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Effect of loading dose of atorvastatin therapy prior to percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of six randomized controlled trials.

ABSTRACT: Purpose:The study sought to summarize the evidence of pre-procedural atorvastatin therapy to improve the prognosis of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Patients and methods:We searched PubMed and Embase from inception to July 2018 for randomized controlled trials that compared loading dose atorvastatin pretreatment with no or low dose for the prevention of cardiovascular events. The primary end points were all-cause mortality and myocardial infarction (MI) at 30 days. The secondary end point was 30-day major adverse cardiovascular events (MACE), a composite of all-cause mortality, MI, and revascularization. Results:Six trials with 4,991 individuals were included in our meta-analysis. High-dose atorvastatin preloading before PCI was associated with a 27% relative reduction in MI (OR: 0.73, 95% CI, 0.56-0.94, P=0.015). All-cause mortality was nonsignificantly reduced by early treatment with high-potency atorvastatin (OR: 0.94, 95% CI, 0.69-1.30, P=0.725). There was a 20% reduction in MACE in the group of patients treated with statin loading prior to PCI (OR: 0.80, 95% CI, 0.66-0.97, P=0.026). When stratified according to the diagnosis of ACS, the results of MACE were only significant for those ST-elevation myocardial infarction patients undergoing PCI (OR: 0.67, 95% CI, 0.48-0.94, P=0.022) and were not noted in the group of non-ST elevation ACS patients (OR: 0.65, 95% CI, 0.35-1.22, P=0.179). Conclusion:High-dose atorvastatin pretreatment leads to a significant reduction in MI and MACE at 30 days in ACS patients undergoing PCI, especially in ST-segment elevation MI.

SUBMITTER: Ma M

PROVIDER: S-EPMC6585398 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Effect of loading dose of atorvastatin therapy prior to percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of six randomized controlled trials.

Ma Mingfeng M Bu Lixia L Shi Li L Guo Renwei R Yang Bin B Cao Huili H Luo Liangping L Lu Ligong L

Drug design, development and therapy 20190416

<h4>Purpose</h4>The study sought to summarize the evidence of pre-procedural atorvastatin therapy to improve the prognosis of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).<h4>Patients and methods</h4>We searched PubMed and Embase from inception to July 2018 for randomized controlled trials that compared loading dose atorvastatin pretreatment with no or low dose for the prevention of cardiovascular events. The primary end points were all-cause mortali ...[more]

PMID: 31354240

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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: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:BackgroundThe acute effects of statin loading dose (LD) on platelet reactivity in patients with chronic stable angina (CSA) are not completely clear.HypothesisWe 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).MethodsFrom 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.Results682 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).ConclusionsLoading 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.

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.

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Effect of loading dose of atorvastatin therapy prior to percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of six randomized controlled trials.

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Effect of loading dose of atorvastatin therapy prior to percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of six randomized controlled trials.

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