Abstract

BACKGROUND
In antihypertensive treatment trials, when randomized therapies do not reach target, additional drugs are administered. However, patients requiring (add-on) or not requiring add-on therapy (no-add-on) may be at different cardiovascular risk and differently susceptible to benefits of antihypertensive treatment.
METHODS AND RESULTS
The Felodipine Event Reduction study included 9711 Chinese hypertensive patients receiving 12.5  mg/day hydrochlorothiazide and randomized to associating either felodipine (5  mg/day) or placebo. Within 6 months, add-on therapy (further diuretic and other drugs) was required by 2185 patients, whereas 7243 did not require it. Despite significant SBP/DBP reductions by add-on therapy, outcome incidence remained much lower in no-add-on than in add-on patients: hazard ratios for various outcomes, after adjusting for baseline variables and blood pressure (BP) at time of add-on decision, were 0.22-0.368 (P always <0.001) and remained substantially unchanged when further adjusted for the small SBP/DBP difference persisting during follow-up treatment (-2.4/-1.1  mmHg in no-add-on). When felodipine was compared to placebo, the benefit of a lower SBP/DBP caused by felodipine was evident in the no-add-on patients (hazard ratio 0.45-0.68, P always <0.001), but it was lost in the add-on group (hazard ratio 0.91-1.17).
CONCLUSION
Comparing patients more or less easily responding to antihypertensive treatment may identify patients at high risk of outcomes and less susceptible to benefits of a lower BP. It remains to be more directly investigated to what extent adding drugs to drugs is effective in reducing outcomes of patients in whom simple antihypertensive therapy does not achieve goal BP.

Links

Publisher Full Text

Authors

Zhang Y, Zhang X, Liu L, Wang Y, Tang X, Zanchetti A, FEVER Study Group

Institution

Divisions of Hypertension and Biometrics, FuWai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, Beijing, China.

Source

Journal of hypertension 30:11 2012 Nov pg 2202-12

MeSH

Aged
Antihypertensive Agents
Blood Pressure
Cardiovascular Diseases
China
Double-Blind Method
Drug Therapy, Combination
Felodipine
Female
Humans
Hydrochlorothiazide
Hypertension
Kaplan-Meier Estimate
Male
Middle Aged
Risk Factors
Treatment Outcome

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22990352