Treatments for Isolated Systolic Hypertension

Background information needed

An 87-year-old Caucasian male with past medical history of hypertension, diabetes, stage IV chronic kidney disease. The patient was admitted to Mesquite Specialty Hospital due to severe cellulitis. Patient went into the acute renal injury and superimposed on chronic kidney disease. He was started on hemodialysis. Patient developed isolated systolic blood pressure (~150/60 mmHg) and was not on any high blood pressure medications.

Responses

Isolated systolic hypertension (ISH) is defined as systolic blood pressure greater than 160 mmHg while the diastolic pressure lesser than 90 mmHg, and it is the most common form of hypertension in patients older than 60 years old.¹ The reasons to develop ISH are either from the exhaustion of diastolic hypertension due to long-term hypertension or the increase in systolic blood pressure secondary to increased arterial stiffness.² There are many causes of ISH include anemia, hyperthyroidism, aortic insufficiency, arteriovenous fistula, or Paget disease of bone.³ According to the 2013 European Society of Cardiology/European Society of Hypertension guidelines, there are three categories for ISH: Grade I (SBP >140-159 mmHg), Grade II (SBP > 160-179 mmHg), and Grade III (SBP > 180 mmHg).²

According to the American Journal of Medicine, the preferred first-line treatment for ISH is dihydropyridine-type calcium channel blockers and thiazide-like diuretics.² Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACE/ ARBs) has less efficacy but are preferred in patients with chronic systolic heart failure, chronic kidney disease or post-myocardial infarction.² The journal also recommended avoiding beta-blockers in patients with ISH due to an increase in arterial stiffness.

The first landmark clinical trials for ISH was the Systolic Hypertension in the Elderly Program (SHEP) trial. It was a randomized double-blind placebo-controlled trial that studied the effect of antihypertensive medications in ISH patients with a 4.5 years follow-up period.³ There were 4736 participants with the mean age of 72 and mean blood pressure of 170/77 mmHg at baseline.³ The participants were given chlorthalidone 12.5 mg per day initially then increase to 25 mg if necessary. Atenolol 25 and reserpine were considered if the patients required further antihypertension medications.³ The results showed that the treatment group had a lower 5-year average systolic and diastolic blood pressure (143/68 mmHg vs 155/72 mmHg) compared to the placebo group. The treatment group also had a significantly lower incidence of stroke compared to the placebo group (5.2% versus 8.2 % with placebo).³ There was also a 25% reduction in coronary artery disease and a 32% reduction in the treatment group. The study concluded that the chlorthalidone used as first line therapy can reduce the incidence of stroke with a 5-year absolute benefit of 30 events per 1000 participants.³

On the other hands, the Hypertension in the Very Elderly Trial (HYVET) trial studied the effectiveness and safety of antihypertensive medications in patients older than 80 years old. There were 3845 participants with the mean age of 84 years and a sustained mean systolic blood pressure 173/91 mmHg.⁴ They were randomized to receive either placebo or the thiazide diuretic indapamide. Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, was added if the participants failed to meet the target blood pressure of 150/80 mmHg. The study found that the treatment group had a significantly lower incidence of fatal stroke (6.5% versus 10.7%) and all stokes (12.4% versus 17.7%, p<0.06) compared to the placebo group.⁴ The mortality from all causes was also lower in the treatment group (59.6 per 1000 persons per year vs 47.2 per 1000 persons per year).⁴ The study concluded that patients over the age of 80 years with ISH would be benefit from a target blood pressure of less than 150/80 mmHg.

In conclusion, thiazide-like diuretics and dihydropyridine-type calcium channel blockers can be used as first-line treatment for patients with ISH. Because the patient has a history of CKD, ACE/ARBs can be used as alternative therapy. The goal is to obtain a target blood pressure of 150/80 mmHg while monitoring the patient closely to prevent worsening outcomes with intensive blood pressure controls.

References:

1. Bavishi C, Goel S, Messerli FH. Isolated Systolic Hypertension: An Update After SPRINT. The American journal of medicine. 2016;129(12):1251-1258.Chobanian AV.
2. Clinical practice. Isolated systolic hypertension in the elderly. N Engl J Med 2007; 357:789.
3. Prevention of Stroke by Antihypertensive Drug Treatment in Older Persons With Isolated Systolic Hypertension: Final Results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265(24):3255–3264. doi:10.1001/jama.1991.03460240051027
4. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008; 358:1887.