Monday, July 15, 2019

Updates in CVD diagnosis, treatment, and prevention

- Jennifer Middleton, MD, MPH

Updates on diagnosis, treatment, and prevention of cardiovascular disease (CVD) abounded in the medical literature over the last month. While these studies' findings were largely non-significant or limited, they still provide clarity regarding current best practices while paving the way for future research.

First, the search for a clinical decision rule to stratify patients presenting to primary care with chest pain regarding risk of acute coronary syndrome (ACS) will have to continue, as the results of a "flash mob" study, published this month in the Annals of Family Medicine, failed to validate the Marburg Heart Score for use in primary care. The investigators recruited nearly 20% of the family physicians in the Netherlands to gather data on patients with suspected ACS during a 2 week time period. The family physicians sent information back to the investigators using a brief case report form, filed either electronically or on paper. Although the study results were disappointing, the feasibility of this novel research method was more promising. Perhaps we'll see more "flash mob" studies in the near future.

In an AFP Medicine By the Numbers summary out today, a Cochrane review of early reperfusion therapy in patients with STEMI received a "no benefits" rating by the The meta-analysis examined data from 8 randomized controlled trials including a total of over 8900 participants, all with chest pain at rest and either EKG changes consistent with STEMI (ST-segment myocardial infarction), NSTEMI (non-ST-segment myocardial infarction), or a previously established diagnosis of coronary artery disease. Participants were randomized to either receive reperfusion immediately or to receive medical therapy first with reperfusion only if symptoms persisted. There was no mortality benefit to early reperfusion, and participants who underwent early reperfusion were also more likely to have a periprocedural myocardial infarction (MI) or a major bleeding event. The risk of these adverse events was deemed to outweigh the found benefits of increased relief from refractory chest pain, decreased repeat hospitalization, and decreased risk of a susbsequent MI in the next year with early reperfusion.

Finally, an umbrella review (a systematic review of prior meta-analyses) sought to identify the best current evidence regarding diet changes and supplements on improving CVD outcomes. These investigators found moderate quality evidence to support reduced salt intake (lower all-cause mortality in individuals without hypertension, and lower cardiovascular mortality in individuals with hypertension). Lower quality evidence correlated omega-3-fatty-acid intake with lower risks for MI and CAD. Folic acid intake correlated with lower stroke risk, though the authors caution that this finding was largely driven by a study based in China, where fewer foods are fortified with folate than in the United States. Interestingly, calcium and vitamin D intake correlated with a higher stroke risk. "Other nutritional supplements, such as vitamin B6, vitamin A, multivitamins, antioxidants, and iron and dietary inter- ventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low– to moderate-certainty evidence)." Given the relative low quality of many studies, the authors' call for further, more rigorous research is understandable.

Studies finding a lack of benefit (the Marburg score "flash mob" and the early reperfusion meta-analysis) are still useful to help family physicians avoid harm and to spur the search for better alternatives. Hopefully, more rigorous research will come to verify the findings of the nutrition and supplement umbrella review. We'll look forward to reporting on these hoped-for follow-up studies; in the meantime, what research would you like see to regarding CVD in primary care?

Tuesday, July 9, 2019

Drugs for patients with chronic heart failure: making evidence-based choices

- Kenny Lin, MD, MPH

Two regular features in the July 1 issue of AFP addressed medication management for patients with chronic heart failure.

In Cochrane for Clinicians, Dr. Pamela Obi discussed a 2018 Cochrane review that evaluated whether therapies that improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF) also help patients with heart failure with preserved ejection fraction (HFpEF). The review included 37 randomized controlled trials (RCTs) with more than 18,000 patients; outcomes assessed included cardiovascular mortality, heart failure hospitalization, all-cause mortality, and quality of life. Beneficial drug classes included mineralocorticoid receptor antagonists (reduce hospitalizations, NNT=42) and beta blockers (reduce cardiovascular mortality, NNT=26). Curiously, although the review found no benefits from angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), the American College of Cardiology recommends considering ARB treatment to reduce hospitalizations in persons with HFpEF.

In FPIN's Help Desk Answers, Drs. Scott Christensen and Rebecca Davis investigated whether the combination of an ACE inhibitor and an ARB improves cardiovascular or overall mortality in patients with symptomatic HFrEF or HFpEF. A 2012 meta-analysis of 7 RCTs (n=8,260) comparing dual therapy vs. monotherapy found that dual therapy was associated with fewer myocardial infarctions and heart failure hospitalizations, but no changes in mortality. Dual therapy was also associated with a greater risk of patients withdrawing from trials due to adverse drug effects (RR=1.34). A small 2008 RCT found that patients with heart failure who received irbesartan in addition to an ACE inhibitor had improvements in disease-oriented outcomes (6-minute walk test distance, metabolic equivalents achieved) and quality of life, but no difference in a composite outcome of mortality and cardiovascular hospitalizations. Overall, the benefits of dual therapy seem to be outweighed by the harms.

Clinicians seeking additional information on diagnosis and management of acute and chronic heart failure should also check out our AFP By Topic collection.

Monday, July 1, 2019

Helping our patients reduce unhealthy alcohol use

- Jennifer Middleton, MD, MPH

The June 15 issue of AFP includes several excellent resources to aid family physicians in efficiently and effectively responding to unhealthy alcohol use. With an estimated 88,000 deaths every year in the United States related to alcohol, screening and intervening can be lifesaving and are recommended by the United States Preventive Services Task Force (USPSTF) (B recommendation).

This AFP USPSTF update article reviews the definition of unhealthy alcohol use:

The USPSTF uses the term unhealthy alcohol use to define a spectrum of behaviors, from risky drinking to alcohol use disorder (e.g., harmful alcohol use, abuse, dependence). Risky or hazardous alcohol use means drinking more than the recommended daily, weekly, or per-occasion amounts, resulting in increased risk for health consequences but not meeting criteria for alcohol use disorder.

The article discusses optimal screening instruments, all of which are very brief, such as the AUDIT-C and the SASQ. The perhaps better known CAGE is less useful because it can miss risky alcohol use that doesn't meet criteria for alcohol dependence disorder. A positive screen should prompt follow-up with a more in-depth instrument such as AUDIT. The meta-analysis that informed the USPSTF recommendation statement, however, noted that in "population groups with lower prevalence of unhealthy alcohol use—older adults, pregnant women, and adolescents—the estimated positive predictive value [of AUDIT] was much lower." For older adults, consider using CARET, and, for pregnant women, consider using TWEAK or T-ACE. Although the USPSTF deemed the evidence insufficient for making a recommendation regarding screening adolescents (I recommendation), CRAFFT is one tool available for family physicians wishing to screen this group.

The USPSTF found that a median of 30 minutes of brief intervention was effective in reducing unhealthy alcohol use. Screening, Brief Intervention, and Referral to Treatment [SBIRT] was commonly employed in these studies as was motivational interviewing, simple education regarding alcohol consumption recommendations, and several cognitive behavioral strategies. 6-12 months following these interventions, the previously mentioned meta-analysis found a mean decrease of 1.6 drinks per week; in binge drinkers (heavy episodic use), total drinks per week decreased from a mean of 26.0 to a mean of 19.1. Trials in pregnant women, which tended to use abstinence as an outcome, found pooled odds ratio [OR] for abstinence after intervention, compared to no intervention, of 2.26 (95% CI, 1.43 to 3.56)

After reading the AFP USPSTF update article, you can test your knowledge by reviewing these case studies and accompanying answers. The Substance Abuse and Mental Health Services Administration's (SAMHSA) SBIRT website includes a lengthy list of online resources covering different patient care settings with a variety of methods (articles, videos, patient education, and even a free online training course). The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has both in-depth and pocket guides titled "Helping Patients Who Drink Too Much" available online. This FPM article, referenced in an accompanying AFP editorial, reviews alcohol screening and brief intervention strategies, includes an excellent 4-minute video example of a brief intervention, and also reviews billing and coding for these services.

Monday, June 24, 2019

Guest Post: Transcend helplessness, advocate for transgender patients

- Hayley E. Cummingham, MD and Tonia Poteat, PA-C, PhD

Do you remember that feeling as a medical student, back against a wall as you watched life and death unfold? You may have felt disappointed when that sense of helplessness did not disappear with a medical degree. It is easy to feel helpless when your patients fear being “defined out of existence.” In October 2018, the New York Times uncovered a memo from the U.S. Department of Health and Human Services (HHS) that proposed redefining “sex” as written in numerous anti-discrimination laws to be “based on immutable biological traits identifiable by or before birth.” This represented a dramatic policy reversal from 2016, when HHS passed a regulation clarifying that discrimination on the basis of sex encompasses gender identity.

Emboldened by the current administration’s perceived animosity toward the transgender community, conservative state representatives and organizations sued the HHS in 2016, rendering it unable to enforce protections against gender identity discrimination as the executive branch reviewed the regulation. The outcome was a proposed rule issued last month, which includes a narrowed definition of “sex” that will allow health care providers and insurers to refuse to provide or cover medically necessary and potentially life-saving care.

According to a 2015 survey, 40% of transgender adults have attempted suicide and 82% have seriously considered it. Rates of suicidal ideation and attempts among transgender adolescents reach 51% and 30%, respectively. A growing body of evidence indicates that access to gender affirming therapies, including but not limited to exogenous hormones and surgery, can reduce the risk for suicide among transgender people.

It is easy to feel helpless in the face of injustice, but physicians have the power to influence social and political determinants of health. For example, having entered a 60-day period for public comment on the proposed HHS regulation, physicians and others can voice their opposition at Physicians can attend advocacy events wearing white coats, meet with elected representatives, or publish opinion pieces. Consider keeping a de-identified record of patient stories and reach out to an advocacy organization for guidance on using them to advocate for those patients. Physician educators, testing boards, and residency programs can train future physicians on the health care needs of gender-diverse individuals.

Within your own practice, ensure that you are not part of the problem, and empower yourself to provide gender-affirming care. One third of transgender persons have had at least one negative experience with a clinician in the past year related to being transgender, including verbal harassment (6%), treatment denial (8-11%), invasive or unnecessary questioning (15%), or clinician ignorance requiring education by the patient (24%). Reading the December 2018 AFP article, Caring for Transgender and Gender-Diverse People: What Clinicians Should Know, is an excellent place to start. In addition to the steps outlined in the article, you can offer to write “carry letters,” which explain that a patient is undergoing gender transition and that appropriate pronouns and facilities are medically necessary. These documents advocate for patients in situations involving bathrooms, airport security, police interactions, employers, residential placement, etc. You can dive deeper by familiarizing yourself with national and global guidelines and utilize online resources offered by the Fenway Institute. Before making referrals, contact providers to assess their level of comfort caring for transgender patients or use a gender-affirming provider directory.

Every day that we care for patients, we put ourselves at risk for feeling helpless. When our patients face increasing social and political injustice, we cannot be wallflowers. For the well-being of our patients and ourselves, we must advocate.

Friday, June 14, 2019

Behind the scenes of the AAFP guideline on depression after acute coronary syndrome

- Kenny Lin, MD, MPH

The June 15 issue of AFP features the original publication of an updated guideline from the American Academy of Family Physicians (AAFP) on screening and treatment of patients with depression following acute coronary syndrome. This is the first product of a new partnership between the best-read journal in primary care and the AAFP's Clinical Practice Guidelines development team. As a past Chair (2015-2017) of the AAFP's Subcommittee on Clinical Practice Guidelines (SCPG) of its Commission on Health of the Public and Science (CHPS), I know how much time and effort goes into creating evidence-based guidelines for family physicians. A series of four short videos on the AAFP website provides a general overview of the clinical practice guideline development and assessment process, which is documented in detail in its Clinical Practice Guideline Manual.

For this specific topic, a panel of 4 family physicians, an internist, a patient representative, and a PhD clinical policies strategist with no relevant conflicts of interest updated a 2009 AAFP guideline on detection and management of post-myocardial infarction depression. This topic was deemed still relevant to family medicine and nominated by the AAFP in 2016 to the Agency for Healthcare Research and Quality (AHRQ)'s Effective Health Care Program for an updated systematic evidence report. The independent systematic review team solicited input from subject experts and panel members to develop a structured research protocol that focused on answering two key questions:

1. What is the accuracy of depression screening instruments or screening strategies compared to a validated criterion standard for post-acute coronary syndrome (ACS) patients?

2. What are the comparative safety and effectiveness of pharmacologic and nonpharmacologic depression treatments in post-ACS patients?

The completed evidence report, posted on AHRQ's website and published in condensed form in the Annals of Internal Medicine in November 2017, served as the basis for the panel's recommendations. The panel rated the evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, which differs somewhat from AFP's Strength of Recommendation Taxonomy. GRADE provides a framework to assess the certainty of the evidence and develop structured statements based on that evidence and the values/considerations that influenced the recommendation.

The draft post-ACS depression guideline was internally peer reviewed by members of the SCPG and the AAFP's Science Advisory Panel, followed by external reviews by cardiology experts, mental health professionals, and representatives of other relevant organizations. After changes were made in response to peer review comments, the revised guideline was reviewed by the full SCPG and CHPS, then forwarded to the AAFP's Board of Directors for approval. The guideline makes two major recommendations:

1. The American Academy of Family Physicians recommends that clinicians screen for depression, using a standardized depression screening tool, in patients who have recently experienced an acute coronary syndrome event (weak recommendation, low-quality evidence). Individuals should undergo further assessment to confirm the diagnosis of depression (good practice point).

2. The American Academy of Family Physicians strongly recommends that clinicians prescribe antidepressant medication, preferably selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors, and/or cognitive behavior therapy to improve symptoms of depression in patients who have a history of acute coronary syndrome and have been diagnosed with depression (strong recommendation, moderate-quality evidence).

Notably, although treating depression after ACS improves depression symptoms, there remains insufficient evidence that depression treatments reduce cardiovascular or overall mortality. A Practice Guidelines synopsis in the June 15 issue also discusses barriers to implementing the guideline in practice such as lack of time, reimbursement, and institutional support for routine depression screening; and limited access to behavioral health services. Implementation resources available in the guideline itself include Tables comparing depression screening tools and medications and advice about use of practice champions.

Saturday, June 8, 2019

Has aspirin for primary prevention of CVD reached its expiration date?

- Kenny Lin, MD, MPH

A daily low-dose (81 mg) aspirin was once considered an essential component of cardiovascular disease (CVD) prevention for middle-aged and older adults. In 2006, the National Commission on Prevention Priorities ranked "discussing aspirin use in high-risk adults" the highest priority preventive service based on clinically preventable burden and cost effectiveness, and two years ago, in an updated set of rankings, it still rated aspirin use as the fifth highest priority for improving utilization. However, in 2018 the results of three large randomized trials suggested that the harms of aspirin taken to prevent a first CVD event outweigh its benefits for most persons. In an editorial in the June 1 issue of AFP, Dr. Jennifer Middleton and I reviewed the latest evidence and concluded:

The new data do not exclude the possibility that aspirin may still benefit adults at very high CVD risk (e.g., 20% or more over 10 years) or those at lower risk who are unable to tolerate statins, but the data otherwise suggest that the risks of low-dose aspirin therapy for primary prevention outweigh any potential benefits. For most patients, we should be deprescribing aspirin for primary prevention of CVD. To prevent heart attacks and strokes, family physicians should focus instead on smoking cessation and lifestyle changes, controlling high blood pressure, and prescribing statins when indicated.

In a 2019 clinical practice guideline, the American College of Cardiology / American Heart Association largely concurred, recommending against prescribing aspirin for primary prevention of CVD in adults older than age 70 and downgrading its role in other adults at high risk to "may be considered" on a case-by-case basis.

Although aspirin is still strongly recommended to prevent recurrent CVD events, its rise and fall in primary prevention seems to have become another case of medicine reversing itself. Unlike other notable examples of medical reversal such as menopausal hormone therapy and tight glucose control in type 2 diabetes, the effectiveness of aspirin was supported by many well-conducted randomized, controlled trials. Aspirin worked ... until it didn't. In a recent commentary in the Journal of General Internal Medicine, Palmer Greene and colleagues suggested that it may be a good idea to consider established evidence-based practices as having an "expiration date":

An “evidentiary statute of limitations” would require the occasional reassessment of accepted therapies to consider which might no longer be of use—possibly because of changes in the population as a whole, a changing understanding of whom the treatment is appropriate for, or evolving therapies for the prevention or treatment of the disease in question. Not only should we consider if older data still applies, we should also strive to anticipate the factors to which the results of a newly published positive study might be sensitive. For instance, is there an event rate in the control group below which the harms of the therapy might outweigh the benefit? Is there a treatment success rate that, when achieved, would make screening inefficient?

Not starting aspirin is relatively straightforward, but patients who have taken aspirin for many years without adverse effects or CVD events may resist discontinuing it. What approaches have you taken to this complex discussion?