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Jonathan L Halperin

Publications and source records attributed to Jonathan L Halperin.

14 recordsLinked to original sources
PubMed2003

Lessons from the Stroke Prevention in Atrial Fibrillation trials.

Atrial fibrillation predisposes to left atrial thrombus formation and carries a sixfold increased risk for stroke. Antithrombotic therapies are the mainstay for stroke prevention. The National Institute of Neurological Disorders and Stroke-sponsored Stroke Prevention in Atrial Fibrillation (SPAF) studies assessed the value of warfarin, aspirin, and their combination for preventing stroke in six multicenter trials involving 3950 participants. This review presents the major results and implications, which offer unique perspectives on antithrombotic therapies for stroke prevention in atrial fibrillation. Warfarin and aspirin reduce stroke. Anticoagulation substantially benefits high-risk patients with atrial fibrillation, while many younger patients with atrial fibrillation have a low stroke rate when given aspirin. Pathogenetic and transesophageal echocardiographic correlations shed light on mechanisms by which antithrombotic agents prevent stroke. Warfarin inhibits formation of atrial appendage thrombi and markedly reduces cardioembolic strokes, while aspirin primarily prevents smaller, noncardioembolic strokes. The SPAF III stroke risk stratification scheme has been validated for identifying patients with high versus moderate versus low risk for stroke. Women with atrial fibrillation benefit from anticoagulation significantly more than men do. Many elderly patients with recurrent paroxysmal atrial fibrillation have high rates of stroke. Antithrombotic prophylaxis should be individualized on the basis of the estimated risk for stroke during aspirin therapy and the risk for bleeding during anticoagulation. Overall, nearly one third of patients with atrial fibrillation are low risk and should be treated with aspirin, and about one third are high risk and should receive warfarin if it can be given safely. For patients at moderate risk for stroke, patient preferences and access to reliable anticoagulation monitoring are particularly relevant.

Anticoagulants↗
PubMed2003

Active-control clinical trials to establish equivalence or noninferiority: methodological and statistical concepts linked to quality.

The randomized, double-blind, placebo-controlled trial is the optimum method for clinical evaluation of new treatments, as assessed by clinicians and statisticians. However, if a known standard of therapy exists, it may be difficult to prove that a new therapy is superior. Equivalence and noninferiority clinical trial designs are now frequently utilized in clinical medical research. This article reviews the statistical differences between superiority, equivalence, and noninferiority design schemes, which pose specific ethical questions and have important implications for interpretation and clinical application of trial results. A guideline is proposed as a standard approach for reporting to facilitate qualitative assessment of the methodology of these trials.

Bias↗
PubMed2003

Ximelagatran compared with warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation: Rationale, objectives, and design of a pair of clinical studies and baseline patient characteristics (SPORTIF III and V).

BACKGROUND: Ximelagatran is a novel, oral direct thrombin inhibitor under investigation as an alternative to warfarin for prevention of thromboembolism in patients with nonvalvular atrial fibrillation (AF). Two long-term studies in patients with AF and at least one additional risk factor for stroke are underway to compare the safety and efficacy of fixed-dose ximelagatran (36 mg bid) without coagulation monitoring with dose-adjusted warfarin (international normalized ratio 2.0-3.0). METHODS: SPORTIF III is a randomized, open-label, parallel-group study with blinded event assessment involving 3407 patients at 259 sites in 23 countries. SPORTIF V is similar, but with double-blind treatment allocation involving 3922 patients at 409 North American sites. The primary end point in each study is the incidence of all strokes and systemic embolic events, and the objective is to establish the noninferiority of ximelagatran relative to warfarin. Secondary end point constellations include (1) death, stroke, systemic embolism, and myocardial infarction; (2) ischemic stroke, transient ischemic attack, and systemic embolism; and (3) bleeding and treatment discontinuation. Blinded central committees adjudicate all end points and monitor patient safety. The studies commenced July 2000; enrollment ended in December 2001. Each study will accrue > or =4000 patient-years and > or =80 primary end points with a minimum per-patient exposure of 12 months. Combined analysis of both studies is also planned. RESULTS: The demographics of the 2 patient populations are similar and should allow the studies to meet the objective. CONCLUSIONS: The program, the largest conducted in this indication, will determine the safety and antithrombotic efficacy of ximelagatran as an alternative to warfarin for prevention of thromboembolism in patients with AF.

Administration, Oral↗
PubMed2002

Evaluation of patients with peripheral vascular disease.

Approximately 10% of people age >55 years have asymptomatic peripheral atherosclerotic disease (PAD), 5% have intermittent claudication (IC, the cardinal symptom), and 1% critical leg ischemia (rest pain or gangrene). In patients with IC, worsening occurs in approximately 16%, bypass surgery is required in approximately 7%, and amputation in approximately 4%. Disease progresses more frequently in diabetics and in tobacco smokers. Patients with PAD suffer increased cardiovascular morbidity related mainly to coronary artery disease with a mortality rate of approximately 30% after 5 years. Compared to patients without PAD, the relative risk of coronary death is approximately 6.6, overall cardiovascular mortality 5.9, and all-cause mortality 3.1. Pain at rest or ischemic gangrene indicates severe, often multilevel arterial occlusive disease and calls for aggressive management, which usually includes angiography and revascularization by percutaneous angioplasty or surgery. Critical limb ischemia results in some 150,000 amputations annually in the U.S., with perioperative mortality rates of 5-10% for below-knee and up to 50% for above-knee amputation because of comorbidities. Physical findings include trophic signs of ischemia, vascular bruits and peripheral pulse deficits. Ischemic ulcers usually involve the tips of the toes or the heel of the foot, and are typically painful on elevation and most bothersome at night. Ancillary diagnostic modalities begin with the ankle/arm systolic pressure index (ABI); a value <0.90 indicates PAD with significant prognostic implications. More precise assessment in the noninvasive vascular laboratory may involve a combination of segmental limb pressure measurements and pulse volume waveform recording, which is over 90% accurate for predicting the level and extent of PAD. Exercise testing enhances the value of these observations. Magnetic resonance imaging methods are emerging to characterize the arterial wall and atherosclerotic lesions. The diagnosis of PAD does not generally require invasive techniques, and most patients with IC do not need contrast angiography. Angiography is indicated for mapping of the extent and location of arterial pathology prior to revascularization.

Arteriosclerosis↗