CARDIOLOGY

What's new in cardiovascular medicine

ARRHYTHMIAS

Pacemaker insertion for asymptomatic Mobitz type I second degree AV block

The optimal management of asymptomatic patients with Mobitz type I second degree AV block is controversial, with European guidelines recommending for and American guidelines against pacemaker placement. Among a cohort of 299 mostly male patients (mean age 75) with Mobitz type I AV block followed for an average of 3.3 years, 59 percent remained asymptomatic, while 41 percent required a pacemaker for symptomatic bradycardia or progression to higher grade AV block [ 1 ]. Patients who received a pacemaker had a 46 percent reduction in total mortality compared to those patients who remained asymptomatic and did not receive a pacemaker. However, because this was a single center study of mostly elderly male patients with a high mortality rate, we feel these data are insufficient to recommend pacemaker placement for all patients with Mobitz type I second degree AV block. For the majority of patients with Mobitz type I AV block and asymptomatic bradycardia, we still favor not implanting a permanent pacemaker. Exceptions include patients with infranodal AV block and some elderly patients. (See "Second degree atrioventricular block: Mobitz type I (Wenckebach block)", section on 'Asymptomatic patients' .)

Azithromycin and torsades de pointes

In 2013, the US Food and Drug Administration issued a warning about the risk of QT interval prolongation and potentially fatal torsades de pointes among patients taking azithromycin [ 2 ]. Patients at particular risk include those with existing QT prolongation, hypokalemia, hypomagnesemia, significant bradycardia, and those receiving certain antiarrhythmic drugs [ 2-4 ]. The warning was based on a review following the publication of a study that showed an increased risk of death in patients receiving azithromycin [ 5 ]. Clinicians should assess the risk of torsades de pointes when considering antibiotic treatment options for patients at risk for cardiovascular events [ 2 ]. Other macrolides and certain non-macrolides, such as fluoroquinolones, also have the potential for prolonging the QT interval. (See "Azithromycin, clarithromycin, and telithromycin", section on 'Long QT syndrome' .)

Safety of competitive athletic participation in patients with LQTS

The long QT syndrome (LQTS), a genetic disorder whose phenotypic expression is a prolonged corrected QT interval on the electrocardiogram (ECG), has been associated with a significant risk for ventricular arrhythmias and sudden cardiac death (SCD). As of 2005, both European and American professional societies have recommended significant restrictions in activity in patients with LQTS to reduce the risk of ventricular arrhythmias and SCD. However, among 130 patients (out of a total cohort of 353 patients) with LQTS who remained active in competitive athletics and were followed for an average of 5.5 years, there were no cardiac events among 70 genotype positive/phenotype negative patients (ie, QT interval within the normal range) and only one arrhythmic event among 60 genotype positive/phenotype positive patients [ 6 ]. While our experts continue to recommend restricted athletic participation in accordance with the Bethesda Conference recommendations, these cohort data are reassuring that continued athletic participation in patients with genotype positive LQTS is relatively safe. (See "Risk of sudden cardiac death in athletes", section on 'Congenital long QT syndrome' .)

Oxycodone toxicity and QTc prolongation

Opioids are well known to cause depressed mental status and respirations. Additional toxicities may be specific to particular agents. Methadone has been associated with an increase in the QTc interval and torsade des pointes, leading to a safety alert in the U.S. 2006. A new retrospective review of 137 patients with oxycodone overdose found associated bradycardia in 24 patients and prolongation of the QTc interval in 20 of the 116 patients for whom electrocardiograms were available [ 7 ]. (See "Opioid intoxication in adults", section on 'Electrocardiography' .)

Efficacy of radiofrequency catheter ablation for atrial fibrillation

Radiofrequency catheter ablation (RFA) is used to prevent episodes of atrial fibrillation (AF) in patients who have failed antiarrhythmic drug therapy. The best available evidence on the rates of AF after RFA come from the DISCERN AF study, which evaluated episodes of symptomatic and asymptomatic AF before and after RFA in 50 patients using an implantable cardiac monitor [ 8 ]. The total atrial arrhythmia burden was significantly reduced by 86 percent from a mean of 2.0 hours per day per patient before to 0.3 hours per day after RFA. After 18 months and a mean of 1.4 ablations, only 58 percent of patients were symptom free. (See "Radiofrequency catheter ablation to prevent recurrent atrial fibrillation", section on 'AF recurrence after three months'.)

Apixaban for prevention of embolic events in atrial fibrilllation

Apixaban has been approved by the US Food and Drug Administration and the European Medicines Agency for use in patients with atrial fibrillation to reduce the risk of stroke and systemic embolization [ 9,10 ]. Approval was based on the results of the large randomized ARISTOTLE trial, which found that apixaban was non-inferior to warfarin in terms of efficacy and superior in terms of safety [ 11 ]. In patients with atrial fibrillation who meet criteria for anticoagulation, we prefer either a factor Xa inhibitor (apixaban or rivaroxaban) or a direct thrombin inhibitor (dabigatran) to warfarin. (See"Antithrombotic therapy to prevent embolization in atrial fibrillation", section on 'Apixaban' and "Antithrombotic therapy to prevent embolization in atrial fibrillation", section on 'Indications for and choice of therapy' .)

Bleeding rates with warfarin and dabigatran in atrial fibrillation

Despite favorable results in the initial randomized trials, post-marketing reports have raised concerns that patients with atrial fibrillation may have a higher rate of serious bleeding with dabigatran than warfarin. In November 2012, the US Food and Drug Administration issued a statement that a review of information from insurance claims and administrative data sources suggested that the rate of bleeding with dabigatran did not appear to be higher than with warfarin in patients who were using either drug for the first time [ 12 ]. (See "Antithrombotic therapy to prevent embolization in atrial fibrillation", section on 'Studies of anticoagulant monotherapy' .)

Radiofrequency catheter ablation as primary therapy for atrial fibrillation

For most patients with paroxysmal atrial fibrillation who wish to pursue a rhythm rather than a rate control strategy, radiofrequency catheter ablation (RFA) is performed after antiarrhythmic drug therapy has failed. The MANTRA-PAF trial evaluated the potential role of RFA as first-line therapy and found that it was as safe and as effective as antiarrhythmic drug therapy for the long-term maintenance of sinus rhythm [ 13 ]. In addition, patients had fewer symptomatic episodes. While promising, we believe that the evidence is not strong enough to warrant a recommendation to prefer RFA as primary therapy. (See "Radiofrequency catheter ablation to prevent recurrent atrial fibrillation", section on 'Comparison to antiarrhythmic therapy' .)

Optimal programming for primary prevention ICDs

The optimal strategy for implantable cardioverter-defibrillator (ICD) programming, until now, has been to deliver antitachycardia therapy (either pacing or shocks) with minimal delay for any sustained ventricular arrhythmia. In MADIT-RIT, 1500 patients receiving an ICD for primary prevention were randomly assigned to one of three different ICD programming and therapy strategies [ 14 ]: 

• "Conventional" therapy programming – 2.5 second delay at rates of 170 to 199 beats per minute; 1 second delay at rates of 200 or more beats per minute.
• Delayed therapy programming – 60 second delay at rates of 170 to 199 beats per minute; 12 second delay at rates of 200 to 249 beats per minute; 2.5 second delay at rates of 250 or more beats per minute.
• High-rate therapy programming – No therapy at rates of 170 to 199 beats per minutes; 2.5 second delay at rates of 200 or more beats per minute.

Both high-rate and delayed therapy programming led to significant reductions in the primary outcome of inappropriate ICD therapies; reduced mortality was also seen with both strategies but was statistically significant only with high-rate programming. In patients receiving an ICD for primary prevention, we recommend strategies that delay therapy or only institute therapy for very high heart rates, rather than a "conventional" ICD strategy that rapidly administers therapy with minimal delay. For the two alternative strategies investigated in MADIT-RIT, we suggest using the high-rate therapy programming strategy rather than the delayed therapy programming strategy. (See "General principles of the implantable cardioverter-defibrillator", section on 'Optimal ICD programming' .)

CORONARY ARTERY BYPASS GRAFT SURGERY

Off– compared to on-pump CABG

Older studies have suggested similar outcomes between off– and on-pump coronary artery bypass graft surgery (CABG). The large, randomized CORONARY and GOPCABE trials found no significant difference between the two techniques at 30 days and 1 year for a composite outcome including death, stroke, myocardial infarction, or new renal failure requiring dialysis [ 15,16 ]. However, there was a trend toward a higher rate of revascularization with off-pump CABG. We prefer the on-pump approach for most patients undergoing CABG. (See "Off-pump and minimally invasive direct coronary artery bypass graft surgery: Outcomes", section on 'Compared to on-pump CABG' .)

CORONARY HEART DISEASE, ACUTE

Time to first cardiac rehabilitation visit

Despite the benefits of cardiac rehabilitation programs for patients with coronary heart disease, including those who have had a myocardial infarction or have undergone revascularization, participation rates are low. A single-blind trial randomly assigned 148 patients to an appointment for cardiac rehabilitation orientation either within the initial 10 days or at 35 days of a nonsurgical qualifying CAD diagnosis [ 17 ]. The median time to orientation was 8.5 and 42 days and the attendance rate was significantly higher in the group that received appointments in the shorter time frame (77 versus 59 percent, respectively). We suggest that early appointments for cardiac rehabilitation be arranged for qualifying patients. (See "Components of cardiac rehabilitation and exercise prescription", section on 'Timing of first visit' .)

Blood transfusion thresholds for acute upper GI bleeding

The decision to initiate blood transfusions in patients with acute upper gastrointestinal bleeding is based on the rapidity of bleeding and the patients' comorbid conditions. A randomized trial of patients with and without cardiovascular disease suggests that in patients who are not at increased risk for complications from anemia, outcomes are improved if a lower hemoglobin threshold (<7 g/dL rather than <9 g/dL) is used for initiating blood transfusion [ 18 ]. Patients transfused when the hemoglobin was <7 g/dL had lower mortality rates, were less likely to have further bleeding, and were less likely to suffer complications.

We recommend giving blood transfusions to maintain the hemoglobin at ≥7 g/dL, rather than ≥9 g/dL, for the majority of patients with acute upper gastrointestinal bleeding who do not have significant comorbid illnesses. However, patients with active bleeding and hypovolemia may require blood transfusion despite an apparently normal hemoglobin. Additionally, we suggest transfusing to maintain the hemoglobin at ≥9 g/dL for patients at increased risk of adverse events in the setting of significant anemia, such as those with unstable coronary artery disease. (See "Approach to acute upper gastrointestinal bleeding in adults", section on 'Blood transfusions' and "Overview of the non-acute management of unstable angina and non-ST elevation myocardial infarction", section on 'Blood transfusion' .)

CORONARY HEART DISEASE, STABLE

Cardiotoxicity in women with breast cancer after radiation therapy

A case-control study of women treated for breast cancer with surgery and radiation therapy (RT) found that incidental radiation to the heart is associated with an increased risk for a significant coronary event (myocardial infarction, revascularization, or death from ischemic heart disease) [ 19 ]. The increased risk can be seen after relatively-low doses of radiation and the presence of cardiac risk factors markedly increased the impact of radiation. Despite this, the absolute risk associated with RT appears to be small and to be outweighed by the benefits in patients for whom radiation is typically recommended. (See "Cardiotoxicity of radiation therapy for malignancy", section on 'Effect of radiation dose to the heart' .)

Duration of beta blocker after myocardial infarction

Although beta blocker (BB) therapy reduces mortality in patients with recent myocardial infarction (MI), the optimal duration of beta blocker therapy after MI is unknown. Beta blocker therapy is continued indefinitely for many patients, based on studies performed in the 1980s and 1990s. A 2013 observational study evaluated outcomes in over 5000 patients with ST-elevation MI treated with primary percutaneous coronary intervention [ 20 ]. Adjusted mortality rates over approximately four years did not differ between patients who did or did not continue BB therapy. However, subgroup analyses revealed that BB treatment was associated with a significantly lower mortality for high-risk patients, such as those with heart failure. We believe the available evidence supports the use of beta blockers in patients with MI for as long as three years. We make a weak recommendation for BB beyond three years in patients with high-risk features such as cardiogenic shock, heart failure, or chronic kidney disease. (See "Beta blockers in the management of acute coronary syndrome", section on 'Duration of therapy' .)

New stable ischemic heart disease guidelines

A multisociety guideline for the diagnosis and management of patients with stable ischemic heart disease has been published and is referenced in multiple topics [ 21,22 ]. The guideline includes recommendations, with which we agree, that most patients with suspected stable ischemic heart disease undergo stress testing to confirm the diagnosis and to gain prognostic information and that beta blockers are first line therapy to reduce anginal episodes and improve exercise tolerance. (See "Overview of the care of patients with stable ischemic heart disease" .)

HEART FAILURE

Erythropoiesis stimulating agents in heart failure

The available evidence does not support the use of erythropoiesis stimulating agents to treat anemia in patients with heart failure. The best evidence on the lack of efficacy and risk of complications of such treatment in this population comes from the RED-HF trial which randomly assigned 2278 patients with systolic heart failure to treatment with either darbepoetin alfa or placebo [ 23 ]. Darbepoetin alfa and placebo-treated groups had similar rates of the primary outcome of death from any cause or hospitalization for worsening heart failure at median 28 months follow-up. Rates of thromboembolic adverse events were more frequent in the darbepoetin alfa-treated group (13.5 versus 10.0 percent). (See "Impact of anemia in patients with heart failure", section on 'Erythropoiesis stimulating agents' .)

Ultrafiltration in acute decompensated heart failure

The efficacy and safety of ultrafiltration in patients with acute decompensated heart failure has been evaluated in a few randomized trials. In CARRESS-HF, 188 patients with acute decompensated heart failure, worsened renal function, and persistent congestion were randomly assigned to stepped pharmacologic therapy or ultrafiltration [ 24 ]. Ultrafiltration was an effective method for fluid volume removal that provided similar amounts of weight loss to stepped pharmacologic therapy, but it was inferior to stepped pharmacologic therapy for preservation of renal function at 96 hours and was associated with a higher rate of adverse events. (See "Treatment of acute decompensated heart failure: Components of therapy", section on 'Ultrafiltration' .)

LIPID DISORDERS

CETP inhibition in patients at high risk for cardiovascular disease

Inhibition of cholesteryl ester transfer protein (CETP) function with torcetrapib, anacetrapib, evacetrapib, or dalcetrapib leads to a rise in HDL-cholesterol(C) levels as well as other favorable effects on lipids. However, such an effect on HDL-C has not yet been shown to lower the risk of cardiovascular disease events in individuals at increased risk. The dal-OUTCOMES trial, which randomly assigned acute coronary syndrome patients to dalcetrapib or placebo, was terminated early for futility as there was no significant difference in the two groups with regard to the primary composite end point of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation [ 25 ]. (See "HDL metabolism and approach to the patient with abnormal HDL-cholesterol levels", section on 'Dalcetrapib' .)

Monoclonal antibody to PCSK9 in patients with drug-resistant hypercholesterolemia

Proprotein convertase subtilisin kexin 9 (PCKS9) is a serine protease that leads to the degradation of low density lipoprotein (LDL) receptors and increased LDL-cholesterol levels. In four independent, new randomized trials, differing patient groups with hypercholesterolemia were randomly assigned to receive a human monoclonal antibody to PCSK9 (AMG 145) or placebo [ 26-29 ]. LDL-cholesterol levels were lowered by as much as 40 to 60 percent with AMG 145 compared to placebo, including in patients on maximal tolerated doses of statin therapy. Phase III trials with several years of follow-up are needed to evaluate the impact of treatment with AMG 145 on clinical outcomes and long-term safety. (See "Treatment of drug-resistant hypercholesterolemia", section on 'Monoclonal antibody to PCSK9' .)

MYOPERICARDIAL DISEASE

Pericardiectomy for recurrent pericarditis

Recurrent pericarditis, a recurrence or persistence of the symptoms of acute pericarditis thought to be autoimmune in nature, typically requires a prolonged course of medical therapy. While treatment with pericardiectomy is available for patients with refractory symptoms, the surgery is not universally successful and has been considered as high risk for morbidity and mortality. Among a cohort of 184 patients with chronic recurrent pericarditis (mean six to seven relapses) treated at a single referral center and followed for an average of 5.5 years, the 58 patients who underwent pericardiectomy fared well post-operatively (no immediate deaths, only two major complications) and had significantly fewer relapses (9 versus 29 percent in the medical treatment group) and similar survival as the 126 medically treated patients [ 30 ]. Pericardiectomy does appear to be a safe and frequently effective treatment option when performed by experienced surgeons in a high-volume center, and it should be considered in persons with ongoing symptoms of recurrent pericarditis in spite of medical therapy. (See "Recurrent pericarditis", section on 'Role of pericardiectomy' .)

PREVENTIVE CARDIOLOGY

Aspirin for the primary prevention of cardiovascular disease and cancer

Meta-analyses of randomized trials have shown aspirin to reduce the risk of non-fatal myocardial infarction [ 31 ], and long-term aspirin use reduces overall cancer risk [ 32 ]. While several published guidelines have considered the benefit of aspirin for the prevention of either cardiovascular disease (CVD) or cancer versus the risk of increased bleeding, most have not addressed the potential net benefit of aspirin in preventing both CVD and cancer. A meta-analysis addressing this combined outcome suggests that aspirin use in 1000 average risk patients at age 60 years would be expected to result, over a 10-year period, in six fewer deaths, 19 fewer non-fatal myocardial infarctions, 14 fewer cancers, and 16 more major bleeding events ( table 1). For individuals age 50 years or greater without excess bleeding risks, we suggest daily aspirin at a dose of 75 to 100 mg. Patients who are more concerned about the bleeding risks than the potential benefits may reasonably choose to not take aspirin for primary prevention. (See "Aspirin in the primary prevention of cardiovascular disease and cancer", section on 'Recommendations for primary prevention' .)

REVASCULARIZATION

Five year results of the SYNTAX trial

The SYNTAX trial, which randomly assigned 1800 patients with three-vessel or left main coronary artery disease to either coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention, found that the composite outcome at five years (rate of major adverse cardiac and cerebrovascular events) occurred less often with CABG, consistent with findings at three years [ 33,34 ]. This benefit was seen predominantly in patients with more complex disease as assessed by the SYNTAX score. (See "Bypass surgery versus percutaneous intervention in the management of stable angina pectoris: Clinical trials", section on 'SYNTAX trial' .)

Same-day discharge after uncomplicated PCI

We believe it is reasonable to discharge low-risk percutaneous coronary artery intervention (PCI) patients after four to eight hours of observation if no complications or concerns have arisen. In a 2013 meta-analysis of five randomized trials and eight observational studies, which compared same-day discharge to overnight hospitalization, there was no significant difference between the two approaches with regard to major adverse cardiovascular events or rehospitalization [ 35 ]. (See "General principles of the use of intracoronary stents", section on 'Timing of discharge' .)

PCI without on-site cardiac surgery

It appears reasonable to perform elective percutaneous coronary intervention (PCI) at hospitals without on-site cardiac surgical services when institutional and operator quality are high. The MASS COMM trial randomly assigned over 3600 patients with indications for nonemergency PCI, who presented at  hospitals without on-site cardiac surgery, to undergo PCI at that hospital or a hospital with cardiac surgery services [ 36 ]. PCI procedures performed at hospitals without on-site cardiac surgery were noninferior with regard to the primary outcome of major adverse cardiac events at 30 days and at 12 months. (See "Periprocedural complications of percutaneous coronary intervention", section on 'Absence of on-site cardiac surgery' .)

Platelet monitoring to adjust antiplatelet therapy at PCI

It is unknown whether testing of platelet function and adjustment of antiplatelet therapy as needed, before and after percutaneous coronary intervention (PCI) with stenting, improves clinical outcomes. The ARCTIC trial randomly assigned patients scheduled for coronary stenting and receiving dual antiplatelet therapy to a strategy of platelet-function monitoring (before and after PCI) or no monitoring [ 37 ]. Patients with high platelet reactivity were administered clopidogrel, prasugrel, or aspirin and glycoprotein IIb/IIIa inhibitors during the PCI. No significant difference in the rate of the primary composite end point (death, myocardial infarction, stent thrombosis, stroke, or urgent revascularization at one year) was found, supporting our recommendation to not routinely perform platelet-function testing in patients undergoing PCI. (See "Nonresponse and resistance to clopidogrel" .)

Selection of stent type in acute STEMI

Drug-eluting stents (DES) are used in preference to bare-metal stents (BMS) in many stable patients undergoing percutaneous coronary intervention (PCI) because they reduce the need for repeat target vessel revascularization without a significant increase in the cumulative rate of adverse outcomes. Similar findings have been found in studies of patients undergoing primary PCI for ST-elevation myocardial infarction (STEMI); most of these studies compared first generation DES to BMS.

The EXAMINATION and COMFORTABLE AMI trials randomly assigned STEMI patients to one of two second generation DES (an everolimus-eluting or a biolimus–eluting stent, respectively) or a BMS [ 38,39 ]. Both studies found a lower rate of the need for target vessel/lesion revascularization and suggested a lower rate of definite stent thrombosis with the DES. (See "Primary percutaneous coronary intervention in acute ST elevation myocardial infarction: Periprocedural management", section on 'Selection of stent type' .)

Bilateral internal thoracic artery grafting in patients with diabetes

While all patients with diabetes undergoing coronary artery bypass grafting should receive an internal thoracic (mammary) artery (ITA) graft to improve survival, it has been uncertain whether bilateral ITA grafting would add further benefit. Based on the results of two observational studies, which demonstrated significantly higher rates of long-term survival for bilateral ITA grafts compared with single grafts, we suggest that bilateral ITA grafting be performed in many patients with diabetes who require coronary revascularization, particularly those younger than age 70 to 75 years [ 40,41 ]. (See"Coronary artery revascularization in patients with diabetes mellitus and multivessel coronary artery disease", section on 'Internal thoracic artery grafts'.)

Stenting versus CABG in patients with diabetes and multivessel coronary artery disease

The evidence to guide the choice of revascularization between percutaneous intervention (PCI) with stenting and coronary artery bypass graft surgery (CABG) in patients with diabetes and multivessel coronary artery disease was limited prior to the publication of the FREEDOM trial [ 42 ]. In FREEDOM, 1900 such patients were randomly assigned to either PCI with drug-eluting stents or CABG. The primary composite outcome of death from any cause, nonfatal myocardial infarction, or nonfatal stroke occurred significantly more often in the PCI group at five years. We prefer CABG to PCI with stenting in most patients with diabetes and multivessel disease based on these findings as well as consistent results from older balloon angioplasty and bare metal stent trials. (See "Coronary artery revascularization in patients with diabetes mellitus and multivessel coronary artery disease", section on 'Stenting versus CABG in multivessel disease' .)

Drug-coated balloon angioplasty for restenosis following drug-eluting stent

The optimal treatment for restenosis following implantation of drug-eluting stents (DES) is uncertain. The efficacy of drug-eluting balloon angioplasty for patients with DES restenosis was evaluated in the ISAR-DESIRE 3 trial, which found no significant difference between treatment with a paclitaxel-eluting balloon and a paclitaxel-eluting stent in the rate of the primary end point of diameter stenosis at six- to eight-month angiographic follow-up [ 43 ]. Both of these interventions were superior to balloon angioplasty alone. (See "Intracoronary stent restenosis", section on 'Drug-coated balloon angioplasty' .)

VALVULAR HEART DISEASE

Early anticoagulation after implantation of a bioprosthetic aortic valve

The use of short-term vitamin K antagonist therapy early after bioprosthetic valve implantation in patients without thromboembolic risk factors is controversial. An observational study of data from the Danish National Patient Registry found an association between discontinuation of warfarin within six months after bioprosthetic aortic valve implantation and thromboembolic events and cardiovascular death [ 44 ]. However, a causal relationship was not established. Given the available evidence, the role of warfarin therapy during the first few months after bioprosthetic valve placement (in patients without other indications for anticoagulation) is uncertain. (See "Antithrombotic therapy in patients with prosthetic heart valves", section on 'Early anticoagulation after bioprosthetic valve replacement or mitral valve repair' .)

Avoid dabigatran with prosthetic heart valves

Based upon interim data from the European RE-ALIGN trial, a safety communication warning was issued in the United States by the Food and Drug Administration regarding increased rates of stroke, myocardial infarction, thrombosis, and major bleeding in patients with mechanical prosthetic heart valves who received anticoagulation with dabigatran compared to those receiving dose-adjusted warfarin [ 45-47 ]. We recommend against use of direct thrombin inhibitors such as dabigatran in patients with prosthetic heart valves. A vitamin K antagonist is the preferred anticoagulant in patients with prosthetic valves. (See "Antithrombotic therapy in patients with prosthetic heart valves", section on 'Oral direct thrombin inhibitors and factor Xa inhibitors' .)

OTHER CARDIOLOGY

Antiplatelet therapy in patients with CKD

The effectiveness and safety of antiplatelet therapy to prevent cardiovascular disease (CVD) in patients with chronic kidney disease (CKD) is not clear. In a meta-analysis of over 27,000 patients with CKD who participated in 50 randomized trials, antiplatelet therapy (mostly aspirin) reduced the incidence of fatal or non-fatal myocardial infarction as compared with either placebo or no therapy (6.7 versus 7.0 percent, or 3 myocardial infarctions prevented for every 1000 patients treated) but had no effect on stroke or overall mortality [ 48 ]. Antiplatelet therapy also increased the rate of major bleeding (4.4 versus 2.9 percent, or 15 additional major bleeding events for every 1000 patients treated). Based upon these data, we suggest that decisions about antiplatelet therapy in patients with CKD be individualized based upon the patient's overall risks for CVD and for bleeding. (See "Chronic kidney disease and coronary heart disease", section on 'Antiplatelet therapy' .)

Triple oral antithrombotic therapy for cardiovascular comorbidities

Some patients with cardiovascular disease, such as those with atrial fibrillation and recent coronary artery stent placement, meet indications for oral anticoagulant and dual antiplatelet therapy (eg clopidogrel plus aspirin). However, such "triple oral antithrombotic therapy" (TOAT) is associated with an increased risk of bleeding compared to less agressive therapy. The safety and effacy of clopidogrel alone, compared to clopidogrel plus aspirin, in patients taking long-term warfarin was evaluated in the WOEST trial of over 500 patients undergoing percutaneous coronary intervention [ 49 ]. After one year, the group assigned to clopidogrel without aspirin experienced lower risk of bleeding as well as the combined secondary end point of death, myocardial infarction, stoke, target-vessel revascularization, and stent thrombosis. While the approach of omitting aspirin from the antithrombotic regimen of patients who have indications for TOAT appears promising, we believe the evidence is not sufficiently strong to recommend such an approach at this time.