Influence of blood pressure reduction on composite cardiovascular endpoints in clinical trials.
BACKGROUND
The use of a composite cardiovascular endpoint (CCEP) is frequent in clinical trials. However, the relation between the reduction in blood pressure (BP) and the risk of CCEP is poorly known.


METHODS
We conducted a meta-analysis of trials, which compared different BP-lowering agents with placebo or active treatments in patients with hypertension or composite features of high cardiovascular risk. The outcome measure was a triple (myocardial infarction, stroke and cardiovascular death) or quadruple (those mentioned above and congestive heart failure) CCEP.


RESULTS
Thirty trials fulfilled the inclusion criteria, for a total of 221 024 patients. Experimental treatments reduced the risk of CCEP by 9% (P < 0.0001). In a multivariable meta-regression analysis, for each 5-mmHg reduction in SBP, there was a 13% less risk of CCEP (95% confidence interval 8-19, P = 0.001) and, for each 2-mmHg reduction in DBP, there was a 12% less risk of CCEP (95% confidence interval 7-16, P = 0.001). Use of triple or quadruple CCEP (P = 0.150), its definition as primary or nonprimary endpoint (P = 0.305) and use of placebo or active control as comparators (P = 0.552) did not influence the estimates. A different BP reduction of at least 4.6 mmHg in SBP or at least 2.2 mmHg in DBP was required to achieve a 95% prediction interval entirely lying below the unity.


CONCLUSIONS
BP reduction is important to reduce the risk of CCEP in clinical trials. A significant difference between two treatment groups in the risk of CCEP may be anticipated for a SBP/DBP reduction differing by 4.6/2.2 mmHg or more.
Verdecchia
Paolo
P
Department of Cardiology, Hospital 'Santa Maria della Misericordia', Perugia, Italy. verdec@tin.it
Gentile
Giorgio
G
Angeli
Fabio
F
Mazzotta
Giovanni
G
Mancia
Giuseppe
G
Reboldi
Gianpaolo
G
D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D012306:Risk; D016896:Treatment Outcome
D000959:Antihypertensive Agents