401 - Blood Pressure Targets, COVID Antibody Testing, Clinician Grief
Take 3 – Practical Practice Pointers©
From the Literature
1) SPRINT-ing Toward a Different BP Target?
We have all likely heard of the SPRINT trial – the first results of which were published in 2015. This trial was reported a couple of years after the National Heart, Lung and Blood Institute’s JNC 8 guideline (from which we get the <150/90 target for age >= 60 years) was published. It has served as a primary reason the subsequent American College of Cardiology/American Heart Association guideline for hypertension has tried to set lower blood pressure targets. The SPRINT authors have recently published their final analysis of this study, incorporating data from a year-long post intervention observation period and correcting some data.
This is a large, well-conducted, valid trial. Out of practical necessity, it was an open-label study. The primary arguments about this study have always been the interpretation of the magnitude of the results (especially compared to the adverse events), and the applicability of the study results, not really about its validity.
SPRINT studied almost 9400 adults over age 50, with hypertension and one other cardiovascular disease risk factor (but not diabetes): h/o CVD, high ASCVD risk (>=15% over 10 years), chronic kidney disease, or age >= 75 years. The investigators randomized the subjects to a systolic blood pressure treatment target of below 120 mmHg (intensive group) or below 140 mmHg (usual care group). Medications were adjusted by a standard flowsheet to achieve the desired goals. The primary outcome was a composite outcome (MI, ACS, heart failure admission, or death) assessed by a blinded adjudication panel.
The trial was stopped after 3.3 years due to “evidence of clear benefit” in the treatment group. The intensive group rate of the outcome was 1.77%/year vs. 2.40%/year in the usual care group. This represents a number needed to treat of approximately 159/year or ~48 over the 3.3 years. All-cause mortality was reduced in the intensive group: 1.06%/year in the intensive group and 1.41%/year in the standard-treatment group for an NNT of approximately 285/year or ~87 over the 3.3 years. There were also significant differences in the rates of adverse events. Subjects in the intensive group had greater rates of specific serious adverse events (hypotension, syncope, electrolyte abnormalities and acute kidney injury) than in the usual care group, although the overall rate of serious adverse events was similar between groups. Of note, to be documented as having had a “serious adverse event,” the subject must have been seen in the emergency room or admitted to the hospital for the event. The intensive group reached a mean BP of 120.0 mmHg and the usual care group achieved a mean of 133.9. mmHg. Including the data from the post-intervention observation period (for a total of 3.8 years of observation) did not change the results significantly.
For this narrowly defined group of patients, intensive BP control can result in fewer HTN-related events at the cost of some serious adverse events. I don’t think this proves that “lower is better” for all categories of patients with hypertension, but suggests that for those with the highest risk, we should try to carefully optimize their blood pressure.
By the way, how did they standardize the measurements of blood pressure in this major trial? By using an electronic device and a standard measurement protocol. If it’s good enough for the trials that our blood pressure treatment guidelines are based on, it’s good enough for our routine clinical use.
- Final Report of a Trial of Intensive versus Standard Blood-Pressure Control. New England Journal of Medicine. 2021 May 20;384(20):1921–30. Link
From the US Food and Drug Administration (FDA)
2) COVID Antibody Testing After COVID Vaccination
The FDA recently released a safety communication regarding the presently authorized SARS-CoV-2 antibody tests, all of which have been approved under the emergency use authorization (EUA) and have not yet gone through the full approval process. Specifically, the FDA indicated these tests should not be used to evaluate a person’s level of immunity or protection from COVID-19 at any time, and especially after the person received a COVID-19 vaccination.
While a positive antibody test result can be used to help identify people who may have had a prior SARS-CoV-2 infection, more research is needed in people who have received a COVID-19 vaccination. Currently authorized SARS-CoV-2 antibody tests have not been evaluated to assess the level of protection provided by an immune response to COVID-19 vaccination. This includes the results of qualitative, semi-quantitative, or quantitative SARS-CoV-2 antibody tests.
The FDA further indicated that SARS-CoV-2 antibody tests should be ordered only by health care providers who are familiar with the use and limitations of these tests in general as well as any specific test. Present EUA-approved tests detect either the spike or nucleocapsid proteins (a few do both – see 3rd reference).
There is an important distinction being made here between “evidence of immunity” (presence of antibody) and protection from infection. While the first is often used as a surrogate for the second, it is not clear at what quantitative level of antibody such protection exists and also recognizes that no test is 100% sensitive and specific. Such are the nuances of virology, immunity, and biostatistics. At the same time, there is a growing body of literature that suggests that immunity elicited by infection for SARS-CoV-2 appears to be long-lived, with recent studies out to 1 year showing ongoing and active memory B-cell response.
It is interesting to note that starting last June, the American Red Cross began testing donated blood for the presence of COVID antibodies. Their data indicate that 1.5% of donations tested in the first week of July were positive. That increased to nearly 4% of donations tested in the first week of October, about 12% of donations tested in the first week of January and nearly 21% of donations tested in the first week of March (all samples in unvaccinated individuals). Indeed, in January an unvaccinated (at that time) member of my family had a positive antibody test after giving blood, which means that they (and by extrapolation, I) likely experienced a sub-clinical or mild infection at some point along this pandemic journey. There is so much about this virus yet to learn.
- FDA Safety Communication. May 19, 2021. Antibody Testing Is Not Currently Recommended to Assess Immunity After COVID-19 Vaccination: Link
- CDC Interim Guidance for COVID-19 Antibody Testing. Updated 17 March 2021.
- FDA COVID-19 EUA Authorized Serology Test Performance. Content current as of 5/25/21. Link
Reprise From the 4th Aim – Caring for Those Who Provide the Care
3) Why Clinicians Grieve Differently
How do you grieve? Western society doesn’t talk much about grief, and even less within the medical community. The author of this piece has spent time studying grieving and “doctoring” and has made the following observations. For those readers who are non-physician clinicians, please replace “physician” with your own profession. There are close similarities for those of us who work in healthcare.
1. Most physicians know death more intimately than the general population:
Some of us encounter death quite regularly. While some patients’ deaths tug a little more strongly at the heartstrings, we become skilled at maintaining “professional distance.” Even as we convey genuine care and connection, we are expected to readily disengage from that experience and start fresh with the next patient. The more we do it, the better we become at it. The professional veneer is possibly an impediment to leaning into the experience of grief, as our usual relationship with death is geared to be disengaged from any emotional buy-in.
2. Physicians develop a keen understanding of the limitations of modern medicine and the fickleness of life: We know that not everything can be explained or understood. We know that sometimes bad stuff just happens with there being no good reason. It is unclear if this depth of knowledge helps or hinders the grieving process for physicians, but it often allows for greater peace/acceptance.
3. Physicians are often high achieving, driven, and controlling: While these are generalizations, they are often true. Indeed, we are selected out because of these abilities, as they help us achieve medical school admission and success. This adds a complexity to grief when it so clearly reflects an event mostly out of our control.
4. Physicians spend most of our time observing: We might seem present in the moment but often in a disassociated way rather than fully engaged. We are constantly weighing options and possibilities, causing us often to be “there but not there.” This is not generally a useful skill in personal grief. Grief is a reflection of the depth of our love for that which is lost. Unless we have loved in a dispassionate, dissociated way, we do not give our grief a fair chance if we do not live it.
5. Acute grief is painful, distressing, heart-wrenching: Having lived it and survived the early intense days, we will actively do our best to avoid revisiting the intensity of those feelings. For many, the idea of trying to recount details of such events is too painful to contemplate.
6. Physicians are masters of hiding our emotions, which is a useful skill in some consultations: We see patients at their most vulnerable, transparent, and “human.” Some things shared are sad, humorous, bizarre, embarrassing, shocking, or even horrific. Keeping a straight face is an important skill to help engender trust and create a “safe space” for such reality. This serves us well in the moment but can also mute our emotions when we try to access them in situations of grief.
Whether we recognize it or not, we have all suffered losses since the onset of the pandemic. For some, that has included the literal loss of loved ones and knowing people who have experienced (or experiencing ourselves) the morbidity associated with the disease. We’ve also lost physical connection, in-person relationships, and any sense of normalcy. Perhaps the greatest irony of the pandemic is that not only has it caused a great collective grief, it has largely denied our collective grieving, at least in person.
While there is no one “right way” to grieve, that we grieve is vital. Finding a constructive way to do so is essential for our emotional and spiritual health. Sharing our stories with each other and connecting with someone else who has walked the path is one way to avoid isolation of emotion and the often-negative consequences of this. For those of you who have not explored joining the PeerRxMed movement as part of that process, I would encourage you to recruit a buddy and join in (www.PeerRxMed.org ). Glad to discuss if you have questions.
Alison Edwards, MBBS. Why Physicians Grieve Differently (modified): Kevin MD: Link
Mark and John
Carilion Clinic Department of Family and Community Medicine
Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.