Association of Clopidogrel Treatment With Risk of Mortality and Cardiovascular Events Following Myocardial Infarction in Patients With and Without Diabetes

Andersson, Charlotte; Lyngbæk, Stig; Nguyen, Cu Dinh; Nielsen, Mette; Gislason, Gunnar; Køber, Lars; Torp‐Pedersen, Christian

doi:10.1001/2012.jama.10779

Cited by 51 publications

(24 citation statements)

References 30 publications

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“…We classified patients as having diabetes mellitus if they had claimed at least 1 prescription for glucose-lowering medications (A10) within the same time frame. 11,12 The Danish Register of Medicinal Product Statistics does not contain medication dosage but does include information on strengths and number of dispensed tablets and dispensing time interval. On the basis of these data, we calculated the mean daily dosages of loop diuretics (C03CA01) used at the time of surgery as a proxy for HF severity (up to 3 consecutive prescription claims were considered in a retrospective manner).…”

Section: Methodsmentioning

confidence: 99%

Association of β-Blocker Therapy With Risks of Adverse Cardiovascular Events and Deaths in Patients With Ischemic Heart Disease Undergoing Noncardiac Surgery

et al. 2014

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IMPORTANCE Clinical guidelines have been criticized for encouraging the use of β-blockers in noncardiac surgery despite weak evidence. Relevant clinical trials have been small and have not convincingly demonstrated an effect of β-blockers on hard end points (ie, perioperative myocardial infarction, ischemic stroke, cardiovascular death, and all-cause death).OBJECTIVE To assess the association of β-blocker treatment with major cardiovascular adverse events (MACE) and all-cause mortality in patients with ischemic heart disease undergoing noncardiac surgery. DESIGN, SETTING, PARTICIPANTS, AND EXPOSURE Individuals with ischemic heart disease with or without heart failure (HF) and with and without a history of myocardial infarction undergoing noncardiac surgery between October 24, 2004, and December 31, 2009, were identified from nationwide Danish registries. Adjusted Cox regression models were used to calculate the 30-day risks of MACE (ischemic stroke, myocardial infarction, or cardiovascular death) and all-cause mortality associated with β-blocker therapy. MAIN OUTCOMES AND MEASURESThirty-day risk of MACE and all-cause mortality. RESULTSOf 28 263 patients with ischemic heart disease undergoing surgery, 7990 (28.3%) had HF and 20 273 (71.7%) did not. β-Blockers were used in 4262 (53.3%) with and 7419 (36.6%) without HF. Overall, use of β-blockers was associated with a hazard ratio (HR) of 0.90 (95% CI, 0.79-1.02) for MACE and 0.95 (0.85-1.06) for all-cause mortality. Among patients with HF, use of β-blockers was associated with a significantly lower risk of MACE (HR, 0.75; 95% CI, 0.70-0.87) and all-cause mortality (0.80; 0.70-0.92), whereas among patients without HF, there was no significant association of β-blocker use with MACE (1.11; 0.92-1.33) or mortality (1.15; 0.98-1.35) (P < .001 for interactions). Among patients without HF, β-blockers were also associated with a lowered risk among those with a recent myocardial infarction (<2 years), with HRs of 0.54 (95% CI, 0.37-0.78) for MACE and 0.80 (0.53-1.21) for all-cause mortality (P < .02 for interactions between β-blockers and time period after myocardial infarction), but with no significant association in the remaining patients. Results were similar in propensity score-matched analyses.CONCLUSIONS AND RELEVANCE Among patients with ischemic heart disease undergoing noncardiac surgery, use of β-blockers was associated with lower risk of 30-day MACE and mortality only among those with HF or recent myocardial infarction.

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Section: Methodsmentioning

confidence: 99%

Association of β-Blocker Therapy With Risks of Adverse Cardiovascular Events and Deaths in Patients With Ischemic Heart Disease Undergoing Noncardiac Surgery

et al. 2014

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“…In addition to ICD-10 codes, use of glucose-lowering agents was used as a proxy for diabetes mellitus and use of loop diuretics as a proxy for heart failure, as done previously (eTable 1 in the Supplement). 23,24 Diagnoses from the National Patient Register included in the Charlson comorbidity index have been validated, with positive predictive values of 96% to 100%. …”

Section: Definition Of Pharmacotherapy Comorbidity and Surgery Riskmentioning

confidence: 99%

β-Blocker–Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery

et al. 2015

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Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk.OBJECTIVE To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy in patients with uncomplicated hypertension undergoing noncardiac surgery. DESIGN, SETTING, AND PARTICIPANTSAssociation study based on in-hospital records and out-of-hospital pharmacotherapy use using a Danish nationwide cohort of patients with uncomplicated hypertension treated with at least 2 antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011.INTERVENTIONS Various antihypertensive treatment regimens, chosen as part of usual care. MAIN OUTCOMES AND MEASURESThirty-day risk of MACEs (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). RESULTSThe baseline characteristics of the 14 644 patients who received β-blockers (65% female, mean [SD] age, 66.1 [12.0] years) were similar to those of the 40 676 patients who received other antihypertensive drugs (57% female, mean [SD] age, 65.9 [11.8] years). Thirty-day MACEs occurred in 1.3% of patients treated with β-blockers compared with 0.8% of patients not treated with β-blockers (P < .001). β-Blocker use was associated with increased risks of MACEs in 2-drug combinations with RAS inhibitors (odds ratio [OR], 2.16 [95% CI, 1.54-3.04]), calcium antagonists (OR, 2.17 [95% CI, 1.48-3.17]), and thiazides (OR, 1.56 [95% CI, 1.10-2.22]), compared with the reference combination of RAS inhibitors and thiazides. Results were similar for all-cause mortality. Risk of MACEs associated with β-blocker use seemed especially pronounced for patients at least 70 years old (number needed to harm [NNH], 140 [95% CI,), for men (NNH, 142 [95% CI,), and for patients undergoing acute surgery (NNH, 97 [95% CI, 57-331]), compared with patients younger than 70 years, women, and patients undergoing elective surgery, respectively.CONCLUSIONS AND RELEVANCE Antihypertensive treatment with a β-blocker may be associated with increased risks of perioperative MACEs and all-cause mortality in patients with uncomplicated hypertension.

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“…Major bleeding associated with clopidogrel treatment is treated with multiple infusions of fresh platelets. Because the effects of clopidogrel may be somewhat reduced in patients with diabetes, these patients may benefi t from one of the more potent antiplatelet agents [ 63 ].…”

Section: Clopidogrelmentioning

confidence: 99%

Medical Treatment of Unstable Angina and Acute Non-ST-Elevation Myocardial Infarction

Willerson¹,

Armstrong

2015

Coronary Artery Disease

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Unstable angina, acute non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI) are a continuum following rupture or fi ssuring of a non-occlusive atherosclerotic plaque and the development of thrombosis and enhanced vasoconstriction at that site. If the period of coronary artery obstruction and enhanced vasoconstriction lasts for less than 20 min and is recurrent, as the thrombus forms and lyses and reforms again, one has unstable angina. If the period of coronary artery occlusion resulting from thrombosis and enhanced vasoconstriction at the site of coronary artery injury lasts for more than 20 min to approximately 2 h, or results in a subtotal coronary artery obstruction, the infarct is limited to the subendocardium and is an NSTEMI. If the period of coronary artery obstruction lasts for more than 2 h, the infarct progresses outward vertically and becomes a STEMI. Mediators of the enhanced vasoconstriction and thrombosis are largely platelet-derived and include thromboxane A 2, serotonin, adenosine diphosphate (ADP), platelet-activating factor, and thrombin and oxygen-derived free radicals. At sites of vascular injury, production of endothelium-derived antithrombotic substances and local vasodilators is attenuated, limiting the availability of nitric oxide, tissue plasminogen activator, and prostacyclin. Thus, an intensively prothrombotic-enhanced vasoconstrictor environment is created locally at sites of plaque fi ssuring and ulceration. Therefore, the medical treatment of unstable angina and NSTEMI rests in inhibiting thrombosis and vasoconstriction at the local vascular site, using nitrates (often intravenous nitroglycerin) and inhibitors of thromboxane, ADP, thrombin, and serotonin. Aspirin, clopidogrel or another ADP antagonist, a heparin, or a direct thrombin inhibitor, and occasionally an inhibitor of the platelet glycoprotein IIb/IIIa receptors are often used in the initial treatment of these patients. A statin should be administered to lower the low-density lipoprotein (LDL) concentration to values less than 100 mg/ml, unless otherwise contraindicated. Those with elevated risk factors, biomarkers of a poor prognosis, and those with continuing chest pain, congestive heart failure, and/or left ventricular dysfunction are generally referred for coronary arteriography and either percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery, depending on the coronary artery anatomy. Randomized trials have shown that the best treatment of these patients who are at higher risk is an aggressive one with PCI or CABG, whichever is most appropriate for the individual patient.

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Association of Clopidogrel Treatment With Risk of Mortality and Cardiovascular Events Following Myocardial Infarction in Patients With and Without Diabetes

Cited by 51 publications

References 30 publications

Association of β-Blocker Therapy With Risks of Adverse Cardiovascular Events and Deaths in Patients With Ischemic Heart Disease Undergoing Noncardiac Surgery

Association of β-Blocker Therapy With Risks of Adverse Cardiovascular Events and Deaths in Patients With Ischemic Heart Disease Undergoing Noncardiac Surgery

β-Blocker–Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery

Medical Treatment of Unstable Angina and Acute Non-ST-Elevation Myocardial Infarction

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