Guidelines generally recommend intensive lowering of blood pressure (BP) in patients with type 2 diabetes. There is uncertainty about the impact of this strategy on case-specific events. Thus, we generated estimates of the effects of BP reduction on the risk of myocardial infarction (MI) and stroke in diabetic patients. We selected studies which compared different BP-lowering agents and different BP intervention strategies in patients with diabetes. Outcome measures were MI and stroke. We abstracted information about study design, intervention, population, outcomes, and methodological quality for a total of 73 913 patients with diabetes (295 652 patient-years of exposure) randomized in 31 intervention trials. Overall, experimental treatment reduced the risk of stroke by 9% (P = 0.0059), and that of MI by 11% (P = 0.0015). Allocation to more-tight, compared with less-tight, BP control reduced the risk of stroke by 31% [relative risk (RR) 0.61, 95% confidence interval (CI) 0.48–0.79], whereas the reduction in the risk of MI approached, but did not achieve, significance [odds ratio (OR) 0.87, 95% CI 0.74–1.02]. In a meta-regression analysis, the risk of stroke decreased by 13% (95% CI 5–20, P = 0.002) for each 5-mmHg reduction in SBP, and by 11.5% (95% CI 5–17, P < 0.001) for each 2-mmHg reduction in DBP. In contrast, the risk of MI did not show any association with the extent of BP reduction (SBP: P = 0.793; DBP: P = 0.832). In patients with diabetes, protection from stroke increases with the magnitude of BP reduction. We were unable to detect such a relation for MI.

Oral disease may be increased in people with chronic kidney disease (CKD) and, due to associations with inflammation and malnutrition, represents a potential modifiable risk factor for cardiovascular disease and mortality. We summarized the prevalence of oral disease in adults with CKD and explored any association between oral disease and mortality. We used systematic review of observational studies evaluating oral health in adults with CKD identified in MEDLINE (through September 2012) without language restriction. We summarized prevalence and associations with all-cause and cardiovascular mortality using random-effects meta-analysis. We explored for sources of heterogeneity between studies using meta-regression. Eighty-eight studies in 125 populations comprising 11 340 adults were eligible. Edentulism affected one in five adults with CKD Stage 5D (dialysis) {20.6% [95% confidence interval (CI), 16.4–25.6]}. Periodontitis was more common in CKD Stage 5D [56.8% (CI, 39.3–72.8)] than less severe CKD [31.6% (CI, 19.0–47.6)], although data linking periodontitis with premature death were scant. One-quarter of patients with CKD Stage 5D reported never brushing their teeth [25.6% (CI, 10.2–51.1)] and a minority used dental floss [11.4% (CI, 6.2–19.8)]; oral pain was reported by one-sixth [18.7% (CI, 8.8–35.4)], while half of patients experienced a dry mouth [48.4% (CI, 37.5–59.5)]. Data for kidney transplant recipients and CKD Stages 1–5 were limited. Oral disease is common in adults with CKD, potentially reflects low use of preventative dental services, and may be an important determinant of health in this clinical setting.

To compare the effects of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on the risk of myocardial infarction, stroke, cardiovascular mortality and total mortality. We conducted a meta-analysis of randomized comparative trials between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. Inclusion criteria were publication in peer-reviewed journals indexed in Medline, randomized comparison of angiotensin II receptor blockers vs. angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers + angiotensin-converting enzyme inhibitors vs. angiotensin-converting enzyme inhibitors, report of major complications including myocardial infarction, stroke, cardiovascular mortality or all-cause mortality; average follow-up of at least 1 year in at least 200 patients. Six trials fulfilled the inclusion criteria, for a total of 49 924 patients. In the pooled estimate, there were no significant differences between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on the risk of myocardial infarction (odds ratio 1.01; 95% confidence interval 0.95–1.07; P = 0.75), cardiovascular mortality (odds ratio 1.03; 95% confidence interval 0.98–1.08; P = 0.23) and total mortality (odds ratio 1.03; 95% confidence interval 0.97–1.10; P = 0.20). This was the case also when the analysis involved only the comparison between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Overall, the risk of stroke was slightly lower with angiotensin II receptor blockers than angiotensin-converting enzyme inhibitors (odds ratio 0.92; 95% confidence interval 0.85–0.99; P = 0.037), the direct angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers comparison showing a nonsignificant trend in a similar direction. Statistical heterogeneity among trials was not significant, with a low to null inconsistency statistic, for stroke (P = 0.67), myocardial infarction (P = 0.86), cardiovascular mortality (P = 0.14) and total mortality (P = 0.12). This overview suggests that angiotensin II receptor blockers are as effective as angiotensin-converting enzyme inhibitors on the risk of myocardial infarction, cardiovascular mortality and total mortality. Angiotensin II receptor blockers may be slightly more protective than angiotensin-converting enzyme inhibitors on the risk of stroke.

Background. A recent clinical trial showed harmful renal effects with the combined use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) in people with diabetes or vascular disease. We examined the benefits and risks of these agents in people with albuminuria and one or more cardiovascular risk factors. Methods. MEDLINE, EMBASE and Renal Health Library were searched for trials comparing ACEI, ARB or their combination with placebo or with one another in people with albuminuria and one or more cardiovascular risk factor. Results. Eighty-five trials (21 708 patients) were included. There was no significant reduction in the risk of all-cause mortality or fatal cardiac–cerebrovascular outcomes with ACEI versus placebo, ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI + ARB versus monotherapy. There was a significant reduction in the risk of nonfatal cardiovascular events with ACEI versus placebo but not with ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI + ARB versus monotherapy. Development of end-stage kidney disease and progression of microalbuminuria to macroalbuminuria were reduced significantly with ACEI versus placebo and ARB versus placebo but not with combined therapy with ACEI + ARB versus monotherapy. Conclusions. ACEI and ARB exert independent renal and nonfatal cardiovascular benefits while their effects on mortality and fatal cardiovascular disease are uncertain. There is a lack of evidence to support the use of combination therapy. A comparative clinical trial with ACE, ARB and its combination in people with albuminuria and a cardiovascular risk factor is warranted.

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. 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. 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. 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.