Faculty Bibliography

AIMS: Angiotensin receptor blockers (ARBs) are available in different dosages and it is common clinical practice to uptitrate if blood pressure goal is not achieved with the initial dose. Data on the incremental antihypertensive efficacy with uptitration are scarce. It is also unclear if antihypertensive efficacy of losartan is comparable with other ARBs. METHODS AND RESULTS: We systematically reviewed PubMed/EMBASE/Cochrane databases for all randomized clinical trials until December 2012 reporting 24 h ambulatory blood pressure (ABP) for most commonly available ARBs in patients with hypertension. Reduction in ABP with ARBs was evaluated at 25% of the maximum (max) dose, 50% of the max dose, and at the max dose. Comparison was made between 24 h BP-lowering effect of losartan 50 and 100 mg and other ARBs at 50% max dose and the max dose, respectively. Sixty-two studies enrolling 15 289 patients (mean age 56 years; 60% men) with a mean duration of 10 weeks were included in the analysis. Overall, the dose-response curve with ARBs was shallow with decrease of 10.3/6.7 (systolic/diastolic), 11.7/7.6, and 13.0/8.3 mmHg with 25% max dose, 50% max dose, and with the max dose of ARBs, respectively. Losartan in the dose of 50 mg lowered ABP less well than other ARBs at 50% max dose by 2.5 mmHg systolic (P < 0.0001) and 1.8 mmHg diastolic (P = 0.0003). Losartan 100 mg lowered ABP less well than other ARBs at max dose by 3.9 mm Hg systolic (P = 0.0002) and 2.2 mmHg diastolic (P = 0.002). CONCLUSION: In this comprehensive analysis of the antihypertensive efficacy of ARBs by 24 h ABP, we observed a shallow dose-response curve, and uptitration marginally enhanced the antihypertensive efficacy. Blood pressure reduction with losartan at starting dose and at max dose was consistently inferior to the other ARBs.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor antagonist is the standard of care in acute coronary syndromes. Additionally, novel P2Y12 receptor antagonists such as prasugrel and ticagrelor are even recommended over clopidogrel in certain clinical guidelines. Despite the fact that clopidogrel is fraught with significant variability in on-treatment platelet reactivity, the novel P2Y12 receptor antagonists come at the price of increased side effects and cost. Therefore, alternative or supplementary antiplatelet therapies are needed. Cilostazol, a phosphodiesterase III inhibitor, has been shown to significantly improve high on-treatment platelet reactivity in patients receiving both aspirin and clopidogrel and has antiproliferative effects (inhibiting neointimal hyperplasia and smooth muscle proliferation), thus reducing the risk of restenosis after coronary stent implantation. Further, cilostazol in addition to aspirin and clopidogrel versus DAPT in patients undergoing percutaneous coronary intervention showed that triple antiplatelet therapy (TAPT) was associated with a significantly greater platelet inhibition, reduced major adverse cardiovascular events, target lesion revascularization, and target vessel revascularization with no increased risk for a hemorrhagic event. Moving forward, larger randomized controlled trials are required comparing TAPT versus DAPT (clopidogrel, prasugrel or ticagrelor on top of aspirin). (c) 2013 S. Karger AG, Basel.

OBJECTIVE: Limited studies suggest that blood pressure variability over time is a risk factor of long-term cardiovascular outcomes. However, most of these were in populations with pre-existing cardiovascular diseases (CVD) and studies in general population are lacking. METHODS: The study included 11,153 participants in a population-based, prospective cohort study in Araihazar, Bangladesh. Resting blood pressure was measured at baseline and every two years thereafter. Participants were followed up for an average of 6.5years (2002-2009). RESULTS: Male gender, older age, baseline systolic blood pressure (SBP), and absence of betel leaf use were independently positively associated with greater SBP variability over time. There was a significant association between SBP variability and the risk of death from overall CVD, especially from major CVD events. The positive association with the risk of death from any cause and stroke in age- and sex-adjusted models was attenuated in fully-adjusted models. In addition, the hazard ratio (HR) of stroke mortality was greater for individuals with both high baseline and high SBP variability. Similar patterns of HRs were observed for all-cause and CVD mortalities. CONCLUSION: In this rural Bangladeshi population, variability in SBP contributes to the risk of death from CVD and may further potentiate the increased mortality risk associated with high SBP.

BACKGROUND: In randomized clinical trials, procedural myocardial infarction (MI) or spontaneous MI is often weighted equally as a component of a composite clinical end point. An underlying assumption of this approach is that procedural and spontaneous MIs have similar prognostic impact. Our aim was to evaluate the prognostic impact of procedural vs spontaneous MI in patients undergoing percutaneous coronary intervention (PCI). METHODS: We used data from the EVENT registry to examine the relative prognostic impact of procedural vs spontaneous MI. For the purposes of this study, patients undergoing initial PCI were stratified into 3 groups-no MI, procedural MI, or spontaneous MI-based on standard definitions applied at the time of the index procedure and followed for 1 year for outcomes of all-cause mortality and cardiovascular mortality. Multiple propensity score adjustment analysis was used to adjust for differences in baseline covariates among the 3 groups. RESULTS: Among 7,380 patients included in this analysis, 4,568 (62%) patients had no MI, 580 (8%) patients had procedural MI at the time of their index procedure, and 2,232 (30%) patients presented with a spontaneous MI before PCI. In unadjusted analyses, there was a graded increase in risk of 1-year mortality (1.9% vs 3.1% vs 3.9%; P < .0001) and cardiovascular death (0.5% vs 1.0% vs 1.7%; P < .0001) across the 3 groups. After adjusting for propensity scores, spontaneous MI (adjusted hazard ratio [HR] 1.62, 95% CI 1.11-2.37, P = .01) but not procedural MI (adjusted HR 1.51, 95% CI 0.89-2.54, P = .12) was independently associated with death at 12 months when compared with the no-MI group. Findings were similar when the analysis was limited to cardiovascular death (adjusted HRs 3.14 [95% CI 1.68-5.90, P < .001] and 1.74 [95% CI 0.69-4.40, P = .24], respectively). CONCLUSIONS: Among patients undergoing PCI, spontaneous but not procedural MI was independently associated with death and cardiovascular death at 1 year. These finding suggest that the prognostic impact of procedural MI may be less than that of spontaneous MI and should be considered in designing end points for future studies of coronary revascularization.