Efficacy and Safety of a Polypill to Reduce Cardiovascular Events: A Review of Clinical Trials.

ABSTRACT: Cardiovascular disease continues to be the leading cause of mortality globally. Modifiable risk factors, such as hypertension and dyslipidemia, can be managed through lifestyle and pharmacotherapy treatments to reduce the risk of primary and secondary major cardiovascular events in patients with elevated risk. Despite effective and available medications to manage and mitigate cardiovascular risk factors, control rates of hypertension and dyslipidemia are suboptimal, and greater efforts are needed to reduce cardiovascular event rates worldwide. A polypill containing several classes of medications proven to lower cardiovascular risk in a single-dose form has been associated with improved medication adherence over multiple single-ingredient medications and may lead to reduced cardiovascular events. The goal of this article is to review available data from clinical trials assessing the efficacy and safety of polypills compared with placebo or usual care for cardiovascular risk reduction. Three databases were searched (PubMed/MEDLINE, CINAHL, and ScienceDirect) for randomized trials that compared a single polypill with usual care or placebo and reported major adverse cardiovascular events for each study group. A total of 6 trials were selected for inclusion. Several polypill formulations were compared with placebo or usual care with multiple single-ingredient medications in study populations consisting of both primary and secondary prevention patients. Overall, the polypill seems to be associated with reduced major adverse cardiovascular event and comparable safety with usual care treatment with an added benefit of improved adherence over multiple single-ingredient medications. The polypill has potential to be a cost-effective intervention to reduce the global burden of cardiovascular disease.

The Dearth of Disability Medical Education and a Partial Solution.

Issue: While over one-quarter of adult Americans have a disability, there is a paucity of disability-specific curricula in American medical schools and residency programs. Potential consequences of this educational dearth include persistent inaccessibility of health care facilities and delivery of inequitable health care to individuals with disabilities. Evidence: Several working groups have proposed disability-specific competencies for health professions education and means by which to integrate them into existing curricula. A limited number of medical schools and residency programs have formally introduced disability-specific materials into their curricula. To our knowledge, however, there are no generalist (internal medicine or family medicine) residency programs that offer specialized training in the clinical care of people with disabilities. Implications: Offering generalist physicians the opportunity to acquire the clinical and cognitive skills required to provide thorough and equitable health care to people with disabilities is critically important. There are too few physiatrists to see to their care needs. In this manuscript, we present a novel concentration in an Internal Medicine residency program in the care of individuals with a variety of disabilities. Our hope is that this work will initiate discussions among educational leaders about how to address the lack of graduate medical education-level training in disability care. We also hope it will afford program directors the opportunity to implement similar concentrations and tracks and will eventually produce a generation of generalists who are well-equipped to help care for people with disabilities.

Renovascular Hypertension.

Renovascular hypertension (RVH) is relatively common but underrecognized cause of resistant hypertension in clinical practice. Most patients with RVH have suboptimal control of hypertension in spite of being on multiple anti hypertensive medications. Prompt diagnosis and management is crucial to prevent long term morbidity and mortality. Initial evaluation by primary care physicians can expedite this to improve patient outcomes by co-managing hypertension specialists. In addition to pharmacologic and nonpharmacologic measures, some patients may benefit from angioplasty. This article discusses various definitions of hypertension, approach to diagnosis of RVH, and management. Data from clinical trials are discussed with evidence-based medicine practice recommendations.

Pocket-sized ultrasound as an aid to physical diagnosis for internal medicine residents: a randomized trial.

BACKGROUND: Proficiency and self-confidence in the physical examination is poor among internal medicine residents and interest in ultrasound technology has expanded. OBJECTIVE: We aimed to determine whether a pocket-sized ultrasound improves the diagnostic accuracy and confidence of residents after a 3-h training session and 1 month of independent practice. DESIGN: This was a randomized parallel group controlled trial. PARTICIPANTS: Forty internal medicine residents in a single program at an academic medical center participated in the study. INTERVENTION: Three hours of training on use of pocket-sized ultrasound was followed by 1 month of independent practice. MAIN MEASURES: The primary outcome was a comparison of the diagnostic accuracy of a physical exam alone versus a physical examination augmented with a pocket-sized ultrasound. Other outcomes included confidence in exam findings and a survey of attitudes towards the physical exam and the role of ultrasound. KEY RESULTS: Residents in the intervention group using a pocket-sized ultrasound correctly identified an average of 7.6 of the 17 abnormal findings (accuracy rate of 44.9 %). Those in the control group correctly identified an average of 6.4 abnormal findings (accuracy rate of 37.6 %, p = 0.11). Residents in the intervention group identified on average 15.9 findings as abnormal when no abnormality existed (false positive rate of 16.8 %). Those in the control group incorrectly identified an average of 15.5 positive findings (false positive rate of 16.3 %). There was no difference between groups regarding self-assessed confidence in physical examination. Residents in the intervention group identified 6.1 of 13 abnormal cardiac findings versus the control group's 4.5 of 13, an accuracy rate of 47.0 % versus 34.6 % (p = 0.023). CONCLUSIONS: The diagnostic ability of internal medicine residents did not significantly improve with use of a pocket-sized ultrasound device after a 3-h training session and 1 month of independent practice. TRIAL REGISTRATION: clinicaltrials.gov: number NCT01948076; URL http://clinicaltrials.gov/ct2/show/study/NCT01948076?term=ultrasound+physical+exam&rank=2.

A simple echocardiographic prediction rule for hemodynamics in pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) has diverse causes with heterogeneous physiology compelling distinct management. Differentiating patients with primarily elevated pulmonary vascular resistance (PVR) from those with PH predominantly because of elevated left-sided filling pressure is critical. METHODS AND RESULTS: We reviewed hemodynamics, echocardiography, and clinical data for 108 patients seen at a referral PH clinic with transthoracic echocardiogram and right heart catheterization within 1 year. We derived a simple echocardiographic prediction rule to allow hemodynamic differentiation of PH attributed to pulmonary vascular disease (PH(PVD), defined as pulmonary artery wedge pressure [PAWP]≤15 mm Hg and PVR>3 WU). Age averaged 61.3±14.8 years, µPAWP and PVR were 16.4±7.1 mm Hg and 6.3±4.0 WU, respectively, and 52 (48.1%) patients fulfilled PH(PVD) hemodynamic criteria. The derived prediction rule ranged from -2 to +2 with higher scores suggesting higher probability of PH(PVD): +1 point for left atrial anterior-posterior dimension <3.2 cm; +1 for presence of a mid systolic notch or acceleration time <80 ms; -1 for lateral mitral E:e'>10; -1 for left atrial anterior-posterior dimension >4.2 cm. PVR increased stepwise with score (for -2, 0, and +2, µPVR were 2.5, 4.5, and 8.1 WU, respectively), whereas the inverse was true for pulmonary artery wedge pressure (corresponding µPAWP were 21.5, 16.5, and 10.4 mm Hg). Among subjects with complete data, the score had an area under the curve (AUC) of 0.921 for PH(PVD). A score ≥0 had 100% sensitivity and 69.3% positive predictive value for PH(PVD), with 62.3% specificity. No patients with a negative score had PH(PVD). Patients with a negative score and acceleration time >100 ms had normal PVR (µPVR=1.8 WU, range=0.7-3.2 WU). CONCLUSIONS: We present a simple echocardiographic prediction rule that accurately defines PH hemodynamics, facilitates improved screening and focused clinical investigation for PH diagnosis and management.

Shape of the right ventricular Doppler envelope predicts hemodynamics and right heart function in pulmonary hypertension.

RATIONALE: Systolic deceleration or "notching" of the right ventricular outflow tract Doppler flow velocity envelope (FVE(RVOT)) relates to pathologic wave reflection in the setting of elevated pulmonary artery impedance. OBJECTIVES: We investigated whether simple visual assessment of FVE(RVOT) morphology aids in hemodynamic differentiation and detection of pulmonary vascular disease among a referral pulmonary hypertension (PH) cohort. METHODS: We reviewed hemodynamics, echocardiography, and clinical data for 88 patients referred for PH and 32 subjects with systolic heart failure and PH. The FVE(RVOT) was categorized as normal (no notch [NN]); late systolic notch (LSN); or midsystolic notch (MSN). MEASUREMENTS AND MAIN RESULTS: The pulmonary vascular resistance (PVR) was highest in the MSN group (9.2 ± 3.5 Wood's units [WU]; P < 0.001) versus the LSN (5.7 ± 3.1 WU) and NN (3.3 ± 2.4 WU) groups. The ratio of stroke volume to pulse pressure (compliance) also differed by FVE(RVOT) morphology (MSN = 1.2 ± 0.5; LSN = 1.7 ± 0.8; NN = 2.6 ± 1.7; P = 0.001 and 0.04, respectively, vs. NN). MSN was 96% specific and 71% sensitive for a PVR >5 WU (positive predictive value, 98%). The MSN group had severe right ventricular dysfunction (tricuspid annular plane systolic excursion 1.6 ± 0.5 cm) relative to the LSN and NN groups (tricuspid annular plane systolic excursion 1.9 ± 0.6 vs. 2.2 ± 0.6 cm; both P < 0.05). In the PH cohort, any FVE(RVOT) notching (MSN or LSN) was highly associated with PVR >3 WU (odds ratio, 22.3; 95% confidence interval, 5.2-96.4), whereas the NN pattern predicted a PVR less than or equal to 3WU and pulmonary artery wedge pressure greater than 15 mm Hg (odds ratio, 30.2; 95% confidence interval, 6.3-144.9). CONCLUSIONS: Visual inspection of the shape of the FVE(RVOT) provides insight into the hemodynamic basis of PH in a referral PH cohort. MSN is associated with the most severe pulmonary vascular disease and right heart dysfunction.