Conclusions

Section snippets

Study design and participants

Study participants

Discussion

Disclosures

Am Heart J

J Am Coll Cardiol

J Am Coll Cardiol

J Thromb Haemost

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Lancet

J Am Coll Cardiol

J Am Coll Cardiol

Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents

JAMA

Clinical and angiographic predictors of restenosis after stent deployment in diabetic patients

Circulation

Clinical Investigation
Bleeding risk following percutaneous coronary intervention in patients with diabetes prescribed dual anti-platelet therapy