Cardiac outcomes with submaximal normal stress echocardiography: a meta-analysis.

OBJECTIVES: The aim of the study was to evaluate the risk of cardiac events in patients with normal stress echocardiography (SE) who attained maximal age-predicted heart rate (APHR) compared with those who did not in the setting of both normal and abnormal SE. BACKGROUND: SE is an important tool in the risk stratification and prognosis of patients with known or suspected coronary artery disease (CAD). The prognostic value of a normal but submaximal SE (<85% of maximal APHR) is conflicting. METHODS: PubMed, EMBASE, and CENTRAL were searched from 1980 to September 2011 for SE studies reporting cardiac outcomes in patients with known or suspected CAD stratified by achieved APHR. Both hard events (cardiac death and myocardial infarction) and total cardiac events (revascularization procedures in addition to hard events) were analyzed separately. Data on all-cause mortality were obtained when available. RESULTS: Fourteen studies with 11,542 patients followed up for a mean duration of 32 months fulfilled the inclusion criteria. In 8 studies with 4,577 patients, the risk of hard events with normal SE (both exercise and dobutamine) was 70% higher in patients who achieved submaximal compared with those with maximal APHR (annualized event rate 2.08% vs. 0.77%; p=0.0008; 95% confidence interval [CI]: 1.25 to 2.31). In 7 studies with 5,798 patients, the risk of total cardiac events with normal SE (both exercise and dobutamine) was 127% higher in patients who achieved submaximal compared with those with maximal APHR (annualized event rate 1.87% vs. 1.02%; p<0.0001; 95% CI: 1.54 to 3.34). The risk of total cardiac events was 278% higher in patients with abnormal SE with submaximal APHR compared with those with normal SE with submaximal APHR (p<0.0001; 95% CI: 2.81 to 5.08). There was a trend toward increased all-cause mortality in patients with normal SE with submaximal compared with maximal APHR (relative risk: 1.36; p=0.15; 95% CI: 0.89 to 2.09). CONCLUSIONS: Patients with submaximal APHR in the setting of normal SE have a higher risk of cardiovascular events than those who attained maximal stress test. Thus, the results of submaximal APHR in the setting of normal SE should be taken into consideration for more accurate risk stratification and prognosis.

Peripheral edema associated with calcium channel blockers: incidence and withdrawal rate--a meta-analysis of randomized trials.

OBJECTIVE: Peripheral edema is considered to be a common and annoying adverse effect of calcium channel blockers (CCBs). It has been thought to occur secondary to arteriolar dilatation causing intracapillary hypertension and fluid extravasation. We aimed to evaluate the incidence and withdrawal rate of peripheral edema with CCBs. METHODS: A systematic search was made in PubMed, EMBASE and CENTRAL from 1980 to January 2011 for randomized clinical trials reporting peripheral edema with CCBs in patients with hypertension. Trials enrolling at least 100 patients in the CCB arm and lasting at least 4 weeks were included in the analysis. Both the incidence and withdrawal rate due to edema were pooled by weighing each trial by the inverse of the variance. Head-to-head comparison was done to evaluate the risk of edema between newer lipophilic dihydropyridine (DHP) CCBs and older DHPs. RESULTS: One hundred and six studies with 99 469 participants, mean age 56 ± 6 years, satisfied our inclusion criteria and were included in this analysis. The weighted incidence of peripheral edema was significantly higher in the CCBs group when compared with controls/placebo (10.7 vs. 3.2%, P < 0.0001). Similarly, the withdrawal rate due to edema was higher in patients on CCBs compared with control/placebo (2.1 vs. 0.5%, P < 0.0001). Both the incidence of edema and patient withdrawal rate due to edema increased with the duration of therapy with CCBs reaching 24 and 5%, respectively, after 6 months. The risk of peripheral edema with lipophilic DHPs was 57% lower than with traditional DHPs (relative risk 0.43; 95% confidence interval 0.34-0.53; P < 0.0001). Incidence of peripheral edema in patients on DHPs was 12.3% compared with 3.1% with non-DHPs (P < 0.0001). Edema with high-dose CCBs (defined as more than half the usual maximal dose) was 2.8 times higher than that with low-dose CCBs (16.1 vs. 5.7%, P < 0.0001). CONCLUSION: The incidence of peripheral edema progressively increased with duration of CCB therapy up to 6 months. Over the long term, more than 5% of patients discontinued CCBs because of this adverse effect. Edema rates were lower with both non-DHPs and lipophilic DHPs.