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Aim The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) showed that tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to estimate the impact of tafamidis on survival and quality-adjusted life-years (QALYs). Methods and results A multi-state, cohort, Markov model was developed to simulate the disease course of ATTR-CM throughout a lifetime. For survival extrapolation, survival curves were fitted by treatment arm and New York Heart Association (NYHA) Class I/II (68% of patients) and NYHA Class III (32% of patients) cohorts using the individual patient-level data from both the ATTR-ACT and the corresponding long-term extension study. Univariate and multivariate sensitivity analyses were conducted. The predicted mean survival for the total population (NYHA Class I/II + III) was 6.73 years for tafamidis and 2.85 years for the standard of care (SoC), resulting in an incremental mean survival of 3.88 years [95% confidence interval (CI) 1.32–5.66]. Of the 6.73 life-years, patients on tafamidis spend, on average, 4.82 years in NYHA Class I/II, while patients on SoC spend an average of 1.60 life-years in these classes. The combination of longer survival in lower NYHA classes produced a QALY gain of 5.39 for tafamidis and 2.11 for SoC, resulting in 3.29 incremental QALYs (95% CI 1.21–4.74) in favour of tafamidis. Conclusion Based on the disease simulation model results, tafamidis is expected to more than double the life expectancy and QALYs of ATTR-CM patients compared to SoC. Longer-term follow-up data from the ATTR-ACT extension study will further inform these findings. Clinical trials.gov identifier NCT01994889 (date of registration: 26 November 2013).

Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) experience infiltrative cardiomyopathy and heart failure symptoms requiring costly hospitalizations. The Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT) demonstrated the efficacy of tafamidis on the frequency of cardiovascular (CV)-related hospitalizations in patients with ATTR-CM.As length of stay can affect the total hospitalization burden, our study aimed to better understand the impact of tafamidis on the number of CV-related hospital days avoided in the management of ATTR-CM patients.Data from ATTR-ACT were used to calculate the total burden of CV-related hospitalization (days) by treatment arm in this post hoc analysis.In the total trial population, patients receiving tafamidis had significantly fewer CV-related hospitalizations per year (relative risk reduction [RRR] 0.68; 0.4750 vs. 0.7025, p0.0001) and a shorter mean length of stay per CV-related hospitalization event (8.6250 vs. 9.5625 days) than patients receiving placebo. Taken together, tafamidis prevented 2.62 CV-related hospitalization days per patient per year. A subgroup analysis showed that with earlier treatment initiation of tafamidis, the annual number of CV-related hospitalizations was significantly lowered by 52% compared with placebo (RRR 0.48; 0.3378 vs. 0.7091, p0.0001). With 1.14 fewer days per hospitalization, tafamidis reduced the annual number of CV-related hospitalization days by 3.96 days per New York Heart Association class I/II patient.In patients with ATTR-CM, tafamidis was associated with a lower rate of CV-related hospitalizations and shorter length of hospital stay. Timely diagnosis and treatment with tafamidis could further decrease the total number of CV-related hospitalization days per year.NCT01994889.

Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is frequently misdiagnosed or diagnosed late in the disease course. ATTRwt-CM can be diagnosed invasively through tissue biopsy, but current diagnostic recommendations indicate technetium-99m pyrophosphate (

Aim: Delayed diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) represents a missed opportunity for intervention. This study estimates the health benefits of timely diagnosis and treatment with tafamidis. Methods: A disease simulation model was developed to predict health outcomes under scenarios of timely and delayed diagnosis and treatment. Efficacy and quality of life (QoL) profiles were derived from the pivotal tafamidis trial and diagnostic delay durations from the literature. Results: Timely diagnosis and treatment were predicted to extend mean life expectancy by 5.46 and 7.76 years, relative to delayed diagnosis, for wild-type and hereditary ATTR-CM, respectively. Corresponding QALY gains were 4.50 and 6.22. Conclusion: Timely diagnosis and treatment with tafamidis are predicted to significantly improve survival and QoL for ATTR-CM patients.

Hypertensive patients, such as those with established coronary artery disease (CAD) or those who have suffered a stroke, are at increased risk of morbidity and mortality. This systematic literature review and meta-analysis assesses the long-term effects of calcium channel blockers (CCBs) compared with other classes of antihypertensive medications on major cardiovascular (CV) outcomes in these high-risk subgroups of hypertensive patients. Randomized, active controlled parallel group trials were included if they compared CCBs with α-blockers, β-blockers, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, or diuretics, had a follow-up of ≥6 months, and had assessments of blood pressure (BP) and CV events [all-cause death, CV death, major CV events (myocardial infarction, MI; congestive heart failure, CHF; stroke; and CV death), MI, stroke, or CHF] in patients with baseline systolic/diastolic BP ≥140/≥90 mm Hg with either concomitant previous stroke and/or CAD. The final dataset included 19 publications reporting on 7 unique trials. In hypertensive patients with previous stroke, there was no difference between CCBs and comparators for any CV outcome. In those with CAD, there was no difference for all-cause death, CV death, major CV events, and MI for CCBs relative to comparators; however, a reduction in the risk of stroke and an increase in the risk of CHF were seen. For BP lowering, CCBs were at least as efficacious as comparators. The findings of our systematic review and analysis add to the body of evidence for the use of CCBs for the long-term treatment of hypertension in difficult-to-treat high CV risk populations.

The long-term cardiovascular (CV) effects of calcium channel blockers, with special focus on amlodipine, were compared with other classes of antihypertensive medications in high-risk hypertensive patient subgroups. A systematic literature review and meta-analysis was undertaken of 38 unique randomized, active-controlled, parallel-group trials comparing amlodipine/calcium channel blockers with diuretics, β-blockers, α-blockers, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers, with ≥6-month follow-up, and which had included assessment of blood pressure (BP) and CV events [all-cause death, CV death, myocardial infarction (MI), stroke, congestive heart failure (CHF), or major CV events (MACE: MI, CHF, stroke, and CV death)], in hypertensive patients (baseline systolic/diastolic BP ≥140/≥90 mm Hg) with either concomitant diabetes and/or renal dysfunction. In hypertensive patients with diabetes, no difference was found for amlodipine versus comparators with respect to all-cause death, CV death, MACE, and MI; a decrease in stroke risk, and an increase in CHF risk, was seen. In hypertensive patients with renal dysfunction, no difference was found for amlodipine versus comparators with respect to all-cause death, CV death, MACE, MI, and CHF; a decrease in stroke risk was seen. Amlodipine was found to be at least as efficacious as all the other classes of antihypertensive agents in reducing systolic and diastolic BP. Long-term control of BP is critical for avoiding complications of hypertension in high-risk patients, particularly CV and cerebrovascular events such as stroke. This analysis has provided evidence that amlodipine is an appealing therapeutic option in the long-term management of hypertension in both diabetic and renal dysfunction patients.

Introduction Migraine headache is a neurological disorder whose attacks are associated with nausea, vomiting, photophobia and phonophobia. Treatments for migraine aim to either prevent attacks before they have started or relieve attacks (abort) after onset of symptoms and range from complementary therapies to pharmacological interventions. A number of treatment-related adverse events such as somnolence, fatigue, and chest discomfort have previously been reported in association with triptans. The comparative tolerability of available agents for the abortive treatment of migraine attacks has not yet been systematically reviewed and quantified. Methods We performed a systematic literature review and Bayesian network meta-analysis for comparative tolerability of treatments for migraine. The literature search targeted all randomized controlled trials evaluating oral abortive treatments for acute migraine over a range of available doses in adults. The primary outcomes of interest were any adverse event, treatment-related adverse events, and serious adverse events. Secondary outcomes were fatigue, dizziness, chest discomfort, somnolence, nausea, and vomiting. Results Our search yielded 141 trials covering 15 distinct treatments. Of the triptans, sumatriptan, eletriptan, rizatriptan, zolmitriptan, and the combination treatment of sumatriptan and naproxen were associated with a statistically significant increase in odds of any adverse event or a treatment-related adverse event occurring compared with placebo. Of the non-triptans, only acetaminophen was associated with a statistically significant increase in odds of an adverse event occurring when compared with placebo. Overall, triptans were not associated with increased odds of serious adverse events occurring and the same was the case for non-triptans. For the secondary outcomes, with the exception of vomiting, all triptans except for almotriptan and frovatriptan were significantly associated with increased risk for all outcomes. Almotriptan was significantly associated with an increased risk of vomiting, whereas all other triptans yielded non-significant lower odds compared with placebo. Generally, the non-triptans were not associated with decreased tolerability for the secondary outcomes. Discussion In summary, triptans were associated with higher odds of any adverse event or a treatment-related adverse event occurring when compared to placebo and non-triptans. Non-significant results for non-triptans indicate that these treatments are comparable with one another and placebo regarding tolerability outcomes.

Small reductions in blood pressure reduce the risk of cardiovascular events. Here, we report 2 post hoc pooled analyses assessing the antihypertensive effect of amlodipine in patients who had not responded to 5 mg and were uptitrated to 10 mg. The first analysis assessed subgroups of patients aged either younger than 55 years or 55 years or older and the second analysis pooled all patients irrespective of age. Of 706 patients in the age-related analysis, a statistically significant decrease in blood pressure from baseline was observed {for younger than 55 years [N = 253]: systolic blood pressure = −12.8 [standard error (SE) = 0.90] mm Hg, diastolic blood pressure = −8.0 [SE = 0.55] mm Hg; for 55 years or older [N = 453]: systolic blood pressure = −12.1 [SE = 0.66] mm Hg, diastolic blood pressure = −6.7 [SE = 0.39] mm Hg; all P < 0.0001}. In total, 45.8% and 39.3% of patients aged younger than 55 and 55 years or older, respectively, achieved their blood pressure goals. Adverse events were experienced by 62 (24.5%) patients aged younger than 55 years and 136 (30.0%) patients aged 55 years or older. Similar efficacy and safety results were seen in the all patient pooled analysis. Titration of amlodipine from 5 mg to 10 mg significantly decreased blood pressure in older hypertensive patients, which is clinically relevant because increased age is associated with hypertension and cardiovascular events.

Objective To assess the efficacy and tolerability of eletriptan in treating migraine attacks occurring within the defined menstrual time period of 1 day before and 4 days after onset of menstruation (menses days –1 to +4) compared with attacks occurring during non-menstrual time periods (occurring outside of menses days –1 to +4). Background Migraine attacks during menses have been associated with longer duration, higher recurrence rates, greater treatment resistance, and greater functional disability than those not associated with menses. The efficacy of eletriptan in treating migraine attacks associated with menstruation vs those outside a defined menstrual period has not been evaluated. Methods Data were pooled from 5 similarly designed, double-blind, randomized, placebo-controlled trials of eletriptan 20 mg/40 mg/80 mg. Two groups were defined for this analysis: women with a single index migraine beginning during the menstrual (group 1) and non-menstrual (group 2) time periods. End points of interest were headache response at 2 hours, migraine recurrence and sustained responses for nausea, photo/phonophobia, and function. Logistic regression was used to compare group 1 vs group 2 and each eletriptan dose (20, 40, or 80 mg) vs placebo. Adverse events were also assessed. Results Of 3217 subjects pooled from 5 studies, 2216 women were either in group 1 (n = 630) or group 2 (n = 1586). Rates of headache response at 2 hours were similar in group 1 vs group 2 (odds ratio [OR] = 1.11 [95% confidence interval (CI) 0.91, 1.36]; P = .2944). The rate of headache recurrence was significantly higher in group 1 vs group 2 (26.8% vs 18.6%; OR = 1.67 [95% CI 1.23, 2.26]; P

Background The most commonly prescribed medications used to treat migraine acutely are single analgesics, ergots, opioids, and triptans. Due to varying mechanisms of action across drug classes, there is reason to believe that some classes may be less likely than others to elicit Medication Overuse Headache (MOH) than others. We therefore aimed to determine whether certain classes of acute migraine drugs are more likely to elicit MOH than others. Methods A comprehensive systematic literature was conducted to identify studies of varying designs that reported on MOH within the considered treatment classes. Only studies that reported MOH according to the International Classification of Headache Disorders (ICHD) were considered. Since no causal comparative design studies were identified; data from prevalence studies and surveys were retrieved. Prevalence-based relative risks between treatment classes were calculated by integrating both medication overuse and medication use from published studies. For each pair wise comparison, pooled relative risks were calculated as the inverse variance weighted average. Results A total of 29 studies informed the relative risk between treatment classes, all of which reported country-specific data. Five studies reported country-specific medication use data. For triptans versus analgesics the study relative risks generally favored triptans. The pooled relative risk was 0.65 (i.e., relative risk reduction of 35 %). For ergots versus analgesics, a similar trend was observed in favor of ergots with a relative risk of 0.41. For triptans versus ergots, the direction of effect was mixed, and the pooled relative risk was 1.07. Both triptans and ergots appeared favorable when compared to opioids, with pooled relative risks of 0.35 and 0.76, respectively. However, the evidence was limited for these comparisons. Analgesics and opioids also appeared to yield similar risk of MOH (pooled relative risk 1.09). Conclusion Our study suggests that in patients receiving acute migraine treatment, analgesics and opioids are associated with a higher risk of developing MOH compared with other treatments. These findings provide incentive for better monitoring of use of analgesics and opioids for treating acute migraine, and suggest possible clinical preference for use of so-called “migraine-specific” treatments, that is, triptans and ergots. Electronic supplementary material The online version of this article (doi:10.1186/s10194-016-0696-8) contains supplementary material, which is available to authorized users.