Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Special Subgroups in Hypertension: Obese Hypertensives

Source: Weber MA, et al. Lancet 2013; 381:537-545.

The inter-relatedness of obesity, hypertension, and cardiovascular (CV) events is complex. Obesity is independently associated with high blood pressure, all-cause mortality, and CV mortality. Yet, some reports have suggested that when parsing out CV events among a secondary prevention population (persons with existing CV disease), subjects with normal body weight bear a disproportionately greater risk than overweight and obese persons.

To further clarify this counterintuitive knowledge base, Weber et al report on an analysis of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension trial (ACCOMPLISH). ACCOMPLISH was performed to determine the relative efficacy of an angiotensin-converting enzyme (ACE) inhibitor + hydrochlorothiazide (HCTZ) vs ACE + amlodipine (CCB) in patients (n = 11,506) with Stage 2 hypertension (blood pressure > 160 mmHg). The trial ultimately demonstrated that ACE + CCB provided a significant mortality advantage over ACE + HCTZ.

In this report, ACCOMPLISH study subjects were divided into normal weight (body mass index [BMI] < 25), overweight (BMI 25-29), and obese categories (≥ BMI 30). CV events were most frequent in the normal weight group, and least frequent in the obese patients in the ACE + HCTZ arm of the trial. In the ACE + CCB arm, there were no differences between weight categories in outcomes.

The seemingly paradoxical relationship between overweight and outcomes in persons with established CV disease (myocardial infarction, cerebrovascular accident, or existing hypertension) is difficult to explain. It may be that obesity-related hypertension is mediated by a different, more benign pathophysiology, hence producing more favorable outcomes, although this concept has been insufficiently explored. Finally, because of relatively higher event rates with ACE + HCTZ in normal-weight patients, clinicians should select ACE + CCB since event reduction is equivalent across weight groups for this combination.


Selection Criteria for Lung Cancer Screening

Source: Tammemagi M, et al. N Engl J Med 2013;368:728-736.

The National Lung Screening Trial (NLST) reported in 2011 that low-dose CT screening in selected smokers (n = 53,454) reduced mortality from lung cancer by 20%. Entry criteria for the NLST included age 55-74 years with at least a 30 pack-years smoking history (former smokers, if they had quit within the last 15 years, were also enrolled). Subsequently, national organizations have variously endorsed lung cancer screening for persons matching NLST eligibility criteria.

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) developed a lung-cancer risk prediction model based on 154,901 subjects. The PLCO determined other predictors of lung cancer beyond age and smoking duration used in the NLST, including body mass index, family history of lung cancer, and presence of chronic obstructive pulmonary disease. Because the PLCO duration of follow-up was longer than NLST (9.2 years vs 6.5 years), the strength of the PLCO prediction model might be anticipated to be greater than NLST.

A comparison between the NLST and PLCO prediction models found that the PLCO criteria had greater sensitivity and specificity, ultimately missing 43% fewer lung cancers than NLST. The PLCO prediction model has the potential to improve outcomes for persons at risk of lung cancer.


Extended Treatment of VTE with Dabigatran vs Warfarin

Source: Schulman S, et al. N Engl J Med 2013;368:709-718.

Current recommendations for treatment of uncomplicated venous thromboembolism (VTE) in the absence of persistent risk factors for recurrence (e.g., protein C, protein S deficiency) suggest at least 3 months of antithrombotic therapy, typically with warfarin. Risk of recurrence, however, is not insubstantial, and recent clinical trials have shown that extending the duration of antithrombotic therapy after a course of warfarin (with aspirin, for instance) reduces the risk for recurrent VTE.

When warfarin is used for extended VTE recurrence prophylaxis, serious bleeding risk is about 1% annually. In comparison trials to warfarin, major bleeding rates on dabigatran have been generally comparable to warfarin, and intracerebral bleeding was demonstrably less with dabigatran than warfarin. Since dabigatran does not require monitoring, monthly physician visits, or dietary modulation, and has infrequent potential for drug interaction, it provides an attractive alternative.

Schulman et al report the results of two randomized, controlled, double-blind trials of dabigatran 150 mg twice daily vs warfarin or placebo in patients who had completed at least 3 months of warfarin treatment. Dabigatran was found to be noninferior to warfarin for prevention of recurrent VTE, with less frequent bleeding than warfarin (0.9% vs 1.8%). Dabigatran may be a viable alternative for extending DVT prophylaxis after a “traditional” course of warfarin.