Background: Women are more likely than men to develop resistant hypertension, which is associated with excess risk of major adverse outcomes; however, the impact of resistant hypertension in women with ischemia has not been explicitly studied. In this Women's Ischemia Syndrome Evaluation ( WISE ) analysis, we assessed long‐term adverse outcomes associated with apparent treatment‐resistant hypertension ( aTRH ) among women with suspected myocardial ischemia referred for coronary angiography. Methods and Results: Women (n=927) were grouped according to baseline blood pressure ( BP ): normotensive (no hypertension history, BP <140/90 mm Hg, no antihypertensive drugs); controlled ( BP <140/90 mm Hg and a hypertension diagnosis or on 1 to 3 drugs); uncontrolled ( BP ≥140/90 mm Hg on ≤2 drugs); or aTRH ( BP ≥140/90 mm Hg on 3 drugs or anyone on ≥4 drugs). Adverse outcomes (first occurrence of death [any cause], nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure or angina) were collected over 10 years of follow‐up. Apparent treatment‐resistant hypertension prevalence was 10.4% among those with hypertension. Women with aTRH had a greater incidence of adverse outcomes, compared with normotensive women (adjusted hazard ratio [ HR], 3.25; 95% confidence interval [ CI], 1.94 to 5.43), and women with controlled ( HR, 1.77; 95% CI, 1.26 to 2.49) and uncontrolled ( HR, 1.62; 95% CI, 1.15 to 2.27) hypertension; outcome differences were evident early in follow‐up. Risk of all‐cause death was greater in the aTRH group, compared to the normotensive women and women with controlled and uncontrolled hypertension. Conclusions: In this cohort of women with evidence of ischemia, aTRH was associated with a profoundly increased long‐term risk of major adverse events, including death, that emerged early during follow‐up.

Little is known of US trends in antihypertensive drug use for patients with treatment-resistant hypertension (TRH). We analyzed antihypertensive use among patients with TRH (treated with ≥4 antihypertensive drugs concurrently) from July 2008 through December 2014 using Marketscan administrative data. We included adults aged 18 to 65 years, with ≥6 months of continuous enrollment, a hypertension diagnosis, and ≥1 episode of overlapping use of ≥4 antihypertensive drugs; patients with heart failure were excluded. We identified 411 652 unique TRH episodes from 261 652 patients with a mean age of 55.9 years. From 2008 to 2014, we observed an increased prevalence, among TRH episodes, of β-blockers (+6.8% [79% to 85.8%]) and dihydropyridine calcium antagonists (+8.1% [69.1% to 77.2%]), and a decreased prevalence of angiotensin-converting enzyme inhibitors (−12.5% [60.4% to 47.9%]) and nondihydropyridine calcium antagonists (−5.0% [15% to 10%]). The prevalence of most other classes changed by <5% from 2008 to 2014. Thiazide diuretic use was largely unchanged from 2008 to 2014, with hydrochlorothiazide being by far the most prevalent thiazide diuretic; chlorthalidone use increased only modestly (+2.6% [3.8% to 6.4%]). Aldosterone antagonist use increased only modestly (+2.9% [7.3% to 10.2%]). Use of optimal regimens increased steadily (+13.8% [50.8% to 64.6%]) during the study period, whereas combined angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use declined (−11.4% [17.7% to 6.3%]). Our results highlight the persistent infrequent use of recommended therapies in TRH, including spironolactone and chlorthalidone, and suggest a need for better efforts to increase the use of such approaches in light of recent evidence demonstrating their efficacy.

Fibromyalgia is a painful disease affecting 1-2% of the United States population. Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as duloxetine and milnacipran, are well studied and frequently used for treating this disorder. However, efficacy data are limited for the SNRI venlafaxine despite its use in nearly a quarter of patients with fibromyalgia. Accordingly, we systematically reviewed the efficacy of venlafaxine for treatment of fibromyalgia. PubMed, Web of Science and the Cochrane Database were searched using the terms 'venlafaxine' and 'fibromyalgia'. Results were classified as primary studies or review articles based on abstract review. References of review articles were evaluated to ensure no primary studies evaluating venlafaxine were overlooked. All clinical studies that investigated venlafaxine for the treatment of fibromyalgia were included and graded on strength of evidence. Five studies met the inclusion criteria, including 4 open-label cohort studies and 1 randomized, controlled trial. Study durations ranged from 6 weeks to 6 months, and study sizes ranged from 11 to 102 participants. Four of the five published studies reported improvement in at least one outcome. Generally consistent improvements were observed in pain-related outcome measures, including the Fibromyalgia Impact Questionnaire (range, 26-29% reduction; n = 2 studies), Visual Analog Scale (range, 36-45% reduction; n = 2 studies), McGill Pain Questionnaire (48% reduction; n = 1 study) and Clinical Global Impression scale (51% had significant score change; n = 1 study). However, the few studies identified were limited by small sample size, inconsistent use of outcomes and methodological concerns. Studies assessing the efficacy of venlafaxine in the treatment of fibromyalgia to date have been limited by small sample size, inconsistent venlafaxine dosing, lack of placebo control and lack of blinding. In the context of these limitations, venlafaxine appears to be at least modestly effective in treating fibromyalgia. Larger randomized controlled trials are needed to further elucidate the full benefit of venlafaxine.