The Journal of Family Practice

This patient had the deep form of erythema annulare centrifugum (EAC). As the name implies, it manifests as an expanding, red circular pattern that often clears in the middle. There is usually a ring of scale that trails behind the advancing border. However, in the deep form, it may be more subtle than the pronounced scale of the superficial form. Pruritus is a very common symptom associated with this condition.

EAC is a hypersensitivity reaction, which can be in response to several stimuli including underlying malignancy, medications, fungal and dermatophyte infections, inflammatory conditions, and pregnancy. A careful history and physical exam can be helpful in determining if a work-up for malignancy is warranted.

Since many medications including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, and biologicals can cause this condition, a history of which medications were started within the previous several months may be helpful.

When EAC is due to an underlying malignancy, it is called paraneoplastic erythema annulare centrifugum. It can be secondary to solid tumors or lymphoproliferative disorders.

More than 50% percent of the cases are idiopathic, and no underlying condition is identified. The skin findings may last for weeks—and even years.

If an underlying cause is found, treatment is directed at that condition, and the skin findings usually improve with resolution of the instigating condition. If no specific cause is found, the itching can be managed with systemic antihistamines or topical steroids. Some case studies have reported success with the use of systemic antibiotics, including erythromycin. Improvement with antibiotics may be due to treatment of an occult underlying bacterial process or owing to the anti-inflammatory effects of many antibiotics.

Since the patient in this case had onychomycosis of his toenails, and fungal and dermatophyte infections are a common trigger, he was placed on a 12-week course of oral terbinafine 250 mg/d. The plan was to biopsy the rash if it didn’t resolve. At 3 weeks, the rash had resolved, and the patient was asymptomatic.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had the deep form of erythema annulare centrifugum (EAC). As the name implies, it manifests as an expanding, red circular pattern that often clears in the middle. There is usually a ring of scale that trails behind the advancing border. However, in the deep form, it may be more subtle than the pronounced scale of the superficial form. Pruritus is a very common symptom associated with this condition.

EAC is a hypersensitivity reaction, which can be in response to several stimuli including underlying malignancy, medications, fungal and dermatophyte infections, inflammatory conditions, and pregnancy. A careful history and physical exam can be helpful in determining if a work-up for malignancy is warranted.

Since many medications including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, and biologicals can cause this condition, a history of which medications were started within the previous several months may be helpful.

When EAC is due to an underlying malignancy, it is called paraneoplastic erythema annulare centrifugum. It can be secondary to solid tumors or lymphoproliferative disorders.

More than 50% percent of the cases are idiopathic, and no underlying condition is identified. The skin findings may last for weeks—and even years.

If an underlying cause is found, treatment is directed at that condition, and the skin findings usually improve with resolution of the instigating condition. If no specific cause is found, the itching can be managed with systemic antihistamines or topical steroids. Some case studies have reported success with the use of systemic antibiotics, including erythromycin. Improvement with antibiotics may be due to treatment of an occult underlying bacterial process or owing to the anti-inflammatory effects of many antibiotics.

Since the patient in this case had onychomycosis of his toenails, and fungal and dermatophyte infections are a common trigger, he was placed on a 12-week course of oral terbinafine 250 mg/d. The plan was to biopsy the rash if it didn’t resolve. At 3 weeks, the rash had resolved, and the patient was asymptomatic.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

This patient had the deep form of erythema annulare centrifugum (EAC). As the name implies, it manifests as an expanding, red circular pattern that often clears in the middle. There is usually a ring of scale that trails behind the advancing border. However, in the deep form, it may be more subtle than the pronounced scale of the superficial form. Pruritus is a very common symptom associated with this condition.

EAC is a hypersensitivity reaction, which can be in response to several stimuli including underlying malignancy, medications, fungal and dermatophyte infections, inflammatory conditions, and pregnancy. A careful history and physical exam can be helpful in determining if a work-up for malignancy is warranted.

Since many medications including nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, and biologicals can cause this condition, a history of which medications were started within the previous several months may be helpful.

When EAC is due to an underlying malignancy, it is called paraneoplastic erythema annulare centrifugum. It can be secondary to solid tumors or lymphoproliferative disorders.

More than 50% percent of the cases are idiopathic, and no underlying condition is identified. The skin findings may last for weeks—and even years.

If an underlying cause is found, treatment is directed at that condition, and the skin findings usually improve with resolution of the instigating condition. If no specific cause is found, the itching can be managed with systemic antihistamines or topical steroids. Some case studies have reported success with the use of systemic antibiotics, including erythromycin. Improvement with antibiotics may be due to treatment of an occult underlying bacterial process or owing to the anti-inflammatory effects of many antibiotics.

Since the patient in this case had onychomycosis of his toenails, and fungal and dermatophyte infections are a common trigger, he was placed on a 12-week course of oral terbinafine 250 mg/d. The plan was to biopsy the rash if it didn’t resolve. At 3 weeks, the rash had resolved, and the patient was asymptomatic.

‌

Photo and text courtesy of Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The patient’s history of a rash that worsened with sweating and clinical findings of erythematous papulosquamous lesions was consistent with Grover disease, also known as transient acantholytic dermatosis. Typically, this is a short-lived condition; however, when symptoms have manifested for years, it is deemed persistent acantholytic dermatosis. The gold standard for diagnostic confirmation is a skin biopsy, although it can also be diagnosed clinically. Since the patient had previously received this diagnosis from another clinician, and his clinical presentation was consistent, a confirmatory biopsy was not performed.

The specific pathophysiology of acantholytic dermatosis is unclear. A study to assess for an autoimmune component found that all participants had autoantibodies that are reactive to proteins involved in cell development, activation, growth, death, adhesion, and motility. Another hypothesis involves occlusion of eccrine sweat glands.

Typical triggers are sweating, heat, sunlight, and mechanical irritation, although it can also be triggered by end-stage renal disease and solid organ transplantation. It has also been linked to certain drugs (eg, ribavirin, anastrozole), other skin diseases (eg, atopic dermatitis, xerosis cutis), bacterial/viral infections, and malignancies.

As heat and perspiration are common triggers, avoidance of activities that expose patients to these conditions is recommended. Otherwise, topical corticosteroids and emollients are the recommended first-line therapy, along with antihistamines to control itching. Other therapies include systemic corticosteroids, topical vitamin D analogs (eg, calcipotriene), systemic retinoids (acitretin or isotretinoin), phototherapy and photochemotherapy (PUVA), red-light 5-aminolevulinic acid photodynamic therapy (ALA-PDT), and etanercept.

Although the patient could not remember the name of the previously prescribed medication, his description suggested that a systemic retinoid had already been tried, with no improvement. Treatment with emollients and oral antihistamines was also unsuccessful, as was topical antiperspirants to control perspiration on his affected skin. The patient agreed to try topical calcipotriene twice daily. He also agreed to switch to a topical emollient containing ceramides.

‌

Image courtesy of Esther Walker, MD, and text courtesy of Esther Walker, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The patient’s history of a rash that worsened with sweating and clinical findings of erythematous papulosquamous lesions was consistent with Grover disease, also known as transient acantholytic dermatosis. Typically, this is a short-lived condition; however, when symptoms have manifested for years, it is deemed persistent acantholytic dermatosis. The gold standard for diagnostic confirmation is a skin biopsy, although it can also be diagnosed clinically. Since the patient had previously received this diagnosis from another clinician, and his clinical presentation was consistent, a confirmatory biopsy was not performed.

The specific pathophysiology of acantholytic dermatosis is unclear. A study to assess for an autoimmune component found that all participants had autoantibodies that are reactive to proteins involved in cell development, activation, growth, death, adhesion, and motility. Another hypothesis involves occlusion of eccrine sweat glands.

Typical triggers are sweating, heat, sunlight, and mechanical irritation, although it can also be triggered by end-stage renal disease and solid organ transplantation. It has also been linked to certain drugs (eg, ribavirin, anastrozole), other skin diseases (eg, atopic dermatitis, xerosis cutis), bacterial/viral infections, and malignancies.

As heat and perspiration are common triggers, avoidance of activities that expose patients to these conditions is recommended. Otherwise, topical corticosteroids and emollients are the recommended first-line therapy, along with antihistamines to control itching. Other therapies include systemic corticosteroids, topical vitamin D analogs (eg, calcipotriene), systemic retinoids (acitretin or isotretinoin), phototherapy and photochemotherapy (PUVA), red-light 5-aminolevulinic acid photodynamic therapy (ALA-PDT), and etanercept.

Although the patient could not remember the name of the previously prescribed medication, his description suggested that a systemic retinoid had already been tried, with no improvement. Treatment with emollients and oral antihistamines was also unsuccessful, as was topical antiperspirants to control perspiration on his affected skin. The patient agreed to try topical calcipotriene twice daily. He also agreed to switch to a topical emollient containing ceramides.

‌

Image courtesy of Esther Walker, MD, and text courtesy of Esther Walker, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

The patient’s history of a rash that worsened with sweating and clinical findings of erythematous papulosquamous lesions was consistent with Grover disease, also known as transient acantholytic dermatosis. Typically, this is a short-lived condition; however, when symptoms have manifested for years, it is deemed persistent acantholytic dermatosis. The gold standard for diagnostic confirmation is a skin biopsy, although it can also be diagnosed clinically. Since the patient had previously received this diagnosis from another clinician, and his clinical presentation was consistent, a confirmatory biopsy was not performed.

The specific pathophysiology of acantholytic dermatosis is unclear. A study to assess for an autoimmune component found that all participants had autoantibodies that are reactive to proteins involved in cell development, activation, growth, death, adhesion, and motility. Another hypothesis involves occlusion of eccrine sweat glands.

Typical triggers are sweating, heat, sunlight, and mechanical irritation, although it can also be triggered by end-stage renal disease and solid organ transplantation. It has also been linked to certain drugs (eg, ribavirin, anastrozole), other skin diseases (eg, atopic dermatitis, xerosis cutis), bacterial/viral infections, and malignancies.

As heat and perspiration are common triggers, avoidance of activities that expose patients to these conditions is recommended. Otherwise, topical corticosteroids and emollients are the recommended first-line therapy, along with antihistamines to control itching. Other therapies include systemic corticosteroids, topical vitamin D analogs (eg, calcipotriene), systemic retinoids (acitretin or isotretinoin), phototherapy and photochemotherapy (PUVA), red-light 5-aminolevulinic acid photodynamic therapy (ALA-PDT), and etanercept.

Although the patient could not remember the name of the previously prescribed medication, his description suggested that a systemic retinoid had already been tried, with no improvement. Treatment with emollients and oral antihistamines was also unsuccessful, as was topical antiperspirants to control perspiration on his affected skin. The patient agreed to try topical calcipotriene twice daily. He also agreed to switch to a topical emollient containing ceramides.

‌

Image courtesy of Esther Walker, MD, and text courtesy of Esther Walker, MD, Department of Internal Medicine, and Daniel Stulberg, MD, FAAFP, Department of Family and Community Medicine, University of New Mexico School of Medicine, Albuquerque.

References 

1. US Preventive Services Task Force. Colorectal cancer: screening [draft recommendation statement]. https://uspreventiveservicestaskforce.org/uspstf/draft-recommendation/colorectal-cancer-screening3. Published October 27, 2020. Accessed November 23, 2020.

References 

1. US Preventive Services Task Force. Colorectal cancer: screening [draft recommendation statement]. https://uspreventiveservicestaskforce.org/uspstf/draft-recommendation/colorectal-cancer-screening3. Published October 27, 2020. Accessed November 23, 2020.

References 

1. US Preventive Services Task Force. Colorectal cancer: screening [draft recommendation statement]. https://uspreventiveservicestaskforce.org/uspstf/draft-recommendation/colorectal-cancer-screening3. Published October 27, 2020. Accessed November 23, 2020.

Close inspection of the plaques revealed multiple small pustules and mahogany colored macules on a broad, well-demarcated scaly red plaque. This pattern was consistent with palmoplantar pustular psoriasis.

Palmoplantar psoriasis is a chronic disease that may manifest at any age and in both sexes. The diagnosis may be clinical, as it was in this case. Bacterial culture of a pustule may demonstrate staphylococcus superinfection—a problem more likely to occur in smokers. More widespread disease, spiking fevers, or tachycardia could indicate a need for hospitalization for further work-up and management.

With disease localized to this patient’s hands and feet, the physician considered dyshidrotic eczema as part of the differential diagnosis. However dyshidrotic eczema, which presents with clear tapioca-like vesicles, is profoundly itchy; pustular psoriasis is often painful. Other differences: The vesicles in dyshidrotic eczema do not uniformly form pustules nor do they form brown macules upon healing, as occurs in palmoplantar pustular psoriasis.

Treatment for very limited disease includes topical ultrapotent steroids, topical retinoids, or phototherapy—either alone or in combination. However, more extensive disease, even if limited to hands and feet, merits systemic therapy with acitretin, methotrexate, or biologic agents. (Acitretin and methotrexate are reliable teratogens and should not be used in women who are, or may become, pregnant.) Individuals with known superinfection often benefit from antibiotic therapy, as well.

In this case, the patient had already undergone a tubal ligation for contraception. Therefore, she was started on acitretin 25 mg PO daily. Patients on systemic retinoids undergo laboratory surveillance for transaminitis and hypertriglyceridemia regularly. Adverse effects are generally well tolerated, but include photosensitivity and dry skin, lips, and eyes. The patient improved significantly on 25 mg/d and the dosage was reduced to 10 mg/d after 3 months. She currently remains clear on this regimen.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

Close inspection of the plaques revealed multiple small pustules and mahogany colored macules on a broad, well-demarcated scaly red plaque. This pattern was consistent with palmoplantar pustular psoriasis.

Palmoplantar psoriasis is a chronic disease that may manifest at any age and in both sexes. The diagnosis may be clinical, as it was in this case. Bacterial culture of a pustule may demonstrate staphylococcus superinfection—a problem more likely to occur in smokers. More widespread disease, spiking fevers, or tachycardia could indicate a need for hospitalization for further work-up and management.

With disease localized to this patient’s hands and feet, the physician considered dyshidrotic eczema as part of the differential diagnosis. However dyshidrotic eczema, which presents with clear tapioca-like vesicles, is profoundly itchy; pustular psoriasis is often painful. Other differences: The vesicles in dyshidrotic eczema do not uniformly form pustules nor do they form brown macules upon healing, as occurs in palmoplantar pustular psoriasis.

Treatment for very limited disease includes topical ultrapotent steroids, topical retinoids, or phototherapy—either alone or in combination. However, more extensive disease, even if limited to hands and feet, merits systemic therapy with acitretin, methotrexate, or biologic agents. (Acitretin and methotrexate are reliable teratogens and should not be used in women who are, or may become, pregnant.) Individuals with known superinfection often benefit from antibiotic therapy, as well.

In this case, the patient had already undergone a tubal ligation for contraception. Therefore, she was started on acitretin 25 mg PO daily. Patients on systemic retinoids undergo laboratory surveillance for transaminitis and hypertriglyceridemia regularly. Adverse effects are generally well tolerated, but include photosensitivity and dry skin, lips, and eyes. The patient improved significantly on 25 mg/d and the dosage was reduced to 10 mg/d after 3 months. She currently remains clear on this regimen.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

Close inspection of the plaques revealed multiple small pustules and mahogany colored macules on a broad, well-demarcated scaly red plaque. This pattern was consistent with palmoplantar pustular psoriasis.

Palmoplantar psoriasis is a chronic disease that may manifest at any age and in both sexes. The diagnosis may be clinical, as it was in this case. Bacterial culture of a pustule may demonstrate staphylococcus superinfection—a problem more likely to occur in smokers. More widespread disease, spiking fevers, or tachycardia could indicate a need for hospitalization for further work-up and management.

With disease localized to this patient’s hands and feet, the physician considered dyshidrotic eczema as part of the differential diagnosis. However dyshidrotic eczema, which presents with clear tapioca-like vesicles, is profoundly itchy; pustular psoriasis is often painful. Other differences: The vesicles in dyshidrotic eczema do not uniformly form pustules nor do they form brown macules upon healing, as occurs in palmoplantar pustular psoriasis.

Treatment for very limited disease includes topical ultrapotent steroids, topical retinoids, or phototherapy—either alone or in combination. However, more extensive disease, even if limited to hands and feet, merits systemic therapy with acitretin, methotrexate, or biologic agents. (Acitretin and methotrexate are reliable teratogens and should not be used in women who are, or may become, pregnant.) Individuals with known superinfection often benefit from antibiotic therapy, as well.

In this case, the patient had already undergone a tubal ligation for contraception. Therefore, she was started on acitretin 25 mg PO daily. Patients on systemic retinoids undergo laboratory surveillance for transaminitis and hypertriglyceridemia regularly. Adverse effects are generally well tolerated, but include photosensitivity and dry skin, lips, and eyes. The patient improved significantly on 25 mg/d and the dosage was reduced to 10 mg/d after 3 months. She currently remains clear on this regimen.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

An excisional biopsy revealed that this was an eccrine poroma, a benign neoplasm of sweat gland tissue in the epidermis.

This lesion was clearly not a wart, as it lacked the common verrucous and keratotic features one would expect, and it did not respond to wart treatments. Other diagnoses that might be considered with a lesion like this include pyogenic granuloma, periungual fibroma, and squamous cell carcinoma.

Poromas are well demarcated papules that grow slowly or are stable in size. They are most commonly flesh colored and smooth, but poromas may also appear verrucous, pigmented, or ulcerated. They are usually found on acral skin—particularly the palms or soles. Due to their location, poromas bleed easily, which is what usually prompts patients to seek care. Friable lesions can mimic acral melanoma.

Poromas occur most often in patients over 40 years of age and are evenly distributed among sexes and skin types. Cases have been associated with trauma, radiation, and chemotherapy. Although exceedingly rare, malignant transformation can occur in the form of eccrine porocarcinoma—a larger tumor that can grow rapidly and that has metastatic potential.

Treatment is optional—but desirable—when lesions are painful or bleed easily. Surgical excision is curative. Shave biopsy or curettage coupled with electrocautery of the base is also curative. Recurrence rates are very low with either method of treatment.

In this case, an excisional biopsy of the lateral nail fold was both diagnostic and curative (second image). The patient remained clear 9 months after treatment.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

An excisional biopsy revealed that this was an eccrine poroma, a benign neoplasm of sweat gland tissue in the epidermis.

This lesion was clearly not a wart, as it lacked the common verrucous and keratotic features one would expect, and it did not respond to wart treatments. Other diagnoses that might be considered with a lesion like this include pyogenic granuloma, periungual fibroma, and squamous cell carcinoma.

Poromas are well demarcated papules that grow slowly or are stable in size. They are most commonly flesh colored and smooth, but poromas may also appear verrucous, pigmented, or ulcerated. They are usually found on acral skin—particularly the palms or soles. Due to their location, poromas bleed easily, which is what usually prompts patients to seek care. Friable lesions can mimic acral melanoma.

Poromas occur most often in patients over 40 years of age and are evenly distributed among sexes and skin types. Cases have been associated with trauma, radiation, and chemotherapy. Although exceedingly rare, malignant transformation can occur in the form of eccrine porocarcinoma—a larger tumor that can grow rapidly and that has metastatic potential.

Treatment is optional—but desirable—when lesions are painful or bleed easily. Surgical excision is curative. Shave biopsy or curettage coupled with electrocautery of the base is also curative. Recurrence rates are very low with either method of treatment.

In this case, an excisional biopsy of the lateral nail fold was both diagnostic and curative (second image). The patient remained clear 9 months after treatment.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

An excisional biopsy revealed that this was an eccrine poroma, a benign neoplasm of sweat gland tissue in the epidermis.

This lesion was clearly not a wart, as it lacked the common verrucous and keratotic features one would expect, and it did not respond to wart treatments. Other diagnoses that might be considered with a lesion like this include pyogenic granuloma, periungual fibroma, and squamous cell carcinoma.

Poromas are well demarcated papules that grow slowly or are stable in size. They are most commonly flesh colored and smooth, but poromas may also appear verrucous, pigmented, or ulcerated. They are usually found on acral skin—particularly the palms or soles. Due to their location, poromas bleed easily, which is what usually prompts patients to seek care. Friable lesions can mimic acral melanoma.

Poromas occur most often in patients over 40 years of age and are evenly distributed among sexes and skin types. Cases have been associated with trauma, radiation, and chemotherapy. Although exceedingly rare, malignant transformation can occur in the form of eccrine porocarcinoma—a larger tumor that can grow rapidly and that has metastatic potential.

Treatment is optional—but desirable—when lesions are painful or bleed easily. Surgical excision is curative. Shave biopsy or curettage coupled with electrocautery of the base is also curative. Recurrence rates are very low with either method of treatment.

In this case, an excisional biopsy of the lateral nail fold was both diagnostic and curative (second image). The patient remained clear 9 months after treatment.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

THE CASE

An obese 90-year-old White man presented for a 1-month follow-up with his family physician after being hospitalized for an acute exacerbation of heart failure (HF). In addition to New York Heart Association (NYHA) Class III heart failure with reduced ejection fraction (HFrEF), he had a history of tobacco abuse, hyperlipidemia, atrial fibrillation, coronary artery disease, stage 3 chronic kidney disease, and benign prostatic hyperplasia. The patient’s family accompanied him during the visit to discuss hospice care.

The patient complained of persistent shortness of breath that limited his activities of daily living (ADLs) and lower extremity and scrotal edema. He denied chest pain, orthopnea, paroxysmal nocturnal dyspnea, ascites, nocturia, and nocturnal cough.

The patient had undergone a coronary artery bypass graft 23 years earlier. His HF was being managed with metoprolol tartrate 25 mg bid, spironolactone 25 mg/d, and furosemide 80 mg/d.

Examination revealed bilateral 3+ pitting edema in the lower extremities midway up the shin, crackles to the inferior scapula bilaterally, and a 3/6 systolic murmur with regular rate and rhythm. The remainder of the physical exam was normal. The patient’s vitals were within normal limits, with an oxygen saturation of 90%.

The patient’s most recent chest x-ray demonstrated mild cardiomegaly. An echocardiogram showed an ejection fraction of 44% with severe bi-atrial enlargement, moderate-to-severe mitral regurgitation, and mild-to-moderate aortic insufficiency. His brain natriuretic peptide (BNP) was 915 pg/mL (normal range for patients ages 75-99 years, < 450 pg/mL).

THE DIAGNOSIS

The differential diagnosis for the patient’s shortness of breath included chronic obstructive pulmonary disease secondary to his smoking history, pulmonary embolus, respiratory infection, anemia, and medication-related adverse effects. The patient’s history of renal disease merited consideration of a nephrotic syndrome causing low albumin, which could explain his edema. Another possible cause of the edema was venous insufficiency. However, given the patient’s extensive cardiac history, the most likely explanation for his shortness of breath and edema was congestive HF that was unresponsive to the current diuretic regimen.

Several changes to the patient’s medications were made. Lisinopril 2.5 mg/d was started due to the mortality benefit of angiotensin-converting enzyme inhibitors in the treatment of HFrEF.¹ Metoprolol tartrate 25 mg/d was transitioned to metoprolol succinate 50 mg/d, as only the longer-acting succinate version has shown mortality benefit in HFrEF.¹ (Other beta-blockers with mortality benefit include carvedilol and bisoprolol.¹) The furosemide 80 mg/d was replaced with torsemide 100 mg/d to provide an enhanced diuretic effect for symptomatic relief. The spironolactone dose was not increased due to concerns about the patient’s renal function. Of note, spironolactone was included in the patient’s regimen based on his NYHA classification, as well as the potential mortality benefits and improvement in edema seen in HFrEF patients.¹ Spironolactone can be used with loop and/or thiazide diuretics in the treatment of HF.

Continue to: Within 5 days...

Within 5 days, the patient had lost 6 lb and his oxygen saturation had improved from 90% to 95%. He reported improvements in his breathing and was able to move around more easily.

DISCUSSION

There are several possible explanations for torsemide’s superior diuretic effect in this patient. Unlike furosemide, torsemide absorption is not influenced by intestinal edema, which is commonly seen in patients with HF. It has a longer half-life and improved bioavailability that is not altered by food intake. Torsemide also inhibits the actions of aldosterone through its interaction with the renin-angiotensin-aldosterone system and aldosterone receptor, leading to further diuresis and reduced cardiac remodeling.²

What the evidence shows. The ­TORIC trial was an open-label, nonrandomized, post-marketing surveillance study of 1377 patients with NYHA Class II–III HF who received diuretic therapy with torsemide 10 mg/d, furosemide 40 mg/d, or another diuretic for 12 months.³ Significantly lower total mortality and cardiac mortality was found in the torsemide group; in addition, a significantly greater proportion of patients in the torsemide group showed improvement in NYHA classification.³ Murray et al reported a reduction in hospitalization rates with torsemide therapy vs furosemide therapy in a randomized trial of 234 HF patients (32% vs 17%, P = 0.01).⁴ The ASCEND-HF trial, a large international acute HF trial comparing torsemide with furosemide, demonstrated a nonsignificant reduction in 30-day and 180-day events (all-cause mortality or HF hospitalization) in those receiving torsemide, after risk adjustment.⁵ Torsemide has also been shown to improve quality of life compared to furosemide.⁶

Given the patient’s extensive cardiac history, the most likely explanation for his shortness of breath and edema was congestive HF that was unresponsive to his diuretic regimen.

Preliminary results from the TORNADO trial,⁷ a multicenter randomized controlled trial, demonstrated superior symptom improvement in HF patients taking torsemide compared to those taking furosemide.⁸ The preliminary endpoint—a composite of improvement in NYHA class, improvement in distance of at least 50 m during a 6-minute walk test, and a decrease in fluid retention of at least 0.5 ohms at 3-month follow-up—was achieved by 94% and 58% of patients on torsemide and furosemide, respectively (P = 0.03).⁸ A total of 7 patients (3 in the torsemide and 4 in the furosemide group) were hospitalized for worsening HF during the follow-up period.⁸

A 2020 meta-analysis of more than 19,000 patients compared furosemide to torsemide and found a number needed to treat (NNT) of 23 to prevent a hospitalization due to HF; an NNT of 5 for improvement in NYHA functional status; and an NNT of 40 for reduction in cardiac mortality.⁹

Continue to: Our patient

Our patient reported feeling “great” at the 6-week follow-up appointment, with significant improvement in breathing and ability to perform his ADLs. His NYHA classification improved to Class II. He had lost 26 pounds (back to his weight 9 months prior), and his oxygen saturation was 97%.

On exam, the bilateral peripheral edema in his lower extremities had improved from 3+ to 1+, with the edema extending just distal to the mid-shin. Only mild crackles were present at the lung bases. The remainder of his physical examination was unchanged. His vital signs were within normal limits with no signs of hypotension. A basic metabolic panel was obtained to confirm his electrolytes were still within normal limits. His BNP had decreased to 230 pg/mL.

The patient declined the referral for hospice evaluation due to the significant improvement in his symptoms.

THE TAKEAWAY

A significant clinical improvement and improved quality of life were achieved with the transition from furosemide to torsemide. It is apparent that the patient’s furosemide had an inferior diuretic effect compared to torsemide, whether that be secondary to his dose or due to the unpredictable nature of furosemide’s bioavailability, especially in the setting of intestinal edema.

A growing body of literature^9-11 suggests torsemide’s superiority over furosemide with no signs of increased adverse effects. Although additional prospective, head-to-head trials are needed, at this point in time it is appropriate to consider the use of torsemide in a patient with HF who does not seem to be fully responding to furosemide.

CORRESPONDENCE
Ryan Paulus, DO, 590 Manning Drive, Chapel Hill, NC 27599; [email protected]

THE CASE

An obese 90-year-old White man presented for a 1-month follow-up with his family physician after being hospitalized for an acute exacerbation of heart failure (HF). In addition to New York Heart Association (NYHA) Class III heart failure with reduced ejection fraction (HFrEF), he had a history of tobacco abuse, hyperlipidemia, atrial fibrillation, coronary artery disease, stage 3 chronic kidney disease, and benign prostatic hyperplasia. The patient’s family accompanied him during the visit to discuss hospice care.

The patient complained of persistent shortness of breath that limited his activities of daily living (ADLs) and lower extremity and scrotal edema. He denied chest pain, orthopnea, paroxysmal nocturnal dyspnea, ascites, nocturia, and nocturnal cough.

The patient had undergone a coronary artery bypass graft 23 years earlier. His HF was being managed with metoprolol tartrate 25 mg bid, spironolactone 25 mg/d, and furosemide 80 mg/d.

Examination revealed bilateral 3+ pitting edema in the lower extremities midway up the shin, crackles to the inferior scapula bilaterally, and a 3/6 systolic murmur with regular rate and rhythm. The remainder of the physical exam was normal. The patient’s vitals were within normal limits, with an oxygen saturation of 90%.

The patient’s most recent chest x-ray demonstrated mild cardiomegaly. An echocardiogram showed an ejection fraction of 44% with severe bi-atrial enlargement, moderate-to-severe mitral regurgitation, and mild-to-moderate aortic insufficiency. His brain natriuretic peptide (BNP) was 915 pg/mL (normal range for patients ages 75-99 years, < 450 pg/mL).

THE DIAGNOSIS

The differential diagnosis for the patient’s shortness of breath included chronic obstructive pulmonary disease secondary to his smoking history, pulmonary embolus, respiratory infection, anemia, and medication-related adverse effects. The patient’s history of renal disease merited consideration of a nephrotic syndrome causing low albumin, which could explain his edema. Another possible cause of the edema was venous insufficiency. However, given the patient’s extensive cardiac history, the most likely explanation for his shortness of breath and edema was congestive HF that was unresponsive to the current diuretic regimen.

Several changes to the patient’s medications were made. Lisinopril 2.5 mg/d was started due to the mortality benefit of angiotensin-converting enzyme inhibitors in the treatment of HFrEF.¹ Metoprolol tartrate 25 mg/d was transitioned to metoprolol succinate 50 mg/d, as only the longer-acting succinate version has shown mortality benefit in HFrEF.¹ (Other beta-blockers with mortality benefit include carvedilol and bisoprolol.¹) The furosemide 80 mg/d was replaced with torsemide 100 mg/d to provide an enhanced diuretic effect for symptomatic relief. The spironolactone dose was not increased due to concerns about the patient’s renal function. Of note, spironolactone was included in the patient’s regimen based on his NYHA classification, as well as the potential mortality benefits and improvement in edema seen in HFrEF patients.¹ Spironolactone can be used with loop and/or thiazide diuretics in the treatment of HF.

Continue to: Within 5 days...

Within 5 days, the patient had lost 6 lb and his oxygen saturation had improved from 90% to 95%. He reported improvements in his breathing and was able to move around more easily.

DISCUSSION

There are several possible explanations for torsemide’s superior diuretic effect in this patient. Unlike furosemide, torsemide absorption is not influenced by intestinal edema, which is commonly seen in patients with HF. It has a longer half-life and improved bioavailability that is not altered by food intake. Torsemide also inhibits the actions of aldosterone through its interaction with the renin-angiotensin-aldosterone system and aldosterone receptor, leading to further diuresis and reduced cardiac remodeling.²

What the evidence shows. The ­TORIC trial was an open-label, nonrandomized, post-marketing surveillance study of 1377 patients with NYHA Class II–III HF who received diuretic therapy with torsemide 10 mg/d, furosemide 40 mg/d, or another diuretic for 12 months.³ Significantly lower total mortality and cardiac mortality was found in the torsemide group; in addition, a significantly greater proportion of patients in the torsemide group showed improvement in NYHA classification.³ Murray et al reported a reduction in hospitalization rates with torsemide therapy vs furosemide therapy in a randomized trial of 234 HF patients (32% vs 17%, P = 0.01).⁴ The ASCEND-HF trial, a large international acute HF trial comparing torsemide with furosemide, demonstrated a nonsignificant reduction in 30-day and 180-day events (all-cause mortality or HF hospitalization) in those receiving torsemide, after risk adjustment.⁵ Torsemide has also been shown to improve quality of life compared to furosemide.⁶

Given the patient’s extensive cardiac history, the most likely explanation for his shortness of breath and edema was congestive HF that was unresponsive to his diuretic regimen.

Preliminary results from the TORNADO trial,⁷ a multicenter randomized controlled trial, demonstrated superior symptom improvement in HF patients taking torsemide compared to those taking furosemide.⁸ The preliminary endpoint—a composite of improvement in NYHA class, improvement in distance of at least 50 m during a 6-minute walk test, and a decrease in fluid retention of at least 0.5 ohms at 3-month follow-up—was achieved by 94% and 58% of patients on torsemide and furosemide, respectively (P = 0.03).⁸ A total of 7 patients (3 in the torsemide and 4 in the furosemide group) were hospitalized for worsening HF during the follow-up period.⁸

A 2020 meta-analysis of more than 19,000 patients compared furosemide to torsemide and found a number needed to treat (NNT) of 23 to prevent a hospitalization due to HF; an NNT of 5 for improvement in NYHA functional status; and an NNT of 40 for reduction in cardiac mortality.⁹

Continue to: Our patient

Our patient reported feeling “great” at the 6-week follow-up appointment, with significant improvement in breathing and ability to perform his ADLs. His NYHA classification improved to Class II. He had lost 26 pounds (back to his weight 9 months prior), and his oxygen saturation was 97%.

On exam, the bilateral peripheral edema in his lower extremities had improved from 3+ to 1+, with the edema extending just distal to the mid-shin. Only mild crackles were present at the lung bases. The remainder of his physical examination was unchanged. His vital signs were within normal limits with no signs of hypotension. A basic metabolic panel was obtained to confirm his electrolytes were still within normal limits. His BNP had decreased to 230 pg/mL.

The patient declined the referral for hospice evaluation due to the significant improvement in his symptoms.

THE TAKEAWAY

A significant clinical improvement and improved quality of life were achieved with the transition from furosemide to torsemide. It is apparent that the patient’s furosemide had an inferior diuretic effect compared to torsemide, whether that be secondary to his dose or due to the unpredictable nature of furosemide’s bioavailability, especially in the setting of intestinal edema.

A growing body of literature^9-11 suggests torsemide’s superiority over furosemide with no signs of increased adverse effects. Although additional prospective, head-to-head trials are needed, at this point in time it is appropriate to consider the use of torsemide in a patient with HF who does not seem to be fully responding to furosemide.

CORRESPONDENCE
Ryan Paulus, DO, 590 Manning Drive, Chapel Hill, NC 27599; [email protected]

THE CASE

An obese 90-year-old White man presented for a 1-month follow-up with his family physician after being hospitalized for an acute exacerbation of heart failure (HF). In addition to New York Heart Association (NYHA) Class III heart failure with reduced ejection fraction (HFrEF), he had a history of tobacco abuse, hyperlipidemia, atrial fibrillation, coronary artery disease, stage 3 chronic kidney disease, and benign prostatic hyperplasia. The patient’s family accompanied him during the visit to discuss hospice care.

The patient complained of persistent shortness of breath that limited his activities of daily living (ADLs) and lower extremity and scrotal edema. He denied chest pain, orthopnea, paroxysmal nocturnal dyspnea, ascites, nocturia, and nocturnal cough.

The patient had undergone a coronary artery bypass graft 23 years earlier. His HF was being managed with metoprolol tartrate 25 mg bid, spironolactone 25 mg/d, and furosemide 80 mg/d.

Examination revealed bilateral 3+ pitting edema in the lower extremities midway up the shin, crackles to the inferior scapula bilaterally, and a 3/6 systolic murmur with regular rate and rhythm. The remainder of the physical exam was normal. The patient’s vitals were within normal limits, with an oxygen saturation of 90%.

The patient’s most recent chest x-ray demonstrated mild cardiomegaly. An echocardiogram showed an ejection fraction of 44% with severe bi-atrial enlargement, moderate-to-severe mitral regurgitation, and mild-to-moderate aortic insufficiency. His brain natriuretic peptide (BNP) was 915 pg/mL (normal range for patients ages 75-99 years, < 450 pg/mL).

THE DIAGNOSIS

The differential diagnosis for the patient’s shortness of breath included chronic obstructive pulmonary disease secondary to his smoking history, pulmonary embolus, respiratory infection, anemia, and medication-related adverse effects. The patient’s history of renal disease merited consideration of a nephrotic syndrome causing low albumin, which could explain his edema. Another possible cause of the edema was venous insufficiency. However, given the patient’s extensive cardiac history, the most likely explanation for his shortness of breath and edema was congestive HF that was unresponsive to the current diuretic regimen.

Several changes to the patient’s medications were made. Lisinopril 2.5 mg/d was started due to the mortality benefit of angiotensin-converting enzyme inhibitors in the treatment of HFrEF.¹ Metoprolol tartrate 25 mg/d was transitioned to metoprolol succinate 50 mg/d, as only the longer-acting succinate version has shown mortality benefit in HFrEF.¹ (Other beta-blockers with mortality benefit include carvedilol and bisoprolol.¹) The furosemide 80 mg/d was replaced with torsemide 100 mg/d to provide an enhanced diuretic effect for symptomatic relief. The spironolactone dose was not increased due to concerns about the patient’s renal function. Of note, spironolactone was included in the patient’s regimen based on his NYHA classification, as well as the potential mortality benefits and improvement in edema seen in HFrEF patients.¹ Spironolactone can be used with loop and/or thiazide diuretics in the treatment of HF.

Continue to: Within 5 days...

Within 5 days, the patient had lost 6 lb and his oxygen saturation had improved from 90% to 95%. He reported improvements in his breathing and was able to move around more easily.

DISCUSSION

There are several possible explanations for torsemide’s superior diuretic effect in this patient. Unlike furosemide, torsemide absorption is not influenced by intestinal edema, which is commonly seen in patients with HF. It has a longer half-life and improved bioavailability that is not altered by food intake. Torsemide also inhibits the actions of aldosterone through its interaction with the renin-angiotensin-aldosterone system and aldosterone receptor, leading to further diuresis and reduced cardiac remodeling.²

What the evidence shows. The ­TORIC trial was an open-label, nonrandomized, post-marketing surveillance study of 1377 patients with NYHA Class II–III HF who received diuretic therapy with torsemide 10 mg/d, furosemide 40 mg/d, or another diuretic for 12 months.³ Significantly lower total mortality and cardiac mortality was found in the torsemide group; in addition, a significantly greater proportion of patients in the torsemide group showed improvement in NYHA classification.³ Murray et al reported a reduction in hospitalization rates with torsemide therapy vs furosemide therapy in a randomized trial of 234 HF patients (32% vs 17%, P = 0.01).⁴ The ASCEND-HF trial, a large international acute HF trial comparing torsemide with furosemide, demonstrated a nonsignificant reduction in 30-day and 180-day events (all-cause mortality or HF hospitalization) in those receiving torsemide, after risk adjustment.⁵ Torsemide has also been shown to improve quality of life compared to furosemide.⁶

Given the patient’s extensive cardiac history, the most likely explanation for his shortness of breath and edema was congestive HF that was unresponsive to his diuretic regimen.

Preliminary results from the TORNADO trial,⁷ a multicenter randomized controlled trial, demonstrated superior symptom improvement in HF patients taking torsemide compared to those taking furosemide.⁸ The preliminary endpoint—a composite of improvement in NYHA class, improvement in distance of at least 50 m during a 6-minute walk test, and a decrease in fluid retention of at least 0.5 ohms at 3-month follow-up—was achieved by 94% and 58% of patients on torsemide and furosemide, respectively (P = 0.03).⁸ A total of 7 patients (3 in the torsemide and 4 in the furosemide group) were hospitalized for worsening HF during the follow-up period.⁸

A 2020 meta-analysis of more than 19,000 patients compared furosemide to torsemide and found a number needed to treat (NNT) of 23 to prevent a hospitalization due to HF; an NNT of 5 for improvement in NYHA functional status; and an NNT of 40 for reduction in cardiac mortality.⁹

Continue to: Our patient

Our patient reported feeling “great” at the 6-week follow-up appointment, with significant improvement in breathing and ability to perform his ADLs. His NYHA classification improved to Class II. He had lost 26 pounds (back to his weight 9 months prior), and his oxygen saturation was 97%.

On exam, the bilateral peripheral edema in his lower extremities had improved from 3+ to 1+, with the edema extending just distal to the mid-shin. Only mild crackles were present at the lung bases. The remainder of his physical examination was unchanged. His vital signs were within normal limits with no signs of hypotension. A basic metabolic panel was obtained to confirm his electrolytes were still within normal limits. His BNP had decreased to 230 pg/mL.

The patient declined the referral for hospice evaluation due to the significant improvement in his symptoms.

THE TAKEAWAY

A significant clinical improvement and improved quality of life were achieved with the transition from furosemide to torsemide. It is apparent that the patient’s furosemide had an inferior diuretic effect compared to torsemide, whether that be secondary to his dose or due to the unpredictable nature of furosemide’s bioavailability, especially in the setting of intestinal edema.

A growing body of literature^9-11 suggests torsemide’s superiority over furosemide with no signs of increased adverse effects. Although additional prospective, head-to-head trials are needed, at this point in time it is appropriate to consider the use of torsemide in a patient with HF who does not seem to be fully responding to furosemide.

CORRESPONDENCE
Ryan Paulus, DO, 590 Manning Drive, Chapel Hill, NC 27599; [email protected]

The miniscule papules arising suddenly on the trunk and genitals with linear arrays and clusters are clinically consistent with lichen nitidus, an uncommon eruption without a clear etiology.

Presentations may be focal or widespread and range from mildly itchy to asymptomatic. Children and young adults are most often affected. Linear arrays may appear in response to the trauma of scratching, which is termed the Koebner phenomenon. The differential diagnosis includes molluscum contagiosum, lichen planus, and lichen spinulosis. Usually these conditions can be distinguished clinically, but a biopsy would differentiate them, if needed. It’s worth noting, too, that lichen nitidus papules are monomorphic and lack the umbilication that is seen with molluscum contagiosum.

Cases of lichen nitidus clear up spontaneously, although usually months to years after diagnosis. Lichen nitidus is not contagious. Reassurance is, however, important as many patients may have experienced misdiagnosis and have concerns about sexual transmission because of the location of the papules on their genitals.

Treatment is often unnecessary. However, if itching is problematic, topical steroids and other topical antipruritics may be used. Topical hydrocortisone 2.5% cream or ointment for skin folds and genitals may be safely used, as well as topical triamcinolone 0.1% for the trunk and extremities. Pramoxine lotion (Sarna) is an over-the-counter nonsteroidal antipruritic. Oral nonsedating antihistamines can also be used as an adjunct.

This patient was reassured that the lesions were not contagious. Due to the itching, he was started on the pramoxine lotion twice daily, as needed, and the lesions cleared in about 6 months.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The miniscule papules arising suddenly on the trunk and genitals with linear arrays and clusters are clinically consistent with lichen nitidus, an uncommon eruption without a clear etiology.

Presentations may be focal or widespread and range from mildly itchy to asymptomatic. Children and young adults are most often affected. Linear arrays may appear in response to the trauma of scratching, which is termed the Koebner phenomenon. The differential diagnosis includes molluscum contagiosum, lichen planus, and lichen spinulosis. Usually these conditions can be distinguished clinically, but a biopsy would differentiate them, if needed. It’s worth noting, too, that lichen nitidus papules are monomorphic and lack the umbilication that is seen with molluscum contagiosum.

Cases of lichen nitidus clear up spontaneously, although usually months to years after diagnosis. Lichen nitidus is not contagious. Reassurance is, however, important as many patients may have experienced misdiagnosis and have concerns about sexual transmission because of the location of the papules on their genitals.

Treatment is often unnecessary. However, if itching is problematic, topical steroids and other topical antipruritics may be used. Topical hydrocortisone 2.5% cream or ointment for skin folds and genitals may be safely used, as well as topical triamcinolone 0.1% for the trunk and extremities. Pramoxine lotion (Sarna) is an over-the-counter nonsteroidal antipruritic. Oral nonsedating antihistamines can also be used as an adjunct.

This patient was reassured that the lesions were not contagious. Due to the itching, he was started on the pramoxine lotion twice daily, as needed, and the lesions cleared in about 6 months.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

The miniscule papules arising suddenly on the trunk and genitals with linear arrays and clusters are clinically consistent with lichen nitidus, an uncommon eruption without a clear etiology.

Presentations may be focal or widespread and range from mildly itchy to asymptomatic. Children and young adults are most often affected. Linear arrays may appear in response to the trauma of scratching, which is termed the Koebner phenomenon. The differential diagnosis includes molluscum contagiosum, lichen planus, and lichen spinulosis. Usually these conditions can be distinguished clinically, but a biopsy would differentiate them, if needed. It’s worth noting, too, that lichen nitidus papules are monomorphic and lack the umbilication that is seen with molluscum contagiosum.

Cases of lichen nitidus clear up spontaneously, although usually months to years after diagnosis. Lichen nitidus is not contagious. Reassurance is, however, important as many patients may have experienced misdiagnosis and have concerns about sexual transmission because of the location of the papules on their genitals.

Treatment is often unnecessary. However, if itching is problematic, topical steroids and other topical antipruritics may be used. Topical hydrocortisone 2.5% cream or ointment for skin folds and genitals may be safely used, as well as topical triamcinolone 0.1% for the trunk and extremities. Pramoxine lotion (Sarna) is an over-the-counter nonsteroidal antipruritic. Oral nonsedating antihistamines can also be used as an adjunct.

This patient was reassured that the lesions were not contagious. Due to the itching, he was started on the pramoxine lotion twice daily, as needed, and the lesions cleared in about 6 months.

‌

Text and photos courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. (Photo copyright retained.)

EVIDENCE SUMMARY

A meta-analysis of 6 RCTs studied the effect of smartphone self-care applications on A1C, weight, blood pressure, and lipids in adult patients with T2DM. All the interventions comprised 4 components: electronic self-management prompts and reminders, personal measuring devices, patient-driven data upload, and remote analysis of the data with feedback. The review excluded studies that used phone calls or lasted fewer than 3 months.

Some improvement in A1C found, but no effect on weight

Telehealth interventions improved A1C more than usual care (6 trials, 884 patients; mean difference = –0.40%; 95% CI, –0.69% to –0.11%).¹ A subset of 4 studies with 560 patients evaluated changes in weight. Patients had a mean age of 61 years and average weight of 84 kg (in 3 of 4 studies reporting baseline weight). Aggregate weight loss was insignificant after 3 to 12 months (mean difference = –0.84 kg; 95% CI, –2.04 kg to 0.36 kg, P = .17). Investigators reported no harms. Limitations of the analysis included high heterogeneity in the main outcome of A1C (I² = 70%) but low heterogeneity within the 4 studies assessing weight (I² = 30%).

Other, small studies found no change in A1C

Two subsequent small RCTs came to different conclusions than the meta-analysis. One compared the impact of individualized physical activity–based text messages in response to pedometer readings with pedometer use alone.² It included 126 adult patients (mean age, 50.5 years) with T2DM who had an A1C > 7% and access to an Internet-connected computer. Researchers excluded patients who were unable to perform moderate physical activity or who had cognitive deficits.

At enrollment, researchers supplied all patients with a pedometer and an appointment with a counselor to set goals for physical activity. They sent 2 text messages daily to the intervention group (and none to the control group) based on uploaded pedometer data. One message detailed physical activity progress and the second encouraged increased physical activity. The primary outcome was mean step counts per month; secondary outcomes included A1C and weight measured at 6 months.

The groups showed no significant difference in A1C (mean difference = 0.07%; 95% CI, –0.47% to 0.34%, P = .75) or weight loss (mean difference = 3.1 lb; 95% CI, –24.5 lb to 18.3 lb, P = .77). Many patients (43%) reported difficulty uploading step counts, receiving texts, and responding to texts. The dropout rate was 24%.

A second RCT with 150 patients, using a less elaborate protocol, assessed the effectiveness of tailored text-message reminders compared with nontailored text messages to improve A1C and body mass index (BMI).³ Patients were adult Iranians (mean age, 52.5 years) with T2DM who owned a cell phone and could receive and read text messages.

Patients filled out a diabetic self-care assessment to identify barriers to improving care and were randomized into 3 groups. The first group received tailored text messages (75% addressing the patient’s top 2 barriers to self-care and 25% general messages). The second group received nontailored text messages of encouragement. The control group received no text messages.

Continue to: After 3 months...

After 3 months, BMI was reduced in both messaging groups but not the control group (tailored text = –0.6 kg/m², nontailored text = –0.5 kg/m², controls = 0.7 kg/m²; P < .05). A1C levels didn’t change significantly. One limitation of the study was that 30% to 35% of the patients in the intervention group had a university-level education, compared with 12% in the control group.

Recommendations

The Department of Veterans Affairs issued guidelines in 2017 regarding management of patients with T2DM in primary care.⁴ The guidelines state that all patients should receive individualized self-management education using “modalities tailored to their preferences” (strong recommendation). They further recommend “offering one or more bidirectional telehealth interventions” in coordination with patients’ health care providers (weak recommendation).

Telehealth interventions may be associated with a decrease in hemoglobin A1C.

The 2017 diabetes self-management recommendations endorsed by the American Diabetes Association state that “strong evidence” shows that incorporating text messaging into diabetes care improves outcomes, enhances feedback loops, and empowers patients.⁵

Editor’s takeaway

Telehealth offers mechanisms for patients and physicians to enhance communication about health behaviors and health status. But does it alter outcomes? The cited literature suggests that benefits aren’t a forgone conclusion and that acceptability, ease of use, cost, and individualization are critical issues in telehealth design.

EVIDENCE SUMMARY

A meta-analysis of 6 RCTs studied the effect of smartphone self-care applications on A1C, weight, blood pressure, and lipids in adult patients with T2DM. All the interventions comprised 4 components: electronic self-management prompts and reminders, personal measuring devices, patient-driven data upload, and remote analysis of the data with feedback. The review excluded studies that used phone calls or lasted fewer than 3 months.

Some improvement in A1C found, but no effect on weight

Telehealth interventions improved A1C more than usual care (6 trials, 884 patients; mean difference = –0.40%; 95% CI, –0.69% to –0.11%).¹ A subset of 4 studies with 560 patients evaluated changes in weight. Patients had a mean age of 61 years and average weight of 84 kg (in 3 of 4 studies reporting baseline weight). Aggregate weight loss was insignificant after 3 to 12 months (mean difference = –0.84 kg; 95% CI, –2.04 kg to 0.36 kg, P = .17). Investigators reported no harms. Limitations of the analysis included high heterogeneity in the main outcome of A1C (I² = 70%) but low heterogeneity within the 4 studies assessing weight (I² = 30%).

Other, small studies found no change in A1C

Two subsequent small RCTs came to different conclusions than the meta-analysis. One compared the impact of individualized physical activity–based text messages in response to pedometer readings with pedometer use alone.² It included 126 adult patients (mean age, 50.5 years) with T2DM who had an A1C > 7% and access to an Internet-connected computer. Researchers excluded patients who were unable to perform moderate physical activity or who had cognitive deficits.

At enrollment, researchers supplied all patients with a pedometer and an appointment with a counselor to set goals for physical activity. They sent 2 text messages daily to the intervention group (and none to the control group) based on uploaded pedometer data. One message detailed physical activity progress and the second encouraged increased physical activity. The primary outcome was mean step counts per month; secondary outcomes included A1C and weight measured at 6 months.

The groups showed no significant difference in A1C (mean difference = 0.07%; 95% CI, –0.47% to 0.34%, P = .75) or weight loss (mean difference = 3.1 lb; 95% CI, –24.5 lb to 18.3 lb, P = .77). Many patients (43%) reported difficulty uploading step counts, receiving texts, and responding to texts. The dropout rate was 24%.

A second RCT with 150 patients, using a less elaborate protocol, assessed the effectiveness of tailored text-message reminders compared with nontailored text messages to improve A1C and body mass index (BMI).³ Patients were adult Iranians (mean age, 52.5 years) with T2DM who owned a cell phone and could receive and read text messages.

Patients filled out a diabetic self-care assessment to identify barriers to improving care and were randomized into 3 groups. The first group received tailored text messages (75% addressing the patient’s top 2 barriers to self-care and 25% general messages). The second group received nontailored text messages of encouragement. The control group received no text messages.

Continue to: After 3 months...

After 3 months, BMI was reduced in both messaging groups but not the control group (tailored text = –0.6 kg/m², nontailored text = –0.5 kg/m², controls = 0.7 kg/m²; P < .05). A1C levels didn’t change significantly. One limitation of the study was that 30% to 35% of the patients in the intervention group had a university-level education, compared with 12% in the control group.

Recommendations

The Department of Veterans Affairs issued guidelines in 2017 regarding management of patients with T2DM in primary care.⁴ The guidelines state that all patients should receive individualized self-management education using “modalities tailored to their preferences” (strong recommendation). They further recommend “offering one or more bidirectional telehealth interventions” in coordination with patients’ health care providers (weak recommendation).

Telehealth interventions may be associated with a decrease in hemoglobin A1C.

The 2017 diabetes self-management recommendations endorsed by the American Diabetes Association state that “strong evidence” shows that incorporating text messaging into diabetes care improves outcomes, enhances feedback loops, and empowers patients.⁵

Editor’s takeaway

Telehealth offers mechanisms for patients and physicians to enhance communication about health behaviors and health status. But does it alter outcomes? The cited literature suggests that benefits aren’t a forgone conclusion and that acceptability, ease of use, cost, and individualization are critical issues in telehealth design.

EVIDENCE SUMMARY

A meta-analysis of 6 RCTs studied the effect of smartphone self-care applications on A1C, weight, blood pressure, and lipids in adult patients with T2DM. All the interventions comprised 4 components: electronic self-management prompts and reminders, personal measuring devices, patient-driven data upload, and remote analysis of the data with feedback. The review excluded studies that used phone calls or lasted fewer than 3 months.

Some improvement in A1C found, but no effect on weight

Telehealth interventions improved A1C more than usual care (6 trials, 884 patients; mean difference = –0.40%; 95% CI, –0.69% to –0.11%).¹ A subset of 4 studies with 560 patients evaluated changes in weight. Patients had a mean age of 61 years and average weight of 84 kg (in 3 of 4 studies reporting baseline weight). Aggregate weight loss was insignificant after 3 to 12 months (mean difference = –0.84 kg; 95% CI, –2.04 kg to 0.36 kg, P = .17). Investigators reported no harms. Limitations of the analysis included high heterogeneity in the main outcome of A1C (I² = 70%) but low heterogeneity within the 4 studies assessing weight (I² = 30%).

Other, small studies found no change in A1C

Two subsequent small RCTs came to different conclusions than the meta-analysis. One compared the impact of individualized physical activity–based text messages in response to pedometer readings with pedometer use alone.² It included 126 adult patients (mean age, 50.5 years) with T2DM who had an A1C > 7% and access to an Internet-connected computer. Researchers excluded patients who were unable to perform moderate physical activity or who had cognitive deficits.

At enrollment, researchers supplied all patients with a pedometer and an appointment with a counselor to set goals for physical activity. They sent 2 text messages daily to the intervention group (and none to the control group) based on uploaded pedometer data. One message detailed physical activity progress and the second encouraged increased physical activity. The primary outcome was mean step counts per month; secondary outcomes included A1C and weight measured at 6 months.

The groups showed no significant difference in A1C (mean difference = 0.07%; 95% CI, –0.47% to 0.34%, P = .75) or weight loss (mean difference = 3.1 lb; 95% CI, –24.5 lb to 18.3 lb, P = .77). Many patients (43%) reported difficulty uploading step counts, receiving texts, and responding to texts. The dropout rate was 24%.

A second RCT with 150 patients, using a less elaborate protocol, assessed the effectiveness of tailored text-message reminders compared with nontailored text messages to improve A1C and body mass index (BMI).³ Patients were adult Iranians (mean age, 52.5 years) with T2DM who owned a cell phone and could receive and read text messages.

Patients filled out a diabetic self-care assessment to identify barriers to improving care and were randomized into 3 groups. The first group received tailored text messages (75% addressing the patient’s top 2 barriers to self-care and 25% general messages). The second group received nontailored text messages of encouragement. The control group received no text messages.

Continue to: After 3 months...

After 3 months, BMI was reduced in both messaging groups but not the control group (tailored text = –0.6 kg/m², nontailored text = –0.5 kg/m², controls = 0.7 kg/m²; P < .05). A1C levels didn’t change significantly. One limitation of the study was that 30% to 35% of the patients in the intervention group had a university-level education, compared with 12% in the control group.

Recommendations

The Department of Veterans Affairs issued guidelines in 2017 regarding management of patients with T2DM in primary care.⁴ The guidelines state that all patients should receive individualized self-management education using “modalities tailored to their preferences” (strong recommendation). They further recommend “offering one or more bidirectional telehealth interventions” in coordination with patients’ health care providers (weak recommendation).

Telehealth interventions may be associated with a decrease in hemoglobin A1C.

The 2017 diabetes self-management recommendations endorsed by the American Diabetes Association state that “strong evidence” shows that incorporating text messaging into diabetes care improves outcomes, enhances feedback loops, and empowers patients.⁵

Editor’s takeaway

Telehealth offers mechanisms for patients and physicians to enhance communication about health behaviors and health status. But does it alter outcomes? The cited literature suggests that benefits aren’t a forgone conclusion and that acceptability, ease of use, cost, and individualization are critical issues in telehealth design.

During the COVID-19 pandemic, nearly all primary care clinicians have been engaged in telemedicine. Telemedicine visits have certain ­advantages—especially convenience to patients. But there are dangers, as well. The ­following true story illustrates one of the important dangers.

The outcome might have been much different if there had been further delay.

“I had an interesting experience late last week that reminded me how important it is to be one’s own advocate in health care. I cut my foot going for an outdoor swim. It got infected so I had a telehealth visit with a physician assistant. She prescribed an antibiotic. The next day, Friday, the swelling and redness were rapidly moving up my foot. I called the office twice. I sent a picture of my foot. No call-back.

I texted my podiatrist the same photo with the question: Do I sit tight or go to the ED? A half hour later, he called me: Go to the hospital. I did. I got IV antibiotics and a tetanus shot. I was also told by the ED doc that my itchy palms were a reaction to the antibiotic I’d been prescribed, and that the physician assistant shouldn’t have prescribed a sulfa drug, given that my chart listed a past reaction to sulfa eye drops.”

The patient is a top-flight triathlete and the editor of JFP, Marya Ostrowski. She was gracious to share her story with us, and she did recover uneventfully, although the outcome might have been much different if there had been further delay.

Her story has 3 important teaching points:

1. We must ensure that our office phone system prioritizes calls from patients. If there is any hint that the problem is urgent, it must be handled immediately.^a
2. CAREFULLY check for allergies before prescribing medication. Perhaps the physician assistant did check the medication list and noted an allergy to eye drops but did not zero in on the fact that they were sulfa. Medication allergy lists can be misleading because they can be too specific. Had her medication allergy been listed as “sulfa medications,” rather than the specific eye drop, the physician assistant may have recognized the allergy correctly.
3. Finally, and most important in my estimation: Patients must act as their own health advocates. Patients are the final common barrier against medical ­errors and we must learn to listen to them carefully. We should encourage our patients to report problems and irregularities in care.

^a The physician assistant returned Marya’s calls at 4:30 that Friday afternoon—8 hours after her first outreach. Marya was already in an ED bed and the nursing staff was starting her IV.

During the COVID-19 pandemic, nearly all primary care clinicians have been engaged in telemedicine. Telemedicine visits have certain ­advantages—especially convenience to patients. But there are dangers, as well. The ­following true story illustrates one of the important dangers.

The outcome might have been much different if there had been further delay.

“I had an interesting experience late last week that reminded me how important it is to be one’s own advocate in health care. I cut my foot going for an outdoor swim. It got infected so I had a telehealth visit with a physician assistant. She prescribed an antibiotic. The next day, Friday, the swelling and redness were rapidly moving up my foot. I called the office twice. I sent a picture of my foot. No call-back.

I texted my podiatrist the same photo with the question: Do I sit tight or go to the ED? A half hour later, he called me: Go to the hospital. I did. I got IV antibiotics and a tetanus shot. I was also told by the ED doc that my itchy palms were a reaction to the antibiotic I’d been prescribed, and that the physician assistant shouldn’t have prescribed a sulfa drug, given that my chart listed a past reaction to sulfa eye drops.”

The patient is a top-flight triathlete and the editor of JFP, Marya Ostrowski. She was gracious to share her story with us, and she did recover uneventfully, although the outcome might have been much different if there had been further delay.

Her story has 3 important teaching points:

1. We must ensure that our office phone system prioritizes calls from patients. If there is any hint that the problem is urgent, it must be handled immediately.^a
2. CAREFULLY check for allergies before prescribing medication. Perhaps the physician assistant did check the medication list and noted an allergy to eye drops but did not zero in on the fact that they were sulfa. Medication allergy lists can be misleading because they can be too specific. Had her medication allergy been listed as “sulfa medications,” rather than the specific eye drop, the physician assistant may have recognized the allergy correctly.
3. Finally, and most important in my estimation: Patients must act as their own health advocates. Patients are the final common barrier against medical ­errors and we must learn to listen to them carefully. We should encourage our patients to report problems and irregularities in care.

^a The physician assistant returned Marya’s calls at 4:30 that Friday afternoon—8 hours after her first outreach. Marya was already in an ED bed and the nursing staff was starting her IV.

During the COVID-19 pandemic, nearly all primary care clinicians have been engaged in telemedicine. Telemedicine visits have certain ­advantages—especially convenience to patients. But there are dangers, as well. The ­following true story illustrates one of the important dangers.

The outcome might have been much different if there had been further delay.

“I had an interesting experience late last week that reminded me how important it is to be one’s own advocate in health care. I cut my foot going for an outdoor swim. It got infected so I had a telehealth visit with a physician assistant. She prescribed an antibiotic. The next day, Friday, the swelling and redness were rapidly moving up my foot. I called the office twice. I sent a picture of my foot. No call-back.

I texted my podiatrist the same photo with the question: Do I sit tight or go to the ED? A half hour later, he called me: Go to the hospital. I did. I got IV antibiotics and a tetanus shot. I was also told by the ED doc that my itchy palms were a reaction to the antibiotic I’d been prescribed, and that the physician assistant shouldn’t have prescribed a sulfa drug, given that my chart listed a past reaction to sulfa eye drops.”

The patient is a top-flight triathlete and the editor of JFP, Marya Ostrowski. She was gracious to share her story with us, and she did recover uneventfully, although the outcome might have been much different if there had been further delay.

Her story has 3 important teaching points:

1. We must ensure that our office phone system prioritizes calls from patients. If there is any hint that the problem is urgent, it must be handled immediately.^a
2. CAREFULLY check for allergies before prescribing medication. Perhaps the physician assistant did check the medication list and noted an allergy to eye drops but did not zero in on the fact that they were sulfa. Medication allergy lists can be misleading because they can be too specific. Had her medication allergy been listed as “sulfa medications,” rather than the specific eye drop, the physician assistant may have recognized the allergy correctly.
3. Finally, and most important in my estimation: Patients must act as their own health advocates. Patients are the final common barrier against medical ­errors and we must learn to listen to them carefully. We should encourage our patients to report problems and irregularities in care.

^a The physician assistant returned Marya’s calls at 4:30 that Friday afternoon—8 hours after her first outreach. Marya was already in an ED bed and the nursing staff was starting her IV.

ILLUSTRATIVE CASE

A 55-year-old man with well-controlled diabetes, hypertension, and sleep apnea arrives at your office for a routine annual physical. In reviewing his medications, you note that he takes a low-dose aspirin daily for “heart health.” He has no known cardiovascular disease (CVD). His calculated 10-year risk of a major cardiovascular event is 11%.

Should this patient continue taking a daily aspirin for primary prevention of CVD?

Many patients in the United States take aspirin for primary prevention of CVD as recommended by the US Preventive Services Task Force (USPSTF).² This recommendation was based on older studies of populations in which smoking rates were higher and statin use was less common, leading to an overall higher risk of CVD.³ (The USPSTF is currently in the process of updating its recommendation.) More recent RCTs have been done in patients with a lower baseline risk of CVD, and these outcomes are more generalizable to today’s population. This new meta-analysis includes recent RCTs that evaluated whether there is value in using aspirin for the primary prevention of CVD.

STUDY SUMMARY

No reduction in risk, increased chance of bleeding

Mahmoud and colleagues conducted a meta-analysis of 11 randomized controlled trials that included 157,248 patients and assessed the efficacy and safety of aspirin for primary prevention of cardiovascular events.¹ The mean age of the total population was 61.3 years; 52% were women and 14% were smokers. The doses of aspirin used in most of the studies were ≤ 100 mg/d, although 2 of the studies examined doses that were higher. Patients were followed for a mean of 6.6 years. The primary efficacy outcome was all-cause mortality, and the primary safety outcome was major bleeding (as defined by each study). The secondary outcomes included cardiovascular mortality, fatal and nonfatal myocardial infarction (MI), and fatal and ­nonfatal ischemic stroke.

Aspirin did not lower all-cause mortality (risk ratio [RR] = 0.98; 95% confidence ­interval [CI], 0.93-1.02) and was associated with an increased risk of major bleeding (RR = 1.47; 95% CI, 1.31-1.65; number needed to harm = 250) and intracranial hemorrhage (RR = 1.33; 95% CI, 1.13-1.58). Aspirin also had no effect on all-cause mortality in subgroup analyses of patients with diabetes mellitus or high cardiovascular risk (10-year risk > 7.5%). There was (again) an increased risk of major bleeding.

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice.

Aspirin had no effect on the secondary outcomes—with the exception of the incidence of MI (RR = 0.82; 95% CI, 0.71-0.94; number needed to treat = 333). However, this outcome was associated with considerable heterogeneity (I² = 67%), and the reduction was no longer evident after limiting the analysis to the more recent trials.

WHAT’S NEW?

Study is emblematic of a shift away from daily aspirin

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice, but the change has been gradual. Newer studies—large RCTs such as ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) and ASCEND (A Study of Cardiovascular Events iN Diabetes)—found no mortality benefit (all-cause or cardiovascular) from using aspirin in this context.

Continue to: The USPSTF guidelines...

The USPSTF guidelines in 2016 recommended prescribing daily aspirin for adults ages 50 to 59 who have a > 10% 10-year CVD risk and discussing with adults ages 60 to 69 the risks and benefits of daily aspirin.²

The 2019 American College of ­Cardiology/American Heart Association guidelines state that aspirin should no longer be used routinely for primary prevention, given the lack of net benefit. Patients ages 40 to 70 who are not at increased risk of bleeding with a higher risk of CVD may be considered for daily low-dose aspirin. The guidelines also state that adults > 70 years or those with increased risk of ­bleeding should not be started on a daily aspirin.⁴

CAVEATS

Jury is still out regarding very high-risk patients

While the meta-analysis by Mahmoud and colleagues makes a good case for discontinuing aspirin for primary prevention in most patients, the data do not examine in detail whether there is a benefit in patients with very high risk (> 20%) for atherosclerotic CVD. More studies are needed before making recommendations for that specific subgroup.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to give up an accepted practice

Physicians have been recommending aspirin for primary prevention of CVD for decades and many patients, who purchase aspirin themselves, are vested in the notion that aspirin protects them. It will take time for this change in practice to be accepted. Some patients may continue taking aspirin despite recommendation to stop. Primary care physicians will need to educate patients and clearly explain the rationale for stopping daily aspirin.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 55-year-old man with well-controlled diabetes, hypertension, and sleep apnea arrives at your office for a routine annual physical. In reviewing his medications, you note that he takes a low-dose aspirin daily for “heart health.” He has no known cardiovascular disease (CVD). His calculated 10-year risk of a major cardiovascular event is 11%.

Should this patient continue taking a daily aspirin for primary prevention of CVD?

Many patients in the United States take aspirin for primary prevention of CVD as recommended by the US Preventive Services Task Force (USPSTF).² This recommendation was based on older studies of populations in which smoking rates were higher and statin use was less common, leading to an overall higher risk of CVD.³ (The USPSTF is currently in the process of updating its recommendation.) More recent RCTs have been done in patients with a lower baseline risk of CVD, and these outcomes are more generalizable to today’s population. This new meta-analysis includes recent RCTs that evaluated whether there is value in using aspirin for the primary prevention of CVD.

STUDY SUMMARY

No reduction in risk, increased chance of bleeding

Mahmoud and colleagues conducted a meta-analysis of 11 randomized controlled trials that included 157,248 patients and assessed the efficacy and safety of aspirin for primary prevention of cardiovascular events.¹ The mean age of the total population was 61.3 years; 52% were women and 14% were smokers. The doses of aspirin used in most of the studies were ≤ 100 mg/d, although 2 of the studies examined doses that were higher. Patients were followed for a mean of 6.6 years. The primary efficacy outcome was all-cause mortality, and the primary safety outcome was major bleeding (as defined by each study). The secondary outcomes included cardiovascular mortality, fatal and nonfatal myocardial infarction (MI), and fatal and ­nonfatal ischemic stroke.

Aspirin did not lower all-cause mortality (risk ratio [RR] = 0.98; 95% confidence ­interval [CI], 0.93-1.02) and was associated with an increased risk of major bleeding (RR = 1.47; 95% CI, 1.31-1.65; number needed to harm = 250) and intracranial hemorrhage (RR = 1.33; 95% CI, 1.13-1.58). Aspirin also had no effect on all-cause mortality in subgroup analyses of patients with diabetes mellitus or high cardiovascular risk (10-year risk > 7.5%). There was (again) an increased risk of major bleeding.

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice.

Aspirin had no effect on the secondary outcomes—with the exception of the incidence of MI (RR = 0.82; 95% CI, 0.71-0.94; number needed to treat = 333). However, this outcome was associated with considerable heterogeneity (I² = 67%), and the reduction was no longer evident after limiting the analysis to the more recent trials.

WHAT’S NEW?

Study is emblematic of a shift away from daily aspirin

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice, but the change has been gradual. Newer studies—large RCTs such as ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) and ASCEND (A Study of Cardiovascular Events iN Diabetes)—found no mortality benefit (all-cause or cardiovascular) from using aspirin in this context.

Continue to: The USPSTF guidelines...

The USPSTF guidelines in 2016 recommended prescribing daily aspirin for adults ages 50 to 59 who have a > 10% 10-year CVD risk and discussing with adults ages 60 to 69 the risks and benefits of daily aspirin.²

The 2019 American College of ­Cardiology/American Heart Association guidelines state that aspirin should no longer be used routinely for primary prevention, given the lack of net benefit. Patients ages 40 to 70 who are not at increased risk of bleeding with a higher risk of CVD may be considered for daily low-dose aspirin. The guidelines also state that adults > 70 years or those with increased risk of ­bleeding should not be started on a daily aspirin.⁴

CAVEATS

Jury is still out regarding very high-risk patients

While the meta-analysis by Mahmoud and colleagues makes a good case for discontinuing aspirin for primary prevention in most patients, the data do not examine in detail whether there is a benefit in patients with very high risk (> 20%) for atherosclerotic CVD. More studies are needed before making recommendations for that specific subgroup.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to give up an accepted practice

Physicians have been recommending aspirin for primary prevention of CVD for decades and many patients, who purchase aspirin themselves, are vested in the notion that aspirin protects them. It will take time for this change in practice to be accepted. Some patients may continue taking aspirin despite recommendation to stop. Primary care physicians will need to educate patients and clearly explain the rationale for stopping daily aspirin.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 55-year-old man with well-controlled diabetes, hypertension, and sleep apnea arrives at your office for a routine annual physical. In reviewing his medications, you note that he takes a low-dose aspirin daily for “heart health.” He has no known cardiovascular disease (CVD). His calculated 10-year risk of a major cardiovascular event is 11%.

Should this patient continue taking a daily aspirin for primary prevention of CVD?

Many patients in the United States take aspirin for primary prevention of CVD as recommended by the US Preventive Services Task Force (USPSTF).² This recommendation was based on older studies of populations in which smoking rates were higher and statin use was less common, leading to an overall higher risk of CVD.³ (The USPSTF is currently in the process of updating its recommendation.) More recent RCTs have been done in patients with a lower baseline risk of CVD, and these outcomes are more generalizable to today’s population. This new meta-analysis includes recent RCTs that evaluated whether there is value in using aspirin for the primary prevention of CVD.

STUDY SUMMARY

No reduction in risk, increased chance of bleeding

Mahmoud and colleagues conducted a meta-analysis of 11 randomized controlled trials that included 157,248 patients and assessed the efficacy and safety of aspirin for primary prevention of cardiovascular events.¹ The mean age of the total population was 61.3 years; 52% were women and 14% were smokers. The doses of aspirin used in most of the studies were ≤ 100 mg/d, although 2 of the studies examined doses that were higher. Patients were followed for a mean of 6.6 years. The primary efficacy outcome was all-cause mortality, and the primary safety outcome was major bleeding (as defined by each study). The secondary outcomes included cardiovascular mortality, fatal and nonfatal myocardial infarction (MI), and fatal and ­nonfatal ischemic stroke.

Aspirin did not lower all-cause mortality (risk ratio [RR] = 0.98; 95% confidence ­interval [CI], 0.93-1.02) and was associated with an increased risk of major bleeding (RR = 1.47; 95% CI, 1.31-1.65; number needed to harm = 250) and intracranial hemorrhage (RR = 1.33; 95% CI, 1.13-1.58). Aspirin also had no effect on all-cause mortality in subgroup analyses of patients with diabetes mellitus or high cardiovascular risk (10-year risk > 7.5%). There was (again) an increased risk of major bleeding.

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice.

Aspirin had no effect on the secondary outcomes—with the exception of the incidence of MI (RR = 0.82; 95% CI, 0.71-0.94; number needed to treat = 333). However, this outcome was associated with considerable heterogeneity (I² = 67%), and the reduction was no longer evident after limiting the analysis to the more recent trials.

WHAT’S NEW?

Study is emblematic of a shift away from daily aspirin

Review of current guidelines and studies regarding the use of aspirin for primary prevention of CVD shows that the tide has been turning against this practice, but the change has been gradual. Newer studies—large RCTs such as ARRIVE (Aspirin to Reduce Risk of Initial Vascular Events) and ASCEND (A Study of Cardiovascular Events iN Diabetes)—found no mortality benefit (all-cause or cardiovascular) from using aspirin in this context.

Continue to: The USPSTF guidelines...

The USPSTF guidelines in 2016 recommended prescribing daily aspirin for adults ages 50 to 59 who have a > 10% 10-year CVD risk and discussing with adults ages 60 to 69 the risks and benefits of daily aspirin.²

The 2019 American College of ­Cardiology/American Heart Association guidelines state that aspirin should no longer be used routinely for primary prevention, given the lack of net benefit. Patients ages 40 to 70 who are not at increased risk of bleeding with a higher risk of CVD may be considered for daily low-dose aspirin. The guidelines also state that adults > 70 years or those with increased risk of ­bleeding should not be started on a daily aspirin.⁴

CAVEATS

Jury is still out regarding very high-risk patients

While the meta-analysis by Mahmoud and colleagues makes a good case for discontinuing aspirin for primary prevention in most patients, the data do not examine in detail whether there is a benefit in patients with very high risk (> 20%) for atherosclerotic CVD. More studies are needed before making recommendations for that specific subgroup.

CHALLENGES TO IMPLEMENTATION

Patients may not be eager to give up an accepted practice

Physicians have been recommending aspirin for primary prevention of CVD for decades and many patients, who purchase aspirin themselves, are vested in the notion that aspirin protects them. It will take time for this change in practice to be accepted. Some patients may continue taking aspirin despite recommendation to stop. Primary care physicians will need to educate patients and clearly explain the rationale for stopping daily aspirin.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.