Timeline of History of Hypertension Treatment

Abstract

It is surprising that only about 50 years ago hypertension was considered an essential malady and not a treatable condition. Introduction of thiazide diuretics in late 50s made some headway in successful treatment of hypertension and ambitious multicenter VA co-operative study (phase 1 and 2) started in 1964 for diastolic hypertension ranging between 90 and 129 mmHg and completed by 1971 established for the first time that treating diastolic hypertension reduced CV events such as stroke and heart failure and improved mortality. In the following decade, these results were confirmed for the wider US and non-US population, including women and goal-oriented BP treatment to diastolic 90 became the standard therapy recommendation. But isolated systolic hypertension (accounting for two-thirds of the 70 million hypertensive population in USA alone) was not considered treatable until 1991 when SHEP study (systolic hypertension in elderly program) was completed and showed tremendous benefits of treating systolic BP over 160 mmHg using only a simple regimen using small dose chlorthalidone with addition of atenolol if needed. In the next two decades, ALLHAT and other studies examined the comparability of outcomes with use of different classes and combinations of antihypertensive drugs. Although diastolic BP goal was established as 90 in the late 70s and later confirmed by HOT study, the goal BP for systolic hypertension was not settled until very recently with completion of SPRINT study. ACCORD study showed no significant difference in outcome with sys 140 vs. 120 in diabetics. But recently completed SPRINT study with somewhat similar protocol as in ACCORD but in non-diabetic showed almost one-quarter reduction in all-cause mortality and one-third reduction of CV events with systolic BP goal 120.

Keywords: history; hypertension; multicenter trial; randomized controlled trials; treatment outcome.

Figure 1

VA-co-op study phase 1 followed by 2 established for the first time that diastolic HTN > 90 to 129 was treatable with available drugs and reduced stroke, CHF, and mortality. HDFP study affirmed that BP treatment target to diastolic goal of 90 gave much better CV outcome results than usual BP treatment. MRC and EWHPE confirmed this for younger and older patients, respectively, in non-US population. MRFIT study showed that of three risk factors for CHD (hyperlipidemia, smoking, and hypertension) only hypertension was effectively treatable by drugs available that time. SHEP study broadened the definition of treatable hypertension to include isolated systolic hypertension, treatment of which in elderly gave profound CV and mortality benefits. DASH study convincingly showed the benefits of Mediterranean type diet in lowering BP and that salt restriction adds to that benefit. HOT study established that lowering diastolic BP goal <90 (85 or 80) does not add any further benefits. TOMHS and MRC 2 were relatively minor studies. UKPDS Hypertension studies showed that moderately tight BP control <150/85 goal-reduced diabetic mortality by 32% – much higher level of benefits than in non-diabetics. AASK study was done in African-Americans with CKD and showed that tight BP control over usual BP control did not affect CKD progression but use of ACEI caused superior reno-protection over CCB. ALLHAT study showed that use of thiazide drugs (Chlorthalidone) did not increase incidence of MI or mortality over other classes of drugs (CCB, ACEI, or AB). It also showed incidence of CHF was more with use of AB, CCB, and ACEI than CTDN. ASCOT study showed superiority of combination of ACEI and CCB over BB and thiazide (HCTZ) in preventing CV outcomes. CAFE, a sub study of ASCOT showed that BB failed to lower central aortic BP as opposed to peripheral BP. HYVET showed that treatment of hypertension in very elderly (>80) is even more beneficial than in any other age group. ACCOMPLISH study showed superiority of combination of ACEI and CCB over ACE and thiazide (HCTZ and not CTDN) for CV outcomes. ACCORD study showed that in diabetics, lowering BP target to 120 sys over conventional 140 added no further reduction in CV or renal outcomes. SPRINT study showed significant mortality and cardiovascular benefits in group with Systolic BP treatment goal of 120 compared to goal of 140 in non-diabetic patients.