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Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study.

ABSTRACT: BACKGROUND:The acute effects of statin loading dose (LD) on platelet reactivity in patients with chronic stable angina (CSA) are not completely clear. HYPOTHESIS:We hypothesized that LDs of atorvastatin and rosuvastatin have different pharmacodynamic acute effects on platelet aggregability in CSA patients with baseline normal platelet reactivity while on dual antiplatelet therapy (DAPT). METHODS:From September 2011 to February 2014, all consecutive CSA patients on chronic DAPT (aspirin and clopidogrel) were evaluated before elective percutaneous coronary intervention (PCI). An initial assessment of platelet reactivity in response to thrombin receptor agonist, ADP, and ASP (respectively, indicative of the response to clopidogrel and aspirin) was performed with impedance aggregometry. Patients with high platelet reactivity to ADP test (area under the curve >47) were excluded. The remaining patients were randomized into 3 treatment groups: Group A, atorvastatin LD 80 mg; Group B, rosuvastatin LD 40 mg; and Group C, no statin LD (control group). A second assessment of platelet reactivity was performed ?12 hours after statin LD. RESULTS:682 patients were screened and 145 were randomized into the 3 groups. At baseline and after statin LD, no significant difference was found in platelet reactivity in response to 3 different agonists between the 3 groups. Subgroup analysis showed that platelet reactivity to ADP test was significantly lower in patients chronically treated with low-dose statins (n = 94) compared with statin-naïve patients (n = 51; 15.32 ± 1.50 vs 18.59 ± 1.30; P = 0.007). CONCLUSIONS:Loading dose of atorvastatin (80 mg) or rosuvastatin (40 mg) did not induce significant variation in platelet reactivity in CSA patients with baseline reduced platelet reactivity as in chronic DAPT. Our data confirm that chronic concomitant treatment with low-dose statins and clopidogrel resulted in significantly lower platelet reactivity compared with clopidogrel alone.

SUBMITTER: Godino C

PROVIDER: S-EPMC6490637 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study.

Godino Cosmo C Pavon Anna Giulia AG Mangieri Antonio A Salerno Anna A Cera Michela M Monello Alberto A Chieffo Alaide A Magni Valeria V Cappelletti Alberto A Margonato Alberto A Colombo Antonio A

Clinical cardiology 20170419 8

<h4>Background</h4>The acute effects of statin loading dose (LD) on platelet reactivity in patients with chronic stable angina (CSA) are not completely clear.<h4>Hypothesis</h4>We hypothesized that LDs of atorvastatin and rosuvastatin have different pharmacodynamic acute effects on platelet aggregability in CSA patients with baseline normal platelet reactivity while on dual antiplatelet therapy (DAPT).<h4>Methods</h4>From September 2011 to February 2014, all consecutive CSA patients on chronic D ...[more]

PMID: 28422300

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Project description:BackgroundAcute coronary syndrome (ACS) is an important disease threatening human life and health. Many studies have shown that the loading dose of atorvastatin can significantly improve the prognosis of patients with ACS, and reduce the mortality. However, this conclusion is not consistent. Thus, we aimed to evaluate the effect of high-dose rosuvastatin loading before percutaneous coronary intervention (PCI) in Chinese patients with ACS using a meta-analysis based on a systematic review of published articles.MethodsWe systematically reviewed published studies, evaluating the effect of high-dose rosuvastatin loading before percutaneous coronary intervention in Chinese patients with ACS. The retrieval time is limited from inception to 2 November 2016, and the retrieved databases included PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, the VIP database and the Wang Fang database. Two researchers independently assessed the quality of the included studies and then extracted the data. Stata 11.0 was used for data analysis.ResultsIn total, 11 articles, which included 802 patients, were included in our meta-analysis. Among these patients, 398 patients were in the high-dose group (20 mg/day) and 404 patients were in the conventional dose group (10 mg/day). Meta-analysis results showed that compared with the conventional dose group: 1) The loading dose of rosuvastatin can significantly reduce the hs-CRP level after PCI, including at 24 hours (SMD = -0.65, 95%CI -0.84 ~ -0.47, P = 0.000), 48 hours (SMD = -0.40, 95%CI -0.68 ~ -0.11, P = 0.006), and four weeks (SMD = -1.64, 95%CI -2.01 ~ -1.26, P = 0.000). 2) The loading dose of rosuvastatin can significantly reduce the levels of LDL-C and cTnT, including the level of LDL-C at 30 d after PCI (SMD = -0.89, 95%CI -1.10 ~ -0.69, P = 0.000), and the level of cTnT at 24 h after PCI (SMD = -1.93, 95%CI -2.28 ~ -1.59, P = 0.000), and increase the level of HDL-C at 48 h after PCI (SMD = 0.61, 95%CI 0.34 ~ 0.88, P = 0.000). 3) The loading dose of rosuvastatin can significantly reduce the levels of TG and TC, including the level of TG at 30 d after PCI (SMD = -0.94, 95%CI -1.17 ~ -0.71, P = 0.000), the level of TC at 48 h after PCI (SMD = -0.35, 95%CI -0.68 ~ -0.01, P = 0.043), and the level of TC at 30 d after PCI (SMD = -0.77, 95%CI -0.98 ~ -0.56, P = 0.000).ConclusionsOur systematic review and meta-analysis showed that, compared with the conventional dose, the loading dose of rosuvastatin was more beneficial to patients with ACS in China and is suitable for clinical application. Due to the limitations of the quality and quantity of included articles, this conclusion still needs to be confirmed by multicenter clinical trials.

Project description:INTRODUCTION:Atorvastatin-80mg/day and Rosuvastatin-40mg/day are the commonest high-dose statin (3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitors) regimes for post-PCI (Percutaneous Coronary Interventions) patients to lower (by ?50%) blood low-density-lipoprotein cholesterol (LDL-C). Dearth of conclusive evidence from developing world, regarding overall safety, tolerability and comparative effectiveness (outcome/safety/tolerability/endothelial inflammation control) of Rosuvastatin over Atorvastatin in high-dose, given its higher cost, called for an overall and comparative assessment among post-PCI patients in a tertiary cardiac-care hospital of Kolkata, India. METHODS:A record-based non-concurrent cohort study was conducted involving 942 post-PCI patients, aged 18-75 years, on high-dose statin for three months and followed up for ?one year. Those on Atorvastatin-80mg (n = 321) and Rosuvastatin-40mg (n = 621) were compared regarding outcome (death/non-fatal myocardial infarction: MI/repeated hospitalization/target-vessel revascularisation/control of LDL and high-sensitivity C-reactive protein: hsCRP), safety (transaminitis/myopathy/myalgia/myositis/rhabdomyolysis), tolerability (gastroesophageal reflux disease: GERD/gastritis) and inflammation control adjusting for socio-demographics, tobacco-use, medications and comorbidities using SAS-9.4. RESULTS:Groups varied minimally regarding distribution of age/gender/tobacco-use/medication/comorbidity/baseline (pre-PCI) LDL and hs-CRP level. During one-year post-PCI follow up, none died. One acute MI and two target vessel revascularizations occurred per group. Repeated hospitalization for angina/stroke was 2.18% in Atorvastatin group vs. 2.90% in Rosuvastatin group. At three-months follow up, GERD/Gastritis (2.18% vs 4.83%), uncontrolled hs-CRP (22.74% vs 31.08%) and overall non-tolerability (4.67% vs. 8.21%) were lower for Atorvastatin group. Multiple logistic regression did show that compared to Atorvastatin-80mg, Rosuvastatin-40mg regime had poorer control of hs-CRP (A3OR = 1.45,p = 0.0202), higher (A3OR = 2.07) adverse effects, poorer safety profile (A3OR = 1.23), higher GERD/Gastritis (A3OR = 1.50) and poorer overall tolerability (A3OR = 1.50). CONCLUSION:Post-PCI high dose statins were effective, safe and well-tolerated. High dose Rosuvastatin as compared to high dose Atorvastatin were similar in their clinical efficacy. Patients treated with Atrovastatin had significantly lower number of patients with hs-CRP (high-sensitivity C-reactive protein)/C-reactive protein (CRP) level beyond comparable safe limit and relatively better tolerated as opposed to Rosuvastatin-40mg.Thus given the lower price, Atorvastatin 80mg/day appeared to be more cost-effective. A head-to-head cost-effectiveness as well as efficacy trial may be the need of the hour.

Project description:ImportanceLoading doses of atorvastatin did not show reduction on clinical outcomes in the overall population of patients with acute coronary syndrome (ACS) enrolled in the Statins Evaluation in Coronary Procedures and Revascularization (SECURE-PCI) trial, but a potential benefit was identified in patients who subsequently underwent percutaneous coronary intervention (PCI).ObjectivesTo determine whether periprocedural loading doses of atorvastatin are associated with decreased 30-day major adverse cardiovascular events (MACE) in patients with ACS undergoing PCI according to type of ACS and timing of atorvastatin administration before PCI.Design, setting, and participantsSecondary analysis of a multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites that enrolled 4191 patients with ACS intended to be treated with PCI between April 18, 2012, and October 06, 2017.InterventionsPatients were randomized to 2 loading doses of 80 mg of atorvastatin or matching placebo before and 24 hours after a planned PCI. By protocol, all patients (regardless of treatment group) received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication.Main outcomes and measuresThe primary outcome was MACE through 30 days, composed by all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization. Cox regression models adjusting for key baseline characteristics were used to assess the association between atorvastatin and MACE in patients undergoing PCI.ResultsFrom the overall trial population, 2710 (64.7%) underwent PCI (650 women [24.0%]; mean [SD] age, 62 [11.3] years). Loading atorvastatin was associated with reduced MACE at 30 days by 28% in the PCI group (adjusted hazard ratio [HR], 0.72; 95% CI 0.54-0.97; P = .03). Loading dose of atorvastatin was administered less than 12 hours before PCI in 2548 patients (95.3%) (45.1% < 2 hours and 54.3% between 2 and 12 hours). There was no significant interaction between treatment effect and timing of study drug administration. The treatment effect of loading atorvastatin was more pronounced in patients with ST-segment elevation myocardial infarction than in patients with non-ST-segment elevation ACS (adjusted HR, 0.59; 95% CI, 0.38-0.92; P = .02; HR, 0.85; 95% CI, 0.58-1.27; P = .43, respectively).Conclusions and relevanceIn patients with ACS undergoing PCI, periprocedural loading doses of atorvastatin appeared to reduce the rate of MACE at 30 days, most clearly in patients with ST-segment elevation myocardial infarction. This beneficial effect seemed to be preserved and consistent, irrespective of the timing of atorvastatin administration, including within 2 hours before PCI.Trial registrationclinicaltrials.gov Identifier: NCT01448642.

Project description:The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain.To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management.Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017.Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication.The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days.Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group.Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management.clinicaltrials.gov Identifier: NCT01448642.

Project description:Background:High platelet reactivity (HPR) and low platelet reactivity (LPR) are associated with an increased risk of ischemic/bleeding events in patients undergoing percutaneous coronary intervention (PCI). The role platelet miRNAs carry out in platelet reactivity regulation is largely unknown. Methods:In this study, we profiled the expression pattern of platelet miRNA in patients undergoing PCI with HPR (n=4) and LPR (n=4) by miRNA microarray screening. The candidate miRNAs were further validated in a larger sample of 17 LPR and 22 HPR patients by quantitative reverse-transcription polymerase chain reaction (RT-qPCR), and miR-15b was found differentially expressed. MiR-15b mimic and inhibitor were transfected into MEG-01 cells, then Bcl-2 protein expression and cell apoptosis were assessed. The relationship between platelet reactivity and platelet apoptosis was further evaluated. ABT-737, a Bcl-2 inhibitor was used to induce platelet apoptosis in PCI patients in vitro, and the influence of enhanced platelet apoptosis on platelet reactivity was explored. Results:Two miRNAs were found to be differentially expressed in patients with LPR and HPR using microarray system. Furthermore, the expression of miR-15b, a miRNA known to induce cell apoptosis via targeting of Bcl-2, was confirmed by RT-qPCR (P=0.020) to be 1.4× higher in the platelets of LPR patients than in those of HPR patients. Overexpression of miR-15b was demonstrated to suppress Bcl-2 protein expression and enhance cell apoptosis in a megakaryocyte cell line (MEG-01). The platelets of LPR patients expressed lower levels of Bcl-2 protein than those of HPR patients, and an inverse relationship between platelet reactivity and platelet apoptosis was observed among 44 patients who underwent PCI. Inducing platelet apoptosis in PCI patients in vitro, we observed that their platelet reactivity was decreased in a dose-dependent manner. Conclusions:Through the promotion of platelet apoptosis, platelet miR-15b negatively regulates platelet reactivity in patients undergoing PCI. Platelet apoptosis may represent a novel antiplatelet target for overcoming HPR in PCI treatment.

Dataset Information

Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study.

Publications

Platelet reactivity in response to loading dose of atorvastatin or rosuvastatin in patients with stable coronary disease before percutaneous coronary intervention: The STATIPLAT randomized study.

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