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Abstract

  1. Top of page
  2. Abstract
  3. CAUSES AND RISK FACTORS
  4. CHARACTERISTICS AND PREVALENCE IN THE ELDERLY
  5. CHARACTERISTICS OF HYPERTENSION IN THE ELDERLY
  6. EVIDENCE-BASED TREATMENT STRATEGIES AND RECOMMENDATIONS FOR TREATING ELDERLY HYPERTENSIVE PATIENTS
  7. TREATMENT APPROACH IN OLDER HYPERTENSIVES
  8. CONCLUSION
  9. References

Hypertension is the most common reason Americans visit a physician. Recent analyses from the Framingham Heart Study and others have shown that there will be 70 million hypertensive Americans by the year 2020 and that the overwhelming majority of hypertensives will be 65 years of age or older (what we used to call “elderly”). The lifetime risk of Americans who live to age 85 years of becoming hypertensive is approximately 90% for both men and women. These individuals, even if they develop an elevated blood pressure late in life, are at significantly increased risk of the many medical complications attributable to hypertension (coronary artery disease, strokes, heart failure, chronic renal disease, and more). Older hypertensives are more likely to have an elevated systolic blood pressure and a low diastolic blood pressure, both of which are related to a loss of article compliance and have an increase in left ventricular mass and a decrease in peripheral resistance. We now have a substantial body of evidence from well done clinical trials that older hypertensives benefit as much or more than younger patients from antihypertensive therapy, so there is no longer any justification for withholding medication from any hypertensive patient whose competing risk or other medical problems are not a contraindication to treatment. These same studies, and practice-based analyses, have shown that the major barrier to reaching blood pressure goal is our failure to reduce systolic blood pressure to <140 mm Hg in most patients and to <130 mm Hg in diabetics and those with renal failure. The basis for all antihypertensive therapy, especially in older people, is thiazide diuretics with either angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β blockers, or calcium entry blockers as appropriate add-on treatment. The choice of the second agent depends on other factors, such as comorbidity, lifestyle, and affordability. We must be more aggressive in getting the message out that older hypertensives benefit from treatment and we must overcome the “clinical inertia” that seems to be a factor in the decision of many physicians not to treat an older patient. No older person should suffer a preventable, life-threatening event or become confined to a wheel chair if attention to lifestyle issues and a few pills a day could avoid that outcome.

Hypertension affects approximately 50 million individuals in the United States.1 As our population ages, the prevalence of hypertension is likely to increase even further unless more effective measures are implemented to reduce the seemingly inevitable increase in systolic blood pressure (SBP) that accompanies “normal” aging.2 Recent data from the Framingham Heart Study suggest that individuals who are normotensive at age 55 years and reach age 65 years have a 90% lifetime risk for developing hypertension during the next 20 years of their life.2 Currently there are almost 35 million Americans over age 65 years, and by the year 2050, there will be 79 million persons aged 65 years and older in the United States.3 It is estimated that by the year 2020, 29% of Americans (70 million persons) will be classified as hypertensive. Eighty percent of hypertensives will be 65 years of age or older.4

CAUSES AND RISK FACTORS

  1. Top of page
  2. Abstract
  3. CAUSES AND RISK FACTORS
  4. CHARACTERISTICS AND PREVALENCE IN THE ELDERLY
  5. CHARACTERISTICS OF HYPERTENSION IN THE ELDERLY
  6. EVIDENCE-BASED TREATMENT STRATEGIES AND RECOMMENDATIONS FOR TREATING ELDERLY HYPERTENSIVE PATIENTS
  7. TREATMENT APPROACH IN OLDER HYPERTENSIVES
  8. CONCLUSION
  9. References

Heart disease is the primary cause of mortality in elderly persons aged 75 years and older, causing between 225,000 and 250,000 deaths per year.5 In persons aged 85 years and older, heart disease, diabetes, and cerebrovascular disease, which are all closely related to high blood pressure (BP), are the major causes of death.5

Data from the Prospective Collaborative Studies Group,6 which reviewed results from 61 epidemiologic studies with more than 1 million subjects, reported on 34,000 deaths from coronary heart disease (CHD) and 12,000 deaths from stroke. They showed a direct correlation between the risk of mortality from CHD and stroke and baseline SBP and diastolic blood pressure (DBP). They found that for all age groups between 40 and 89 years of age, risk doubles for each 20 mm Hg increase in SBP and each 10 mm Hg increase in DBP. This increase occurred regardless of the presence or absence of other risk factors or comorbidity. There was a 25% reduction of risk in mortality from CHD for each 20 mm Hg decrease in SBP and for each 10 mm Hg decrease in DBP.

This study did show some evidence of an increase in cardiovascular (CV) event rate (a “J” curve) if the BP in the decade the event occurred was less than 115/75 mm Hg, but no study has ever conclusively shown that aggressive BP reduction will result in more CV events. Most investigators believe concerns about lowering BP too far are much exaggerated, and while an occasional patient, especially an older person, many experience symptoms from aggressive lowering of BP, many more patients will benefit.

CHARACTERISTICS AND PREVALENCE IN THE ELDERLY

  1. Top of page
  2. Abstract
  3. CAUSES AND RISK FACTORS
  4. CHARACTERISTICS AND PREVALENCE IN THE ELDERLY
  5. CHARACTERISTICS OF HYPERTENSION IN THE ELDERLY
  6. EVIDENCE-BASED TREATMENT STRATEGIES AND RECOMMENDATIONS FOR TREATING ELDERLY HYPERTENSIVE PATIENTS
  7. TREATMENT APPROACH IN OLDER HYPERTENSIVES
  8. CONCLUSION
  9. References

There are significant changes in mean SBP and DBP by age and ethnicity in men compared with women aged 18 years and older.7 The SBP increases with advancing age in both men and women, with an increase in DBP up to about age 55 years. DBP then begins to decrease as a result of increased arterial stiffness and, as a result, pulse pressure (the difference between SBP and DBP) widens.8 As would be anticipated, most older individuals have elevated SBP and a DBP <90 mm Hg.4

CHARACTERISTICS OF HYPERTENSION IN THE ELDERLY

  1. Top of page
  2. Abstract
  3. CAUSES AND RISK FACTORS
  4. CHARACTERISTICS AND PREVALENCE IN THE ELDERLY
  5. CHARACTERISTICS OF HYPERTENSION IN THE ELDERLY
  6. EVIDENCE-BASED TREATMENT STRATEGIES AND RECOMMENDATIONS FOR TREATING ELDERLY HYPERTENSIVE PATIENTS
  7. TREATMENT APPROACH IN OLDER HYPERTENSIVES
  8. CONCLUSION
  9. References

Numerous studies have reviewed the physiologic and biomedical characteristics of hypertension in older persons.9–11 The usual hemodynamic profile in these individuals includes an increase in SBP, pulse pressure, cardiac mass, left ventricular wall thickness, arterial stiffness, and peripheral vascular resistance. Cardiac output, heart rate, renal blood flow, plasma renin activity, angiotensin II levels, arterial compliance, blood volume, and DBP are usually decreased. There is good evidence that older individuals with the lowest DBPs have the highest mortality rate.11 Thus, those with the widest pulse pressure (highest SBP and lowest DBP) have the worst prognosis4,11 (Table I).

Table I.  Characteristics of Hypertension in the Elderly
Increased
  Systolic blood pressure and pulse pressure
  Left ventricular mass and wall thickness
  Arterial stiffness
  Calculated total peripheral resistance
Decreased
  Cardiac output and heart rate
  Renal blood flow, plasma renin activity, and angiotensin II levels
Arterial compliance and blood volume
Diastolic blood pressure

It is also well established that elderly individuals have more cardiovascular risk factors (hyperlipidemia, diabetes, and obesity) than younger people.12 However, fewer older people smoke cigarettes-perhaps because cigarette smokers tend to have shorter life spans and have already died before reaching old age.

Two consequences of hypertension are particular problems in older individuals: heart failure (HF) and dementia. Hypertension may progress to HF by two different pathways13: HF with preserved systolic function and normal ejection fraction (diastolic dysfunction) or HF with left ventricular dysfunction and a low ejection fraction (systolic dysfunction).

Left ventricular hypertrophy (LVH) is often present in cases of HF from diastolic dysfunction and usually results from an elevated BP. HF from systolic dysfunction is most often the result of CHD. Hypertension is clearly a major risk factor both for LVH and CHD. Prevention of both LVH and HF from hypertension and the occurrences of CHD have both been achieved by lowering BP. This benefit has been amply demonstrated in middle-aged and older people.

The relationship between hypertension and dementia has been more difficult to prove and prevent. A recent study14 looked at mental examination scores in untreated hypertensives (n=107) compared with normotensives (n=116) to determine if there was an association between hypertension and dementia. Testing of individuals with normal mental status test scores indicated that hypertensive individuals were slower (impaired) in all eight areas examined. For example, people with high BP did not remember numbers as well as normotensives did, and their word and picture recognition and spatial memory were also worse. Though small, this well done study suggests that the presence of hypertension does affect mentation in older people and can be demonstrated if sophisticated measures are used.

Early treatment of hypertension may help to prevent some forms of dementia. In the Systolic Hypertension in the Elderly Trial in Europe (Syst-EUR), dementia was less frequent in the treated compared with placebo subjects.15 This study treated subjects with nitrendipine, a dihydropyridine, as initial therapy with multiple medications added to achieve goal BP. At the 1-year and 5-year follow-ups, there was a significant reduction in dementia, most of which was diagnosed clinically as Alzheimer's disease, not multi-infarct dementia or vascular dementia, as would be expected. On the other hand, the larger and longer Systolic Hypertension in the Elderly Program (SHEP) trial,16 which began treatment with the diuretic chlorthalidone followed by atenolol, did not find improvement in dementia in the actively treated group compared with placebo.

EVIDENCE-BASED TREATMENT STRATEGIES AND RECOMMENDATIONS FOR TREATING ELDERLY HYPERTENSIVE PATIENTS

  1. Top of page
  2. Abstract
  3. CAUSES AND RISK FACTORS
  4. CHARACTERISTICS AND PREVALENCE IN THE ELDERLY
  5. CHARACTERISTICS OF HYPERTENSION IN THE ELDERLY
  6. EVIDENCE-BASED TREATMENT STRATEGIES AND RECOMMENDATIONS FOR TREATING ELDERLY HYPERTENSIVE PATIENTS
  7. TREATMENT APPROACH IN OLDER HYPERTENSIVES
  8. CONCLUSION
  9. References

Lowering BP in treatment trials focusing on DBP in the elderly has resulted in a 34% reduction in strokes, a nearly 20% reduction for CHD events, a 23% reduction in CV events, and a very small and insignificant increase in other deaths.17 In subjects with both elevated diastolic and systolic hypertension, there is also a dramatic reduction in the occurrence of HF18 (Table II). Treatment of diastolic hypertension in the elderly, even those patients 80 years of age or older, unquestionably reduces morbidity and mortality17,19 (Figure 1).

Table II.  Effects of Therapy in Elderly Hypertensive Patients
 Relative Difference in Rate Between Treated and Placebo Groups
 SHEPSTOP-HTMRCSYST-EUREWPHE
Stroke−33*−47*−25*−42*36*
CAD−27*−13**−19−3022
CHF−55*−51*−2920
All CVD−32*−40*−17*−31*29*
CAD=coronary artery disease; CHF=congestive heart failure; CVD=cardiovascular disease; STOP-HT: Swedish Trial in Old Patients with Hypertension; MRC=Medical Research Council Trial of Treatment of Hypertension in Older Adults; EWPHE=European Working Party on High Blood Pressure in the Elderly; other trial acronyms expanded in text; *statistically significant; **myocardial infarction, sudden death reduced from 13 to 4
image

Figure 1. Meta-analysis of hypertension treatment trials in people geqslant R: gt-or-equal, slanted80 years old; NS=nonsignificant; CHD=coronary heart disease; CF=heart failure; Adapted from Lancet. 1999;353:793–796.24

Outcome trials of isolated systolic hypertension, the most common form of hypertension in older people, indicate similar if not more dramatic benefits.17 More than 15,000 patients were studied over a period of 3.8 years in the SHEP, Syst-EUR, and Syst-CHINA trials. A 30% reduction in strokes, 23% reduction in CHD events, and 26% reduction in CV deaths were found. In addition, there was also a highly significant reduction in all-cause mortality in actively treated subjects compared with the placebo-treated controls.

There are concerns about the optimal way to treat hypertension in older persons. The Seventh Report of Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines recommend that thiazide or thiazide-like diuretics be the initial choice for treatment in most hypertensives, particular older individuals,1 but this recommendation needs to be tempered by concerns about potassium loss and hypokalemia. In elderly patients in the SHEP trial, where 2000 people were treated with a chlorthalidone-based regimen, 151 patients had serum potassium levels <3.5 mg/dL.20 The benefit of diuretic-based therapy was less in this group than in the subjects in SHEP whose potassium remained >3.5 mg/dL. This suggests that efforts should be made to prevent potassium loss—by either careful potassium supplementation or by using potassium-sparing diuretics in combination with thiazides.

Since most older persons will need combination therapy to get SBP <140 mm Hg, the use of thiazide/angiotensin-receptor blockers (ARBs) or thiazide/angiotensin-converting enzyme (ACE) inhibitors in fixed-dose combinations may be particularly effective. Blood pressure is lowered and potassium was to be decreased.

Two recently published, large, long-term clinical trials already showed that a rigorous step-wise regimen could achieve BP goals in older hypertensives.21,22 One such study, the Controlled Onset Verapamil Investigation of Cardiovascular Endpoints (CONVINCE) trial,21 enrolled 16,602 hypertensive subjects at least 55 years of age in 13 countries and treated them either with a regimen that began with verapamil or one beginning with either hydrochlorothiazide or atenolol. DBP was reduced to <90 mm Hg in 90% of subjects (average age 67 years), but only 68% of the study participants had their SBP reduced to <140 mm Hg. In most cases, two or more drugs were required to achieve this level of control. Only about 25% of CONVINCE participants were treated with one drug.

The second study, the Antihypertensive Lipid Lowering Trial to Prevent Heart Attack (ALLHAT) study is the largest BP treatment trial to date and showed the same pattern of BP control.22 This trial began with only 27% of subjects (mean age 67 years) at BP goal (<140/90 mm Hg) despite being on active treatment. Participants were then switched to one of four initial treatment regimens (chlorthalidone, lisinopril, amlodipine, doxazosin) and treated to achieve a goal BP of <140/90 mm Hg. At 5 years, 66% had reached SBP goal (<140 mm Hg), and more than 90% had reached a DBP of <90 mm Hg, just as seen in CONVINCE.

ALLHAT also showed the need for more than one drug in the majority of hypertensives. At the end of the trial, 80% of the participants were still receiving the initial medication or a representative of the four classes of study drugs, but only 39% were on a single drug.22 Another 39% were on two medications, and many were taking three or four different agents. Those participants not reaching goal were more likely to be older and/or African American. About 6000 people in this trial were older than 85 years of age.

At 5 years, the subjects whose initial therapy was chlorthalidone had a 2 mm Hg lower SBP compared with subjects who began treatment with lisinopril. In African-American participants, the SBP difference was 4 mm Hg. The BP results with amlodipine were similar to those with chlorthalidone, with chlorthalidone-first subjects having a 1 mm Hg lower SBP and amlodipine-first subjects having a 1 mm Hg lower DBP.

There was no difference in the primary outcome (fatal and nonfatal myocardial infarction) among the three groups whose treatment began with one of those three medications.23 When patients between age 55 and 65 years were compared with those older than age 65 years, the outcomes were similar.

There were some differences in specific end points when subjects whose initial treatment with the three different drugs (chlorthalidone, amlodipine, lisinopril) were compared.22 For example, there were more episodes of HF in the amlodipine-first group compared with subjects started on chlorthalidone. In the lisinopril-first subjects, there were more disease-specific outcome differences compared with the chlorthalidone-first patients (Figure 2). There were more strokes, especially in African Americans, which was not surprising, but there were also more episodes of HF (a statistically significant 20% increase), which was quite unexpected. There was also a 10% increase in combined CV disease events, which included HF, and an 11% increase in CHD events when treatment began with the ACE inhibitor compared with subjects who started on a diuretic. The majority of the increased events occurred in African Americans, but the whites and Hispanics who received lisinopril as initial therapy did not do better either. The ALLHAT study demonstrated that beginning treatment with chlorthalidone was more effective in preventing all types of events in all demographic subgroups compared with these two newer agents.

image

Figure 2. Cumulative event rates for heart failure by Antihypertensive and Lipid Lowering Treatment to Frevent Heart Attack Trial treatment group; HR=hazard ratio; CI=confidence interval; A=amlodipine; C=chlorthalidone; L=lisinopril; CHF=congestive heart failure; HF=heart failure

Some believe the study design of ALLHAT may have favored the diuretic or calcium channel blocker arms of the trial. A diuretic could not, by protocol, be added to lisinopril if BP was not at goal. The second choice drugs were β blockers, which are excellent agents to add to chlorthalidone or amlodipine, or alternatively clonidine or reserpine. Lisinopril/β blocker therapy is not a logical combination, especially in older subjects and African Americans whose BP may not be reduced as well by this combination as it would with of the other possible two-drug combinations. BP control was predictably less in the lisinopril-first subjects. This seemingly minor difference in SBP response could well explain the difference in outcomes in ALLHAT for all events except, perhaps, HF.

It is important to note that in the ALLHAT study, the major decrease in SBP with chlorthalidone occurred within the first 6 months of treatment.23 The Prospective Collaborative Studies Group also noted that the benefit of BP lowering and prevention of stroke may be evident very early with effective treatment.5 Our advice to “go slow and not too low” when treating hypertension in older individuals may need to be re-examined.

Surprisingly, too, end-stage renal disease was not protected better by an ACE inhibitor than by the diuretic or calcium channel blocker in this group of primarily elderly patients. Also, the ACE inhibitor did not confer any special benefit to those already diabetic but did reduce the incidence of new diabetes compared with the other agents (lisinopril, 8% new diabetes; amlodipine, 10% new diabetes; and chlorthalidone, 12% new diabetes).

TREATMENT APPROACH IN OLDER HYPERTENSIVES

  1. Top of page
  2. Abstract
  3. CAUSES AND RISK FACTORS
  4. CHARACTERISTICS AND PREVALENCE IN THE ELDERLY
  5. CHARACTERISTICS OF HYPERTENSION IN THE ELDERLY
  6. EVIDENCE-BASED TREATMENT STRATEGIES AND RECOMMENDATIONS FOR TREATING ELDERLY HYPERTENSIVE PATIENTS
  7. TREATMENT APPROACH IN OLDER HYPERTENSIVES
  8. CONCLUSION
  9. References

There does not appear to be any appropriate specially designed algorithm limited to or particularly designed for the treatment of hypertension in older persons. As with all hypertensives, treatment should start with lifestyle modifications. If patients are not at goal BP (<140/90 mm Hg), treatment choices should be made based on whether or not compelling indications are present.1 Use two drugs if the patient has stage 2 hypertension (BP >160/100 mm Hg) or even in some stage 1 (140/90 mm Hg to 159/99 mm Hg) patients, especially if there are other comorbid conditions present, such as diabetes or overt heart disease.

Treatment for older patients with isolated systolic hypertension or predominantly systolic hypertension may be especially challenging and difficult. A thiazide or thiazide-like diuretic should almost always be part of the treatment regimen with a β blocker, ACE inhibitor, ARB, or calcium channel blocker added if goal BPs are not reached. Some older patients will not achieve a SBP <140 mm Hg regardless of therapy, but even a decrease of 10–15 mm Hg may prevent many CV episodes.

CONCLUSION

  1. Top of page
  2. Abstract
  3. CAUSES AND RISK FACTORS
  4. CHARACTERISTICS AND PREVALENCE IN THE ELDERLY
  5. CHARACTERISTICS OF HYPERTENSION IN THE ELDERLY
  6. EVIDENCE-BASED TREATMENT STRATEGIES AND RECOMMENDATIONS FOR TREATING ELDERLY HYPERTENSIVE PATIENTS
  7. TREATMENT APPROACH IN OLDER HYPERTENSIVES
  8. CONCLUSION
  9. References

More recent findings may suggest that the conventional advice to “go slow, and not too low” in treating older hypertensive patients may not be the best approach. Earlier and more aggressive initial treatment may be needed to reduce SBP, especially in people at high risk. It is clear that older people with hypertension, whether systolic/diastolic or isolated systolic pressure, should be treated and that greater efforts should be made to lower their BPs (especially SBP). Effective agents that are well tolerated are available, and although BP may not be lowered to <140/90 mm Hg in some patients, a more vigorous approach to management will result in better control of SBP. A thiazide or thiazide-like diuretic should almost always be part of any therapeutic regimen, but the addition of an ACE inhibitor, ARB, β blocker, or calcium channel blocker may be necessary to achieve goal BP in many cases.

The fact that treating hypertension in older people is difficult and challenging should not deter us from our efforts. The benefit of treatment in preventing CHD, stroke, HF, and possibly dementia is realized much sooner than in younger people. The cost of caring for debilitated older persons is enormous and much more than the cost of preventing these complications. We must dedicate ourselves to being certain that all of our citizens enjoy the fruits of the decades-long struggle to understand whether and how to treat hypertension. Yes, “no child left behind” is appropriate, but no older person should suffer a preventable, life-threatening event or become confined to a wheelchair if a few pills a day could have prevented that outcome.

References

  1. Top of page
  2. Abstract
  3. CAUSES AND RISK FACTORS
  4. CHARACTERISTICS AND PREVALENCE IN THE ELDERLY
  5. CHARACTERISTICS OF HYPERTENSION IN THE ELDERLY
  6. EVIDENCE-BASED TREATMENT STRATEGIES AND RECOMMENDATIONS FOR TREATING ELDERLY HYPERTENSIVE PATIENTS
  7. TREATMENT APPROACH IN OLDER HYPERTENSIVES
  8. CONCLUSION
  9. References
  • 1
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  • 2
    Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: the Framingham Heart Study. JAMA. 2002;287:10031010.
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    Foot DK, Lewis RP, Pearson TA, et al. Demographics and cardiology, 1950–2050. J Am Coll Cardiol. 2000;35(4):10671081.
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    Forette F, Seux ML, Staessen JA, et al. Prevention of dementia in randomized double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998;352:13471351.
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    Di Bari M, Pahor M, Franse LV, et al. Dementia and disability outcomes in large hypertension trials: lessons learned from the systolic hypertension in the elderly program (SHEP) trial. Am J Epidemiol. 2001;153(1):7278.
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    Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: metaanalysis of outcome trials. Lancet. 2000;355(9207):865872.
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    Moser M, Hebart P, Hennekens CH. An overview of the meta-analysis of the hypertension treatment trials. Arch Intern Med. 1991;151:12771279.
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    Franse LV, Pahor M, Di Bari M, et al. Hypokalemia associated with diuretic use and cardiovascular events in the Systolic Hypertension in the Elderly Program. Hypertension. 2000;35(5):10251030.
  • 21
    Black HR, Elliott WJ, Neaton JD, et al. Baseline characteristics and elderly BP control in the Controlled Onset Verapamil Investigation of Cardiovascular Endpoints (CONVINCE) Trial. Hypertension. 2001;37:1218.
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    Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of BP control in diverse North American settings: the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). J Clin Hypertens (Greenwich). 2002;4:393405.
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    The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA. 2002;288:29812997.
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    Gueyffier F, Bulpitt C, Boissel JP, et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. INDIANA Group. Lancet. 1999, 353:793796.