Benjamin Z. Galper

Extended duration dual antiplatelet therapy and mortality: a systematic review and meta-analysis

BACKGROUND Treatment with aspirin and a P2Y12 inhibitor is commonly used in patients with cardiovascular disorders. The overall effect of such treatment on all-cause mortality is unknown. In the Dual Antiplatelet Therapy (DAPT) Study, continuation of dual antiplatelet therapy beyond 12 months after coronary stenting was associated with an unexpected increase in non-cardiovascular death. In view of the potential public health importance of these findings, we aimed to assess the effect of extended duration dual antiplatelet therapy on mortality by doing a meta-analysis of all randomised, controlled trials of treatment duration in various cardiovascular disorders. METHODS We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomised controlled trials assessing the effect of extended duration versus no or short duration dual antiplatelet therapy, published before Oct 1, 2014. We did a meta-analysis to pool results with a hierarchical Bayesian random-effects model. The primary outcomes were hazard ratios comparing rates of all-cause, cardiovascular, and non-cardiovascular death. FINDINGS Including the DAPT Study, we identified 14 eligible trials that randomly assigned 69,644 participants to different durations of dual antiplatelet therapy. Compared with aspirin alone or short duration dual antiplatelet therapy (≤6 months), continued treatment was not associated with a difference in all-cause mortality (hazard ratio [HR] 1·05, 95% credible interval [CrI] 0·96-1·19; p=0·33). Similarly, cardiovascular (1·01, 0·93-1·12; p=0·81) and non-cardiovascular mortality (1·04, 0·90-1·26; p=0·66) were no different with extended duration versus short duration dual antiplatelet therapy or aspirin alone. INTERPRETATION Extended duration dual antiplatelet therapy was not associated with a difference in the risk of all-cause, cardiovascular, or non-cardiovascular death compared with aspirin alone or short duration dual antiplatelet therapy. FUNDING None.

Association of body mass index with mortality and cardiovascular events for patients with coronary artery disease: a systematic review and meta-analysis

Objectives The association between obesity and prognosis in patients with coronary artery disease (CAD) remains uncertain. We undertook a meta-analysis for the effects of body mass index (BMI) on mortality and cardiovascular events in these patients. Methods We identified studies that provided risk estimates for mortality or cardiovascular events on the basis of BMI in patients with CAD. Summary estimates of relative risks were obtained for five BMI groups: underweight, normal-weight, overweight, obese and grade II/III obese. Mortality was analysed separately as short-term (<6 months) and long-term (≥6 months). Results Data from 89 studies with 1 300 794 patients were included. Mean follow-up of long-term estimates was 3.2 years. Using normal-weight as the reference, underweight was associated with higher risk of short-term mortality (2.24 (1.85 to 2.72)) and long-term mortality (1.70 (1.56 to 1.86)), overweight and obesity were both associated with lower risk of short-term mortality (0.69 (0.64 to 0.75); 0.68 (0.61 to 0.75)) and long-term mortality (0.78 (0.74 to 0.82); 0.79 (0.73 to 0.85)), but the long-term benefit of obesity disappeared after 5 years of follow-up (0.99 (0.91 to 1.08)). Grade II/III obesity was associated with lower risk of mortality in the short term (0.76 (0.62 to 0.91)) but higher risk after 5 years of follow-up (1.25 (1.14 to 1.38)). The similar J-shaped pattern was also seen for cardiovascular mortality and across different treatment strategies. Meta-regression found an attenuation of the inverse association between BMI and risk of mortality over longer follow-up. Conclusions Our data support a J-shaped relationship between mortality and BMI in patients with CAD. The limitation of current literature warrants better design of future studies.

Balancing the risks of bleeding and stent thrombosis: A decision analytic model to compare durations of dual antiplatelet therapy after drug-eluting stents

BACKGROUND After coronary stent placement, whether dual antiplatelet therapy (DAPT) duration should be extended to prevent late stent thrombosis (ST) or adverse cardiovascular events is uncertain. METHODS To define the reduction in ischemic events required to outweigh increased bleeding with longer-duration DAPT, we developed a decision-analytic Markov model comparing DAPT durations of 6, 12, and 30 months after DES. Separate models were developed for patients presenting with and without an acute coronary syndrome (ACS). We used sensitivity analyses to identify the incremental benefit of longer-duration DAPT on either ST or the composite of cardiac death, myocardial infarction, and ischemic stroke (major adverse cardiovascular and cerebrovascular events [MACCEs]) required to outweigh the increased risk of bleeding associated with longer DAPT. The outcome from each strategy was quantified in terms of quality-adjusted life years. RESULTS In the non-ACS population, in order for 30 months of DAPT to be preferred over 12 months of therapy, DAPT would have to result in a 78% reduction in the risk of ST (relative risk [RR] 0.22, 3.1 fewer events per 1000) and only a 5% reduction in MACCE (RR 0.95, 2.2 fewer events per 1000) as compared with aspirin alone. For the ACS population, DAPT would have to result in a 44% reduction in the risk of ST (RR 0.56, 3.4 fewer events per 1000) but only a 2% reduction in MACCE (RR 0.98, 2.3 fewer events per 1000) as compared with aspirin alone, for 30 months of DAPT to be preferred for 12 months. CONCLUSIONS Small absolute differences in the risk of ischemic events with longer DAPT would be sufficient to outweigh the known bleeding risks.

Strategies for Primary Prevention of Coronary Heart Disease Based on Risk Stratification by the ACC/AHA Lipid Guidelines, ATP III Guidelines, Coronary Calcium Scoring, and C-Reactive Protein, and a Global Treat-All Strategy: A Comparative--Effectiveness Modeling Study

Background Several approaches have been proposed for risk-stratification and primary prevention of coronary heart disease (CHD), but their comparative and cost-effectiveness is unknown. Methods We constructed a state-transition microsimulation model to compare multiple approaches to the primary prevention of CHD in a simulated cohort of men aged 45–75 and women 55–75. Risk-stratification strategies included the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the treatment of blood cholesterol, the Adult Treatment Panel (ATP) III guidelines, and approaches based on coronary artery calcium (CAC) scoring and C-reactive protein (CRP). Additionally we assessed a treat-all strategy in which all individuals were prescribed either moderate-dose or high-dose statins and all males received low-dose aspirin. Outcome measures included CHD events, costs, medication-related side effects, radiation-attributable cancers, and quality-adjusted-life-years (QALYs) over a 30-year timeframe. Results Treat-all with high-dose statins dominated all other strategies for both men and women, gaining 15.7 million QALYs, preventing 7.3 million myocardial infarctions, and saving over

Cost‐Effectiveness of Supervised Exercise, Stenting, and Optimal Medical Care for Claudication: Results From the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) Trial

238 billion, compared to the status quo, far outweighing its associated adverse events including bleeding, hepatitis, myopathy, and new-onset diabetes. ACC/AHA guidelines were more cost-effective than ATP III guidelines for both men and women despite placing 8.7 million more people on statins. For women at low CHD risk, treat-all with high-dose statins was more likely to cause a statin-related adverse event than to prevent a CHD event. Conclusions Despite leading to a greater proportion of the population placed on statin therapy, the ACC/AHA guidelines are more cost-effective than ATP III. Even so, at generic prices, treating all men and women with statins and all men with low-dose aspirin appears to be more cost-effective than all risk-stratification approaches for the primary prevention of CHD. Especially for low-CHD risk women, decisions on the appropriate primary prevention strategy should be based on shared decision making between patients and healthcare providers.

Comparison of adverse event and device problem rates for transcatheter aortic valve replacement and Mitraclip procedures as reported by the Transcatheter Valve Therapy Registry and the Food and Drug Administration postmarket surveillance data

Background Both supervised exercise (SE) and stenting (ST) improve functional status, symptoms, and quality of life compared with optimal medical care (OMC) in patients with claudication. The relative cost‐effectiveness of these strategies is not well defined. Methods and Results The Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) study randomized patients with claudication due to aortoiliac stenosis to a 6‐month SE program, to ST, or to OMC. Participants who completed 6‐month follow‐up (n=98) were included in a health economic analysis through 18 months. Costs were assessed using resource‐based methods and hospital billing data. Quality‐adjusted life‐years were estimated using the EQ‐5D. Markov modeling based on the in‐trial results was used to explore the impact of assumptions about the longer term durability of observed differences in quality of life. Through 18 months, mean healthcare costs were

Late Stent Thrombosis : Can it Be Prevented?∗

5178,

IMPLEMENTATION OF A POST-TRANSCATHETER VALVE REPLACEMENT (TAVR) FAST-TRACK CARE PROTOCOL WITH A FOCUS ON NEXT-DAY DISCHARGE

9804, and

IMPLEMENTATION OF THE FIRST REPORTED ROUTINE ONE-DAY TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR) PATIENT EVALUATION

14 590 per patient for OMC, SE, and ST, respectively. Measured quality‐adjusted life‐years through 18 months were 1.04, 1.16, and 1.20. In our base case analysis, which assumed that observed differences in quality of life would dissipate after 5 years, the incremental cost‐effectiveness ratios were

A COST-EFFECTIVE ANALYSIS OF SHORT DURATION DUAL ANTI-PLATELET THERAPY (DAPT) WITH A BIOABSORBABLE POLYMER STENT PLATFORM VERSUS LONGER DURATION DAPT WITH A DURABLE POLYMER DRUG-ELUTING STENT IN A PATIENT POPULATION UNDERGOING ELECTIVE PERCUTANEOUS CORONARY INTERVENTION

24 070 per quality‐adjusted life‐year gained for SE versus OMC,