Editorial Commentary on Dilemmas in Treating Hypertension in Octogenarians

Hypertension is a major risk factor for coronary events, stroke, congestive heart failure, peripheral arterial disease, a dissecting aortic aneurysm, sudden cardiac death, angina pectoris, atrial fibrillation, diabetes mellitus, the metabolic syndrome, chronic kidney disease, thoracic and abdominal aortic aneurysms, left ventricular hypertrophy, vascular dementia, Alzheimer’s disease, and ophthalmologic disorders.1,2 Hypertension is present in approximately 69% of patients with a first myocardial infarction,3 in approximately 77% of patients with a first stroke,3 in approximately 74% of patients with congestive heart failure,3 and in 60% of patients with peripheral arterial disease.4 In the absence of randomized control data, the American Heart Association 2007 guidelines recommended that patients with hypertension at high risk for coronary events such as those with coronary artery disease, a coronary artery risk equivalent, diabetes mellitus, chronic kidney disease, or a 10-year Framingham risk score ≥10% should have their blood pressure (BP) reduced to <130/80 mm Hg.5 These guidelines also recommended that patients with hypertension and left ventricular dysfunction should have their BP reduced to <120/80 mm Hg.5 At 24-month mean follow-up of 4162 patients with an acute coronary syndrome in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI) 22 trial, however, the lowest cardiovascular events rates occurred with a systolic BP between 130 mm Hg and 140 mm Hg and a diastolic BP between 80 mm Hg and 90 mm Hg with a nadir of 136/85 mm Hg.6 Data from 6400 patients with diabetes mellitus and coronary artery disease in the International Verapamil SR-Trandolapril Study (INVEST),7 4733 patients with type 2 diabetes mellitus in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) BP trial,8 and 9603 diabetics and 15,981 nondiabetics in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)9,10 support the reduction of BP to <140/90 mm Hg to reduce cardiovascular events. A meta-analysis was performed of 2272 patients with hypertensive chronic kidney disease without diabetes mellitus in the African American Study of Kidney Disease and Hypertension (AASK),11 the Modification of Diet in Renal Disease (MDRD),12 and the Ramipril Efficacy in Nephropathy 2 (REIN-2)13 trials.14 This meta-analysis demonstrated that a BP <125/75 mm Hg to 130/80 mm Hg did not improve clinical outcomes more than a target BP of <140/90 mm Hg.14 The Prevention Regimen for Effectively Avoiding Second Strokes (PROFESS) trial included 20,330 patients with a recent noncardioembolic ischemic stroke.15 Mean follow-up was 2.5 years. The primary outcome was first recurrence of stroke of any type. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. The systolic BP associated with the best clinical outcomes was 130 mm Hg to 139 mm Hg. Unfortunately, BP treatment data in octogenarians with hypertension at high risk for cardiovascular events are not available. The 2009 European Society of Hypertension guidelines recommended that reducing the BP to <130/80 mm Hg in patients at high risk for cardiovascular events was unsupported by prospective trial data and that the systolic BP should be reduced to <140 mm Hg in these patients.16 The American College of Cardiology Foundation/American Heart Association 2011 expert consensus document on hypertension in the elderly recommended that BP should be reduced to <140/90 mm Hg in adults younger than 80 years who are at high risk for cardiovascular events.2 On the basis of data from the Hypertension in the Very Elderly trial (HYVET),17 these guidelines recommended that the systolic BP should be reduced to 140 mm Hg to 145 mm Hg if tolerated in adults aged 80 years and older. The review article on dilemmas in treating hypertension in octogenarians in this issue is an excellent review article that discusses the sparse data we have on treatment of hypertension in octogenarians.18 Despite the fact that approximately one quarter of Americans will be older than 80 years old by 2030, HYVET is the only prospective, randomized, double-blind, placebo-controlled study that investigated clinical outcomes in octogenarians with hypertension.17 In HYVET, 3845 persons aged 80 years and older (mean age 83.6 years) with a sustained systolic BP of ≥160 mm Hg were randomized to indapamide (sustained release 1.5 mg) or matching placebo.17 Perindopril 2 mg or 4 mg, or matching placebo, was added if needed to achieve the target BP of 150/80 mm Hg. Median follow-up was 1.8 years. Antihypertensive drug treatment reduced the incidence of the primary end point (fatal or nonfatal stroke) by 30% (P=.06). Antihypertensive drug treatment reduced fatal stroke by 39% (P=.05), all-cause mortality by 21% (P=.02), death from cardiovascular causes by 23% (P=.06), and heart failure by 64% (P<.001). The significant 21% reduction in all-cause mortality by antihypertensive drug treatment was unexpected. The benefits of antihypertensive drug treatment began to be apparent during the first year of follow-up. The prevalence of baseline cardiovascular disease was only 12% in the patients in HYVET. In a cohort of patients with hypertension seen in a university geriatrics practice, mean age 80 years, 70% had baseline cardiovascular disease, target organ damage, or diabetes mellitus.19 An older population such as this one with a high prevalence of cardiovascular disease would be expected to have a greater absolute reduction in cardiovascular events resulting from antihypertensive drug therapy. However, data are needed in octogenarians with hypertension with a high prevalence of cardiovascular disease, with comorbidities, with frailty, and especially in those 85 years and older. Although the results of HYVET clearly indicate that hypertensive patients 80 years and older should be treated with antihypertensive drug therapy, the study does not give us data on target BP.20 Further research is needed to answer this question.2 How low should the systolic BP and diastolic BP be allowed to fall? The pathophysiology of hypertension in the elderly is extensively discussed elsewhere.2 Physiologic changes with aging affect the absorption, distribution, metabolism, and excretion of antihypertensive drugs.2 The majority of elderly persons with hypertension will require ≥2 antihypertensive drugs to control their hypertension.2 A meta-analysis of 147 randomized trials including 464,000 persons with hypertension showed that except for the extra protective effect of β-blockers given after myocardial infarction and a minor additional effect of calcium channel blockers in preventing stroke, use of β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, diuretics, and calcium channel blockers cause a similar reduction in coronary events and stroke for a given decrease in BP.16,21 The proportionate decrease in cardiovascular events was the same or similar regardless of pretreatment BP and the presence or absence of cardiovascular events.16,21 The use of antihypertensive drugs in elderly persons depends on their associated medical conditions.2 In HYVET, the antihypertensive drugs used were the diuretic indapamide and the ACE inhibitor perindopril.17 Clinical trial data on other antihypertensive drugs in octogenarians need to be obtained. All antihypertensive drugs may predispose older persons to develop symptomatic orthostatic hypotension and postprandial hypotension and syncope or falls.22 Diuretics may cause volume depletion. Numerous adverse effects may occur from antihypertensive drugs in elderly persons, especially from drug interactions.2 It is extremely important to measure BP in the standing position in elderly persons.2 Clinical trial data are needed to determine the efficacy of lifestyle measures, different types of antihypertensive drugs, and other interventional approaches to control hypertension in octogenarians. I agree with the unresolved questions stated by Tabriziani and colleagues.18 Finally, there is no evidence in elderly persons to support the use of lower BP targets in elderly patients at high risk for cardiovascular events.2 Disclosures: The author does not have any conflicts of interest.