Laura Morris, MD, MSPH, FAAFP

ILLUSTRATIVE CASE

An otherwise healthy 45-year-old man sustained an acute right-side Achilles tendon rupture while playing tennis. He has not taken quinolones recently, has no history of previous Achilles tendon rupture, and prior to this injury had no difficulty walking. He presents initially to his primary care physician and wants advice: Does he need surgery?

Acute Achilles tendon rupture manifests as acute-onset pain and impaired plantar flexion.² Older, active, male patients are at increased risk. There is disagreement among treating physicians regarding best practices for managing this common and debilitating injury. Prior clinical trials comparing operative to nonoperative management, as well as those comparing different surgical techniques, were limited by small sample sizes.^3-5

A 2019 systematic review and meta-­analysis that relied heavily on observational data suggested that nonoperative management carries greater risk for rerupture but lower risk for complications than surgical treatment, without differences in patient-reported functional outcomes.⁵ This 2022 RCT adds certainty to comparisons of surgical and nonoperative treatment.

STUDY SUMMARY

Equivalent outcomes but higher rates of rerupture for nonoperative patients

Norwegian investigators conducted a prospective, single-blind RCT at 4 treating facilities among patients ages 18 to 60 years with unilateral acute Achilles tendon rupture. A total of 554 patients were randomized in a 1:1:1 ratio to 1 of 3 groups: nonoperative treatment, open-repair surgery, or minimally invasive surgery. Ultimately, 526 patients who completed the intervention and at least 1 follow-up survey were included in the final analysis, which exceeded the number needed according to the pre-study 80% power calculation. Seventy-four percent of the patients were male, and the average age at time of injury was 40 years. Nearly all patients were classified as healthy or having only mild or well-controlled chronic illnesses.

Before randomization, patients completed the 10-item Achilles tendon Total Rupture Score (ATRS) questionnaire to gauge their pre-injury baseline function. ATRS is scored 0 to 100, with lower scores indicating more limitation in function; a clinically important difference is 8 to 10 points. There were no statistically significant differences in pre-injury baseline ATRS (92.7, 93.9, and 94.2 for the nonoperative, open-repair, and minimally invasive groups, respectively) or other patient characteristics among the 3 groups.

For all participants, application of a below-the-knee equinus cast with plantar flexion was performed within 72 hours after the injury. Patients in the surgical arms had surgery within 8 days, followed by application of a new cast. For all study groups, the cast was maintained for a total of 2 weeks, followed by 6 weeks of weight-bearing in an ankle-foot orthosis with heel wedges that were gradually reduced in number. All patients were treated with identical serial immobilization and physical therapy programs for 36 weeks.

The primary study outcome was change from baseline ATRS at 12 months after injury. Secondary outcomes included ATRS at 3 and 6 months and domain-specific quality-of-life scores (from the 36-Item Short Form Health Survey; SF-36) at 6 and 12 months. Patients also underwent physical testing of their Achilles tendon function at 6 and 12 months, during which they wore knee-high socks in order to blind the evaluators. Reruptures were recorded as secondary outcomes as well.

Continue to: There were no significant...

There were no significant differences between groups in the primary outcome. The mean changes in ATRS were −2.6 points (95% CI, −6.5 to 2.0) for nonoperative treatment compared with minimally invasive surgery, and 1.0 point (95% CI, −5.2 to 3.1) for nonoperative treatment compared with open repair.

All groups had similar secondary self-reported ATRS at 3 and 6 months and SF-36 scores at 6 and 12 months. Blinded physical test results also were similar between groups at 6 and 12 months.

Tendon rerupture within 12 months was more common in the nonoperative arm than in the 2 surgical arms (6.2% vs 0.6% in both operative groups; 5.6% difference; 95% CI for difference, 1.9-10.2 for open repair and 1.8-10.2 for minimally invasive surgery). Risk for nerve injury was higher in both the minimally invasive surgery group (5.2%) and the open-repair surgery group (2.8%) compared with the nonoperative group (0.6%; no P value given for comparison).

WHAT’S NEW

Largest RCT to date showed ­effectiveness of nonoperative Tx

This study is the largest well-powered and rigorously conducted RCT to show that nonoperative management of acute Achilles tendon rupture offers equivalent patient-reported outcomes at 12 months after injury. Nonoperative management was associated with a lower risk for nerve injury but higher risk for tendon rerupture.

Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

These findings support previous studies on the topic. As previously mentioned, a 2019 systematic review and meta-analysis of 10 RCTs (N = 944) and 19 observational studies (N = 14,918) examined operative compared with nonoperative treatment of acute Achilles tendon rupture and found a lower rerupture rate in the operative group but a higher complication rate.⁵ An underpowered 2010 RCT (N = 97) of operative vs nonoperative treatment of acute Achilles tendon rupture found no statistical difference in ATRS.³ Another underpowered RCT conducted in 2013 (N = 100) compared surgical treatment, accelerated rehabilitation, and nonsurgical treatment in acute Achilles tendon rupture and found no statistical difference in ATRS.⁴

CAVEATS

Study results may not apply to some patient groups

These findings may not apply to patients older than 60 years, who were excluded from this RCT, or patients with debilitation or significant chronic disease. Patients with prior Achilles rupture also were excluded.

The study population in Norway, which is more physically active than nearby countries, may not be generalizable worldwide.⁶ Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

CHALLENGES TO IMPLEMENTATION

Potentially limited options for patients

Most patients with acute Achilles tendon rupture are evaluated by orthopedic surgeons, who may or may not offer nonoperative management. Availability of practitioners to provide serial casting, appropriate heel wedges, and rehabilitation may vary regionally. All patients in this study were evaluated within 72 hours of injury; these findings may not be applicable for patients at a longer time since injury.

ILLUSTRATIVE CASE

An otherwise healthy 45-year-old man sustained an acute right-side Achilles tendon rupture while playing tennis. He has not taken quinolones recently, has no history of previous Achilles tendon rupture, and prior to this injury had no difficulty walking. He presents initially to his primary care physician and wants advice: Does he need surgery?

Acute Achilles tendon rupture manifests as acute-onset pain and impaired plantar flexion.² Older, active, male patients are at increased risk. There is disagreement among treating physicians regarding best practices for managing this common and debilitating injury. Prior clinical trials comparing operative to nonoperative management, as well as those comparing different surgical techniques, were limited by small sample sizes.^3-5

A 2019 systematic review and meta-­analysis that relied heavily on observational data suggested that nonoperative management carries greater risk for rerupture but lower risk for complications than surgical treatment, without differences in patient-reported functional outcomes.⁵ This 2022 RCT adds certainty to comparisons of surgical and nonoperative treatment.

STUDY SUMMARY

Equivalent outcomes but higher rates of rerupture for nonoperative patients

Norwegian investigators conducted a prospective, single-blind RCT at 4 treating facilities among patients ages 18 to 60 years with unilateral acute Achilles tendon rupture. A total of 554 patients were randomized in a 1:1:1 ratio to 1 of 3 groups: nonoperative treatment, open-repair surgery, or minimally invasive surgery. Ultimately, 526 patients who completed the intervention and at least 1 follow-up survey were included in the final analysis, which exceeded the number needed according to the pre-study 80% power calculation. Seventy-four percent of the patients were male, and the average age at time of injury was 40 years. Nearly all patients were classified as healthy or having only mild or well-controlled chronic illnesses.

Before randomization, patients completed the 10-item Achilles tendon Total Rupture Score (ATRS) questionnaire to gauge their pre-injury baseline function. ATRS is scored 0 to 100, with lower scores indicating more limitation in function; a clinically important difference is 8 to 10 points. There were no statistically significant differences in pre-injury baseline ATRS (92.7, 93.9, and 94.2 for the nonoperative, open-repair, and minimally invasive groups, respectively) or other patient characteristics among the 3 groups.

For all participants, application of a below-the-knee equinus cast with plantar flexion was performed within 72 hours after the injury. Patients in the surgical arms had surgery within 8 days, followed by application of a new cast. For all study groups, the cast was maintained for a total of 2 weeks, followed by 6 weeks of weight-bearing in an ankle-foot orthosis with heel wedges that were gradually reduced in number. All patients were treated with identical serial immobilization and physical therapy programs for 36 weeks.

The primary study outcome was change from baseline ATRS at 12 months after injury. Secondary outcomes included ATRS at 3 and 6 months and domain-specific quality-of-life scores (from the 36-Item Short Form Health Survey; SF-36) at 6 and 12 months. Patients also underwent physical testing of their Achilles tendon function at 6 and 12 months, during which they wore knee-high socks in order to blind the evaluators. Reruptures were recorded as secondary outcomes as well.

Continue to: There were no significant...

There were no significant differences between groups in the primary outcome. The mean changes in ATRS were −2.6 points (95% CI, −6.5 to 2.0) for nonoperative treatment compared with minimally invasive surgery, and 1.0 point (95% CI, −5.2 to 3.1) for nonoperative treatment compared with open repair.

All groups had similar secondary self-reported ATRS at 3 and 6 months and SF-36 scores at 6 and 12 months. Blinded physical test results also were similar between groups at 6 and 12 months.

Tendon rerupture within 12 months was more common in the nonoperative arm than in the 2 surgical arms (6.2% vs 0.6% in both operative groups; 5.6% difference; 95% CI for difference, 1.9-10.2 for open repair and 1.8-10.2 for minimally invasive surgery). Risk for nerve injury was higher in both the minimally invasive surgery group (5.2%) and the open-repair surgery group (2.8%) compared with the nonoperative group (0.6%; no P value given for comparison).

WHAT’S NEW

Largest RCT to date showed ­effectiveness of nonoperative Tx

This study is the largest well-powered and rigorously conducted RCT to show that nonoperative management of acute Achilles tendon rupture offers equivalent patient-reported outcomes at 12 months after injury. Nonoperative management was associated with a lower risk for nerve injury but higher risk for tendon rerupture.

Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

These findings support previous studies on the topic. As previously mentioned, a 2019 systematic review and meta-analysis of 10 RCTs (N = 944) and 19 observational studies (N = 14,918) examined operative compared with nonoperative treatment of acute Achilles tendon rupture and found a lower rerupture rate in the operative group but a higher complication rate.⁵ An underpowered 2010 RCT (N = 97) of operative vs nonoperative treatment of acute Achilles tendon rupture found no statistical difference in ATRS.³ Another underpowered RCT conducted in 2013 (N = 100) compared surgical treatment, accelerated rehabilitation, and nonsurgical treatment in acute Achilles tendon rupture and found no statistical difference in ATRS.⁴

CAVEATS

Study results may not apply to some patient groups

These findings may not apply to patients older than 60 years, who were excluded from this RCT, or patients with debilitation or significant chronic disease. Patients with prior Achilles rupture also were excluded.

The study population in Norway, which is more physically active than nearby countries, may not be generalizable worldwide.⁶ Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

CHALLENGES TO IMPLEMENTATION

Potentially limited options for patients

Most patients with acute Achilles tendon rupture are evaluated by orthopedic surgeons, who may or may not offer nonoperative management. Availability of practitioners to provide serial casting, appropriate heel wedges, and rehabilitation may vary regionally. All patients in this study were evaluated within 72 hours of injury; these findings may not be applicable for patients at a longer time since injury.

ILLUSTRATIVE CASE

An otherwise healthy 45-year-old man sustained an acute right-side Achilles tendon rupture while playing tennis. He has not taken quinolones recently, has no history of previous Achilles tendon rupture, and prior to this injury had no difficulty walking. He presents initially to his primary care physician and wants advice: Does he need surgery?

Acute Achilles tendon rupture manifests as acute-onset pain and impaired plantar flexion.² Older, active, male patients are at increased risk. There is disagreement among treating physicians regarding best practices for managing this common and debilitating injury. Prior clinical trials comparing operative to nonoperative management, as well as those comparing different surgical techniques, were limited by small sample sizes.^3-5

A 2019 systematic review and meta-­analysis that relied heavily on observational data suggested that nonoperative management carries greater risk for rerupture but lower risk for complications than surgical treatment, without differences in patient-reported functional outcomes.⁵ This 2022 RCT adds certainty to comparisons of surgical and nonoperative treatment.

STUDY SUMMARY

Equivalent outcomes but higher rates of rerupture for nonoperative patients

Norwegian investigators conducted a prospective, single-blind RCT at 4 treating facilities among patients ages 18 to 60 years with unilateral acute Achilles tendon rupture. A total of 554 patients were randomized in a 1:1:1 ratio to 1 of 3 groups: nonoperative treatment, open-repair surgery, or minimally invasive surgery. Ultimately, 526 patients who completed the intervention and at least 1 follow-up survey were included in the final analysis, which exceeded the number needed according to the pre-study 80% power calculation. Seventy-four percent of the patients were male, and the average age at time of injury was 40 years. Nearly all patients were classified as healthy or having only mild or well-controlled chronic illnesses.

Before randomization, patients completed the 10-item Achilles tendon Total Rupture Score (ATRS) questionnaire to gauge their pre-injury baseline function. ATRS is scored 0 to 100, with lower scores indicating more limitation in function; a clinically important difference is 8 to 10 points. There were no statistically significant differences in pre-injury baseline ATRS (92.7, 93.9, and 94.2 for the nonoperative, open-repair, and minimally invasive groups, respectively) or other patient characteristics among the 3 groups.

For all participants, application of a below-the-knee equinus cast with plantar flexion was performed within 72 hours after the injury. Patients in the surgical arms had surgery within 8 days, followed by application of a new cast. For all study groups, the cast was maintained for a total of 2 weeks, followed by 6 weeks of weight-bearing in an ankle-foot orthosis with heel wedges that were gradually reduced in number. All patients were treated with identical serial immobilization and physical therapy programs for 36 weeks.

The primary study outcome was change from baseline ATRS at 12 months after injury. Secondary outcomes included ATRS at 3 and 6 months and domain-specific quality-of-life scores (from the 36-Item Short Form Health Survey; SF-36) at 6 and 12 months. Patients also underwent physical testing of their Achilles tendon function at 6 and 12 months, during which they wore knee-high socks in order to blind the evaluators. Reruptures were recorded as secondary outcomes as well.

Continue to: There were no significant...

There were no significant differences between groups in the primary outcome. The mean changes in ATRS were −2.6 points (95% CI, −6.5 to 2.0) for nonoperative treatment compared with minimally invasive surgery, and 1.0 point (95% CI, −5.2 to 3.1) for nonoperative treatment compared with open repair.

All groups had similar secondary self-reported ATRS at 3 and 6 months and SF-36 scores at 6 and 12 months. Blinded physical test results also were similar between groups at 6 and 12 months.

Tendon rerupture within 12 months was more common in the nonoperative arm than in the 2 surgical arms (6.2% vs 0.6% in both operative groups; 5.6% difference; 95% CI for difference, 1.9-10.2 for open repair and 1.8-10.2 for minimally invasive surgery). Risk for nerve injury was higher in both the minimally invasive surgery group (5.2%) and the open-repair surgery group (2.8%) compared with the nonoperative group (0.6%; no P value given for comparison).

WHAT’S NEW

Largest RCT to date showed ­effectiveness of nonoperative Tx

This study is the largest well-powered and rigorously conducted RCT to show that nonoperative management of acute Achilles tendon rupture offers equivalent patient-reported outcomes at 12 months after injury. Nonoperative management was associated with a lower risk for nerve injury but higher risk for tendon rerupture.

Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

These findings support previous studies on the topic. As previously mentioned, a 2019 systematic review and meta-analysis of 10 RCTs (N = 944) and 19 observational studies (N = 14,918) examined operative compared with nonoperative treatment of acute Achilles tendon rupture and found a lower rerupture rate in the operative group but a higher complication rate.⁵ An underpowered 2010 RCT (N = 97) of operative vs nonoperative treatment of acute Achilles tendon rupture found no statistical difference in ATRS.³ Another underpowered RCT conducted in 2013 (N = 100) compared surgical treatment, accelerated rehabilitation, and nonsurgical treatment in acute Achilles tendon rupture and found no statistical difference in ATRS.⁴

CAVEATS

Study results may not apply to some patient groups

These findings may not apply to patients older than 60 years, who were excluded from this RCT, or patients with debilitation or significant chronic disease. Patients with prior Achilles rupture also were excluded.

The study population in Norway, which is more physically active than nearby countries, may not be generalizable worldwide.⁶ Patients wishing to minimize the risk for rerupture may still prefer to have surgery after acute Achilles tendon rupture.

CHALLENGES TO IMPLEMENTATION

Potentially limited options for patients

Most patients with acute Achilles tendon rupture are evaluated by orthopedic surgeons, who may or may not offer nonoperative management. Availability of practitioners to provide serial casting, appropriate heel wedges, and rehabilitation may vary regionally. All patients in this study were evaluated within 72 hours of injury; these findings may not be applicable for patients at a longer time since injury.

ILLUSTRATIVE CASE

A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?

Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.^2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.⁴ Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.³

Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.² Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.^5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.

STUDY SUMMARY

Active BP treatment yielded better pregnancy outcomes

In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.

The American College of Obstetricians and Gynecologists and the Society for Maternal– Fetal Medicine have issued statements recommending a change in practice based on this trial.

First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention­-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.

Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.

WHAT’S NEW

Target BP of < 140/90 mm Hg reduced risk

This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-­gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.^8,9

Continue to: CAVEATS

Patient characteristics and medication choices were limited

This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.

Most patients in the trial who required medications received labetalol or extended-­release nifedipine. It is unclear if other medications would produce similar outcomes.

CHALLENGES TO IMPLEMENTATION

Limited challenges anticipated

There should be limited challenges to implementation.

ILLUSTRATIVE CASE

A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?

Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.^2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.⁴ Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.³

Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.² Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.^5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.

STUDY SUMMARY

Active BP treatment yielded better pregnancy outcomes

In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.

The American College of Obstetricians and Gynecologists and the Society for Maternal– Fetal Medicine have issued statements recommending a change in practice based on this trial.

First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention­-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.

Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.

WHAT’S NEW

Target BP of < 140/90 mm Hg reduced risk

This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-­gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.^8,9

Continue to: CAVEATS

Patient characteristics and medication choices were limited

This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.

Most patients in the trial who required medications received labetalol or extended-­release nifedipine. It is unclear if other medications would produce similar outcomes.

CHALLENGES TO IMPLEMENTATION

Limited challenges anticipated

There should be limited challenges to implementation.

ILLUSTRATIVE CASE

A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?

Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.^2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.⁴ Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.³

Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.² Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.^5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.

STUDY SUMMARY

Active BP treatment yielded better pregnancy outcomes

In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.

The American College of Obstetricians and Gynecologists and the Society for Maternal– Fetal Medicine have issued statements recommending a change in practice based on this trial.

First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention­-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.

Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.

WHAT’S NEW

Target BP of < 140/90 mm Hg reduced risk

This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-­gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.^8,9

Continue to: CAVEATS

Patient characteristics and medication choices were limited

This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.

Most patients in the trial who required medications received labetalol or extended-­release nifedipine. It is unclear if other medications would produce similar outcomes.

CHALLENGES TO IMPLEMENTATION

Limited challenges anticipated

There should be limited challenges to implementation.

ILLUSTRATIVE CASE

A 67-year-old man with hypertension that is well controlled on hydrochlorothiazide 25 mg po daily was admitted to the family medicine inpatient service for community-­acquired pneumonia requiring antibiotic therapy and oxygen support. Despite improvement in his overall condition, his blood pressure was consistently > 160/90 mm Hg during his hospitalization. He was treated with lisinopril 10 mg po daily in addition to his home medications, which helped achieve recommended blood pressure goals.

Prior to discharge, his blood pressure was noted to be 108/62 mm Hg. He asks if it is necessary to continue this new blood pressure medicine, as his home blood pressure readings had been within the goal set by his primary care physician. Should you continue this new antihypertensive agent at discharge?

Outpatient antihypertensive medication regimens are commonly intensified at hospital discharge in response to transient short-term elevations in blood pressure during inpatient encounters for noncardiac conditions.^1,2 This is typically a reflexive response during a hospitalization, despite the unknown long-term, patient-oriented clinical outcomes. These short-term, in-­hospital blood pressure elevations may be due to numerous temporary causes, such as stress/anxiety, a pain response, agitation, a medication adverse effect, or volume overload.³

The transition from inpatient to outpatient care is a high-risk period, especially for older adults, as functional status is generally worse at hospital discharge than prehospitalization baseline.⁴ To compound this problem, adverse drug reactions are a common cause of hospitalization for older adults. Changing blood pressure medications in response to acute physiologic changes during illness may contribute to patient harm. Although observational studies of adverse drug reactions related to blood pressure medications are numerous, researchers have only evaluated adverse drug reactions pertaining to hospital admissions.^5-8 This study sought to evaluate the clinical outcomes associated with intensification of antihypertensive regimens at discharge among older adults.

STUDY SUMMARY

Increased risk of readmission, adverse events after intensification at discharge

This retrospective cohort study, which was conducted across multiple Veterans Health Administration (VHA) hospitals, evaluated the association between intensifying blood pressure medication regimens at hospital discharge and sustained clinical outcomes in the outpatient setting. Study participants were community-dwelling adults (98% male) ages 65 years or older who had a prehospitalization diagnosis of hypertension and were admitted for pneumonia, urinary tract infection, or venous thromboembolism over a 3-year period (n = 4056).

This first study to address outcomes related to intensification of BP regimens at discharge found increased risk of readmission and serious adverse events within 30 days.

Antihypertensive medication changes at discharge were evaluated using information pulled from VHA pharmacies, combined with clinical data merged from VHA and Medicare claims. Intensification was defined as either adding a new blood pressure medication or a dose increase of more than 20% on a previously prescribed antihypertensive medication. Patients were excluded if they were discharged with a secondary diagnosis that required modifications to a blood pressure medication (such as atrial fibrillation, acute coronary syndrome, or stroke), were hospitalized in the previous 30 days, were admitted from a skilled nursing facility, or received more than 20% of their care (including filling prescriptions) outside the VHA system.

Primary outcomes included hospital readmission or SAEs (falls, syncope, hypotension, serious electrolyte abnormalities, or acute kidney injury) within 30 days or having a cardiovascular event within 1 year of hospital discharge. Secondary outcomes included the change in systolic blood pressure (SBP) within 1 year after discharge. Propensity score matching was used as a balancing factor to create a matched-pairs cohort to compare those receiving blood pressure medication intensification at hospital discharge with those who did not.

Continue to: Intensification of the blood pressure...

Intensification of the blood pressure regimen at hospital discharge was associated with an increased risk in 30-day hospital readmission (hazard ratio [HR] = 1.23; 95% CI, 1.07–1.42; number needed to harm [NNH] = 27) and SAEs (HR = 1.41; 95% CI, 1.06–1.88; NNH = 63). There was no associated reduction in cardiovascular events (HR = 1.18; 95% CI, 0.99–1.40) or change in mean SBP within 1 year after hospital discharge in those who received intensification vs those who did not (mean BP, 134.7 vs 134.4 mm Hg; difference-in-differences estimate = 0.2 mm Hg; 95% CI, −2.0 to 2.4 mm Hg).

WHAT’S NEW

First study on outcomes related to HTN med changes at hospital discharge

This well-designed, retrospective cohort study provides important clinical data to help guide inpatient blood pressure management decisions for patients with noncardiac conditions. No clinical trials up to that time had assessed patient-oriented outcomes when antihypertensive medication regimens were intensified at hospital discharge.

CAVEATS

Study population: Primarily older men with noncardiac conditions

Selected populations benefit from intensive blood pressure control based on specific risk factors and medical conditions. In patients at high risk for cardiovascular disease, without a history of stroke or diabetes, intensive blood pressure control (SBP < 120 mm Hg) improves cardiovascular outcomes and overall survival compared with standard therapy (SBP < 140 mm Hg).⁹ This retrospective cohort study involved mainly elderly male patients with noncardiac conditions. The study also excluded patients with a secondary diagnosis requiring modifications to an antihypertensive regimen, such as atrial fibrillation, acute coronary syndrome, or cerebrovascular accident. Thus, the findings may not be applicable to these patient populations.

CHALLENGES TO IMPLEMENTATION

Clinicians will need to address individual needs

Physicians have to balance various antihypertensive management strategies, as competing medical specialty society guidelines recommend differing targets for optimal blood pressure control. Given the concern for medicolegal liability and potential harms of therapeutic inertia, inpatient physicians must consider whether hospitalization is the best time to alter medications for long-term outpatient blood pressure control. Finally, the decision to leave blood pressure management to outpatient physicians assumes the patient has a continuity relationship with a primary care medical home.

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 67-year-old man with hypertension that is well controlled on hydrochlorothiazide 25 mg po daily was admitted to the family medicine inpatient service for community-­acquired pneumonia requiring antibiotic therapy and oxygen support. Despite improvement in his overall condition, his blood pressure was consistently > 160/90 mm Hg during his hospitalization. He was treated with lisinopril 10 mg po daily in addition to his home medications, which helped achieve recommended blood pressure goals.

Prior to discharge, his blood pressure was noted to be 108/62 mm Hg. He asks if it is necessary to continue this new blood pressure medicine, as his home blood pressure readings had been within the goal set by his primary care physician. Should you continue this new antihypertensive agent at discharge?

Outpatient antihypertensive medication regimens are commonly intensified at hospital discharge in response to transient short-term elevations in blood pressure during inpatient encounters for noncardiac conditions.^1,2 This is typically a reflexive response during a hospitalization, despite the unknown long-term, patient-oriented clinical outcomes. These short-term, in-­hospital blood pressure elevations may be due to numerous temporary causes, such as stress/anxiety, a pain response, agitation, a medication adverse effect, or volume overload.³

The transition from inpatient to outpatient care is a high-risk period, especially for older adults, as functional status is generally worse at hospital discharge than prehospitalization baseline.⁴ To compound this problem, adverse drug reactions are a common cause of hospitalization for older adults. Changing blood pressure medications in response to acute physiologic changes during illness may contribute to patient harm. Although observational studies of adverse drug reactions related to blood pressure medications are numerous, researchers have only evaluated adverse drug reactions pertaining to hospital admissions.^5-8 This study sought to evaluate the clinical outcomes associated with intensification of antihypertensive regimens at discharge among older adults.

STUDY SUMMARY

Increased risk of readmission, adverse events after intensification at discharge

This retrospective cohort study, which was conducted across multiple Veterans Health Administration (VHA) hospitals, evaluated the association between intensifying blood pressure medication regimens at hospital discharge and sustained clinical outcomes in the outpatient setting. Study participants were community-dwelling adults (98% male) ages 65 years or older who had a prehospitalization diagnosis of hypertension and were admitted for pneumonia, urinary tract infection, or venous thromboembolism over a 3-year period (n = 4056).

This first study to address outcomes related to intensification of BP regimens at discharge found increased risk of readmission and serious adverse events within 30 days.

Antihypertensive medication changes at discharge were evaluated using information pulled from VHA pharmacies, combined with clinical data merged from VHA and Medicare claims. Intensification was defined as either adding a new blood pressure medication or a dose increase of more than 20% on a previously prescribed antihypertensive medication. Patients were excluded if they were discharged with a secondary diagnosis that required modifications to a blood pressure medication (such as atrial fibrillation, acute coronary syndrome, or stroke), were hospitalized in the previous 30 days, were admitted from a skilled nursing facility, or received more than 20% of their care (including filling prescriptions) outside the VHA system.

Primary outcomes included hospital readmission or SAEs (falls, syncope, hypotension, serious electrolyte abnormalities, or acute kidney injury) within 30 days or having a cardiovascular event within 1 year of hospital discharge. Secondary outcomes included the change in systolic blood pressure (SBP) within 1 year after discharge. Propensity score matching was used as a balancing factor to create a matched-pairs cohort to compare those receiving blood pressure medication intensification at hospital discharge with those who did not.

Continue to: Intensification of the blood pressure...

Intensification of the blood pressure regimen at hospital discharge was associated with an increased risk in 30-day hospital readmission (hazard ratio [HR] = 1.23; 95% CI, 1.07–1.42; number needed to harm [NNH] = 27) and SAEs (HR = 1.41; 95% CI, 1.06–1.88; NNH = 63). There was no associated reduction in cardiovascular events (HR = 1.18; 95% CI, 0.99–1.40) or change in mean SBP within 1 year after hospital discharge in those who received intensification vs those who did not (mean BP, 134.7 vs 134.4 mm Hg; difference-in-differences estimate = 0.2 mm Hg; 95% CI, −2.0 to 2.4 mm Hg).

WHAT’S NEW

First study on outcomes related to HTN med changes at hospital discharge

This well-designed, retrospective cohort study provides important clinical data to help guide inpatient blood pressure management decisions for patients with noncardiac conditions. No clinical trials up to that time had assessed patient-oriented outcomes when antihypertensive medication regimens were intensified at hospital discharge.

CAVEATS

Study population: Primarily older men with noncardiac conditions

Selected populations benefit from intensive blood pressure control based on specific risk factors and medical conditions. In patients at high risk for cardiovascular disease, without a history of stroke or diabetes, intensive blood pressure control (SBP < 120 mm Hg) improves cardiovascular outcomes and overall survival compared with standard therapy (SBP < 140 mm Hg).⁹ This retrospective cohort study involved mainly elderly male patients with noncardiac conditions. The study also excluded patients with a secondary diagnosis requiring modifications to an antihypertensive regimen, such as atrial fibrillation, acute coronary syndrome, or cerebrovascular accident. Thus, the findings may not be applicable to these patient populations.

CHALLENGES TO IMPLEMENTATION

Clinicians will need to address individual needs

Physicians have to balance various antihypertensive management strategies, as competing medical specialty society guidelines recommend differing targets for optimal blood pressure control. Given the concern for medicolegal liability and potential harms of therapeutic inertia, inpatient physicians must consider whether hospitalization is the best time to alter medications for long-term outpatient blood pressure control. Finally, the decision to leave blood pressure management to outpatient physicians assumes the patient has a continuity relationship with a primary care medical home.

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 67-year-old man with hypertension that is well controlled on hydrochlorothiazide 25 mg po daily was admitted to the family medicine inpatient service for community-­acquired pneumonia requiring antibiotic therapy and oxygen support. Despite improvement in his overall condition, his blood pressure was consistently > 160/90 mm Hg during his hospitalization. He was treated with lisinopril 10 mg po daily in addition to his home medications, which helped achieve recommended blood pressure goals.

Prior to discharge, his blood pressure was noted to be 108/62 mm Hg. He asks if it is necessary to continue this new blood pressure medicine, as his home blood pressure readings had been within the goal set by his primary care physician. Should you continue this new antihypertensive agent at discharge?

Outpatient antihypertensive medication regimens are commonly intensified at hospital discharge in response to transient short-term elevations in blood pressure during inpatient encounters for noncardiac conditions.^1,2 This is typically a reflexive response during a hospitalization, despite the unknown long-term, patient-oriented clinical outcomes. These short-term, in-­hospital blood pressure elevations may be due to numerous temporary causes, such as stress/anxiety, a pain response, agitation, a medication adverse effect, or volume overload.³

The transition from inpatient to outpatient care is a high-risk period, especially for older adults, as functional status is generally worse at hospital discharge than prehospitalization baseline.⁴ To compound this problem, adverse drug reactions are a common cause of hospitalization for older adults. Changing blood pressure medications in response to acute physiologic changes during illness may contribute to patient harm. Although observational studies of adverse drug reactions related to blood pressure medications are numerous, researchers have only evaluated adverse drug reactions pertaining to hospital admissions.^5-8 This study sought to evaluate the clinical outcomes associated with intensification of antihypertensive regimens at discharge among older adults.

STUDY SUMMARY

Increased risk of readmission, adverse events after intensification at discharge

This retrospective cohort study, which was conducted across multiple Veterans Health Administration (VHA) hospitals, evaluated the association between intensifying blood pressure medication regimens at hospital discharge and sustained clinical outcomes in the outpatient setting. Study participants were community-dwelling adults (98% male) ages 65 years or older who had a prehospitalization diagnosis of hypertension and were admitted for pneumonia, urinary tract infection, or venous thromboembolism over a 3-year period (n = 4056).

This first study to address outcomes related to intensification of BP regimens at discharge found increased risk of readmission and serious adverse events within 30 days.

Antihypertensive medication changes at discharge were evaluated using information pulled from VHA pharmacies, combined with clinical data merged from VHA and Medicare claims. Intensification was defined as either adding a new blood pressure medication or a dose increase of more than 20% on a previously prescribed antihypertensive medication. Patients were excluded if they were discharged with a secondary diagnosis that required modifications to a blood pressure medication (such as atrial fibrillation, acute coronary syndrome, or stroke), were hospitalized in the previous 30 days, were admitted from a skilled nursing facility, or received more than 20% of their care (including filling prescriptions) outside the VHA system.

Primary outcomes included hospital readmission or SAEs (falls, syncope, hypotension, serious electrolyte abnormalities, or acute kidney injury) within 30 days or having a cardiovascular event within 1 year of hospital discharge. Secondary outcomes included the change in systolic blood pressure (SBP) within 1 year after discharge. Propensity score matching was used as a balancing factor to create a matched-pairs cohort to compare those receiving blood pressure medication intensification at hospital discharge with those who did not.

Continue to: Intensification of the blood pressure...

Intensification of the blood pressure regimen at hospital discharge was associated with an increased risk in 30-day hospital readmission (hazard ratio [HR] = 1.23; 95% CI, 1.07–1.42; number needed to harm [NNH] = 27) and SAEs (HR = 1.41; 95% CI, 1.06–1.88; NNH = 63). There was no associated reduction in cardiovascular events (HR = 1.18; 95% CI, 0.99–1.40) or change in mean SBP within 1 year after hospital discharge in those who received intensification vs those who did not (mean BP, 134.7 vs 134.4 mm Hg; difference-in-differences estimate = 0.2 mm Hg; 95% CI, −2.0 to 2.4 mm Hg).

WHAT’S NEW

First study on outcomes related to HTN med changes at hospital discharge

This well-designed, retrospective cohort study provides important clinical data to help guide inpatient blood pressure management decisions for patients with noncardiac conditions. No clinical trials up to that time had assessed patient-oriented outcomes when antihypertensive medication regimens were intensified at hospital discharge.

CAVEATS

Study population: Primarily older men with noncardiac conditions

Selected populations benefit from intensive blood pressure control based on specific risk factors and medical conditions. In patients at high risk for cardiovascular disease, without a history of stroke or diabetes, intensive blood pressure control (SBP < 120 mm Hg) improves cardiovascular outcomes and overall survival compared with standard therapy (SBP < 140 mm Hg).⁹ This retrospective cohort study involved mainly elderly male patients with noncardiac conditions. The study also excluded patients with a secondary diagnosis requiring modifications to an antihypertensive regimen, such as atrial fibrillation, acute coronary syndrome, or cerebrovascular accident. Thus, the findings may not be applicable to these patient populations.

CHALLENGES TO IMPLEMENTATION

Clinicians will need to address individual needs

Physicians have to balance various antihypertensive management strategies, as competing medical specialty society guidelines recommend differing targets for optimal blood pressure control. Given the concern for medicolegal liability and potential harms of therapeutic inertia, inpatient physicians must consider whether hospitalization is the best time to alter medications for long-term outpatient blood pressure control. Finally, the decision to leave blood pressure management to outpatient physicians assumes the patient has a continuity relationship with a primary care medical home.

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.