Randomized Controlled Trials of Intensive Versus Standard Blood Pressure Control

2.3.2.0 Ran­dom­ized Con­trolled Tri­als of In­ten­sive Ver­sus Stan­dard Blood Pres­sure Con­trol

The Ac­tion to Con­trol Car­dio­vas­cu­lar Risk in Di­a­betes blood pres­sure (AC­CORD BP) trial pro­vides the strongest di­rect as­sess­ment of the benefits and risks of in­ten­sive blood pres­sure con­trol among peo­ple with type 2 di­a­betes (28). In AC­CORD BP, com­pared with stan­dard blood pres­sure con­trol (tar­get sys­tolic blood pres­sure <140 mmHg), in­ten­sive blood pres­sure con­trol (tar­get sys­tolic blood pres­sure <120 mmHg) did not re­duce total major atheroscle­rot­ic car­dio­vas­cu­lar events but did re­duce the risk of stroke, at the ex­pense of in­creased ad­verse events (Table 10.1). The AC­CORD BP re­sults sug­gest that blood pres­sure tar­gets more in­ten­sive than <140/90 mmHg are not like­ly to im­prove car­dio­vas­cu­lar out­comes among most peo­ple with type 2 di­a­betes but may be rea­son­able for pa­tients who may de­rive the most benefit and have been ed­u­cat­ed about added treat­ment bur­den, side ef­fects, and costs, as dis­cussed below.

Ad­di­tion­al stud­ies, such as the Sys­tolic Blood Pres­sure In­ter­ven­tion Trial (SPRINT) and the Hy­per­ten­sion Op­ti­mal Treat­ment (HOT) trial, also ex­am­ined ef­fects of in­ten­sive ver­sus stan­dard con­trol (Table 10.1), though the rel­e­vance of their re­sults to peo­ple with di­a­betes is less clear. The Ac­tion in Di­a­betes and Vas­cu­lar Dis­ease: Preter­ax and Di­ami­cron MR Con­trolled Eval­u­a­tion–Blood Pres­sure (AD­VANCE BP) trial did not ex­p­li­cit­ly test blood pres­sure tar­gets (29); the achieved blood pres­sure in the in­ter­ven­tion group was high­er than that achieved in the AC­CORD BP in­ten­sive arm and would be con­sis­tent with a tar­get blood pres­sure of <140/90 mmHg. No­tably, AC­CORD BP and SPRINT mea­sured blood pres­sure using au­to­mat­ed office blood pres­sure mea­sure­ment, which yields val­ues that are gen­er­ally lower than typ­i­cal office blood pres­sure read­ings by ap­prox­i­mate­ly 5–10 mmHg (30), sug­gesting that im­ple­ment­ing the AC­CORD BP or SPRINT pro­to­cols in an outpa­tient clin­ic might re­quire a sys­tolic blood pres­sure tar­get high­er than <120 mmHg, such as <130 mmHg.

A num­ber of post hoc anal­y­ses have at­tempt­ed to ex­plain the ap­par­ent­ly di­ver­gent re­sults of AC­CORD BP and SPRINT. Some in­ves­ti­ga­tors have ar­gued that the di­ver­gent re­sults are not due to dif­ferences be­tween peo­ple with and with­out di­a­betes but rather are due to dif­ferences in study de­sign or to char­ac­ter­is­tics other than di­a­betes (31-33). Oth­ers have opined that the di­ver­gent re­sults are most read­i­ly ex­plained by the lack of benefit of in­ten­sive blood pres­sure con­trol on car­dio­vas­cu­lar mor­tal­i­ty in AC­CORD BP, which may be due to dif­ferential mech­a­nisms un­der­ly­ing car­dio­vas­cu­lar dis­ease in type 2 di­a­betes, to chance, or both (34).

Table 10.1—Ran­dom­ized con­trolled tri­als of in­ten­sive ver­sus stan­dard hy­per­ten­sion treat­ment strate­gies

Clin­i­cal trial

AC­CORD BP (28)

Pop­u­la­tion

4,733 par­tic­i­pants with T2D aged 40–79 years with prior ev­i­dence of CVD or mul­ti­ple car­dio­vas­cu­lar risk fac­tors

In­ten­sive

Sys­tolic blood pres­sure tar­get: <120 mmHg
Achieved (mean) sys­tolic/‍di­as­tolic: 119.3/64.4 mmHg

Stan­dard

Sys­tolic blood pres­sure tar­get: 130–140 mmHg
Achieved (mean) sys­tolic/‍di­as­tolic: 133.5/70.5 mmHg

Out­comes

No ben­e­fit in pri­ma­ry end point: com­pos­ite of non­fa­tal MI, non­fa­tal stroke, and CVD death

Stroke risk re­duced 41% with in­ten­sive con­trol, not sus­tained through fol­low-‍up be­yond the pe­ri­od of ac­tive treat­ment

Ad­verse events more com­mon in in­ten­sive group, par­tic­u­lar­ly el­e­vat­ed serum cre­a­ti­nine and elec­trolyte ab­nor­mal­i­ties

Clin­i­cal trial

AD­VANCE BP (29)

Pop­u­la­tion

11,140 par­tic­i­pants with T2D aged 55 years and older with prior ev­i­dence of CVD or mul­ti­ple car­dio­vas­cu­lar risk fac­tors

In­ten­sive

In­ter­ven­tion: a sin­gle-‍pill, fixed­dose com­bi­na­tion of perindo­pril and in­da­pamide
Achieved (mean) sys­tolic/‍di­as­tolic: 136/73 mmHg

Stan­dard

Con­trol: place­bo
Achieved (mean) sys­tolic/‍di­as­tolic: 141.6/75.2 mmHg

Out­comes

In­ter­ven­tion re­duced risk of pri­ma­ry com­pos­ite end point of major macrovas­cu­lar and mi­crovas­cu­lar events (9%), death from any cause (14%), and death from CVD (18%)

6-year ob­ser­va­tion­al fol­low-‍up found re­duc­tion in risk of death in in­ter­ven­tion group at­ten­u­at­ed but still sig­nif­i­cant (174)

Clin­i­cal trial

HOT (173)

Pop­u­la­tion

18,790 par­tic­i­pants, in­clud­ing 1,501 with di­a­betes

In­ten­sive

Di­as­tolic blood pres­sure tar­get: ≤80 mmHg

Stan­dard

Di­as­tolic blood pres­sure tar­get: ≤90 mmHg

Out­comes

In the over­all trial, there was no car­dio­vas­cu­lar ben­e­fit with more in­ten­sive tar­gets

In the subpop­u­la­tion with di­a­betes, an in­ten­sive di­as­tolic tar­get was as­so­ci­at­ed with a sig­nif­i­cantly re­duced risk (51%) of CVD events

Clin­i­cal trial

SPRINT (39)

Pop­u­la­tion

9,361 par­tic­i­pants with­out di­a­betes

In­ten­sive

Sys­tolic blood pres­sure tar­get: <120 mmHg
Achieved (mean): 121.4 mmHg

Stan­dard

Sys­tolic blood pres­sure
tar­get: <140 mmHg
Achieved (mean): 136.2 mmHg

Out­comes

In­ten­sive sys­tolic blood pres­sure tar­get low­ered risk of the pri­ma­ry com­pos­ite out­come 25% (MI, ACS, stroke, HF, and death due to CVD)

In­ten­sive tar­get re­duced risk of death 27%

In­ten­sive ther­a­py in­creased risks of elec­trolyte ab­nor­mal­i­ties and AKI

ACS, acute coro­nary syn­drome; AKI, acute kid­ney in­jury; CVD, car­dio­vas­cu­lar dis­ease; HF, heart fail­ure; MI, my­ocar­dial in­farc­tion; T2D, type 2 di­a­betes.

Data from this table can also be found in the ADA po­si­tion state­ment “Di­a­betes and Hy­per­ten­sion” (17).